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II INTERNACIONAL SYMPOSIUM OF PHARMACEUTICAL SCIENCE Pharmacy School -UFOP ABSTRACT BOOK October 28 and 29, 2015. Ouro Preto-MG, Brazil http://www.cipharma.ufop.br/

ABSTRACT BOOK - cipharma.ufop.br · 13- Débora Faria Silva ... 23- Kelly Christyne Miranda Pereira de Castro 24- Laryssa Freitas Guimarães 25- Leidiane Vieira Simões

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II INTERNACIONAL SYMPOSIUM

OF PHARMACEUTICAL SCIENCE

Pharmacy School -UFOP

ABSTRACT BOOK

October 28 and 29, 2015. Ouro Preto-MG, Brazil

http://www.cipharma.ufop.br/

2

PRESENTATION

Dear Participants,

It is an honor to invite all to the II Symposium to be held by Pharmaceutical

Science Program of Pharmacy Scholl. Taking advantage of the Symposium

success in 2013 and the importance of this action continuity, which strengthens

the program, through the integration with graduate students, with the extension

programs and amplifying the internationalization, this second edition is intended

to enlarge the audience. Graduate students linked to research and extension

projects are also called to participate and share their experiences with

CiPharma master and PhD students. The event is the result of professors’ work

in order to improve the program actions and to improve integration, inclusion

and diffusion of new knowledge and technologies, as well as to contribute to the

excellence of masters and PhD in Pharmaceutical Science. The event is

supported by a project CAPES/COFECUB, coordinated by Prof. Vanessa Carla

F. Mosqueira, by CiPharma and Pharmacy School - UFOP. So, we would like to

welcome the participants who will contribute to the achievement and success of

this event.

Thank You.

3

SUPPORT:

4

Symposium Organization Committee

Neila Márcia Silva Barcellos, PhD - DEFAR/UFOP

Andrea Grabe Guimarães, PhD - DEFAR/UFOP

Vanessa Carla Furtado Mosqueira, PhD - DEFAR/UFOP

Mrs. Mirela Pena Fagundes - CiPharma Secretary

Scientific Committee

Carlos Henryque Souza e Silva – Post doc CiPharma

Elton Luiz Silva – Post doc CiPharma

Giane Martins Garcia – Post doc CiPharma

Gisele Vieira Rodovalho – Post doc CiPharma

Gwenaelle Elza Nathalie Pound-Lana – Post doc CiPharma

Hygor Mezadri - CiPharma Pharmacist

Nádia das Dores Moreira – Post doc CiPharma

Renata Tupinambá Branquinho - CiPharma Pharmacist

Sidney de Almeida Ferreira - Post doc NUPEB

5

REGISTERED PARTICIPANTS

1- Adriana Cotta Cardoso Reis

2- Alessandra Hermógenes Gomes Tobias

3- Amanda Maria Silva Gonçalves

4- Ana Barbosa Zanoti

5- Ana Carolina da Silva Santos

6- Ana Carolina Moreira Souza

7- Ana Paula Amariz Silveira

8- Bruno de Rezende Vieira

9- Catarina Stivali Teixeira

10- Daiane Teixeira de Oliveira

11- Danielle Cristiane Corrêa de Paula

12- Danielle Murta Silva

13- Débora Faria Silva

14- Débora Priscila de Campos

15- Douglas Gualberto Sales Pereir

16- Fernanda Barçante Perasoli

17- Fernanda Cristina Ferrari

18- Isabela Matoso Lopes

19- Izabel Cristina Trindade

20- Jéssica Campolina de Souza

21- Josemar da Conceição Mendes

22- Juliane Morais da Fonseca

6

23- Kelly Christyne Miranda Pereira de Castro

24- Laryssa Freitas Guimarães

25- Leidiane Vieira Simões

26- Letícia Paiva de Matos

27- Lidiane Rodrigues Antunes

28- Lorena Barbosa Arrunátegui

29- Lorena de Souza Rosa

30- Lorena Ulhôa Araújo

31- Luan Silvestro Bianchini Silva

32- Luana Beatriz Araújo Vaz

33- Lucas Felipe Fernandes Bittencourt

34- Luciene Gonçalves da Paixão

35- Ludmila Correia Barbosa

36- Mariana Mafia Penido Ferreira Ribeiro

37- Mariana Reis Di Mambro

38- Mariana Trevisan Rezende

39- Michelle Karoline Conceição Miranda

40- Nayara Nascimento Toledo Silva

41- Quênia Janaína Tomaz de Castro

42- Regislainy Gomes da Silva

43- Rodrigo Chaves

44- Samara Stéfani de Castro Silva

45- Samira Fagundes de Andrade

7

46- Tamara Cristina Moreira Lopes

47- Tamires Guedes Caldeira

48- Tatiane Martins Barros

49- Tatiane Roquete Amparo

50- Thayná Vichiato Silva

51- Thaís dos Santos Paulino Soares

52- Thaís Faco Maganhoto

53- Thaís Santos Rodrigues

54- Thales de Andrade Martins

55- Thiago Magalhães Gouvea

56- Vanessa Santos

57- Vittorio Amadeus Kasten Avery

58- Zilma Schimith Ferraz Filha

8

Program

Wednesday, 28 october

Time Event

8:30 am Registration, Welcome

9 am Opening Section:

Neila Márcia Silva Barcellos – CiPharma Coordinator

Celia Maria Nunes – UFOP Vice-President

Fábio Faversani – UFOP research Head

Vanessa Carla F. Mosqueira - CAPES/COFECUB Project Coordinator

Carlos Magno de Souza Paiva – CAINT - UFOP

10:30 am Coffee break

10:45 am I Roundtable: New Knowledge to the future of cardiovascular therapeutics –

Andrea Grabe Guimaraes, PhD (DEFAR/UFOP)

1. Evaluation of cardiac function: from in vivo to cells and molecules.

Applications to cardiac diseases and drugs cardiotoxicity - Sylvain Richard,

PhD (INSERM 1046, UM1, França).

2. Heart as a pharmacological target for essential oils - Jader dos Santos

Cruz, PhD (ICB/UFMG).

3. - Study of Ang(1-7) and its analogues actions as future pharmacological

strategies for treatment of cardiovascular diseases - Andréia Carvalho

Alzamora, PhD (DECBI/UFOP).

13 pm Lunch

14 pm II Roundtable: Parasitic diseases chemotherapy - Vanessa Carla Furtado

Mosqueira, PhD (DEFAR/UFOP)

1. Andréa Teixeira de Carvalho (Rene Rachou)

2. Maria Terezinha Bahia (DECBI/UFOP)

3. Marta de Lana (DEACL/UFOP)

16 to 18 pm Painel Section I

Thursday, 28 october

Time Event

9 am Students Oral Presentation

10:30 am Coffee break

10:30 am to

12:30 pm

Painel Section II

12:30 pm Lunch

14:30 pm III Roundtable : Research on women's health

1. Vanja Maria Veloso, PhD (DEFAR/UFOP)

2. Antônio Carlos Pinto Guimarães, PhD (UFSJ)

3. Romulo Leite, PhD (DEFAR/UFOP)

16:30 pm Finish section

ABSTRACTS

1

QUALITY CONTROL IN CERVICAL

CYTOPATHOLOGY: PERFORMANCE OF RAPID

PRESCREENING, 100% RAPID REVIEW AND THE

REVIEW BASED ON CLINICAL RISK CRITERIA

Alessandra Hermógenes Gomes Tobias1,2

, Aline Costa

Vitalino2, Renata Rocha Rezende e Oliveira

2, Mariana

Trevisan Rezende1,2

, Jennefer Aparecida do

Nascimento Gonçalves2, Cláudia Martins Carneiro

1,2

1CIPHARMA/Pharmacy School/Federal University of

Ouro Preto/Ouro Preto/MG 2Cytology Sector/Pilot Laboratory of Clinical

Analysis/Pharmacy School/Federal University of Ouro

Preto/Ouro Preto/MG

Background: The Pap smear or cervical cytology

exam is a screening strategy widely used in the

prevention of cervical cancer. This examination consists

of several steps, and conducting internal quality

monitoring methods (MIQ) is indispensable to confer

quality to the final result, mainly because these

methods help to reduce false-negative. Objective: To

evaluate the performance of Rapid Prescreening, 100%

Rapid Review and the Review based on Clinical Risk

Criteria as MIQ methods. Methodology: This study

was conducted in Cytology Sector of LAPAC, between

October 2012 and October 2014. It was first performed

the Rapid Prescreening and noted in a spreadsheet if

the exam was suspicious, negative or unsatisfactory.

Subsequently was realized the routine screening of the

exam. Then all exams considered negative by the

routine screening were reviewed by the 100% Rapid

Review and the result was classified as suspicious,

negative or unsatisfactory. Exams classified as

negative by the routine screening that showed clinical

risk criteria were reviewed and classified as positive or

not after detailed review and final diagnosis. All smears

considered positive and unsatisfactory for routine

screening or suspects and unsatisfactory by MIQ

methods were referred for detailed review to confirm or

not the presence of positivity for then determinate the

final diagnosis, which was the gold standard for

calculate the MIQ method performance. It was done a

database with the results of the methods of MIQ and

final diagnosis and finally we calculated the sensitivity

and specificity for each one of the methods using the

OpenEpi program, version 3. Results: During the

period established for this work the Cytology Sector of

LAPAC received a total of 9.751 cervical cytology

exams from all Basic Health Units in the city of Ouro

Preto, Minas Gerais. Of these tests, 357 were rejected

and returned to Basic Health Units, getting a total of

9.394 to be analyzed. The Rapid Prescreening, the

100% Rapid Review and the Review based on Clinical

Risk Criteria was conducted in a total of 9.394, 8.244

and 1.381 exams, respectively. The sensitivity of the

Rapid Prescreening, the 100% Rapid Review and the

Review based on Clinical Risk Criteria was 48.2%,

42.6% and 22.6% and the specificity was 90%, 95%

and 84% respectively. Conclusion: The MIQ method

which demonstrated better performance in laboratory

routine was 100% Rapid Review.

Acknowledgment: FAPEMIG, CNPQ, CAPES E

UFOP.

2

FACTORS ASSOCIATED WITH QUALITY OF LIFE

AND HEALTH IN WOMEN IN CLIMACTERIC.

ZANOTI AB*1,MIRANDA MKC

1, VELOSO VM

1,SOUSA

JC1,RIBEIRO MMPF

1, FERREIRA MCBC

1, CARRILLO

MRG1, LIMA AA SERPA MA

1,SEBASTIAO ECO

1,

CARRILLO MRG1, LIMA AA

1 , NUNES DDC

1,COURA-

VITAR W1.

1Escola de Farmácia/UFOP, Ouro Preto – MG

*e-mail: [email protected]

With increasing of life expectancy of the population,

especially women, it is important to exchange

knowledge about the climacteric. The objective was to

disseminate knowledge about the risk factors

associated with perimenopause and menopause that

affect quality of life. This project was undertaken in the

city of Ouro Preto, in partnership with SUS, which has

as priority actions to disease prevention and health

promotion. The beneficiaries were women aged 45-60

years in different stages of menopause, which were

invited to attend lectures given by students and project

contributors. The themes covered in the lectures were

related to health-disease process, focusing on risk

factors, which occur more often during this period of

life. Among the topics covered, hypertension, diabetes,

dyslipidemia and osteoporosis were those that had

more prominence, since they arouse greater interest

from the beneficiaries. Added to this idea, other

activities have been offered to contribute to the

empowerment of the women, such as cosmetics and

10

food workshops in order to promote the redefinition of

this phase of life, awakening autonomy and interlace

the links between population, SUS and university. It is

believed that the actions taken have contributed to

improving the quality of life of these women and a more

critical and human formation of the students involved.

Thanks: The basic health Units - UBS in the city of

Ouro Preto Ouro, which has always collaborated with

our project assisting in contact with women benefited.

Financial support: FAPEMIG e Pró-reitoria de

extensão- PROEX.

3

ANTIMALARIAL EFFICACY OF ARTEMETHER

ADMINISTERED ORALLY IN NANOCAPSULES

SOUZA ACM1,VIDAL-DINIZ AT

1, ANDRADE RP

1,

SILVEIRA APA1, CASTRO Q.J.T

1, GUIMARÃES H.N

2,

RICHARD S3, MOSQUEIRA V.C.F

1, GRABE-

GUIMARÃES A1

1CiPharma, Escola de Farmácia, UFOP, Ouro Preto,

MG;

2DEE, Escola de Engenharia, UFMG, Belo Horizonte,

MG, Brazil;

3Universitè de Montpellier 1, INSERM 1046;

Introduction: Malaria is a public health disease caused

by Plasmodium sp and it is an important cause of

illness and death in children and adults in 97 malaria

endemic countries (WORLD MALARIA REPORT, 2014;

WHO, 2015). The artemisinin derivatives, as

Artemether (ATM), are an alternative to malaria

Plasmodium falciparum treatment (WHO, 2015). The

nanosystems development offers the necessary tools to

deliver active molecules to specific sites. New

nanostructures can protect the molecule from

degradation by the oral route, modify the biodistribution

and pharmacokinetic profile and bioavailability.

Objective: Evaluate the antimalarial efficacy of ATM in

nanocapsules (NC) administered orally. Methods: the

production of ATM NC was previously described

(VIDAL-DINIZ, 2014). The animals were infected with

Plasmodium berguei and three days after, treatments

were initiated. ATM formulations were administered

during 4 days, every 12 hours. The animals groups

treatment were: a) ATM NC (40, 80 and 120 mg/kg); b)

free ATM (40, 80 and 120 mg/kg); c) empty NC; d)

vehicle. The animals survival index was evaluated and

also the percentage of parasitemia after different

treatments. The animals were evaluated over 30 days.

Results: The animals treated with ATM NC showed a

significant reduction of parasitemia compared to groups

treated with the same dose of free ATM. The animals

treated with ATM NC were able to reduce the

parasitemia by 75%; 67% and 64% at 40, 80 and 120

mg/kg, respectively, compared to animals treated with

free ATM. Moreover the survival index of animals

treated with ATM NC was significantly higher than

animals treated with either control as with ATM free.

The animals treated with vehicle and empty NC

survived until the 9th and 19th day, respectively, after

the infection. The higher dose administered, 120 mg/kg,

showed 100% survival for animals treated with ATM

NC, whereas for animals treated with free ATM it was

only 67% until the 30th day. Conclusion: The ATM NC

administered orally has greater effectiveness in

reducing the parasitemia, since it was observed the

increase in animal survival index.

Funding agencies: FAPEMIG (Rede Nanobiomg-

CDS_PPM0481-13) and UFOP

Acknowledgments: CNPq; UFOP; CAPES and Project

APQ 02346-11 (FAPEMIG)

4

ASSESSMENT OF KNOWLEDGE AND PERCEPTION

OF ADOLESCENTS AND MOTHERS ABOUT HPV

AND CERVICAL CANCER IN OURO PRETO: A

PILOT STUDY

Ana Carolina da Silva Santos1, Camila de Paula Dias

2,

Cláudia Martins Carneiro1,3

, Angélica Alves Lima1,4

1Laboratório de Bioquímica Clínica. Programa de Pós-

graduação em Ciências Farmacêuticas UFOP – Ouro

Preto/MG 2 Laboratório de Bioquímica Clínica UFOP – Ouro

Preto/MG 3Laboratório de Imunopatologia/NUPEB. Departamento

de Análises Clínicas da Escola de Farmácia UFOP –

Ouro Preto/MG 4Laboratório de Bioquímica Clínica. Departamento de

Análises Clínicas da Escola de Farmácia UFOP – Ouro

Preto/MG

In Brazil, cervical cancer is the third most prevalent

neoplasia and the fourth leading cause of death in

women. The primary risk factor for cervical cancer is

the persistent infection with high-risk Human

Papillomavirus (HPV). In 2014, the HPV vaccine was

introduced in Brazil's National Vaccination Calendar for

female adolescents. After the implementation of the

vaccine in public health programs, several countries

have developed studies in order to identify local

particularities and improve service to the population.

The objective of this study was to analyze knowledge

and perception of adolescents and their mothers about

HPV and cervical cancer in Ouro Preto, MG. The study

was conducted in two Basic Health Units in Ouro Preto.

11

The interviews were applied to 86 adolescents aged 11

to 13 years old and 62 mothers. For the asessment of

knowledge and perception about HPV, cervical cancer

and the vaccine it was established a score (Very Good-

VG, Good-G, Fair-F and Poor-P) based on the number

of correct answers. In addition, for the survey of

difficulties and lack of knowledge about the subject, an

individualized analysis and a comparative analysis of

the interview questions were accomplished. In the

knowledge and perception analisys it was observed that

14% of adolescents (VG/G) and 56.4% of mothers

(VG/G) declared they were aware of the issue, but only

one adolescents (G) and 35.5 % of mothers (VG/G)

demonstrated a real knowledge about the subject. The

main difficulties observed were regarding to:

applicability of the HPV vaccine, number and frequency

of doses, prevention, signs and symptoms of HPV

infection and cervical cancer causes. The results of this

work has shown the low knowledge of the interviewers

about HPV, vaccine and cervical cancer. In addition,

most of adolescents and mothers believe they are more

updated on the issue addressed (perception) than they

actually are. This reinforces the need of carrying out

educational activities aimed to this population.

Acknowledge and financial support: UFOP,

Cipharma, Capes.

5

CARDIOTOXICITY ASSESSMENT OF FREE

ARTEMETHER CARRIED IN NANOCAPSULES.

Vidal-Diniz AT1, Silveira APA

1, Andrade RP

1, Souza

ACM1, Castro QJT

1, Guimarães HN

2, Richard S

3,

Mosqueira V.C.F1, Grabe-Guimarães A

1

1CiPharma, Escola de Farmácia, Ufop, Ouro Preto, MG;

2DEE, Escola de Engenharia, Ufmg, Belo Horizonte,

MG, Brazil;

3Universitè De Montpellier 1.

Malaria is caused by parasites Plasmodium. Tropical

and subtropical regions are the most affected and the

age group most targeted are children because of their

high susceptibility. The artemether (ATM) is the most

utilized treatment for Malaria, but it presents low oral

bioavailability, low elimination, half-life and toxicity,

mostly, in the central nervous system and cardiac.

Evaluated the cardiotoxicity in vivo of ATM, as well as

in its free form (ATM FREE) and encapsulated (ATM

NANO) form, in chronic treatment. The protocols used

were approved by CEUA UFOP under N° 2011/03.

Male Wistar rats were used, weighing between 220-

250g. To evaluate the cardiovascular parameters of

ECG: QT, RR, PR, QTc intervals and QRS complex,

and arterial pressure parameters (AP). The animals

were distributed in different experimental groups (n=8).

It was received the drug intravenously, at doses of 40,

80 and 120 mg/kg of ATM FREE and ATM NANO, and

as the control group the animals received vehicle and

empty nanocapsules (EN). after vehicle administration

and EN, there were no significant changes in baseline

parameters (BP) and ECG of the animals, the

administration of 120 mg/kg of ATM FREE caused

severe hypotension leading to discontinuation of

experiments with this dose. The administration of ATM

FREE (40 and 80 mg/kg) led to variations of 19% and

33% QT interval, significant reduction in heart rate (HR)

15% and 20% compared to baseline, while the ATM

NANO did not significantly alter the QT interval and HR.

The increase in QTc was reduced by 12%,

approximately, compared to the treatment with ATM

Free and ATM NANO. ATM FREE induced pronounced

decrease in AP and ATM NANO reduced hypotension.

There were no relevant changes in PR interval and

QRS complex. The results demonstrated that ATM

NANO reduced cardiotoxicity. ATM NANO maintained

its antimalarial activity and showed reduced

cardiotoxicity when compared to its free form,

suggesting a change in the drug distribution.

6

THE USE OF CINEMA IN BIOETHICS AND

HUMANISTIC EDUCATION IN PHARMACEUTICAL

SCIENCES; PROVOKING REFLECTIONS

Bruno de Resende Vieira1, Thayná Vichiato Silva

1,

Lidiane Rodrigues Antunes1, Marcela Torisu Lemos

1,

Catarina Stivali Teixeira1, Thiago Gouveia

1; Elza

Conceição De Oliveira Sebastião1.

1Escola de Farmácia, UFOP, Ouro Preto, Minas Gerais,

Brasil.

Audiovisual resources, especially the cinema, have

been widely used as facilitators in the teaching-learning

process. They play complementary role in training

healthcare professionals and provoke reflection on

bioethical and anthropological issues in order to

enhance the structure of the character of the individual.

The Brazilian National Curriculum Guidelines for

Graduation Schools highlight the important role of the

humanities in healthcare professionals training.

Pharmacy Courses, the students need the opportunity

to learn bioethical concepts throughout their

undergraduate training, in order to establish

professional-patient relations based on care and

respect, promoting autonomy and the preservation of

human dignity. To carry out practical alternative and

extracurricular activity, offered to Pharmacy academics,

to the promotion of creative and critical discussions of

relevant anthropological and clinical issues. The

12

development consisted in film screening followed by

discussion/debates. The movie collection was obtained

by donations of original copies of the personal

collection of the tutor of the project. The target

participants were all ongoing Pharmacy undergraduate

students of the Pharmacy School of Ouro Preto

University, in 2015. The promotion of film events was

made by printed posters and social networks like

Facebook, Twitter and the university website. The

participants of each event were invited to evaluate each

event by filling out anonymous and confidential

questionnaires. Seventeen movies were shown from

September/2014 to August/2015 to an audience of 226

participants; The subliminal themes of the movies were

classified as ethics in science, organ donation,

overcoming, psychiatric disorders,

spirituality/faith/belief, sexual orientation, drug use,

alcoholism, human relations, feminism, violence against

women and general discrimination. There was an

average of 13.3 viewers/film and the average time of

debate of 40 minutes; Event was positively reviewed by

96% of viewers. Selected film screenings followed by

respective debates allowed the participants to discuss

taboo themes of social, cultural, psychological and

medical-scientific aspects. It has emerged as an

effective alternative because it recreates situations

close to reality, sparking participant’s feelings capable

of producing reflections on moral and bioethical

dilemmas that can be used in problem-solving of real

life. This project permitted the expansion of the

participants horizons about the topics discussed and

integrated approach between professional practice and

ethics, stimulating their critical evaluation and effective

understanding of patients' unique narratives and needs.

It must be used as a significant teaching tool for

achieving humanistic educational objectives in the

undergraduate Pharmacy curriculum.

Financial support and thanks to: PROGRAD-UFOP e

GEPhar.

7

PHARMACOLOGICAL TREATMENT (NON)

ADHERENCE AMONG WOMEN

DIAGNOSED WITH BREAST CANCER LIVING IN

OURO PRETO

Catarina Stivali Teixeira1, Elza Conceição de Oliveira

Sebastião2, Vanja Maria Veloso

2

1CIPHARMA, Escola de Farmácia, UFOP;

2DEFAR - Escola de Farmácia – UFOP;

Introduction: Although incidence and mortality rates

for women living with breast cancer (WLBC) have

increased in recent years, this type of cancer has a very

good prognosis if diagnosed and treated properly. It is

known that pharmacological treatment (PT)

(non)adherence isinterrelated to factors associated with

the patient, with the treatment itself and with the health

services. Adhering to the PT reduces morbidity and

mortality of cancers as well as the costs of healthcare.

The psycho-socio-economic aspects should not be

neglected, since PT non-compliance possible causes

failure of chemotherapy of WLBC. Objective and

Methodology: This study aims to give insight into the

process of (non-)adherence by researching influencing

factors in breast women cancer taking PT by means of

a qualitative study with semi-structured interviews. The

sample will consist of 30 participants treated with PT.

The consent by the coordinator of the group was

obtained and the research was approved by the

UFOP´s Ethics Committee under the registration

49488415.0.0000.5150. Potential results: At this

moment, there are no results because the data

collection is programmed to be conducted at 2016.

However, there are expectations regarding the impact

of PT, that social support from family and friends, and

recognition from healthcare professionals are expected

to influence the process of (non-)adherence . The

results of this study can help healthcare professionals

understand why WLBC under PT do not always adhere

to taking the therapy and may facilitate patient-tailored

interventions at the specific support group at Ouro

Preto.

Keywords: adherence; Pharmacological therapy;

influencing factors; qualitative study, Pharmaceutical

care.

Acknowledgements: PROPP/UFOP and CIPHARMA

for financial support. To AMBAR and GEPHAR groups

by scientific support.

Financial support: PROPP/ UFOP

8

TOXICOGENETIC EFFECTS OF SILIBININ IN

BLADDER CANCER CELL LINES

Daiane Teixeira de Oliveira¹, André Luiz Ventura

Sávio², João Paulo de Castro Marcondes², Glenda

Nicioli da Silva¹.

1Laboratório de Pesquisas Clínicas /CIPHARMA /

Universidade Federal de Ouro Preto (UFOP) - Ouro

Preto/MG

²Laboratório de Toxicogenômica e Nutrigenômica

/Universidade Estadual Paulista (UNESP)-Botucatu/SP

e-mail: [email protected]

Silibinin is a natural phenol derived from the

Flavonolignan family and founded in seeds of wild

13

artichoke plant or thistle. Recent data have shown its

effectiveness in preventing/treating bladder tumors in

vivo, making it a promising antineoplastic agent. TP53

mutations are the most common alterations in bladder

cancer cells, and are related to treatment response.

Thereby, in this study we investigated the mechanism

of action of silibinin in bladder cancer cells with different

TP53 gene status. Two bladder urothelial carcinoma

cell (UCC) lines were used: RT4, with wild-type TP53

gene; and T24, with mutated TP53 gene. Silibinin was

tested at concentrations of 50, 75, 100, 115, 130, 135,

150, 200 and 250 µM in cell proliferation and

clonogenic survival assays, cell cycle kinetics,

apoptosis rates and comet assay. The data showed

increased primary DNA damage levels in both cell lines.

Furthermore, the results demonstrated decreased cell

proliferation rates in the TP53 mutated cells, but not in

TP53 wild type cells. However, the clonogenic survival

assay revealed significant decreases in RT4 and T24

cell colonies. Increased early apoptosis rates were

observed in both cell lines, while late apoptosis rates

were only detected in T24 cells. No changes in cell

cycle kinetics were observed. In conclusion, silibinin

promoted decreased proliferative capacity in cell lines

of bladder urothelial carcinoma possibly by inducing

DNA damage and activation of cell death independent

TP53 status. These results provide data that can help in

the elucidation faction mechanism of action of silibinin

in the treatment of bladder cancer.

Keywords: Silibinin, Bladder Cancer, Gene TP53,

Comet assay, Cell cycle, Apoptosis, Cytotoxicity.

Acknowledgment: Dra. Daisy Maria Fávero Salvadori,

Me. André Luiz Ventura Sávio, Dr. Alexandre Reis

Barbosa, Dra. Cláudia Martins Carneiro, Dra. Marta de

Lana, UFOP, CiPharma, UNESP-Botucatu, Laboratório

de Imunopatologia-Nupeb, Laboratório de doença de

Chagas-Nubep.

Funding: FAPEMIG, CNPQ, CAPES, UFOP.

9

EVALUATION OF CARDIOTOXICITY OF

CASPOFUNGIN IN VIVO

Paula, DCC1; Garcia, IC

2; Guimarães, HN

3; Grabe-

Guimarães, A2.

1Programa de Pós graduação em Ciências

Farmacêuticas – CiPharma; 2Departamento de

Farmácia da UFOP; 3Departamento de Engenharia

Elétrica da UFMG.

The incidence of fungal infections has increased

considerably. The resistance to conventional antifungal

agents and their toxicity are some factors that suggest

new drug delivery systems development to treat

systemic fungal infections. Objective: To evaluate the

cardiac toxicity of intravenous (IV) caspofungin by the

electrocardiogram signal (ECG) Methods: The ECG

was obtained in vivo in healthy female Swiss mice

treated with free caspofungin 5 mg/kg/IV, once daily

during 7 days (n = 8). The animals were anesthetized

with ketamine/xylazine and ECG signals were obtained:

before treatment, 15 and 21 days after the end of

treatment. At 30 days after the end of treatment,

animals were challenged with IV noradrenaline (NA) 1,

3 and 10 µg/kg. A control group without treatment

received only NA (n = 8). All procedures were

previously approved by the Ethics Committee on

Animal Use UFOP under no. 2014/37. Results: The

multiple doses administration of caspofungin induced a

significant increase of ECG QT interval (10% ± 4.1) at

21 days after last administration. NA induced extra-

ventricular arrhythmias, indicating an arrhythmogenic

potential of free caspofungin. Conclusion: Preliminary

results confirm caspofungin cardiotoxicity already

reported in heart and isolated rat cardiomyocytes. We

expect that the encapsulation of caspofungin in solid

lipid nanoparticles (SLN), the cardiotoxic effects will be

eliminated, and it could be safier to treat fungal

infections.

Financial supports: FAPEMIG (Rede Nanobiomg,

CDS-PPM - 2013), UFOP

10

METHOD DEVELOPMENT BY HPLC FOR

QUANTIFICATION OF CANDESARTAN CILEXETIL

IN BIOPHARMACEUTICAL STUDIES

Campos, D.P. 1, Barcellos, N.M.S.

1, Souza, J

1.

1Universidade Federal de Ouro Preto, Laboratório De

Controle de Qualidade - Ouro Preto, MG, Brasil

Biopharmaceutical studies consist in the determination

of solubility and permeability of a drug and dissolution

from the dosage form. These studies will allow the

allocation of candesartan cilexetil, an antihypertensive

classified as antagonist of angiotensin II receptors

(AT1), in the Biopharmaceutical Classification System,

contributing to a safe decision about the possibility of

bioiwaiver for new products and increasing the supply

of available drugs by the program “Farmácia Popular do

Brasil”. Before performing biopharmaceutical studies it

is necessary to develop an analytical method suitable

for quantification of the drug without interference from

the matrix or the possible degradation products. This

preliminary study aims to demonstrate how the method

for quantification of candesartan cilexetil is being

14

developed. Starting with the identification of the

analytical conditions described in the literature: 1)

Sodium phosphate monobasic buffer, acetonitrile

(50:50), pH 3; flow 1 mL/min; detection photodiode

arrays (DAD)-210nm; CN column (250 x 4.6 mm, 5μm);

Temperature (T) 27°C. 2) 0.05 mol/L Potassium

phosphate monobasic buffer pH 3.0, acetonitrile,

methanol (30:50:20); flow not indicated; detector UV-

visible-215nm; C18 column (250 x 4 mm, 5μm);T not

indicated. 3) Methanol, acetonitrile, 10 mmol potassium

phosphate monobasic pH 4.0 (90:8:2); flow 0.8 mL/min;

detection at 254nm; column not indicated; T not

indicated. 4) Acetonitrile, water, acetic acid 90: 10: 1

and 57: 43: 1 (gradient elution) pH not indicated; flow

0.8 mL/min; detector UV-visible-254nm, C18 column

(150 x 4 mm, 4μm);T 25°C. 5) Acetonitrile, 5 mM

ammonium acetate pH 2.5 (47:53); flow 1.5 mL/min;

mass detector; C18 column (50 x 4.6 mm, 3.5μm); T

20°C. The conditions were tested on C18 column (150

x 4mm, 3,5μm); DAD-254nm; T 25°C. 1) It was not

tested because it showed instability with the media in

which the drug will be quantified; 2) Presented retention

time (rt) 38 minutes; 3) presented rt: 4 minutes; 4) The

two conditions were tested alone in isocratic elution, the

first rt was 3 minutes, very close to the void time and

the second around 18 minutes; 2) and 4) were not

adequate for the required time of analysis; 3) Have a

suitable rt but there was no separation of degradation

products and is therefore not selective, so 5) will be

tested. The method should be developed in accordance

with the required analytical application and it is a

process that aims a smaller rt, higher sensitivity and

symmetry of the chromatographic signal without

interference constituents of matrix or degradation

products.

Acknowledgements: UFOP/CiPharma/Ministério da

Saúde/Anvisa/FAPEMIG/Rede Toxifar/CNPq.

Keywords: Method development, Candesartan

cilexetil, Biopharmaceutics.

11

TOXICOLOGICAL EVALUATION OF THE

ACCELERATED CLEARANCE BLOOD

PHENOMENON FOR THE LIPOSSOMAL

TREATMENT IN LEISHMANIA INFANTUM INFECTED

MICE

Débora Faria Silva¹; Tamara Cristina Moreira Lopes¹;

Walyson Coelho Costa¹;

Adriel Araújo Fernandes

Ferreira2; Neila Márcia Silva Barcellos¹; Rodrigo Dian

De Oliveira Aguiar Soares3; José Mario Barichello¹;

1Simone Aparecida Rezende

1

¹Programa de Pós-graduação em Ciências

Farmacêuticas (CiPharma) - Escola de Farmácia –

Universidade Federal de Ouro Preto (UFOP) 2Departamento de Fisiologia e Biofísica – Instituto de

Ciências Biológicas (ICB) – Universidade Federal de

Minas Gerais (UFMG) 3Núcleo de Pesquisa em Ciências Biológicas (NUPEB)

– Universidade Federal de Ouro Preto (UFOP)

Introduction: The World Health Organization

encourages the study of new drugs or alternative forms

of administration for the treatment of visceral

leishmaniasis, among them the liposomal formulations.

These formulations could lead to reuse of tartar emetic

(TE), a potent anti Leishmania drug with limited use due

to serious toxic effects. Objectives: This study

evaluated the effect of the accelerated blood clearance

(ABC) phenomenon in Leishmania infantum infected

BALB/c mice treated with pegylated liposomes

containing TE. This effect is responsible by the rapid

clearance of a second dose of pegylated liposomes

from the circulation within a certain interval from

injection of the first dose due to the removal by

macrophages. Methods: conventional and pegylated

liposomal formulations were prepared by the hydration

of a thin film of lipids with a solution of the drug. The

effect of TE liposomal formulations on nitric oxide

production by LPS/IFN-gama stimulated J774-A1 cells

was evaluated by Griess method. In order to evaluate

the effect of ABC phenomenon on BALB/c treatment

with TE pegylated liposomes, mice were initially treated

with empty pegylated liposomes. One week later, they

were treated with pegylated liposomes containing 12

mg SbIII/kg. Parasite load was evaluated by limiting

dilution analysis. The effect of infection and treatment

was evaluated by analysis of hematological and

biochemical parameters. Results: TE liposomal

formulations had no effect on nitric oxide production for

J774-A1 cells. Pegylated liposomal formulation of TE

significantly reduced the parasite load in liver, spleen

and bone marrow of L. infantum treated mice. However,

ABC phenomenon had no effect on treatment with

pegylated formulation of TE. Free drug and

conventional formulation was able to reduce parasite

load only in liver. No impairment in the hepatic and

renal functions and hematological parameters was

observed due to the infection or treatment.

Conclusion: Pegylated liposomes containing TE were

more effective in reducing parasite load than

conventional liposomes. ABC phenomenon had no

effect on treatment with pegylated liposomes.

Financial support: CNPq, UFOP.

15

12

ASSESSMENT OF ANTI-HYPERURICEMIC ACTIVITY

AND INHIBITION OF HEPATIC XANTHINE OXIDASE

OF PIMENTA PSEUDOCARYOPHYLLUS AQUEOUS

EXTRACTS

Fernanda Cristina Ferrari1, Zilma Schimith Ferraz

Filha1, Camila Helena Barros

1, Marcus Antônio Ferreira

Santos1, Dênia Antunes Saúde-Guimarães

1.

1Laboratório de Plantas Medicinais, Escola de

Farmácia da Universidade Federal de Ouro Preto,

Brazil.

Gout is an acute inflammatory disease caused by the

deposition of urate crystals in the joints. Pimenta

pseudocaryophyllus (Gomes) Landrum (Myrtaceae) is

known as craveiro or cataia, being used by some

people as sedative, aphrodisiac, diuretic and against

arthritism. This study evaluated the anti-hyperuricemic

activity and inhibition of hepatic xanthine oxidase of

aqueous extracts of the species. A model of

hyperuricemia induced by potassium oxonate in Swiss

mice was used. The extracts were prepared using 70 g

of powdered leaves and branches, extracted with 1 L of

water each. After lyophilization 9.61 g of dried aqueous

extract of the leaves (EAF) and 4.86 g of dry aqueous

extract of the branches (EAG) were obtained. The

hyperuricemic animals that received EAF (125 mg/kg)

and EAG (500 mg/kg) showed statistically lower serum

uric acid compared with hyperuricemic group. The

extracts EAF (125 mg/kg) and EAG (500 mg/kg) were

capable to inhibit the hepatic xanthine oxidase enzyme

in 22.77% and 11.17%, respectively. Allopurinol (10

mg/kg) was able to reduce this enzyme in 82.06%.

Studies showed that the aqueous extracts were able to

reduce serum levels of uric acid. The mechanism of

hipouricemic action of EAF was via inhibition of hepatic

xanthine oxidase. Further studies are needed to

elucidate the anti-hiperuricemic mechanism of action of

EAG. The aqueous extracts of leaves and branches P.

pseudocaryophyllus have potential for use in the

treatment of hyperuricemia and gout.

Keywords: Pimenta pseudocaryophyllus;

Hyperuricemia; Xanthine oxidase; Inflammation, Gout.

Financial support: FAPEMIG CDS APQ-00956-13,

REDE TOXIFAR/FAPEMIG, PROBIC/FAPEMIG,

CAPES, UFOP.

13

ROLE OF IPRIFLAVONE INCORPORATION INTO

SELF-EMULSIFYING DRUG DELIVERY SYSTEMS

ON THE SEXUAL AROUSAL RESPONSE IN

FEMALE WISTAR RATS

LOPES IM1, MENDES JC

1, RODOVALHO GV

1, LEITE

R1.

1CiPharma, Pharmacy School, Federal University of

Ouro Preto, Brazil.

Introduction: The menopausal hypoestrogenism is

related to symptoms of sexual dysfunction such as

decreased sexual arousal and difficulty in achieving

orgasm. Estrogen replacement therapy (ERT) is an

effective treatment, but it is associated with

predisposition to breast and endometrium cancer.

Objective: In this study, we evaluated the effect of the

fitoestrogen ipriflavone incorporation into self-

emulsifying drug delivery systems (SEDDS) as an

alternative to ERT on the female sexual function.

Methodology: We evaluated the sexual arousal

response of adult female Wistar rats with regular

ovulatory cycle (OVR), ovariectomized (OVX),

ovariectomized treated with estradiol cypionate (OVE,

38 µg/kg, subcutaneous) or iprifavone (OVI, 10 and

30mg/kg,) for 7 days. Sexual arousal response was

stimulated by apomorphine (80 µg/kg, subcutaneous), a

dopamine agonist, which causes genital grooming

response associated with temporary clitoris

engorgement. After apomorphine or ascorbic acid

(control) administration, animals were placed in a box

with front and bottom transparent sides and videotaped

for 30 minutes. The number of grooming, during this

period, was considered an indicator of arousal

response. Results: OVR rats had an increased arousal

response induced by apomorphine when compared to

the control (ascorbic acid administration in OVR).

Estrogen replacement was able to restore reduced

arousal response caused by ovariectomy. There was

no apomorphine-induced arousal response in OVI

group, this response was lower than control OVI group

that receive only administration ascorbic acid. The lack

of response stimulated by apomorphine in OVI group

may be related to the preparation or degradation of

apomorphine. Conclusion: It is necessary additional

experiments to conclude the effects of ipriflavone in

facilitating the sexual arousal in female rats.

Key words: hypoestrogenism, fitoestrogen, sexual

arousal, female rats.

Acknowledgements: This work was supported by

Conselho Nacional de Desenvolvimento Científico e

Tecnológico (CNPq) and Fundação de Amparo à

Pesquisa do Estado de Minas Gerais (FAPEMIG).

14

PREVENTIVE EVALUATIONS AND LAB TEST ON

WOMEN AT THE CLIMACTERIC

16

Sousa, J.C.1; Ribeiro, M.M.P.F

1; Faria, A.P.C.

1;

Gouvea, T.M.1; Gaede-Carrillo, M.R.G.

1; Lima, A.A.

1;

Veloso, V.M.1

1Escola de Farmácia, UFOP,

, Ouro Preto, MG

Although the climacteric is a natual and physiological

process, part of women's aging, is too complex,

generating events on a female body, causing

physical,psychic,metabolic and behavioral changes.

Among the metabolic changes in this stage, there are

many factors that increase the risk for osteoporosis and

for cardiovascular diseases, which is the main cause for

post menopausal women's death. The goal of this

project was to measure the knowledge and to check out

if there was any risk factors for osteoporosis and

cardiovascular diseases in the women at the

climacteric. There were 53 evaluated women with the

age between 45 and 60 years old in four health centers.

There was a interview using questionnaire that was

divided into three parts. The first one addressed the

demographic and health profile, the second one had

questions according to the the knowledge of risk factors

for cardiovascular diseases (CVD) and the third one

checked out if there was any risk factors for

osteoporosis diseases. Body measurements and

laboratory evaluations were made with the participants.

The average age for women was 53 years old (± 4,2).

The changed lipid profile was found in 73,6% of the

women. The most risk factors were: 94,1%

changed waist circumference (WC), 81,1% obesity

or overweight. The most part of the women knew that

aspects like: age, obesity, smoking, sedentary

lifestyle, diabetes mellitus, alcoholism and stress, are

the important risk factors for cardiovascular diseases.

Even if they know it 69,8% keep sedentary and 22,6%

keep smoking. All the women did show at least one risk

factor for osteoporosis. We can conclude that even the

knowledge and changed risk factors for CVD it is not

enough to motivate changes in the lifestyle. The results

show the importance and necessity of information

programs, specially proposing changes that motivate

changing behavior.

Financial support: PROEX - Pró-reitoria de Extensão

Universidade Federal de Ouro Preto, FAPEMIG -

Fundação de Amparo a Pesquisa de Minas Gerais

15

ROLE OF THE NO/cGMP PATHWAY IN TISSUES

INCUBATED WITH DAF-FM OF YOUNG AND

SENESCENT FEMALE SHR RATS.

MENDES J.C1, MARTINS T. A.

1, RODOVALHO G. V.

1,

LEITE R.1

1CiPharma, Escola de Farmácia, UFOP, Ouro Preto,

MG;

The hypoestrogenism common in menopause can lead

to potentially pathological and universal manifestation

consequences, such as sexual dysfunction, directly

affecting the life quality of women. The involvement of

estrogens in the female genitalia function appears to be

mediated by nitric oxide, the expression of nitric oxide

synthase (nNOS) regulated by estrogen levels. The

cellular distribution of NOS in the vagina of female rats

suggests that nitric oxide (NO) can modulate both the

blood supply to the mucosa as for vaginal smooth

muscle. This study aimed to qualitatively analyze the

presence of NO in cells of vaginal tissues by

fluorescence technique, using reagent diamine

diacetate (DAF-FM) which interacts with the NO

molecule present in tissues, forming a fluorescent

compound. The vaginal tissue were incubated with

DAF-FM (2,5 µM, 1 µM and 0,5 µM) associated with 5

µM of acetylcholine for 10 minutes at room

temperature. Then the tissues were washed in PBS

(three times for 5 min) and incorporated into "tissue tek”

and frozen in -80°C overnight. Adjacent sections (10

µM) were then prepared with the aid of a cryostat.

Tissues were mounted in special blades (chrome-

alum), air dried, and covered with glycerol/tris mounting

medium. Subsequently, the slides were analyzed by

fluorescence microscopy (488 nm).

Our results confirm that incubation of vaginal tissue with

DAF-FM allow detection of NO produced locally at

basal conditions and after stimulantion with

acetylcholine.

Financial support: FAPEMIG, CAPES and UFOP.

16

LC/MS PROFILING OF XANTHONES AND

FLAVONOIDS OF THE ANTI-DENGUE EXTRACTS

AND CONSTITUENTS OF ARRABIDAEA

SAMYDOIDES (BIGNONIACEAE)

Fonseca, J.M.1; Silva, B.M.

2; Kroon, E.G.

3; Oliveira,

A.B.4; Brandão, G.C.

1,

1Universidade Federal de Ouro Preto - Departamento

de Farmácia;

2Universidade Federal de Ouro Preto - Departamento

de Ciências Biológicas;

3Universidade Federal de Minas Gerais - Microbiologia;

4Universidade Federal de Minas Gerais - Departamento

de Produtos Farmacêuticos;

Introduction: Arrabidaea samydoides (Cham.)

Sandwith belongs to the Bignoniaceae family that is

17

represented by more than 100 genera and about 800

species. Chemically, bignoniaceous plants are

characterized by the presence of flavonoids,

terpenoids, quinones, mainly naphthoquinones, and

aromatic compounds such as lignans, cinnamoyl,

benzoyl and acetophenone derivatives. Several species

of this family are reported as used for treatment of

diseases possibly related to viral infections which

motivated the evaluation of A. samydoides [1].

Methods: The in vitro antiviral activity against Dengue

virus 2 (DENV-2) was carried out by the MTT

colorimetric method (n =4); the cytotoxicity was

determined in vitro in LLCMK2 cell lines (n=4);

interferon was used as positive controls (2.5×103 UI/ml)

[2,3]. Ethanol extracts from stems, and leaves were

prepared and submitted to analyzsis by TLC and RP-

UPLC-DAD-MS using previously validated methodology

[1]. The isolation of constituents was done using silica

gel chromatography column, Sephadex LH20 and High-

performance liquid chromatography for preparative

scale. Results: Results are presented as cytotoxic

concentration to 50% (CC50), antiviral effective

concentration to 50% (EC50) and Selectivity Index (SI)

values. The extracts presented low cytotoxicity (CC50 >

90 g/ml). All ethanol extracts were active against

DENV-2, EC50 < 25.0 g/ml and SI > 3.0. UPLC-MS

analyses of extracts, allowed the identification of the

majority of flavonoids and xanthones present in those

extracts. The flavonoids have been identified: as

vitexin, isovitexin, orientin, isoorientin, chrysin, O-

methylchrysin, and xanthones as mangiferin,

isomangiferin, 2’-trans-O-caffeoylmangiferin, 2’-trans-O-

coumaroylmangiferin, 2’-trans-O-cinnamoylmangiferin,

muraxanthone, and 2’-O-benzoylmangiferin. The

chromatographic fractionation leads to the isolation of

three flavonoids called AS1, AS2 and AS3. AS1, AS2

and AS3 were identified as vitexin, isovitexin and

orientin, respectively. AS2 and AS3 showed antiviral

activity with EC50 of 79.3 ± 3.2 and 85.6 ± 4.8,

respectively. AS1 showed no antiviral activity.

Conclusions: The results of the phytochemical studies

here described suggest that flavonoids and xanthones

are the substances that contribute to the antiviral

activity of the ethanol extract of this species.

Financial support: FAPEMIG and CNPq.

17

IN VITRO EVALUATION OF CYTOTOXICITY

NANOSTRUCTURED SYSTEMS CONTAINING

DRUGS ANTI-TRYPANOSOMA CRUZI

de Castro, Kelly Christyne Miranda Pereira1; Mazzeti,

Ana Lia1; Trindade, Izabel Cristina

1; Mosqueira,

Vanessa Carla1; Bahia, Maria Terezinha

1.

1Laboratório de Doenças Parasitárias - Escola de

Medicina – CiPharma - Universidade Federal de Ouro

Preto

Current specific anti-T. cruzi chemotherapies are

unsatisfactory. These therapies are based on

nitroimidazoles or nitrofurans agents such as

benznidazole (Rochagan®, Rodanil®, Roche) and

nifurtimox (Lampit®, Bayer) that were developed

empirically three decades ago. The major limitation of

these compounds is their lower anti-parasitic activity in

the chronic phase of the disease, as 80% to 100% of

treated patients are not cured. Recently newer

strategies based on reformulation have been used to

improve the efficacy of old drugs lacking adequate

pharmacokinetic and biodistribution profile. There has

been a resurgence of interest in nanoemulsions for

various pharmaceutical applications since low-energy

emulsification methods, such as spontaneous or self-

nanoemulsification, have been described. Self-

nanoemulsifying drug delivery systems (SNEDDS) are

anhydrous homogenous liquid mixtures consisting of

oil, surfactant, drug and coemulsifier or solubilizer,

which spontaneously form oil-in-water nanoemulsion

improving the drug delivery. In vitro and in vivo models

are fundamental tools for the evaluation of the

therapeutic efficacy of antimicrobial agents. There are

well established intracellular and extracellular screens

for in vitro hit identification and rodent models for in vivo

screening and evaluation of anti-T.cruzi drug activities.

But studies using these models have not addressed

their predictive value. More specifically, there has been

no analysis linking data in vitro and in vivo studies in

order to gain an understanding of the predictability of in

vitro models used in drug development. The aim of the

present study is to analyze the toxicity and anti-T. cruzi

activity of nifurtimox- and ravuconazole-SNEDDS in

vitro providing a basis for refined drug lead

optimization. The toxicity and anti-T.cruzi activity of the

nifurtimox- and ravuconazole-SNEDDS, of each of its

components alone and of the free compound were

evaluated using the H9c2 rat cardiomyoblast and

HepG2 cell lines as experimental model. Our

preliminary results indicate that both, nifurtimox- and

ravuconazole-SNEDDS, have an increased activity

against the amastigote forms of T. cruzi, compared to

free drugs. However, this formulation had no effect in

the toxicity reduction for mammal host cells.

Supported by: CNPq, Fapemig e UFOP.

18

SOLUBILITY IN EQUILIBRIUM AMILORIDE

HYDROCHLORIDE BY ORBITAL SHAKE FLASK

METHOD: A PILOT STUDY.

18

Laryssa Freitas Guimarães1, Jacqueline de Souza

1,

Bruna Pegorelli1 e Neila Márcia Silva-Barcellos

1.

1Curso de Pós-graduação em Ciências Farmacêuticas -

CiPharma - Universidade Federal de Ouro Preto, Ouro

Preto, Minas Gerais, Brasil.

The drug solubility, permeability and dissolution are

determinant factors in their absorption process. The

drug solubility can be studied and determined by

various methods, among them the orbital shake- flask.

This work has as one of its objectives the solubility

equilibrium study by the shake-flask method of the

amiloride hydrochloride, a potassium-sparing diuretic

used for treating hypertension. To this end, is being

developed an analytical HPLC method aiming at the

amiloride hydrochloride quantification in buffered media

pH = 1.2; 4.5 and 6.8. The chromatographic conditions

were initially evaluated: photo diode detector, C18

column (3.5µm x 4,6 x 150 mm) at 25 ° C, mobile phase

composed of 10% acetonitrile and 90% acidified water

acetic acid (pH adjusted to 4), flow 1.0 ml/min. The

chromatograms were shown to be adequate for

quantification of amiloride hydrochloride and have

allowed their identification in 4 min. A pilot study of the

solubility has evaluated as amount of initial raw material

of excess drug 7.09 mg, 42.47 mg and 2.12 mg in

buffer pH 1.2 ; 4.5 and 6.8, respectively. The samples

were continuously agitated in apparatus orbital shaker-

flask (Incubator Shaker IKA) for 24 hours. The results

showed that the amiloride hydrochloride solubility in

medium of pH 1.2 was 706.05 µg/mL related and

established after 2 hours and 30 minutes from the start

of the experiment. For the medium of pH 4.5 the

solubility was 3949.65 µg/mL after 4 hours of

experiment. Already in the medium of pH 6.8, the

solubility was 226.01 µg/mL after 4 hours of the onset

of the experiment. It can be concluded that the solubility

shake-flask method is able to estimate the solubility of

the drug as well as the analytical method development

is shown to be suitable for their quantification.

Acknowledgments: UFOP; FAPEMIG; CAPES for

their support.

19

POSSIBLE INTERACTION BETWEEN

CANDESARTAN AND THE PHYTOESTROGEN

"IPRIFLAVONE" ON FEMALE SEXUAL FUNCTION

OF HYPERTENSIVE (SHR) AND NORMOTENSIVE

(WKY) RATS

Leidiane V. SIMÕES, Thales A. MARTINS, Vanessa C.

F. MOSQUEIRA, Andrea G. GUIMARÃES, Romulo

LEITE.

Sexual dysfunction is characterized by disturbances

and psychophysiological changes in sexual response

cycle (desire, arousal, orgasm and resolution). Factors

such as age, hypertension, smoking,

hypercholesterolemia and pelvic surgeries interfere in

men's and women's sexual function. It is known that

drugs used for the treatment of hypertension also

interfere on the sexual response, however, studies

have shown that the angiotensin II receptor antagonists

(ARAs), effective in controlling blood pressure,

apparently do not cause, or even mitigate, sexual

dysfunctions. The beneficial effect of ARAs was

observed in studies performed on experimental models

of erectile dysfunction in male rats. In this context, it is

relevant to assess the therapeutic potential of the

combination of an antihypertensive agent with a

substance capable of improving the sexual response in

hypertensive female rats. A strong candidate to be

studied is a phytoestrogen called ipriflavone, synthetic

derivative of daidzein (isoflavones), whose chemical

structure is similar to estradiol and can bind to estrogen

receptors simulating a similar effect of the hormone.

Ipriflavone is already used in the prevention and

treatment of osteoporosis and studies have

demonstrated its high potential to minimize the

symptoms of menopause. Therefore, our goal is to

study the therapeutic potential of candesartan, of

ipriflavone, and the combination of both in the

regulation of sexual function in hypertensive young rats

(SHR) and normotensive (WKY). Young hypertensive

rats (SHR) and normotensive rats (WKY) (with 4 and 5

months) will receive treatment for 30 days, periodically

monitoring the estrous cycle, blood pressure and

vasocongestive response induced by apomorphine. At

the end of treatment changes in temperature,

lubrication and intravaginal pressure induced by pelvic

nerve stimulation will be evaluated. It will be determined

the expression of isoforms of nitric oxide neuronal

enzyme (nNOS) and endothelial (eNOS) by Western

Blotting technique and the reactivity of vaginal tissue

strips will be evaluated in a system for isolated organs.

Nitric oxide and superoxide anion detection in isolated

vaginal tissue will be performed by means of

fluorescence techniques. It is expected that both

candesartan as ipriflavone, as well as the combination

of those substances, improve sexual function in young

female hypertensive rats (SHR) with responses similar

to those observed for female normotensive rats (WKY).

Acknowledgements: CiPharma. Financial Suport:

CNPq, FAPEMIG, CAPES e UFOP.

19

20

EXTENSION PROJECT OF HEALTHCARE

COMMUNITY AGENTS EDUCATION ON

PREGNANCY AND MOTHERHOOD AT TWO BASIC

HEALTH UNITIES FROM OURO PRETO IN 2015.

Lidiane Rodrigues Antunes1; Thayná Vichiato Silva

1,

Bruno de Rezende Vieira1, Marcela Torisu Lemos

1,

Catarina Stivali Teixeira2, Thiago Gouveia

2; Elza

Conceição de Oliveira Sebastião1

1Escola de Farmácia/UFOP, Ouro Preto, Minas Gerais,

Brasil, 2CIPHARMA, Escola de Farmácia, UFOP, Ouro Preto,

Minas Gerais, Brasil;

Pregnancy brings many changes and expectations for

women and their families, since it demands new

emotional, social, and legal responsibilities that go

along with motherhood. The health of pregnant women

and prenatal care are important and current topics that

aim to reduce morbidity and mortality of both mothers

and newborns and improve their quality of life. In public

healthcare services in Brazil, the Healthcare

Community Agents (HCA) are responsible for educating

families and their job must be based on the reality of

each one, considering individuals in their particularity,

complexity and completeness, as well as socio-cultural

integration. To carry out this role, it is essential that

these agents have knowledge and proper information.

This extension project intended to prepare HCA by an

educational approach to pregnant women, both

prenatally and at the postpartum period. Teaching

strategies of lectures, group dynamics, display

instructional videos and practical classes were used at

the classes for 11 HCA of two Basic Health Units, in

Ouro Preto at 2015. It was prepared an auxiliary digital

material after compiling scientific available information

containing training information and its references and

sources. Highlights: General care during pregnancy,

childbirth, complicated conditions, breastfeeding, care

of the newborn, drugs in pregnancy and breastfeeding.

The project was developed through the participative

methodology techniques. It has provided 5 day-events

of 20 hours total of learning and experience

opportunities to the CHA in the field of health education

with pregnant women; providing the elaboration of

teaching technologies that were used to guide the

Agents in the theme; undertake educational activities

among students; develop research projects among the

students that will revert to new teaching, intervention,

and knowledge generation practices. The participants

responded to a questionnaire which showed high

suitability of topics, perceived importance and

satisfaction with the implemented project. The didactical

techniques involved the experience of different social

and psychological realities, represented a space for

reflection about pregnancy and motherhood, enhancing

the HCA knowledge’s about the basic care including

prevention, health promotion and treatment of problems

that can occur during that particular period and after

delivery. The training course was a rich source of

exchange of information, experience and gaining

knowledge about the subject matter. The workshops

were effective tools in the education on prevention and

on the promotion of pregnant/babies healthcare, and

may be carried out in the health services by

interdisciplinary teams.

Financial support: PROEX/UFOP. Thanks:

PROEX/UFOP.

21

DEVELOPMENT OF THE ANALYTICAL METHOD

AND PROSPECTS OF CHEMOMETRICS AIMING

BIOPHARMACEUTICAL STUDIES

Lorena Barbosa Arrunátegui*1; Dâmaris Laignier

Rodrigues de Lacerda2 ; Lara Maria Lopes de Castro

1;

Bruna de Carvalho Mapa1; Neila Márcia Silva

Barcellos1,2

; Jacqueline de Souza1,2

.

1Programa de Pós-graduação em Ciências

Farmacêuticas (CiPharma) - Universidade Federal de

Ouro Preto; 2Escola de Farmácia - Universidade Federal de Ouro

Preto;

*[email protected]

Introduction: To infer the biopharmaceutical

classification of drugs is necessary to promote

dissolution and solubility experiments that should be

executed with the use of properly developed and

validated analytical methods. The chemometrics is

intended for analysis of chemical data of multivariate

nature and collaborates to the development. Thus, the

first step of a biopharmaceutical evaluation is to

develop a reliable quantification method. Objective:

Identify favorable chromatographic conditions for

quantification of desloratadine and loratadine for

subsequent application of chemometrics and validation,

so obtaining a reliable method to start the

biopharmaceutical studies. Methods: The method was

developed in chromatograph Waters and DAD detector.

Samples were prepared containing one or both drugs.

Different conditions for the quantification of the drugs

were performed. The components of mobile phase

tested were: ultra purified water, acetonitrile, methanol,

phosphate buffer, 0.1% acetic acid in water. Column

temperature: 25°C and 30°C. Wavelengths: 247 nm

20

and 254 nm. Flow: 0.8 to 1.2 ml / min. The injection

volume: 20 to 60 µl. Columns: (1) C18 Waters

Simmetry® (150 x 4,6 mm, 5 µm); (2) C18 Varian® (50

x 4,6 mm, 5 µm); (3) C18 Waters SunFire® (150 x 4,6,

3,5 µm); (4) C18 Macherey-Nagel® (150 x 4,6 mm, 5

µm). When the condition that offered more satisfactory

selectivity, efficiency, symmetry and retention time was

found, it was evaluated purity of peak in the Empower

software. Results: It was noted that the peaks that

seemed satisfactory initially began to exhibit unusual

aspect under other exploratory conditions. After careful

critical analysis it has been interpreted as evidence of

coelution even when there should be one drug in the

sample. It was confirmed by the analysis of peak purity.

By comparing the chromatograms, it was concluded

that the sample loratadine, also contained

desloratadine, due to contamination or degradation. It

was possible to find a satisfactory condition. It was

found a condition capable of identifying and separating

loratadine and desloratadine: column temperature 25

°C, volume injection 20ul, flow 1.2 ml / min., DAD

detection with extraction at 247 nm, Varian column (50

x 4.6 mm, 5 um), mobile phase A-water / B-acetonitrile

as gradient (55% to 100% B - 0 to 8 minutes, 100% to

55% B - 8 to 9 minutes). Conclusion: Once one has

succeeded in the separation and purity peak, it is

suggested that this condition should be optimized under

chemometric techniques and validated to advance to

the biopharmaceutical studies.

Acknowledgment: UFOP/CiPharma/Ministério da

Saúde/Anvisa/FAPEMIG/Rede Toxifar/CNPq.

22

DISSOLUTION STUDIES OF ORAL SUSPENSIONS

AND BIOPHARMACEUTICAL CLASSIFICATION

USING NYSTATIN AS MODEL.

Rosa, L.S.1; Marques-Marinho, F.D

1; Souza, J

1;

1Universidade Federal de Ouro Preto, Escola de

Farmácia. Ouro Preto, Minas Gerais, Brasil.

INTRODUCTION: Dissolution studies are needed to

prove quality of manufactured medicines. Such

procedures are well established for solid oral dosage

forms, however, there is a lack of data for oral

suspensions. To evaluate the interferences in

dissolution studies of oral suspensions, the model will

be nystatin, a polyene antibiotic effective against

candidiasis in oral mucosa, skin and gastrointestinal

tract. This drug is commercially available as oral

suspension, which innovator medicine is Canditrat®.

OBJECTIVES: Considering the divergences related to

the biopharmaceutical classification of nystatin and

absence of established experimental conditions for

dissolution profiles of oral suspension, this work aims to

evaluate and establish conditions to execute dissolution

tests, perform solubility studies and summarize data

about permeability to then classify this drug in the

biopharmaceutical system. METHODS: A bibliographic

review will be made about the theme, development and

validation of a quantification method for nystatin in the

biorelevant media simulating gastrointestinal liquid used

in dissolution and solubility tests. A dissolution test for

comparison of profiles of commercialized nystatin will

be executed; the equilibrium solubility using the active

principle ingredient will be determined, permeability in

silico will be performed following data obtained from

scientific literature and databases. RESULTS: Early

tests showed that the viscosity of the oral suspension

when using a rotative viscometer in 100 rpm and L2

apparatus was 247 mPa.s, which indicates a low-

medium viscosity comparing with water, a low viscosity

liquid (0.890 mPa.S) or glycerin, a high viscosity liquid

(934 mPa.s); a scan in UV spectrophotometer (range

from 200 to 400 nm) showed that the maximum

wavelength absorbed was near to those preconized in

the Brazilian Pharmacopeia 5th edition: 291, 305 e 319

nm. However, the ratio between the absorbances were

out of the limit established in the Brazilian

Pharmacopea 5th ed , since the 296/318 nm (0.61 a

0.73), was 0.59, and the ratio 304/318 nm (0.83 a 0.96),

was 1.12. Permeability data obtained through free

access programs Marvin® and Mollinspiration®, and

were logP -1.04 and logP 0.21, respectively. These

results indicate low permeability for nystatin against

metoprolol, a high permeability control, whose logP

1.72.

ACKNOWLEDGMENTS: UFOP/CiPharma/ Ministério

da Saúde/Anvisa/Rede Toxifar. FUNDING:

FAPEMIG/CNPq/CAPES.

23

HEALTH CARE AND BIOPHARMACEUTICAL

ASPECTS OF DRUGS TO TREAT HIGH BLOOD

PRESSURE, DIABETES AND COMORBIDITIES:

SIMVASTATIN IN THE BIOWAIVER CONTEXT

ARAÚJO, L.U1,2

, FERREIRA, A.C.S2, SOUZA, J

2,

SILVA-BARCELLOS, N.M2

1Universidade Federal dos Vales do Jequitinhonha e

Mucuri – UFVJM 2Universidade Federal de Ouro Preto – UFOP

The health care with chronic non-communicable

diseases (NCDs) generates high costs to patients and

the Unified Health System. Thus, the study of NCDs,

the health care aspects in two towns and

biopharmaceutical aspects of applicable drugs

21

comorbidities of these diseases consist the general aim

of this work. Data from simvastatin study in the

biowaiver context will be display here. The

biopharmaceutical parameters such as solubility and

permeability, as well as drugs dissolution from the

dosage form are used to classify the drug into four

different classes according to the Biopharmaceutical

Classification System (BCS). In this context BCS has

been used as a regulatory tool aiming at the

replacement of in vivo bioequivalence studies by in vitro

test, what we call biowaiver. This study review and

discuss in detail existing information in the scientific

literature related to biopharmaceutical aspects of

solubility, permeability and dissolution of the

simvastatin and compile sufficient information to

support a safe discussion about the possibility of

biowaiver. Databases such as Capes, Medline,

ScienceDirect, Scopus and Web of Science were the

sources used for research. Simvastatin’s solubility and

permeability, its therapeutic use and therapeutic index,

pharmacokinetic properties, data related to the

possibility of excipient interactions, and reported

bioequivalence, bioavailability and dissolution data

were taken into consideration. The available data

suggest that according to the BCS and all current

guidances, simvastatin would be assigned to BCS class

II (low solubility and high permeability), with rapid

dissolution from dosage forms, action and metabolism

in liver. Also, in view of its therapeutic use, its wide

therapeutic index and action and metabolism in liver, a

biowaiver for immediate release simvastatin solid oral

drug products could be justified according to the World

Health Organization, if strictly follow the requirements

for immediate release products containing drugs of this

class: product contains only those excipients reported

in this paper in their usual amounts, the dosage form is

rapidly dissolving (85% in 30 minutes or less) in buffer

pH 6.8 and the test product also exhibits similar

dissolution profiles to the reference product in buffer pH

1.2, 4.5, and 6.8.

Acknowledgements: UFOP, FAPEMIG and CAPES.

24

SYNTHESIS OF POLY(LACTIC ACID) (PLA) WITH

ALLYL PENDANT GROUP AND DEVELOPMENT OF

NANOSPHERES

Luan Silvestro Bianchini Silva1, Gwenaelle Pound-

Lana1, Vanessa Carla Furtado Mosqueira

1,

1Laboratório de Desenvolvimento Galênico e

Nanotecnologia (LDGNANO), CiPharma, UFOP.

A major challenge addressed in the pharmaceutical

field of nanotechnology is the development of polymeric

nanocarriers with functional ligands on the surface,

allowing such systems to bind to specific cell sites. PLA

is a histocompatible polymer, biodegradable and which

degradation products are non-toxic; copolymerization of

lactide with allyl glycidyl ether (AGE) provides a

versatile platform for the insertion of ligands along the

polymer chain. In this context, the synthesis of PLA-co-

AGE polymer is interesting. The aim of this study was

to synthesize the copolymer PLA-co-AGE and develop

nanospheres with a chemically modifiable group. The

copolymer PLA-co-AGE was synthesized by ring

opening polymerization (ROP) from comonomers D,L-

lactide and AGE; Sn(Oct)2 as a catalyst and benzyl

alcohol as a co-initiator. The parameters Mn, Mw and

dispersity (Đ) of the copolymers were determined by gel

permeation chromatography (GPC). Nanospheres were

prepared via the nanoprecipitation method using the

synthesized copolymer and were characterized in terms

of size and Đ via the technique of photon correlation

spectroscopy (PCS) and of their zeta potential via the

technique of microelectrophoresis coupled to

anemometry laser Doppler (LDA). The characterization

by GPC showed a polymer with Mn = 25,600 g/mol and

Đ = 1.28; which characterizes the copolymer as uniform

and within a suitable range for nanocarrier preparation.

Stable Nanospheres were obtained with this copolymer,

having a reduced size (86.21 nm ± 1.05) and low Đ

(0.12 ± 0.02), the zeta potential was (-13.43 mV ±

0.64). The negative value obtained is expected for PLA

nanocarriers. PLA-co-AGE copolymer was synthesized

and stable nanospheres were obtained. The insertion of

a chain coupling agent, such as AGE, in the chains of

PLA is a strategy that can allow the coupling of

biological ligands along the polymer chain and therefore

the preparation of vectorized nanocarriers.

Acknowledgement: LDGNANO, Laboratório

Multiusuário do Cipharma. Financial support: CAPES.

25

CLEANING METHODS AND AIR QUALITY

CONTROL IN THE PROCESS OF COSMETIC

PRODUCTS MANUFACTURING AND PERSONAL

HYGIENE

Luana Beatriz Araujo Vaz1, Vanja Maria Veloso

2, Flávia

Dias Marques Marinho2, Jacqueline Souza

2, Iara

Gizelle Carvalho Silva3, José Mauro Nahim Trópia

2 e

Maria do Pilar Pinto Coelho Santos2

1Escola de Farmácia, UFOP, Ouro Preto, Minas Gerais,

Brasil. 2Fábrica de Cosméticos de Ouro Preto – Pérola.

Introduction: The factory Pérola Ouro Preto was

created by Fundação Sorria to generate income

through the production and marketing of cosmetics and

personal hygiene products in order to ensure their

22

sustainability and the foundation. In the quest for

competitiveness and meet the quality requirements of

the consumer market, it is necessary implementation of

cleaning and sanitization procedures, as they are

factors that can interfere with the physical, chemical

and microbiological properties of the products. In this

context, it is important to note that the indoor air quality

of the manufacturing environment can affect the quality

of the final product. Thus, it is important to emphasize

the need for air monitoring and the establishment of

parameters for analysis, to contribute to improving the

quality of products. Little has been documented in the

literature on these parameters, bering necessary to

establish methods and acceptance criteria for

evaluation. Objective: Evaluate cleaning methods used

in the manufacturing of cosmetics and toiletries

process, and analyze the influence of air quality control

in the production ambient. Methodology: If wish to

monitor the quality control of internal air through

sedimentation plates to evaluate the microbial load, and

also to evaluate the control unit and room temperature.

Validation of cleaning will be tested two methods of

sanitizing the equipment and then evaluating the

efficacy and fungal microbial removal, besides the

reduction of cross-contamination. Expected results: It

is hoped that this work establishing cleaning methods

and air quality control in production ambient of the

cosmetics and toiletries. The aim is to optimize the

cleaning process for the production of cosmetics

partner factory, minimizing reprocesses, cost savings,

reduced waste generation, can serve as a model for

other companies.

Supports: This project has the support of the

Universidade Federal de Ouro Preto, of the Escola de

Farmácia and of the Coordenação de Aperfeiçoamento

de Pessoal de Nível Superior.

26

NOVEL SYNTHETIC CHALCONES INDUCES

APOPTOSIS IN HUMAN GLIOBLASTOMA CELLS

Lucas Felipe Fernandes Bittencourt1, Karen Andrinéia

de Oliveira1,2

, Carine Bropp Cardoso1, Flávia Garcia

Lopes1, Tharine Dal-Cim

2, Louise Domeneghini

Chiaradia-Delatorre3, Alessandra Mascarello

3, Rosendo

Augusto Yunes3, Ricardo Castilho Garcez

1, Carla Inês

Tasca2 and Cláudia Beatriz Nedel

1*

1Laboratório de Biologia de Gliomas, Centro de

Ciências Biológicas, Universidade Federal de Santa

Catarina, Campus Trindade, CEP: 88040-900,

Florianópolis-SC, Brasil. 2Laboratório de Neuroquímica-4, Centro de Ciências

Biológicas, Universidade Federal de Santa Catarina,

Campus Trindade, CEP: 88040-900, Florianópolis-SC,

Brasil. 3Laboratório Estrutura e Atividade, Departamento de

Química, Universidade Federal de Santa Catarina,

Campus Trindade, CEP: 88040-900, Florianópolis-SC,

Brasil.

The glioblastoma multiforme is the main tumor of the

central nervous system and the most frequent in adults.

With a survival average of 5% two years after

diagnosis, this type of cancer is a main health issue.

Substances like the chalcones have been tested in

order to develop new treatments. In this work, we

studied the effects of three novel synthetic chalcones

(A23, C31 and J11) on A172 commercial cell lineage

and in surgery obtained-glioma cells, hereby referred as

GBM1. All chalcones showed a decrease in cell viability

by MTT cell viability assay, in both cell lines with 24 and

48 hours, especially C31. No effects on normal cells (rat

astrocytes) were observed. Also, C31 was the only

chalcone that caused an increase in apoptosis levels

with no further increase of necrosis; detected by

Annexin V assay kit in flow cytometry. Using the DCF-

DA and DAF-2 fluorimetric detection kits we suggest

that this augmentation may be linked to the high

oxidative effect found, caused by increased presence of

reactive oxygen species and nitric oxide levels. Flow

cytometry using propidium iodide revealed that C31

affected the cell cycle distribution, causing an arrest at

G0/G1 and S phases, suggesting that C31 interfere in

the cell cycle control, preventing neoplastic cells to

complete the mitosis cycle. Our results show that C31 is

a putative safe new antineoplasic substance that

induces apoptosis in a ROS-dependent manner,

causing cycle disruption and an increase in NO levels.

This study shall aid and direct future research regarding

this and similar substances and their antiproliferative

effects.

Acknowledgements: We wish to thank the Brazilian

funding agencies CAPES/CNPq for the financial

support.

27

PET PHARMACY UFOP RETROSPECTIVE AND

IMPORTANCE IN THE PROFESSIONAL AND

SCIENTIFIC PREPARATION

Amariz, A. P1; Silva, D. S

1; Alves, J.V.S

1 ;Rosa, J. S

1;

Silva, J.E.S1 ; Paixão, L. G

1; Oliveira, M. A

1; Matos, M.

B1; Cordeiro, N. N

1; Watai, P

1; Mendes, P. F

1;

Conceição, R.R1; Lima, R. R

1; Silva, S. S. C

1; Santos

T.M1; Ostolin, T. L. V. D. P

1; Souza, J

1;

1Programa de Educação Tutorial - Escola de Farmácia

-Universidade Federal de Ouro Preto.

23

Tutorial education program starts in 1979, in the

Coordenação de Aperfeicoamento de Pessoal de Nível

Superior-CAPES, being transferred in 1999 to the

Ministry of Education. PET is an academic investment

on the graduation courses that has as goal preparing

recognizably qualified professionals for creating, with

potential, activities that demonstrate a unique

preparation, qualified and recognized by the society.

PET Pharmacy started in april of 1992, and during

these 23 years of existence, the program counted with

6 tutors and about 70 students. The PET Pharmacy

group of Ouro Preto University is currently composed

by 16 students from all stages of the Pharmacy

graduation course and coordinated by a tutor professor,

Dr. Jacqueline de Souza. The main goal of the group is

the encouragement to collective learning, through

experiences, reflections and discussions in an

environment of cooperation, approaching to activities

oriented by the principle of non-dissociation between

teaching, research and continuing education and

tutorial education. Among the activities developed, the

Congress of Pharmaceutic Sciences of Ouro Preto,

which will have its fifth edition in 2016, is remarkable,

symposiums, improvement courses and continuing

education projects and research aiming the community

of Ouro Preto. All the activities have as goal

complement the academic preparation of the students

and meet the needs of the graduation degree. A survey

has been taken on the professional status of the

students who participated in the program, seven of

those are currently post-graduation students in UFOP

and five of them are part of CiPharma. Post-graduated

in Pharmacy or are post-graduation students in other

institutions, not mentioning those who followed a

professional career and excel in the work field. The

professional improvement provided by PET is

unanimous, being remarked specially: leadership,

speech, group work, learning how to organize events,

interaction with the community, mainly from continuing

education projects. Since it is also necessary run

research projects in PET, it is believed that it might

have encouraged many students to follow the research

field, considering that many of them did a strictu sensu

post-graduation or are currently doing it. According to

the collected data, one can affirm that PET-Pharmacy

contributed, not only during graduation, but also in the

future of those who made part of it, providing learning

and abilities that are essential in professional life.

Thanks to UFOP and Ministry of Education.

28

Effects of silibinin on AKT2 gene and miR-203

expression in bladder tumor cells

Ludmila Correia Barbosa1, Glenda Nicioli da Silva

1.

1UFOP – Universidade Federal de Ouro Preto, Escola

de Farmácia, Departamento de Análises Clínicas, Ouro

Preto, MG, Brazil.

Cancer is the second cause of death in Brazil and in the

world, leading to 8.2 million deaths, 14.9 million

incident cases and 196.3 million disability-adjusted life-

years in 2013. Among these tumors, the urothelial cell

carcinoma (UCC) is the most common genitourinary

malignancy, presenting a high prevalence, especially in

industrialized countries.Disturbances in pathways of

PI3K/AKT2 are associated with a majority of sporadic

human cancers, as breast carcinoma, ovarian and

bladder cancer. Treatment protocols for UCC include

the MVAC, a combination of methotrexate, vinblastine,

doxurrubicin and cisplatin; and the association of

gemcitabine and cisplatin, but they presents evere side

effects such as high toxicity. In this sense,the searching

for alternative treatments, especially the identification of

potential anticancer compounds isolated from natural

products, such as silibinin(wild artichoke),has deserve

special attention. Phytochemical products derived from

medicinal plants have some advantages such as better

compatibility with the human body, few side effects, and

are less costly and relatively non-toxic. However, the

molecular mechanisms of silibinin involved in the

observed changes on cell cycle kinectics and apoptosis

rates in tumoral cells were not fully elucidated,

especially when cells with different status of TP53 gene

(a main genetic alteration observed in bladder tumors)

were studied. Therefore, the aim of this study was to

characterize molecular events such as AKT2 gene and

microRNAs expression changes in bladder tumor cells

with wild (RT4) and mutated (T24) TP53 gene treated

with silibinin(135 µM, 150µM and 200 µM).The results

showed that silibinin decreased AKT gene expression

only in RT4 cells after different treatments with silibinin.

However, miR-203 expression modulation was not

observed in both tested cell lines. These data show

action mechanism of silibinin might depend on the

TP53 status.

Financial support: FAPEMIG, CNPq and UFOP

29

Evaluation of Type I Laboratory (Pharmacy School-

UFOP) cervical cytological diagnostics of submitted

to external quality control

Mariana Trevisan Rezende1; Alessandra Hermógenes

Gomes Tobias1; Claudia Martins Carneiro

1,2.

1CIPHARMA/Pharmacy School/Federal University of

Ouro Preto/Ouro Preto/MG. 2Cytology Sector/Pilot Laboratory of Clinical

Analysis/Pharmacy School/Federal University of Ouro

Preto/Ouro Preto/MG.

24

The external quality control has been proposed as a

method able to improve performance of laboratories

that performs cytological exams for a public health

service, through minimizing interobserver variation,

which is a major cause of the high rates of false-

negative results. The objective is to evaluate the

diagnoses of cytological exams issued by the Type I

Laboratory of Pharmacy School of UFOP comparing

with the results released by Type II Laboratory

responsible for conducting external quality control in

Minas Gerais state. The frequency of concordant and

discordant cases, of false-negatives and false-positives

by Type I Laboratory will be calculated according the

agreement with the Type II Laboratory results.

Moreover it will be calculated the Type I Laboratory

quality indicators before and after evaluation by Type II

Laboratory. The frequency of discordant cases that had

change clinical management will be determined. The

methods of internal quality control will be analyzed

against the results Type II Laboratory.The quality of

slidescoloring and assembling of Type I Laboratory will

be examined in accordance with the required quality

criteria by Qualicito/2013. Thus, we expect to identify

the major causes of errors and discrepancies

diagnostics. With training and continuing education,

professionals involved in Pap smear testing can

standardize criteria cytomorphological, improving

performance in the diagnosis of precursor lesions of

cervical cancer.

Acknowledgements: CAPES, UFOP.

30

EVALUATION OF THREE PRIMERS FOR HPV

DETECTION BY CONVENTIONAL PCR IN FFPE

CERVICAL SAMPLES

Silva, NNT1, Tafuri, A

2, Lima, AA

1

1Escola de Farmácia, Universidade Federal de Ouro

Preto;

2Laboratório Tafuri;

Introduction: The detection of human papillomavirus

(HPV) is an important tool to complement the diagnosis,

treatment and cervical cancer screening. The main form

HPV detection is through the viral DNA amplification by

polymerase chain reaction (PCR). However, is difficult

to perform this technique in formalin fixed paraffin

embedded (FFPE) samples due to the DNA

degradation that occurs during the fixing process and

paraffinization. Objective: To compare the HPV

detection results in cervical biopsy samples using PCR

with three different primers: MY09/MY11 [PCR

(MY09/MY11)], GP5+/GP6+ [PCR (GP5+/GP6+)] and

SPF [PCR (SPF)], to choose the best methodology for

HPV detection in FFPE samples. Material and

Methods: 150 cervical biopsy blocks were selected ang

divided into 5 groups of 30 samples [Cervicitis (control),

cervical intraepithelial neoplasia (CIN) grades I, II and

III, and invasive cervical carcinoma (ICC)]. DNA

extraction was performed with DNA FFPE Tissue

QIAamp® Kit (QIAGEN). The HPV detection was

performed by PCR (MY09/MY11), PCR (GP5+/GP6+)

and PCR (SPF) that generate fragments of 450bp,

160pb and 95pb, respectively. Results: HPV was not

detected in any sample using PCR (MY09/ MY11), so

this technique was excluded in other analyzes. The

concordance index (Kappa) between PCR

(GP5+/GP6+) and PCR (SPF) was very light (κ=0.022).

The HPV positivity analyzed by PCR (SPF) was high

(96.7%, n=145) and higher than that found by PCR

(GP5+/GP6+) (24.7%, n = 37). Higher positive

correlation was noted between the results obtained with

PCR (SPF) and PCR (GP5+/GP6+) in samples

presenting lesions compared to the control group.

Considering the different types of cellular alterations,

increased positive correlation between the two methods

was observed with the evolution of the lesion degree.

Among the samples that the infection was detected by

both methods, the most showed ICC (43.3%, n=13).

According to the age, most positive agreement has

been found in samples of women aged >30 years old.

PCR (SPF) showed higher sensitivity compared to PCR

(GP5+/GP6+). Conclusion: This study showed that the

PCR using the SPF primer set showed better results for

HPV detection in FFPE samples.

Financial Support: Conselho Nacional de

Desenvolvimento Científico e Tecnológico (CNPq) e

Coordenação de Aperfeiçoamento de Pessoal de Nível

Superior (CAPES).

31

CARDIOPROTECTIVE ACTIVITY OF IPRIFLAVONE

IN SPONTANEOUSLY HYPERTENSIVE RATS

SUBMITTED TO THE LEFT CORONARY LIGATURE

CASTRO Q.J.T.1, MOSQUEIRA V.C.F.

1, PEREIRA

S.C.1, SOUZA A.C.M.

1, AMANCIO, G.C.S.

1,

GUIMARÃES H.N.2, LEITE R.

1, GRABE-GUIMARÃES

A.1.

1CiPharma, Escola de Farmácia, UFOP, Ouro Preto,

MG; 2DEE, Escola de Engenharia, UFMG, Belo Horizonte,

MG, Brazil.

Introduction: Ipriflavone (7-isopropoxy-3-phenyl-4H-1-

benzopyran- 4-one) is a semi-synthetic soy derivative,

used in several countries for prevention and treatment

of osteoporosis. Its cardioprotective effect administered

orally was demonstrated in isolated heart of rabbits

25

(Feuer et al, 1981). Self-emulsifying drug delivery

systems (SEDDS) have gained great importance as a

promising technology to improve the bioavailability of

poorly water-soluble drugs like ipriflavone. Objective:

The objective was to evaluate the cardioprotective

effect of ipriflavone in self-emulsifying drug delivery

system (SEDDS) administered in female spontaneously

hypertensive rats (SHR) submitted to the left coronary

ligature. Methods: All the procedures were approved

by CEUA/UFOP (2013/02). The rats were submitted

first to the heart coronary ligature and treated during 21

days with ipriflavone-SEDDS (30 mg/kg) or with blank

SEDDS, in single daily dose. Sham animals treated

with ipriflavone-SEEDS or blank SEDDS were used as

control group. At the 22th day, under anesthesia

(ketamine 100 mg/kg/xylazine 14 mg/kg), the lead II

ECG signal was obtained. The cardioprotective activity

of ipriflavone was evaluated for its ability to prevent

cardiovascular disorders, demonstrated in signs of

ECG induced by IV administration of norepinephrine

(NE), doses of 3 and 10 µg/kg. Results: For the PR

and QRS intervals there were not significantly

differences in animals treated with vehicle or

ipriflavone. The QT and QTc increases after the ligature

were significantly reduced in ipriflavone treated animals

compared to the vehicle treated animals. The reduction

of the QT prolongation induced by 3 and 10 µg/kg of NE

respectively was 78% and 73%. And the reduction of

the QTc was 58 % and 53 %, after 3 and 10 µg/kg,

respectively. Conclusion: The QT and QTc intervals

prolongation are predictors of cardiac arrhythmias, thus

the reduced alterations induced by NE in SHR treated

female rats reveals the ipriflavone-SEDDS

cardioprotective activity and its potential for further

clinical investigation.

Funding agencies: FAPEMIG (Rede Nanobiomg) and

UFOP

Acknowledgments: CNPq; UFOP; CAPES and Project

APQ 02346-11 (FAPEMIG)

32

Morpho-anatomic and Phytochemistry Studies in

Leaves of Abatia americana(Gardner) Eichler

(Salicaceae)

Regislainy Gomes da SILVA1*

, Hildeberto Caldas de

SOUSA2, Gustavo Henrique Bianco de SOUZA

1

1Universidade Federal de Ouro Preto-MG,

Departamento de Farmácia - Escola de Farmácia;

Laboratório de Fitotecnologia, Campus Morro do

Cruzeiro, s/n CEP 35400-000 Ouro Preto – MG, Brasil.

2Universidade Federal de Ouro Preto-MG,

Departamento de Biodiversidade, Evolução e Meio

Ambiente - Instituto de Ciências Exatas e Biológicas;

Laboratório de Anatomia Vegetal, Campus Morro do

Cruzeiro, s/n CEP 35400-000 Ouro Preto - MG, Brasil.

*autora para correspondência: [email protected].

Biologically active metabolites emerged in nature by

ecological needs and biosynthetic possibilities.

Secondary metabolites often present interesting

biological activities, in spite of they have been

considered as plant waste products. Phenolic

compounds, a class of secondary metabolites are

formed in plants under stress, and flavonoids, a

subclass of phenolic compounds, have various

pharmacological functions described in the literature,

such as antiviral, antioxidant and anti-inflammatory. The

Salicaceae family often has phenolic glycosides usually

with tannins, but, in general, they lack cyanogenic

glycosides. Casearia sylvestris Sw., a specie of this

family, has biological activities already mentioned by

the reasearches, such as antitumor, antiviral,

antibacterial, antifungal, molluscicide,

hypocollesterolemic and analgesyc. Salix alba L.,

another specie from this family was the source of

salicilic acid, molecule that origined the acetilsalicilic

acid, commercialized until today, for several

pharmacologial activities. Abatia americana (Gardner)

Eichler, from Salicaceae family, is a native specie,

endemic to Brazil, and doesn’t have a popular use

described yet; therefore it lacks research on its possible

pharmacological applications. In this project, a botanical

and phytochemicals study were conducted to determine

the morphological and anatomical characteristics of its

leaves. To this end, fully expanded leaves were

collected in Ouro Preto; part of this material was fixed in

FAA70, and after 48 hours stored in 70% ethanol.

Transversal cuts and epidermis dissociations were

made in order to perform morphoanatomic study. The

leaf lamina is dorsiventral and hypostomatic. There are

multiseriate adaxial epidermis and uniseriate abaxial

epidermis with paracytic stomata and tectores

ornamented trichomes on both sides. It has collateral

vascular bundle in an open arc. In order to carry out

phytochemical studies, another part of the collected

material was stored in plastic bags, dried and

pulverized, and then subjected to sequential extractions

by means of percolation technique, with the intention of

isolating major secondary metabolites. Identification

was made using chromatographic techniques such as

Thin Layer Chromatography Comparative and

Preparative, Classical Liquid Chromatography and Ultra

Performance Liquid Chromatography acopled to Mass

Spectrometry. In conclusion, the anatomical features

are important to characterize the future herbal medicine

and has been identified the flavonoid lucenin-2.

Key-words: Abatia americana (Gardner) Eichler,

lucenin, flavon.

26

Acknowledgements: This work was supported by

CAPES (Coordenadoria de Aperfeiçoamento Pessoal

de Nível Superior), by CIPHARMA (Programa de Pós-

Graduação em Ciências Farmacêuticas), by

Laboratório de Fitotecnologia and by Laboratório de

Anatomia Vegetal from Universidade Federal de Ouro

Preto, Minas Gerais, Brazil.

33

A KNOWLEDGE EXCHANGE BETWEEN UNIVERSITY AND COMMUNITY AS AN INSTRUMENT TO MITIGATE SOCIAL PROBLEMS

Rodrigo Chaves Ângela L. Andrade (PQ), Carolina

M.S.A. Maranhão (PQ), Diego L.N. Ventrella (PQ),

Fábio V. Moura (PQ), Kerley S. Alves (PQ), Tays T.R.

Chagas (PQ), Vera L.M. Guarda (PQ)

Professores do Núcleo da Cátedra UNESCO: Água,

Mulheres e Desenvolvimento da Universidade Federal

de Ouro Preto, Ouro Preto, Minas Gerais, Brasil

Introduction: The occupation of Antônio Pereira district

of Ouro Preto, dating from the eighteenth century. The

height of the growth of this district occurred in the 70s,

with the installation of large mining companies in the

region, including mining company Vale do Rio Doce

and Samarco. After this growth phase, Antonio Pereira

went into decline, which was only eased in the 1980s,

when the district received new mining companies that

still operate in the region. Currently, mining companies

are coming back into recession, causing large numbers

of unemployment. Adding to this scenario, we have a

population dominated by women, many single mothers

and unemployed. In an attempt to modify part of this

situation, UFOP teachers came together to look for

ways to improve the quality of life of a group of women,

through new ways of generating income from the

creation of associations. Objectives: Increase the self-

esteem of women participants; empower associates in

new role and business activities; legalize associations;

develop new knowledge production and management

of a Community collective. Methods: During the project

were offered training courses in business management,

marketing, sales and cooperatives, where, taking

advantage of the expertise of teachers in charge of

related fields, was seeking a sustainable productive

arrangement in the financial and operational level.

These associations were structured for the production

of cleaning products, crafts and making clothes and

uniforms. Results: The achievements include working

knowledge of production equipment in the associations,

hierarchy establishment through internal voting, working

knowledge of routines employed, gradual increase in

profit, improved self-esteem, and coexistence. From the

completion of the courses, and analyzes problems

occurred during the project, it may be noted that

member is being able to run the business without the

help of the University, despite the constant support.

Conclusion: After completion of training courses and

early operational management process of associations,

there was a personal growth, self-esteem and desire for

finding new forms of income of women generation, will

this perceived from the commitment of women to hold a

profitable venture for all.

Thanks and Financial Support: The project thanks

mainly to the Federal University of Ouro Preto,

FAPEMIG, Fundação Gorceix, NuCat and mining

company Samarco, at both financial and operationally

unrestricted support of the project.

34

EVALUATION OF ACCELERATED BLOOD

CLEARANCE PHENOMENON MICE INFECTED WITH

LEISHMANIA INFANTUM TREATED WITH

PEGYLATED LIPOSOMES FORMULATIONS

CONTAINING TARTAR EMETIC

Tamara Cristina Moreira Lopes¹; Débora Faria Silva¹;

Walyson Coelho Costa¹; Wanderson Geraldo de Lima2;

Adriel Araújo Fernandes Ferreira3; Neila Márcia Silva

Barcellos1; Rodrigo Dian de Oliveira Aguiar Soares

4;

José Mario Barichello¹; Simone Aparecida Rezende¹.

1CiPharma - Escola de Farmácia – Universidade

Federal de Ouro Preto (UFOP) 2Departamento de Ciências Biológicas – UFOP

3Departamento de Fisiologia e Biofísica – Universidade

Federal de Minas Gerais (UFMG) 4Núcleo de Pesquisa em Ciências Biológicas – UFOP

Accelerated blood clearance (ABC) phenomenon has

been observed during the repeated administration of

PEG-conjugated nanosystems, including PEGylated

liposomes (LPEG). ABC phenomenon promotes the

capture of LPEG macrophages during therapy. We

evaluated if ABC phenomenon modifies the toxicity and

targeting of LPEG of tartar emetic (TE) to liver and

spleen in a murine model of leishmaniasis. We also

evaluated if the ABC phenomenon improves the

efficacy of leishmaniasis therapy. The liposome

formulations were characterized by size, polydispersity

index and drug encapsulation. The hemolytic activity of

formulations and blood count were correlated. Non-

infected and Leishmania infantum infected mice were

divided in two groups, one in which ABC phenomenon

was not induced: 1) PBS; 2) free TE; 3) empty

conventional liposomes (LC); 4) LC+TE; 5) LPEG+TE;

and another in which ABC phenomenon was induced

27

by the endovenous administration of empty LPEG: 6)

LC+TE; 7) empty LPEG and 8) LPEG+TE. After two

weeks the animals were euthanized and biometric

parameters were evaluated. The level of antimony (Sb)

in the tissues was accessed in non-infected animals.

Histological analyses were performed to evaluate the

therapy toxicity. All formulations showed size of

200nm, polydispersity index 0.3 and drug

encapsulation efficiency of 14%. TE formulations and

free TE induced low in vitro hemolytic activity (15%).

Non-infected mice showed no blood count alteration

due to treatment. No alteration was observed in body,

liver or spleen mass. Treatment with free TE induced

higher level of Sb in liver. Among the liposomal

formulations, treatment with LPEG+TE with ABC

phenomenon was able to increase Sb level when

compared to LPEG + TE without ABC phenomenon. In

the spleen, higher levels of Sb were observed in mice

treated with LPEG+TE without ABC phenomenon in

relation to treatment with conventional liposomes of TE.

In relation to histopathological analysis, non-infected

animals showed no alteration in liver and spleen due to

treatment. Treatment with free TE and liposomal

formulations of TE was able to reduce parasite load in

liver. Otherwise, in spleen and bone marrow, only

PEGylated liposomes of TE were able to suppress

parasite load. No alteration in parasite load was

observed in ABC phenomenon groups. Although ABC

phenomenon favors the accumulation of TE in the liver,

it no changes the parasitism in the organs. Only LPEG

of TE reduced parasite load in the organs.

Financial support: CAPES, CNPQ and UFOP.

35

BIOPHARMACEUTICAL POTENTIAL OF A

BIOLOGICALLY ACTIVE SUBSTANCE ISOLATED

FROM TYPICAL BRAZILIAN CERRADO PLANT

Caldeira, T. G.1; Saúde-Guimarães, D. A.

1; Souza, J.

1

1Curso de Pós-Graduação em Ciências Farmacêuticas

- CiPharma - Universidade Federal de Ouro Preto,

Ouro Preto, Minas Gerais, Brasil.

Biopharmaceutical parameters consisting of solubility

and permeability characteristics and are directly related

to the degree of a drug or biologically active substance

absorption along the gastrointestinal tract. Therefore, in

1995 was proposed the Biopharmaceutics

Classification System (BCS), which classifies drugs into

four classes according to solubility and permeability

characteristics, and subsidizes the replacement of in

vivo studies, such as bioavailability and/or

bioequivalence, for in vitro assays, which allow

conclusions about the solubility in biological fluids and

permeability of drugs. Besides, this system is also used

in research the new molecules with potential

pharmacological. In this context, a biologically active

substance isolated from typical specie of the Brazilian

Cerrado has been studied due to promising

trypanocidal, antitumor, anti-inflammatory, anti-

hyperuricemic and anti-gouty arthritis activities and low

toxicity. Regarding the biopharmaceutical studies, this

substance has a low solubility in silico and in

equilibrium, exhibiting LogS between -3.83 and -4.33,

values comparable to other poorly soluble drugs on the

market today. And, high permeability, to present LogP

(2.00) comparable to drug metoprolol (LogP = 1.80) and

effective permeability (Peff = 34.40 x 10-6) higher than

the high permeability standard drug, propranolol

hydrochloride (Peff = 9.23 x 10-6). Considering the

initial biopharmaceutical characteristics of the

substance, pharmacological activity and low toxicity is

necessary to evaluate the variables that can affect the

process of absorption of this along the gastrointestinal

tract. Therefore, this study aims to evaluate the

biopharmaceutical potential for biologically active

substance isolated from typical specie of the Brazilian

Cerrado, by determining the intrinsic dissolution rate

and the permeability of Caco-2 cells. The intrinsic

dissolution rate will be standardized, validated and

determined in biorelevant media: acetate buffer (pH

4.5), intestinal fluid simulated without enzymes (pH 6.8)

and phosphate buffer (pH 7.4). Similarly, the

permeability technique evaluation using Caco-2 cells

undergo validation and standardization. Expected that

the experimental procedures established to clarify more

effectively the behavior this substance along the

gastrointestinal tract, since that polymorphism and

absorption by carriers will be evaluated. Thus

contributing for the development of a suitable

pharmaceutical formulation to promote maximum oral

bioavailability, coming this be a new therapeutic option

for the treatment of various diseases by the public

health service.

Acknowledgements: UFOP/CiPharma/Ministério da

Saúde/Anvisa/FAPEMIG/Rede Toxifar/CNPq/CAPES.

Key-words: Solubility, Permeability, Intrinsic

dissolution, Caco-2 cells, Biologically active substance.

36

EFFECTS OF THE SILIBININ (SILYBUM MARIANUM)

ON FRAP/MTOR GENE AND MICRORNA 100

EXPRESSION IN BLADDER TUMOR CELLS

Tatiane Martins Barros1, Glenda Nicioli da Silva

1

28

1Escola de Farmácia, Departamento de Análises

Clínicas, Universidade Federal de Ouro Preto- UFOP-

Ouro Preto, MG, Brazil.

Bladder cancer is characterized by being a highly

morbid disease due to high recurrence rates. Genetic

alterations in TP53 gene are related to cellular

transformation, malignancy and tumor progression.

Moreover, disturbances in pathways of PI3K-

FRAP/mTOR are associated with a majority of

sporadic human cancers, as breast carcinoma, ovarian

and bladder cancer. The drugs used to treat bladder

cancer present high toxicity and adverse side effects.

Thus, the searching for alternative compounds to

improve the efficacy of standard treatments and to

reduce the undesirable side effects has become

imperative. Among the compounds studied with

potential for anticancer activity in the bladder, the

silibinin, a naturally occurring flavonoid isolated from

the fruits and seeds of milk thistle (Silybum marianum),

is one of the less evaluated. The aim of this study was

to evaluate the effects of silibinin (135 µM, 150 µM and

200 µM) on miR-100 and its target FRAP/mTOR gene

expression in tumor cells of the bladder with wild (RT4)

and mutated (T24) TP53 gene. The results showed that

silibinin decreased FRAP/mTOR gene expression only

in RT4 cells after different treatments with silibinin.

However, miR-100 expression modulation was not

observed in both tested cell lines. In conclusion,

changes in mTOR mechanism may be associated with

antiproliferative effects of silibinin in the wild TP53 cells.

Financial support: FAPEMIG, CNPq and UFOP.

37

COMPOUNDS IDENTIFIED ON THE LEAVES OF

PROTIUM SPRUCEANUM (BENTH.) ENGLER BY

GC-MS

Tatiane Roquete Amparo1, Adriana Akemi Okuma

2,

Sidney Augusto Vieira Filho1, Vivette Appolinário

Rodrigues Cabral3, Gustavo Henrique Bianco de

Souza1

1Universidade Federal de Ouro Preto, Departamento de

farmácia;

2Centro Federal de Educação Tecnológica de Minas

Gerais, Departamento de química;

3Universidade Federal de Lavras, Departamento de

Ciências Florestais

Due the chemical diversity of the medicinal plants the

phytochemical studies are important to the discovery of

new drugs. Protium spruceanum (Benth.) Engler,

known as almécega-de casca-lisa or breu, is used by

the population like anti-inflammatory and expectorant,

however, it is necessary to expand studies about this

specie. The aim of this work was the identification of the

volatiles components of leaves of P. spruceanum. The

crude extract (37,54 g) was obtained by maceration of

the fragmented leaves (221,66 g) with ethanol (yield:

16,93 %). The extract (20,0 g) was resuspended in

Methanol:Water (1:1) and subjected to liquid-liquid

partition with hexane and ethyl acetate to obtain the

fractions: hexane (3,6 g), ethyl acetate (6,0 g) and

hydromethanolic (9,3 g). The extract and the fractions

were analysed by gas chromatography-mass

spectrometry (GC-MS). Sixteen compounds were

identified in the crude ethanolic extract and in the

hexane fraction. The majority in the crude extract was

methyl hexadecanoate and α- and β-amirin were the

majority in the hexane fraction. Four compounds were

identified in the ethyl acetate fraction and in the

hydromethanolic fraction, with the majorities:

hexanedioic acid, bis(2-ethylhexyl) ester and methyl

benzoate, respectively. These compounds were found

in others medicinal plants and can be associated to the

biological activities of P. spruceanum.

Apoio financeiro: FAPEMIG, CNPQ

38

INFLUENCE OF HYDROCHLOROTHIAZIDE RAW

MATERIALS IN SUSPENSION CHARACTERISTICS

SOARES, T.S.P.1; SOUZA, J.

1; MARQUES-MARINHO,

F.D.1;

1Laboratório de Controle de Qualidade, Departamento

de Farmácia, Escola de Farmácia, Universidade

Federal de Ouro Preto.

The thiazide diuretic hydrochlorothiazide (HCTZ) is a

water insoluble drug, only commercially available in

solid oral dosage form (SODF). Due to its low solubility,

HCTZ liquid oral dosage forms need to be prepared as

suspension. Suspension is a preparation of finely

divided drug in a suitable aqueous fluid vehicle. Drug

particles in the vehicle tend to sediment and the formed

sediment must be easily redispersed by agitation

(flocculated system), otherwise compact sediment is

formed (deflocculated system). After oral suspension

administration, the drug is available to immediate

dissolution in the biological fluids that represents

advantage to the SODF administration. Aiming to

propose dissolution test for HCTZ suspension, in this

part of the work, HCTZ raw materials (n=4) and their

respective suspensions had the physicochemical

properties evaluated. The suspensions´ storage at

different temperatures was also studied. HTCZ raw

29

materials were analyzed according to Brazilian

Pharmacopoeia tests: physical properties, solubility,

melting point, infrared and ultraviolet identification.

Suspensions of 2.5mg/ml and 5mg/ml were

compounded from each HCTZ sample and the batches

(1,2,3,4) were characterized regarding viscosity, pH,

sedimentation volume, redispersibility, zeta potential

and particles size. The freshly prepared suspensions

were evaluated and 15, 30 and 120 days after storage

at room temperature and at 8ºC. The HCTZ samples

met the pharmacopeia tests except the ultraviolet

identification. The viscosity of the suspensions at

2.5mg/ml and 5 mg/ml ranged from 150-125 mPa.s and

140-118 mPa.s, respectively. After 120 days, the pH of

all suspensions increased (max. 3.86) compared to the

initial pH (3.3). Sedimentation volume of freshly

suspensions (0.93-0.42) was greater than those after

120 days (0.70-0.39). Only batch 4 had a compact

sediment formation. Time required to sediment re-

dispersion ranged from 17 to 28s, with greater time

being observed for batch 4 (21-28s). After 120 days,

there was a reduction in the absolute zeta potential of

all the batches, except batch 4 that presented little

change. The suspensions showed different particle

sizes according to the batch: intermediate, batches 1-2;

bigger, batch 3 and much smaller, batch 4,

corroborating with the results of sedimentation volume

and redispersibility. The batches showed differences in

tests related to the particles characteristics as

redispersibility and zeta potential. Similar

characteristics were observed between suspensions

stored at room temperature and at 8ºC, so there is no

need to store in the refrigerator. Except for batch 4, all

other were classified as flocculated systems. Among

the batches, batch 2 was considered the most suitable

for the dissolution test.

Key-words: Hydrochlorothiazide. Dissolution. Raw

material. Suspension.

Acknowledgemets:CIPHARMA /EF /UFOP /FAPEMIG

/Anvisa/CAPES.

39

THERAPEUTIC POTENTIAL OF IPRIFLAVONE

CONVEYED IN A SELF-EMULSIFYING DRUG

DELIVERY SYSTEM (SEDDS) IN SEXUAL

DYSFUNCTION IN FEMALE SHR RATS DURING

THE CLIMACTERIC PERIOD

MARTINS T. A.1, MENDES J.C

1,RODOVALHO G. V.

1,

LEITE R.1

1CiPharma, Escola de Farmácia, UFOP, Ouro Preto,

MG;

Female sexual dysfunction (FSD) is a condition in

which there are alterations in the processes involved

in the female sexual response cycle. A decline in

serum estrogen, which occurs in menopause,

results in a significant decrease in the clitoral

intracavernosal, vaginal, and urethral blood flow,

thinning of vaginal mucosal epithelium and atrophy

of vaginal wall smooth muscle. The conventional

hormone therapy has proven effective in the

treatment of FSD, however, this therapy is associated

with an increased risk of the incidence of ischemic

cardiovascular events, as well as venous embolism.

Therefore, there is great interest in the development

of therapeutic alternatives that minimize the

deleterious effects of hypoestrogenism on sexual

function without causing side effects and avoiding

contraindications. The fitoestrogen ipriflavone

(7‐isopropoxy‐3‐phenyl‐chromen‐4‐one), a derivative

of daidzein (a naturally occurring isoflavone), is used

in the prevention and treatment of osteoporosis

however, the potential role of ipriflavone in the

treatment of FSD is unknown. The aim of this study

was to investigate the therapeutic potential of

ipriflavone in the treatment of FSD. For that, we used

young (4-5 months) and senescent (18-19 months)

female spontaneously hypertensive rats (SHR)

treated for 30 days with ipriflavona 10 or 30mg/Kg

conveyed in a self-emulsifying drug delivery systems

(SEDDS). Control group received only SEDDS

vehicle. Physiological parameters were evaluated

during pelvic nerve stimulation. Intravaginal

temperature significantly increased at the dose of 10

mg/Kg in the senescent SHR group. The vaginal

lubrication was improved after treatment with

ipriflavone 30 mg/Kg in the young and in the

senescent rats. Intravaginal pressure was

significantly higher in both young and senescent

groups treated with either 10 or 30 mg/Kg of

ipriflavone. Chronic treatment with ipriflavone with

doses of 10 and 30 mg/kg improved the

vasocongestive responses observed during the

subsequent 30 minutes interval after subcutaneous

injection of apomorphine (80μg/kg) in conscious young

and senescent female SHR rats. Furthermore, using

the same model to study sexual function in conscious

rats, the improvement in the vasocongestive reponses

observed in ipriflavone treated rats was similar to that

observed for the estradiol treated group. Histological

evaluation of liver and kidney, along with the

characterization of the lipid profile and some enzyme

levels (kidney and liver enzymes). Also, the amount of

intact glomeruli was significantly greater than the

degraded glomeruli, suggesting absence of hepatic

and renal toxicity. Therefore, the chronic treatment for

30 days with the ipriflavone phytoestrogen conveyed

in SEDDS, seemed to be safe and significantly

30

improved female rat sexual function, suggesting a

therapeutic potential for the treatment of the sexual

dysfunction induced by hypoestrogenism observed in

menopause/climacteric woman. Statistical analyses:

p<0.05 for all groups except for glomeruli quantitation

(p <0.001); ANOVA followed by Bonferroni post-

test.

Financial support: FAPEMIG, CAPES and UFOP.

40

EVALUATION OF METABOLIC SYNDROME IN

CLIMACTERIC WOMEN

Gouvea TM*1, Lopes ACF

1, Veloso VM

1, Carrillo MRG

1,

Lima AA1

1Escola de Farmácia/UFOP, Ouro Preto – MG

INTRODUCTION: The menopause corresponds to a

physiological transition in women's lives, where

changes are observed in physical, psychological and

social level. It has been associated with menopause, an

increased risk of obesity and metabolic syndrome, a

relationship which, although controversial, could be

explained by the decrease in basal metabolic rate,

physical inactivity and hormonal changes resulting from

this stage. The importance of studies and interventions

aimed at seeking healthy aging then it should be

recognized, as well as prevention and treatment of

cardiovascular risk factors.

OBJECTIVE: To determine the prevalence of metabolic

syndrome (MS) and its individual components in

menopausal women.

METHODS: Cross-sectional study with 75 women aged

45 to 60, selected in Basic Health Units

of Ouro Preto, Minas Gerais. The presence of MS was

determined according to the classification criteria of the

National Cholesterol Education Program's (NCEP-

ATPIII) and the International Diabetes Federation (IDF).

For this, glucose, total cholesterol and fractions, as well

as measuring blood pressure and waist circumference

were taken in the sample. Structured interviews with

participants enabled the raising of socio-demographic

and behavioral factors.

RESULTS AND CONCLUSION: The prevalence of MS

by the NCEP-ATPIII criteria was 48,0%, while at the

IDF, was slightly higher (53,3%). The agreement

between these two classifications was excellent (k =

0,894). There was no statistically significant association

between age, education, marital status, smoking and

alcohol with the development of MS. When the

components of MS were analyzed separately, the most

obvious change was abdominal obesity (waist

circumference: 96,1±14,2cm). The profile of the

selected women showed that the mean/standard

deviation age of the study population was 52,5±3,9

years; fasting glucose 112,3±47,4 mg/dL; HDLc

56,6±13,3 mg/dL; triglycerides 127,9±70,2 mg/dL and

mean arterial pressure 128x81 mmHg. Regardless of

classification method, this study showed a considerable

prevalence of menopausal women diagnosed with MS,

and waist circumference as amended factor.

ACKNOWLEDGMENTS AND FINANCIAL SUPPORT:

PROPP/UFOP, CAPES e FAPEMIG.

41

TRAINING FOR FOOD HANDLERS AND

CHAMBERMAID

Amanda Maria Silva Gonçalves; Fagner Parreiras Egg;

Thais Santos Rodrigues; Crislaine Custódia Rosa;

Kerley dos Santos Alves; Vera Lúcia de Miranda

Guarda.

Nucleus of the UNESCO Chair: water, women and

development.

Introduction: From 2011-14, 102 people, among which

82.35% women were trained in food handling by the

UNESCO Chair. In the same period, at the request of

VISA Mariana-MG we carried out a survey of the

bacteriological quality of snacks sold by bakeries, snack

bar and private salting. Of the 23 samples analyzed,

82.61% presented some type of contamination and

13% were rejected because they presented

contamination by Staphylococcus aureus and

Escherichia coli. Given this reality, the training in Food

handler showed up necessary because the study there

was noncompliance with the rules of Good Practices of

Food Handling.

The hosting industry, directly linked to tourism is facing

a market increasingly competitive to meet your needs in

the areas of hospitality and tourism in Ouro Preto and

Mariana. The numerous hotel establishments

continually suffer from a lack of skilled labor to work

mainly in camaria sector, which is occupied almost

exclusively by women. Objectives: To provide for the

market people trained to work as food handlers and

maids, training courses were given in Soares District, in

Reference Centers for Social Assistance São

Cristóvão, Engenheiro Corrêa and in Soares District

(Food Handlers) and CRAS Mariana and Antonio

Pereira (Chambermaids). Methodology: Lectures and

technical visits to lodging facilities were used in the

training of maids. For the course of food handlers, as

well as lessons and dynamic on food hygiene (ANVISA)

and homemade pasta production workshops, applying

the best practices, a practical lesson demonstrating the

issue of bacterial contamination, justifying the use of

31

caps and hand hygiene was also performed. Results:

In 2015 were trained 16 maids and 20 food handlers.

The technical part added with environmental education

content and entrepreneurship leads to women trained

full workouts, which allow them to enter the labor

market or set up associations and cooperatives.

Conclusions: The project contributes to the

improvement of food handling practices, often already

carried out by the students in their own homes; to

decrease the number of disease case foodborne and to

hand training of skilled labor in chambermaid service,

the which makes a difference because we are in a

tourist pole and the need for skilled labor in the means

of local accommodation is always checked.

Acknowledgements:

Pró-Reitoria de Extensão

Reference Centers for Social Assistance of Ouro Preto

and Mariana/MG

Financial Resources: Universidade Federal de Ouro

Preto

42

WORKSHOP OF ENVIRONMENTAL EDUCATION

AND WATER QUALITY MONITORING

Danielle Murta da Silva; Ícaro Mateus Silva; Samira

Fagundes de Andrade; Eduardo Antunes Almeida;

Aline Fonseca Bornachi; Beatriz Tonhela Rocha Araújo;

Vera Lúcia de Miranda Guarda;

Nucleus of the UNESCO Chair: water, women and

development.

Introduction: Environmental education aims at training

people to exercise responsible and conscious

citizenship, transforming and improving the relationship

between human beings and of these with the

environment in which they live. The study of water is

one of the most important subjects of study of

environmental education, because of its economic and

social value and the water crisis that overwhelms the

planet. Water for home and hospital use must have

constant monitoring in order to prevent waterborne

diseases that can lead to death children and the elderly.

The lack of drinkability is considered a serious public

health problem. Objectives: The Environmental

education workshops are intended to complement the

training of the training courses of the UNESCO Chair:

Water, women and development. In order to provide the

course participants the importance of responsible use

of natural resources, avoiding waste, generating

income and highlighting the problems resulting from

compulsive and predatory actions. The second

objective of the project is the monitoring of water

quality, which helps to reduce borne diseases by

consumption of contaminated water and inform the

public of the risks of contamination, also seeking to

raise awareness for the preservation of this good.

Methodology: environmental education workshops

were held in the UNESCO Chair of courses. The

workshops were composed of lectures and practices,

addressing we have: Environment (perception and

impacts); Water (consumption awareness and

waterborne diseases); Solid Waste (recycling and

composting); Gender (women's role in water

governance); Protection of springs; Care wells and food

security. To carry out quality monitoring, bacteriological

parameters were analyzed in several samples using the

method defined Chromogenic substrate ONPG-MUG

trademark Colilert. Results: With regard to

environmental education, the 36 students from various

training of the Chair were very receptive and attentive,

especially in practical classes, when debates on the

use of waste as tetrapark box and cooking oil come into

play, or in building a box composting. Monitoring,

samples were from the rural district of Santa Rita (water

springs); Of Saramenha at the request of the

Prosecutor and the Hospital. Most of these samples are

found contaminated by fecal coliforms demonstrated by

fluorescence under ultraviolet light. Conclusion:

Environmental Education complies with of the UNESCO

Chair of the prerogative of awareness and care for the

environment and especially water. It notes the

existence of non-potable water consumption.

Acknowledgements:

Pró-Reitoria de Extensão.

Reference Centers for Social Assistance of Ouro Preto

and Mariana/MG.

Financial Resources: Universidade Federal de Ouro

Preto.

43

UNESCO CHAIR ON WATER, WOMEN AND

DEVELOPMENT

Thais Santos Rodrigues; Samira Fagundes de

Andrade; Ícaro Mateus Silva; Danielle Murta Silva;

Beatriz Tonhela Araújo; Aline Fonseca Bornachi;

Amanda Maria Silva Gonçalves;

Fagner Parreiras Egg; Isadora Iannini Cota Dutra;

Thaís Pinto da Rocha Torres; Luiz Fernando de

Medeiros Teixeira; Ângela Leão Andrade; Fábio Viana

de Moura; Carolina Maranhão Albuquerque; Kerley dos

Santos Alves; Tays Torres Ribeiro das Chagas; Vera

Lúcia de Miranda Guarda.

Nucleus of the UNESCO Chair: water, women and

development.

32

Introduction: The mission of the UNESCO Chair on

Water, Women and Development in Brazil is to

encourage the construction of a sustainable society

through environmental education and empowerment of

women. The chair actively Works towards becoming a

Center of Excellence for preserving water resources,

promoting sustainable development and encouraging

women’s participation in all water-related activities. The

chair undertakes its projects through teamwork with

individuals from multiple fields and disciplines,

volunteer services and networking with diferente

parteners. Aims: The Chair primarily aims to creat

synergies between local actors and projects already

being undertaken in this area of focus, in order to

enhancetheir integration and sustentability. Other major

objectives include the promotion of education of women

in all areas related to water, enhacing women’s

entrepreneurial skills, and encouraging women to invest

in themselves and achieve decision-making power on

equal terms with men. In addition, the Chair also seeks

to train and qualify men and women as conscious

peers, striving to live ina balanced and sustainable

environment. Methods; The project reaches women in

conditions of social vulnerability in the city of Ouro

Preto and Mariana and promotes, through the Program

of Permanent Capacity, qualification courses in the

areas of hospitality, food and health. Not only qualify

them professionally, but also encourage to build their

own business are prospects for future plans in the

program of social entrepreneurship courses and

enviromental education . This women in the training

programme has two 20-hour modules. The first

focuses on gender and water issues while the second

targets entrepreneurial skills, to aid in assembly of

associations or cooperatives. Results: Classes and

dynamic in training courses in the areas of Crafts;

Hygiene, Maids; Food handler; Receptionists and used

oil soap production reached about 200 women and

many of them are employed in Ouro Preto hostels and

restaurants. Conclusion: Among the partners are the

companies Vale and Samarco, City Council of Ouro

Preto, Reference Center for Social Assistance (CRAS),

Gorceix Foundation. And internationals: Hydrological

International Programme of UNESCO for Latin America

and the Caribbean, Hidroex Institute: Foundation

International Center of Education, Capacity and Applied

Research in Waters of the Government of Minas and

Network of Chairs on Gender. Recently, the core of the

Chair has signed a collaboration agreement with the

Dominican Republic, through the National Institute of

Hydraulic Resources. All this partners helps to improve

women's quality of life and their families, where

women's empowerment has immediate impact.

Acknowledgement: International Hydrological

Programme, Pró-Reitoria de Extensão, Federal

University of Ouro Preto.

Financial resources: Federal University of Ouro Preto.

44

ANTIOXIDANT AND ANTI-INFLAMMATORY

ACTIVITIES OF ETHANOLIC AND AQUEOUS

EXTRACTS OF THE LEAVES FROM Tabebuia

roseo-alba.

Zilma S. Ferraz-Filha1, Iális P. A. R. Dutra

1, Fernanda

C. Ferrari1, Marcela C. P. Michel

1, Dênia A. Saúde-

Guimarães1.

1Laboratório de Plantas Medicinais – CiPharma -

Escola de Farmácia – Universidade Federal de Ouro

Preto – Ouro Preto – MG

Tabebuia species have several uses in folk medicine,

including their use in inflammation and rheumatism.

Tabebuia roseo-alba (Ridl.) Sandwith (Bignoniaceae) is

popularly known as “white ipe”. This study evaluated in

vitro antioxidant and in vivo anti-inflammatory activities

of ethanolic and aqueous extracts of leaves from T.

roseo-alba. Leaves powder was extracted by

percolation with ethanol and water, separately. Ethanol

was removed under reduced pressure to afford dried

ethanolic extract. Water was removed by lyophilization

to afford dried aqueous extract. These extracts were

evaluated in an experimental model of gouty arthritis at

doses of 125, 250 and 500 mg/kg, using monosodium

urate crystal-induced paw oedema, in Swiss mice.

Indomethacin was used as positive control. The

measurement of the paws of mice was made with a

caliper at times of 4, 24, 48 and 72 h after

administration of the extracts and controls. The paw

volume of monosodium urate crystal-induced mice

revealed an increase in paw diameter, whereas

indometacin (3 mg/kg) caused significant anti-

inflammatory activity with reduction of edema in 4, 24,

48 and 72 h. Treatments with both extracts, in all

evaluated doses, were capable of promoting a

significant reduction of paw oedema of the animals,

demonstrating the anti-inflammatory activity. Evaluation

of antioxidant activity was performed in vitro using three

methodologies: Capture of free radicals 2,2-diphenyl-2-

picrylhydrazyl (DPPH), azinobis 2,2-(3-

ethylbenzthiazoline-6-sulfonic acid) (ABTS) and by β-

carotene/linoleic acid system. Ethanolic and aqueous

extracts showed antioxidant activity of 58.14; 51.48 %

(DPPH/100 µg/mL); 74.43; 87.77 % (ABTS/40 µg/mL)

and 76.75; 81.28 % (β-carotene/linoleic acid/40 µg/mL),

respectively. Trolox and quercetin, in different

concentrations depending on the methodology, were

used as positive controls. The results showed that the

ethanolic and aqueous extracts of leaves from T. roseo-

alba showed promising antioxidant and anti-

inflammatory properties and may contain bioactive

33

substances useful in the treatment of gout and

inflammation. Further investigations are necessary for

complete elucidation of antioxidant and anti-

inflammatory pathways from extracts. Financial support:

FAPEMIG - CDS-APQ-01318-12, REDE

TOXIFAR/FAPEMIG, PIBIC/CNPq/UFOP.