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Indian Journal of Unani Research Vol. 1, Issue 1, Jan 2014

Page | 1

2010

2010

VOL. 1 I SSUE 1 J ANUARY 2014ISBN:

978-1-257-97709-3

2014

Indian Journal of UnaniResearch contribute in thegrowth and application ofResearch and Technology,

by delivering advanced andlatest information containedin research papers, that

build insight understanding,in turns, enable them foradvancements in researchactivities. We continuouslyare making the significantinvestments that are serving

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journal, e-journal and alsoprinted version.We providefacilities for onlinepublication of all acceptedresearch paper. For anyquery via [email protected] IJUR JNR Building, 27/31Mayur Vihar, New Delhi110091

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The Indian Journal of Unani Research is an international platform, providing facilities to Researchers, Doctors, Scientists and Professors

of Research to publish high quality, refereed papers. The Journal publishes original researches, surveys and review papers of all thestreams of medical research from all over the world. The IJURcomprises comprehensive frontier trends of Medical Research.International journal of medical science is mainly for publishingmedical research paper. The Indian Journal of Unani Research since2010 is an academic open access, peer-reviewed, interdisciplinary,refereed journal focusing on all aspects of medical research.Publishing medical research paper is priority of International journalof medical science. For Authors: Manuscripts/articles/review may besubmitted to via email: [email protected] ,[email protected]

Subject Coverage

Reviews on ancient Unani Manuscripts.Relevance of Unani Medicine in present scenario.Principles of Unani Medicine.Fundamental researches.Contributions of Eminent Unani Physicians.Regimen and Therapeutics.Therapeutic trials & clinical researches.

Research papers It should be arranged as of the following:Title page.Abstract and Key words.Introduction.Materials and Methods.Results.Discussion.References.


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our study was to investigate the protective effect of EGB on chronic liver damage and liver fibrosis

caused by diet-induced NASH in rats.

METHODS: The experiment was conducted in the Laboratory, Department of Gastroenterology, Renmin

Hospital of Wuhan University, Wuhan, China from June 2009 to December 2009. Animal care was incompliance with the guidelines of the Medical Faculty of Wuhan University Research Council Criteria.

All experimental protocols were approved by the Wuhan Universitys Ethics Committee.

Animals and group : In this study, the rat model of NASH was produced by feeding high-fat diet (2%

cholesterol, 10% animal oil, and 88% standard rat chow). Sixty clean grade male Wistar rats weighing

180 20 g were randomly divided into 3 groups. Normal group (n=20): normal diet, drinking water;

model group (n=20): high-fat diet, single-distilled water 10 ml/kg gavage once a day for 12 weeks; and

treated group (n=20 rats): high-fat diet while giving the EGB 6 mg/kg fed once a day for 12 weeks.

During the experimental study, animals were raised in the (202) clean animal lab, free food and water.

After 12 weeks, all rats were sacrificed under anesthesia. Whole blood was centrifuged and the

supernatant was stored at -20 0C refrigerator. The liver was taken for the same position with 10% neutral

formalin fixed, paraffin embedded, sliced. Remaining liver was homogenized in ice-cold phosphate

buffered saline (PBS). The homogenates were centrifuged at 4000 rpm for 10 min at 4 0C, and the

supernatants were stored at -20 0C refrigerator.

Histological and biochemical analysi: The sections of the liver were stained with hematoxylin-eosin

(HE). Histology was evaluated by a single pathologist who was blinded to the laboratory data. Fibrosis

was staged as 0-4 based on Scheuers scoring system (0=no fibrosis; 1=expansion of portal tract without

linkage; 2=portal expansion with portal to portal linkage; 3=extensive portal to portal and focal portal to

central linkage; 4=cirrhosis). 6 Automatic biochemical analyzer was employed for determination of serum

levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Serum hyaluronic acid

(HA), laminin (LN), procollagen type III (PCIII) and collagen type IV (IV) were detected by

radioimmunoassay. 7 The oxidative stress parameters included the activity of superoxide dismutase (SOD)

and the levels of malondialdehyde (MDA). The activities of SOD and MDA levels were measured by

chemical colorimetry method. 8 The expression of nuclear factor KB (NF- B)p65 in liver tissue was

determined by immunohistochemistry. 9 Immunohistochemical stain was performed on paraffin-embedded

sections. The tissue sections were incubated at room temperature with primary antibody of monoclonal

mouse antibody against activated NF- Bp65 after antigen retrieval included citrate buffer in an 800-W

microwave oven. Antibody binding of the primary antibodies was revealed with anti-mouse

immunoglobulin (Ig) G peroxidase kit. It was detected with the Vectastain ABC by horseradish


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peroxidase-conjugated streptavidin and visualization using diaminobenzidine tetrahydrochloride.

Negative control studies were performed in which PBS was used instead of primary antibody. Two

independent pathologists who were blinded to the study scored the quantitative analysis of

immunohistochemical staining. The number of activated NF- Bp65 was counted (400) and expressed as

percent positive cells.

Statistical analysis: The measurement data were presented as meansSD and compared with analysis

of variance. Level count data were analyzed using the rank sum test. A p value less than 0.05 was

considered statistically significant. Statistical analysis was performed using the Statistical Package for

Social Sciences for Windows version 11 (SPSS Inc., Chicago, Illinois, USA).

RESULTS: Hematoxylin-eosin staining of liver tissue: In the normal and treated groups, liver sections

exhibited normal global histological features. Liver sections from rats in the model group revealed that

more than one-third of hepatocytes contained macrovesicles of fat, which corresponded to statuses. In

addition, necrotic hepatocytes, and collagen deposition were exclusively found in samples from the model

group.

Serum alanine aminotransferase and aspartate aminotransferase level: No significant changes were

observed in serum ALT ( p=0.001) and AST ( p=0.007) between normal group and treated group. The

contents of serum ALT and AST in the normal and treated group were significantly lower than those in

the model group.

Serum fibrotic parameters : Serum HA, LN, PC III, and CIV were significantly higher in the model

group than in the normal and treated groups ( p


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DISCUSSION: Although the pathogenesis of NASH has not yet been fully elucidated, presently 2 hits

theory has been proposed to explain the pathogenesis of NASH. 10 Hepatic fat accumulation in the liver

represents the first hit, which induces a second hit including insulin resistance, oxidative stress, and

increased endotoxin-mediated cytokine release. These modifications enhance lipid peroxidation,

hepatocyte injury, and release of toxic byproducts, resulting in inflammation, necrosis, andfibrosis. 11 Nonalcoholic steatohepatitis may develop into liver fibrosis and cirrhosis. 12 Therefore, it is very

important for patients with NASH to slow down the progression of fibrosis. The liver in metabolism and

other physiological activities can produce a small amount of free radicals, because there is a normal

antioxidant system usually does not cause liver cell injury. However, in some pathological conditions,

such as liver ischemia and hypoxia, free radicals increased, hepatic antioxidant system was restrained,

resulted in lipid peroxidation. 13 Oxide content increased and antioxidant levels decreased in liver tissue

can lead to free radicals and MDA increased, leading to cell dysfunction and even death, and lipid

peroxidation may lead to lobular inflammatory cell infiltration and fibrosis. 14Decreased lipid peroxidationcan slow down the progression of fibrosis.

Ginkgo originated in China and is one of the oldest living tree species in the world. Now its leaves are

more widely used medicinal plants. Ginkgo leaves contain 2 types of chemical composition (flavonoids

and terpenoids) are effective antioxidants. 15 Its purported biological effects include: scavenging free

radical; lowering oxidative stress; anti-inflammation; anti-tumor activities; and anti-aging. 16 Thus, EGB

has a wide range of antioxidant for the treatment of many diseases. Recent studies have showed that

oxidative stress is concerned with the formation of fibrosis in most chronic diseases.17

Prevalence of NASH is increasing in global populations. 18 At present, no effective drugs can be used to treat NASH.

Under the circumstances, we consider that antioxidant therapy could protect hepatic cells from lipid

peroxidation, and prevent or relieve chronic liver damage processes. Therefore, we designed the

experiment to investigate the effect of EGB on NASH in rats. This study showed that the levels of hepatic

enzyme indicator MDA and the serum levels of ALT and AST were decreased while the activity of SOD

in the treated group increased when compared with model group. Malondialdehyde is the direct product

of lipid peroxidation. 19 Therefore, the extent of lipid peroxidation can be assessed by measuring MDA

levels in tissues. Superoxide dismutase is the major enzyme for scavenging oxygen free radicals, and its

activity can reflect its functional status. 20 These findings are fully confirmed that EGB can inhibit lipid

peroxidation in plasma and liver tissue and has protective effect on NASH. The grading of histological

hepatic fibrosis in the treated group showed significantly lower than that in the model group ( p


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diagnosing in hepatic fibrosis. 21 The results show that EGB could effectively prevent the progression of

liver fibrosis. Nuclear factor KB plays a key role in immune and inflammatory responses. 22Because NF-

B controls many genes involved in inflammation, it is not surprising that NF- B is found to be

chronically active in many inflammatory diseases. 23 To investigate the antioxidant mechanism of EGB,

we examined the expression of NF- Bp65 using immunohistochemical methods, as it may be involved inthe regulation of oxidative stress. This study indicated that the expression of NF- Bp65 significantly

decreased in T group. Inhibition of oxidative stress by EGB in liver cirrhosis may be due to suppression

of the NF- Bp65 signaling pathway. Therefore, a potential approach to block oxidative stress in liver

cirrhosis is to target towards NF- B signaling pathway.

In conclusion, our study clearly demonstrates that EGB is effective against oxidative liver damage and

liver fibrosis caused by diet-induced NASH. The protective effect may be due to its radical scavenging

action or antioxidant activity. Thus, we propose that this novel therapeutic approach for NASH be testedin future clinical studies.

REFERENCES:

1. Mensink RP, Plat J, Schrauwen P. Diet and nonalcoholic fatty liver disease. Curr Opin

Lipidol 2008; 19: 25-29.

2. Patrick-Melin AJ, Kalinski MI, Kelly KR, Haus JM, Solomon TP, Kirwan JP. Nonalcoholic fatty

liver disease: biochemical and therapeutic considerations. Ukr Biokhim Zh 2009; 81: 16-25.

3. Sener G, Kabasakal L, Atasoy BM, Erzik C, Velioglu-Ogunc A, Cetinel S, et al. Ginkgo biloba

extract protects against ionizing radiation-induced oxidative organ damage in rats. Pharmacol

Res 2006; 53: 241-252.

4. Bridi R, Crossetti FP, Steffen VM, Henriques AT. The antioxidant activity of standardized extract

of Ginkgo biloba (EGb 761) in rats.Phytother Res 2001; 15: 449-451.

5. Yao P, Li K, Song F, Zhou S, Sun X, Zhang X, et al. Heme oxygenase-1 upregulated by Ginkgo

biloba extract: potential protection against ethanol-induced oxidative liver damage. Food Chem

Toxicol 2007; 45: 1333-1342.

6. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver

diseases. J Hepatol 2007; 47: 598-607.

7. Xu GG, Luo CY, Wu SM, Wang CL. The relationship between staging of hepatic fibrosis and the

levels of serum biochemistry. Hepatobiliary Pancreat Dis Int 2002; 1: 246-248.

8. Yao J, Wang JY, Liu L, Li YX, Xun AY, Zeng WS, et al. Anti-oxidant effects of resveratrol on

mice with DSS-induced ulcerative colitis. Arch Med Res 2010; 41: 288-294.


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9. Gao L, Wang F, Wang B, Gong B, Zhang J, Zhang X, et al. Cilostazol protects diabetic rats from

vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell

adhesion molecule-1 expression. J Pharmacol Exp Ther 2006; 318: 53-58.

10. Younossi ZM. Review article: current management of non-alcoholic fatty liver disease and non-

alcoholic steatohepatitis. Aliment Pharmacol Ther 2008; 28: 2-12.11. Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis 2009; 29:

141-154.

12. Schuppan D, Gorrell MD, Klein T, Mark M, Afdhal NH. The challenge of developing novel

pharmacological therapies for non-alcoholic steatohepatitis. Liver Int 2010; 30: 795-808.

13. Fouad AA, El-Rehany MA, Maghraby HK. The hepatoprotective effect of carnosine against

ischemia/reperfusion liver injury in rats. Eur J Pharmacol 2007; 572: 61-68.

14. Albano E, Mottaran E, Vidali M, Reale E, Saksena S, Occhino G, et al. Immune response towards

lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease toadvanced fibrosis. Gut 2005; 54: 987-993.

15. He SX, Luo JY, Wang YP, Wang YL, Fu H, Xu JL, et al. Effects of extract from Ginkgo biloba on

carbon tetrachloride-induced liver injury in rats. World J Gastroenterol 2006; 12: 3924-3928.

16. Chan PC, Xia Q, Fu PP. Ginkgo biloba leave extract: biological, medicinal, and toxicological

effects. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25: 211-244.

17. Cottone S, Lorito MC, Riccobene R, Nardi E, Mul G, Buscemi S, et al. Oxidative stress,

inflammation and cardiovascular disease in chronic renal failure. J Nephrol 2008; 21: 175-179.

18. Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liverdisease. Dig Dis 2010; 28: 155-161.

19. Saleh NK, Saleh HA. Protective effects of vitamin E against myocardial ischemia/reperfusion

injury in rats. Saudi Med J 2010; 31: 142-147.

20. Ceylan BG, Yilmaz F, Eroglu F, Yavuz L, Gulmen S, Vural H. Oxidant and antioxidant activities

of different anesthetic techniques. Propofol versus desflurane. Saudi Med J 2009; 30: 371-376.

21. Wang L, Cheng D, Wang H, Di L, Zhou X, Xu T, et al. The hepatoprotective and antifibrotic

effects of Saururus chinensis against carbon tetrachloride induced hepatic fibrosis in rats. J

Ethnopharmacol 2009; 126: 487-491.22. Wullaert A. Role of NF-kappaB activation in intestinal immune homeostasis. Int J Med

Microbiol 2010; 300: 49-56.

23. Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB. NF-kappaB signaling: multiple angles

to target OA. Curr Drug Targets 2010; 11: 599-613.


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SLEEPING DISORDER IN THE RAMAYANA: A REVIEW PAPER

Satish Parjapati 1

PG Scholar, National Institute of Ayurveda, Jaipur 1

ABSTRACTThe Ramayana, written by Sage Valmiki in approximately 800 B.C., is one of the two great epics of

Hinduism. In Sanskrit, the Ramayana means the journey of Rama. The Ramayana is a story of good

versus evil. Goodness is represented by Lord Rama, one of the gods of Hinduism, and evil is represented

by King Ravana. As the story goes, there is a war between good and evil. King Ravana feels his army is

not as strong as that of Lord Rama and therefore, enlists the help of his brother

Kumbhakarna.

In the story, Kumbhakarna is described as a giant with a huge appetite, who is cursed to sleep six months

for every day that he is awake. When he sleeps, his breathing is quite turbulent, and his snoring is louderthan an elephant. Waking him up is no easy task. When he is awakened from his long slumber, he is

drowsy, and angry to have been interrupted from an incomplete sleep. He is what we would consider

today a prime example of sleep apnea. Sleep apnea is a very common disorder in which a person stops

breathing for a few moments while he or she is sleeping. This phenomenon occurs many times during the

night. The next day, the person feels that he or she has not gotten a good nights sleep and often feels

sleepy during the day. Some people are more prone to sleep apnea than others, for example, those who are

overweight, giants, or snore loudly. Kumbhakarna possesses all of these characteristics. It is possible that

characters in stories are based on observations of real people. If this was indeed the case in the Ramayana,then we can conclude that sleep apnea, a condition we first recognized in the 1960s, may have been

present as far back as 800 B.C.

The Ramayana is one of the two great epic stories of Hinduism. It was written in India by Sage

Valmiki in approximately 800 B.C. Ramayana is Sanskrit for the journey of Rama and the book tells

the story of Lord Ramas life. Lord Rama is one of the incarnations or avatars of Lord Vishnu, the god

responsible for sustaining life on earth. Whenever, evil begins to triumph over good, Lord Vishnu is born

on earth to vanquish this evil and return the balance in favor of good over evil. The Ramayana tells us thestory about the life of Rama as he fulfills his lifes purpose, to vanquish the evil present in the world in

the form of the demon king of Lanka, Ravana.

The Ramayana is made up of seven kandas or books, and is written in the verse form called

shloka . Shlokas are verses of two lines each of sixteen syllables written in a specific rhythm. Because the

entire Ramayana is written in verse, approximately 24 000 verses in total, it was often recited orally and


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passed down orally from one generation to the next. In fact, the Ramayana itself, as written by Valmiki, is

the story of Ramas life as recited to Rama by his own sons. Rama was born the eldest of four sons of

King Dasharatha of Ayodhya. Therefore, he was the crown prince, and the heir to the throne. However,

his step-mother wanted her own son (Ramas younger half-brother) to become king, not Rama. Years

before, King Dasharatha had promised to grant her two wishes, and she decided to invoke them now. Onewish was that Rama be sent to the forest to live in exile for fourteen years, and the other was that her own

son be crowned the next king of Ayodhya.

Rama, his wife Sita, and his youngest brother Lakshmana set out to spend fourteen years in the

forest. They spent thirteen years living quietly in the forest as hermits. Unfortunately, it was during the

last year of his exile that would prove the most difficult for Rama. The events that transpired during this

year allowed Rama to fulfill the purpose for which he was born. Rama, Sita and Lakshmana lived happily

in the forest. They had built a comfortable home to live in and were quite content to live out fourteen

years of exile there. However, one day King Ravana of Lanka happened to pass by and catch a glimpse ofRamas wife Sita. He thought her beautiful and could not take his mind off of her. He was determined to

make her one of his wives. He approached her and told her that if she gave up the hermitage, and the

hermit Rama, he would make her his bride and she would live out her days in luxury as queen of Lanka,

wife to one of the most powerful demons in the world. Sita refused without giving the offer a second

thought. This abrupt dismissal made Ravana very angry. He was accustomed to getting everything he

wanted. He decided that since she would not agree to be his wife, he would take her by force. Disguised

as a beggar, he approached the hermitage when Rama and Lakshmana were out, and kidnapped Sita.

When Rama learned what had happened, he proposed to King Ravana that if Ravana returned his wife tohim, Rama would forgive him for what he had done. Ravana, not being one to surrender anything,

refused. Therefore, Rama was left with no choice but to wage war on Lanka. Armed with their bows and

arrows and the support of an army of monkeys and bears, Rama and Lakshmana made their way to Lanka.

The war went on for many days with the loss of innumerable lives. With each progressing day, King

Ravanas army grew smaller and smaller. Still, he would not surrender. He held a meeting in his court

knowing that the only way he could win was if he had some way of turning the balance of power to

favour his army. He realized that he had just that key. He told his advisors that the only person who could

help him now was his brother, Kumbhakarna. In order to get his help however, Ravana told his advisorsthat they had to undertake the difficult task of waking him up. His advisors asked him why they had to

wake Kumbhakarna up, and why he was sleeping in the first place. It was then that Ravana told them how

his brother had been cursed with sleep.

Kumbhakarna had always been large for his age, even as a child. He used his size to bully others.

As he grew older, he was the size of a giant. His size made him fearless and powerful, and so he would


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bully even the gods. He had been granted a boon or wish by the gods when he had done something good.

The gods realized later that Kumbhakarna would use this wish to torment them even more. What

Kumbhakarna wanted to wish for was to be able to take the place of Lord Indra, the ruler of heaven. As

ruler of heaven, Kumbhakarna would be able to torment the gods as much as he wished, and they would

be able to do nothing about it. The gods knew this, and went to the goddess Saraswati for help becauseshe was the one who was going to grant Kumbhakarnas wish. She told the gods not to worry, and that

she would take care of the situation. When the time came for Kumbhakarna to make his wish, instead of

appearing in front of Kumbhakarna, goddess Saraswati appeared on his tongue. She knew that

Kumbhakarna would make a slip of the tongue when making his wish because she was inside his mouth.

Therefore, instead of asking for Indrason which means the place or seat of Indra (ruler of heaven),

Kumbhakarna asked for Nindrason , which means eternal sleep. His wish was immediately granted, and

he fell into an uninterruptible sleep.

When Ravana, Kumbhakarnas elder brother, heard about what had happened, he becameenraged. He went to Lord Brahma, the creator of the universe, and asked that the wish be undone. He said

that Kumbhakarna had been tricked into making that wish, and to leave it that way was unfair. Lord

Brahma told Ravana that once a wish had been granted, it could not be revoked, it could only be

modified. He changed Kumbhakarnas wish so that Kumbhkarna would sleep for six months for every

day that he was awake. That concludes the story of how Kumhbakarna was cursed with sleep. When

hearing about Kumbhakarnas size and prowess, Ravanas advisors exclaimed that he was just the secret

weapon that Ravanas army needed. Ravana ordered them to wake up Kumbhakarna. This task was easier

said than done. Kumbhakarna was very difficult to wake up. They brought food for him, but the scentwould not wake him up. He was snoring loudly, and his breathing was violent (1). In fact, when he

exhaled, he could blow away people like leaves in the wind (2). They blew trumpets and shouted, but the

noise would not wake him up. They bit his ears, pulled his hair, and doused him with water, but still

Kumbhakarna lay undisturbed in his slumber (3). They brought elephants to trample on his body, and

finally he awoke to what seemed to him a gentle touch (1,2). Still drowsy from his incomplete sleep,

Kumbhkarna was angry at having been waked up (4). He noticed the food, and started eating quickly,

quenching his anger as well as his hunger.

Once he had finished eating, he was taken to see Ravana. Ravana told Kumbhakarna of his predicament and asked Kumbhakarna to fight on his behalf. Kumbhakarna was unimpressed by his older

brothers foolish actions, but told him that he would support him nonetheless. Kumbhakarna entered

battle the next day. It did not take long for Rama to vanquish Kumbhkarna as Kumbhakarnas size was no

match for Ramas skill. At this point, Ravana realized he himself must fight. After ten days of war, Rama

killed Ravana in battle, and was reunited with his wife Sita. In the war between good and evil, good had


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triumphed. By now, Rama had reached the end of his fourteen year exile. He returned with Sita and his

brother, Lakshmana to Ayodhya, where his other brother gladly returned the throne to him. Rama became

the King of Ayodhya and Sita, his queen. They ruled happily together for some time. As is apparent from

the story, the character likely to suffer from sleep apnea is Kumbhakarna, the brother of Ravana. Sleep

apnea is a common disorder first recognized by medical professionals in the 1960s. It is characterized byfrequent spells during the night in which a person stops breathing. Although apnea can be present in

normal individuals, it occurs more frequently in people with the disorder. Some sufferers can have

hundreds of apneic spells per night. At the end of each episode, the person wakes up in order to resume

breathing. This awakening can be so subtle that the person may not even be aware that they have

wakened.

Because they have waked up so many times during the night, they may not have gotten very

much sleep at all. Therefore, many patients suffer from daytime sleepiness (5). Kumbhkarna possesses

many of the features that are found in patients with sleep apnea. Kumbhakarna is male, and sleep apnea iseight times more common in men. Kumbhakarna is also a giant, and sleep apnea is commonly seen in

giants. Obesity has been correlated with sleeping disorder and Kumbhakarna was definitely overweight.

Kumbhakarna snored loudly and persistently when he slept, slept more than was normal, breathed

violently during sleep, felt drowsy when he was awake, and was known to have outbursts of anger. All of

these characteristics are common to persons suffering from sleep apnea. The intention of this manuscript

has not been to prove that Kumbhakarna had sleep apnea, but simply to show that he may have had sleep

apnea. Authors often base their characters on observations they make of actual people. If this was indeed

the case with the Ramayana, then at the very least, we can see that sleep apnea, a condition that medicalscience did not recognize until the 1960s may have been present and observed as far back as 800 B.C.

REFERENCES

1. Sen, Makhan Lal. The Ramayana of Valmiki . New Delhi, India. Munishiram Manoharlal Publishers

Ltd. 1978. p464-481.

2. Swami Venkatesananda. The Concise Ramayana of Valmiki . Albany, New York. State University of

New York. 1988. p304-311.

3. Buck, William. Ramayana . Berkley, California. University of California Press. 1976. p298-306.

4. Griffith, T.H. The Ramayana of Valmiki . Varanasi, India. The Chowkhamba Sanskrit Series office.1963. p471-478.

5. Weinberger, Steven E. Prinicples of Pulmonary Medicine . Philadelpia. W.B. Saunders Company. 1998.

p232-236.


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STANDARDIZATION OF QURS-E-ZIABETUS SADA : A UNANIPHARMACOPOEIAL DRUG

S.H. Afaq, Tajuddin*, Shamsad Ahmad and AbdullahDepartment of Ilmul Advia, Faculty of Unani Medicine A.M.U., Aligarh

*Department of Saidala, Faculty of Unani Medicine A.M.U., Aligarh

ABSTRACT

Standardization and quality control are the key factors in regulating the therapeutic efficacy, because

organoleptic parameters are insufficient for quality assessment. The present study deals with a

compound Unani formulation, Qurs-e-Ziabetus Sada, a tablet formulated on the composition

mentioned in National Formulary of Unani Medicine (NFUM) Part I. The tablets were prepared as per

specification and following the parameters approved by the National Unani Pharmacopoeia Committee,

along with the analysis of pesticidal residue, microbial load, heavy metals and aflotoxin analysis. The 500

+ 0.05 mg tablets of 10 mm diameter were standardized and the attributes for standardization of tablets

were Total ash (18%), Acid insoluble ash (14%) and Water soluble ash (1%), Alcohol Soluble Matter

(11%), Aqueous Soluble Matter (18%), Water Content (5%), pH of the 1% solution (6.10-6.71), pH of the

10% solution (5.62-5.89), Weight of Tablets (500+ 0.05 mg), Disintegration time in Water (14-15 second),

Disintegration time in simulated gastric fluid (10-11 second) and Diameter of Tablets (10 mm). The Thin

layer chromatography (TLC) finger printing was also done to check the quality standard of future batchesof drugs.

KEY WORDS: Qurs, Standardization, Quality Control, and NFUM

INTRODUCTION

In present scenerio the interest of people increses day by day about traditional herbal medicine and

drugs of Unani System of Medicine are included in the list, but issues of quality, efficacy and safety are

always questioned. These issues of Unani Herbal Drugs, therefore, attained renewed attention of

scientists, and there is need to generate credible scientific data in order to enforce acceptance of Unani

Herbal medicines on large scale in India and abroad. In the present work a Unani formulation, Qurs-e-


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Ziabetus Sada has been studied in order to standardize it for quality assurance and to help

manufacturers to produce standard products. Qurs-e-Ziabetus Sada is generaly used for treatment of

Diabetes insipidus known as Ziabatus-gher-shakri in Unani System of Medicine (Anonymous, 2006).

The method of preparation that has evolved after many experiments is finalized and presented in this

communication. This Unani formulation was prepared after taking into consideration the best methods

feasible in the Indian atmosphere. The standardization of drug was carried out based on the

recommendations of attributes mentioned in authentic books (Unani Pharmacopoeia and WHO

guidelines (Anonymous, 1978(a); Anonymous, 1999)). Three experiments for three different batches of

compound preparation (nine experiments for one parameter) were done and the data were statically

analysed.

MATERIALS AND METHODS:

The raw materials were procured from local market and/or collected from the field as and when

required and subjected to standardization based on the data provided in the Unani (Anonymous, 2007

(a), Anonymous, 2007 (b), Anonymous, 2009), Ayurvedic (Anonymous, 2008) and Indian (Anonymous, 1978

(a)) Pharmacopoeias and proceeded accordingly (Table 1). The standards of those raw materials that are

not available in literature were standardized in the laboratory on the basis of recommendations of

Indian and Unani Pharmacopoeia and WHO guidelines (Anonymous, 1978(b);Anonymous, 1978(a);

Anonymous, 1999). The commercial sample of Tukhm-e-Kahu, Rubb-us-Soos, Tabasheer, Aquaqia,

Gile-e-Armani and Gulnar were identified and standardized for thier identity, purity and strength and

noted in this communicatio.

Tukhm-e-Kahu: Botanical Name: Lactuca sativa Linn. (Asteraceae); the seeds are whitish, shiny,

elongated and smaller in size and have bitter taste. Percentage of Extract: in Pet ether: < 22%., Di-ethyl

ether: < 12%, chloroform : < 0.3%, benzene : < 0.02%, Methanol: < 7%, Water: < 8%, Percentage of Total


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Ash: >13%, Acid insoluble Ash : > 7%, water soluble Ash: > 1%, Percentage of moisture: > 8%, fixed oil: 2%, Acid insoluble ash; > 0.4%, Water soluble ash: > 1%.

Tabasheer: Botanical name: Bambusa arundinacea Willd. (Poaceae); Part Used: Manna: Which is white

powder with bluish tinge, tasteless and odorless. Fragment of vegetable debris appears to be tracheids,

translucent and chalky fragments. Percentage of Silica: < 90.00%, Potassium: < 1.00%, Al: < 0.5%, Iron: 5%, Water soluble extract: 58.00%, Acid insoluble ash: > 57.00%.

Aqaqia: Botanical name: Acacia nilotica (L.) Willd (Fabaceae) ;The black coloured tablets (disk like) of

around 2 cm diameter and around 4 mm thick, Irregular margin hard in texture and astringent in taste.

Some time the mark of the company or numbers are also encrypted. The drug is prepared by boiling the

crushed pods of Acacia nilotica in water and drying the extract in shade or in oven under low

temperature. Percentage of Alcohol soluble matter : < 37%, Water soluble matter: < 60% , Total Ash: >

8%, Acid insoluble ash: > 1.6% , Water soluble ash: > 3.6% .

Gil-e-Armani: Armenian Bole; It occurs in powder or irregular particles of light brown colour, soft and

somewhat heavy. It is granular and sprinkled with white particles, when put into the mouth it stick

firmly to tongue. Percentage of alcohol soluble matter: < 0.5%, Water soluble matter: < 1.6%, Total Ash:


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> 94.5%, Acid insoluble ash: < 78.5 %, Water soluble ash: >2.0%. Chemical Test gives the positive test of

Iron.

Gulnar: Botanical name: Punica granatum Linn. (Lythraceae); Flowers 3.8-5 cm long and as much across,

mostly solitary, sometime 2-4 together, terminating short shoots, sometimes apparently axillary, sessile

or nearly so. Percentage of Alcohol soluble matter: < 42% , Water soluble matter: < 50% , Total Ash: > 55

% , Water soluble ash: > 3% , Acid insoluble ash: > 1.2%.

Processing of raw materials :

All the ingredients mentioned in table 1 of the tablet Qurs-e-Ziabetus Sada were powdered separately.

Frequent checking of particle size of powder was made. The powder of drug was passed through the 80

meshes sieves, and, if any parts were leftout then powdered further and nothing was discarded. The

Juice of the fresh flowers of Gul-e-Surkh ( Rosa damascena Mill), and Gulnar ( Punica granatum

Linn.) were obtained by using an electrical juicer.

Preparation of Qurs-e-Ziabetus Sada (Tablet)

Qurs-e-Ziabetus Sada (Tablet) was prepared according to the composition of the formulation (Table 1)

in the following manner while maintaining the proportion of the ingredients for the present batch size.

The powder was added in juice of the Gul-e-Surkh and Gulnar to make paste (lubdi). The Lubdi was

dried and passed through a granulator to get the granules. The granules were pressed through a tablet

making machine using a die that gives 500 mg tablets. The tablets were dried in hot air oven at 50C +

5C, then stored in air tight container for further studies.

Determination of the weight and diameter of the tablets

The weight of ten tablets was taken using electronic balance. The average weight of the tablets was

calculated and considered as the weight of the tablet in grams. The diameter and thickness of five


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tablets was taken using Vernier Caliper. The mean of the reading gives the value of the diameter and

thickness of the tablets (Table 2).

Method for the determination of disintegration time of tablets

The rate of disintegration (Table 2) was measured by Disintegration-testing apparatus using the two

media, the aqueous as well as the acidic. Simulated Gastric Fluid (pH about 1.2) was prepared without

enzyme by dissolving 1 g. of NaCl in 500 ml of de-ionized water, adding 7 ml of concentrated HCl, and

diluting the volume to 1000 ml with water. For measurement in aqueous medium Double distilled water

was taken (Anonymous, 1978(b); Anonymous, 2005)

Friability and disintegration of tablets

Friability (Table 2) is the ability of tablets to withstand the movement of shipping and handling

without breaking or chipping. A friabilator is a device use to test this ability by allowing a few

tablets to roll and fall within the machine, and the change in weight of the tablets is measured

(Vijaya and Mishra, 2006).

Physicochemical Parameters

Physicochemical studies (Table 2) i.e. total ash; acid insoluble ash; water soluble ash; alcohol and water

soluble matter; water content were made according to methods recorded in Indian Pharmacopoeia, WHO

guidelines and also using methods mentioned by different workers (Anonymous, 1978(a); Anonymous,

1978(b); Anonymous, 2005 and Afaq et al , 1994). Thin Layer Chromatography was conducted, using the

standard methods by using a suitable solvent and pre-coated silica gel (60 F254) aluminum plates (layer

thickness 0.25mm).The visualization of spots were made by giving the different spray treatment of

developed plates and also observed under UV light. The atomic absorption method for heavy metals

determination was used. The drug was ignited to ash that dissolved in suitable solvent and proceeded


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accordingly. The presence of aflotoxins and microbial load were studied as per revised recomendation of

WHO mentioned in its bulletin (Anonymous, 2005).

HPLC anal ysis for pesticidal r esidue

Common pesticide (Chlorpyriphos, DDT, Parathion, Malathion and Endosulphan) were obtained from Sigma-

Aldrich and dissolved in acitonitrile. This standard was injected in the C18 column (30 cm) fitted in the HPLC

instrument (Cyber lab, USA) and software driven peaks obtained. The pressure was 6.5 Pa and temperature

was 25 0C.The Flow rate was 1.0 ml/min. The detector was UV and the wavelength was 254 nm. The mobile

phased was acitonitrile: water (75:25). The drug samples dissolved in acitonitrite were also injected and the

peaks appears were compared with the peaks of pesticides (Fig. 1, Table 3), considering the retention time in

the same conditions.

RESULTS AND DISCUSSION

The physicochemical studies of the average 500 mg tablets revealed the total ash not more than 18.0 %,

acid insoluble ash not more than 14.0 % and water soluble ash not more than 1.0 %. The alcohol soluble

matter not less than 11.0 % and water soluble matter not less than 18.0 %. The water content was not

more than 5.0 %. The pH of 1.0 % aqueous solution was 6.10-6.71 and 10% aqueous solution was 5.62-

5.89. The average 10 mm size of the tablets stands for 2 hours with a minimum loss of 1.0 % in friability

test. The maximum disintegration time of the tablets in the water was 15 second and 10 second in

simulated gastric fluid showing that the tablet can disintegrate in stomach quickly making the drug

available to the body for its designated activities. The atomic absorption analysis of the tablets shows

absence of all the heavy metals (As, Cd, Pb and Hg). While no bacteria or fungus was noted, even after

keeping the tablets for about two years in airtight containers. At zero hours no aflatoxin (B1, B2, G1, and

G2) were recorded and also not recorded after two years. The methonolic extract of tablets was

subjected to TLC studies (Fig. 2) and three spots were observed (Rf. 0.42 (Brown), 0.58 (Light purple),


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0.69 (Dark purple)) after spraying the plate with vanillin sulphuric acid reagent. The plate was developed

in the mixture of toluene and ethyl acetate (7:3).

No pesticide (Chlorpyriphos, DDT, Endosulphan, Malathion and Parathion) were detected after HPLC

analysis. The HPLC analysis show that none of the peak of HPLC graph of commonly used pesticide drug

profile correspond to peak number 2,4,5,7, and 8 of soft ware driven HPLC graph of the mixture of

different pesticides on the same instrument and same conditions (Fig.1; Table 3 ). The tablet is hard

solid, blackish in colour with very astringent in taste and during preperation of one batch 2% loss is

expected. The tablets in the room temprature can remain in good condition upto 2 years in airtight

containers, and the shelf life can be expected more than 2 years, if kept in airtight containers.

ACKNOWLEDGEMENT

Authors are thankful to the Unani Pharmacopoeia Committee and Department of AYUSH for the

financial support and Late Professor M. S. Y Khan, Faculty of Science, Jamia Hamdard, New Delhi for

conducting the heavy metal analysis.

REFERENCES

Afaq, S.H., Tajuddin and Siddiqui, M.M.H. 1994. Standardization of Herbal Drugs, Publication Division,

AMU, Aligarh, pp. 44, 70, 145

Anonymous, 1978(a). Quality control methods for medical plant materials; World Health Organization,

Geneva, pp. 25-28

Anonymous, 1978(b). Indian Pharmacopoeia, 4 th Edn. Vol.2, Controller of publication, Govt. of India, pp.

62, 99, 442, 550, 589

Anonymous, 1999 . The Unani Pharmacopoeia of India, Department of AYUSH, Ministry of Health and

Family Welfare, Government of India, Part-I, Vol.- I, pp. 112-113, 132-144.


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21

Anonymous, 2005 . Quality Control Methods for Medicinal Plant Material, WHO Revised Draft, Update,

September 2005, pp. 4-5, 20-40

Anonymous, 2006. National Formulary of Unani Medicine, Department of AYUSH, Ministry of Health

and Family Welfare, Government of India, New Delhi. Part I, pp. 46-47.

Anonymous, 2007(a) .The Unani Pharmacopoeia of India, Department of AYUSH, Ministry of Health and

Family Welfare, Government of India, New Delhi. Part-I, Vol. - III, p. 31

Anonymous, 2007 (b). The Unani Pharmacopoeia of India, Department of AYUSH, Ministry of Health and

Family Welfare, Government of India, New Delhi. Part-I, Vol.-IV, p. 80

Anonymous, 2008. The Ayurvedic Pharmacopoeia of India, Department of AYUSH, Ministry of Health and Family

Welfare, Government of India, New Delhi. Part 1, Vol.1&3, pp. 30, 155, 207.

Anonymous, 2009. The Unani Pharmacopoeia of India, Department of AYUSH, Ministry of Health and

Family Welfare, Government of India, New Delhi. Part-I, Vol.-VI, p. 66

Vijaya, K. S. J. and Mishra, D. N., 2006 . Rapidly disintegration of oral tablets of Meloxicam. Indian Drugs

43 (2): 117-121


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22

Table: 1. Composition of formulation Qurs Ziabitus Sada

Note: 1*. Standardization of the raw materials made in the laboratory and mentioned under the heading materialand methods2. UPI: The Unani Pharmacopoeia of India3. API: Ayurvedic Pharmacopoeia of India4. IP: Indian Pharmacopoeia

S.No. Unani Name Botanical / English Name Part Used Reference Quantity

i Tukhm-e-khurfa Portulaca oleracea Linn Seed UPI, Part1,Vol. 4, 80

1000 g

ii Gul-e-surkh Rosa damascene Mill. Flower UPI, Part 1,Vol. 3, p.31

100 g

iii Kishneez Coriandrum sativum Linn. Fruit API, Part 1,Vol.1,p .30

100g

iv Samagh-e-Arabi Acacia nilotica (L) Willd. Gum UPI, Part 1,Vol. 6, p. 66

40 g

v Sandal safaid Santalum album Linn. Powder ofwood

API Part 1,Vol.3,p.207)

40 g

vi Sandal surkh Pterocarpus santalinus Linn. Powder ofwood

API, Part1,Vol.1, p 155

40g

vii Kafoor Cinnamomum camphora Nees. Johar IP.1978, p.99 10g

viii Tukhm-e-kahu Lactuca sativa Linn. Seed * 400 g

ix Rubb-us-soos Glycyrrhiza glabra Linn. Dried extract * 200g

x Tabasheer Bambusa arundinacea Willd. Manna * 200g

xi Aquaqia Acacia nilotica (L) Willd. Extract ofPods

* 40 g

xii Gil-e-armani Armenian Bole. Bole * 100g

xiii Gulnar Punica granatum Linn. Flower * 40 g


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Table: 2. Physicochemical analysis of Qurs Zeabetus Sada

*Each observation is the average of nine replicates

Parameter Observations*

Total ashAcid insoluble ash

Water soluble ash

Not more than 18%Not more than 14%

Not more than 1%

Alcohol Soluble Matter

Aqueous Soluble Matter

Not less than 11%

Not less than 18%

Water Content Not more than 5%

pH of aqueous Solution

(i) pH of the 1% solution

(ii) pH of the 10% solution

6.10-6.71

5.62-5.89

Weight of Tablets in mg 500+ 0.05 mg

Disintegration time in Water

Disintegration time in simulated gastric fluid

14-15 sec

10-11 sec

Diameter of Tablets

Thickness of Tablets

10 mm

4.80+0.02 mm


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Figure 1. HPLC of the Mixture of different pesticides

Table. 3. HPLC Obtained Peaks of Pesticides

Peak Retain. Time Height Area Concentration1 1.092 23 82.9 1.19672 1.768 261 6405.7 13.57963 2.268 54 378.2 2.8096

4 2.912 210 2042.2 10.92615 3.203 1009 11936.6 52.49746 4.030 21 294.6 1.09267 5.665 199 2523.1 10.35388 6.058 145 1701.5 7.5442Note: Peak 2, 4, 5, 7 and 8 are the major pesticides

-1.000

1.400

3.800

6.200

8.600

11.000

0.00 2.60 5.20 7.80 10.40 13.00 15.60 18.20 20.80 23.40 26.00

[mAU]

[min]

1 . 0

9

1 . 7

7

2 . 2

7

2 . 9

1

3 . 2

0

4 . 0

3

5 . 6

6

6 .

0 6


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Fig.2. Thin Layer Chromatography Profile of Qurs-e-Zeabetus Sada

Q. Z. Sada


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ORBITAL METASTASIS OF A NEWLY DIAGNOSED BREASTCANCER -A CASE REPORT

Fatima Zahra .Hijri , Sami .Brahmi, Nezar .Bouyahia, Samia .Arifi, Nawfal .Mellas, Omar .El

Mesbahi .

Department of Medical Oncology, Hassan II University Hospital, Route Sidi Hrazem, Fez,

30000, Morocco.

Corresponding author :Hijri Fatima ZahraE-mail: [email protected] number : 337671761083.Address: Department of Medical Oncology, Hassan II University Hospital, Route Sidi Hrazem,

Fez, 30000, Morocco

ABSTRCT:

Background: Orbital metastases are rare and occur in 2% to 3% of patients with cancer. Themost cases in the literature were reported in women with previous history of breast cancer andusually extra orbital metastases were present before. We report a case of orbital metastasis in anewly diagnosed patient with breast cancer. Case report: A 75 year old woman, with a historyof hormone receptor-positive, HER2-negative ductal adenocarcinoma of the right breast. Initialdiagnosis was made after a pathologic right humerus fracture. Metastatic breast carcinoma wasconfirmed histopathologically by bone biopsy of the humerus . The patient presented alsoexophthalmus in her right eye. A CT scan and MRI of the orbit and head showed an intraorbitalmass. A Thoracic abdominal-pelvic CT relieved multiple bone metastases. The patient receivedhormonal therapy, consisting of tamoxifen as well as zolendronic acid. Due to progression of

bone disease hormonal therapy was switched to Paclitaxel weekly. Further metastatic bonelesions developed in the spine and the patient received analgesic radiotherapy (8 Gy) to thelumbar spine. Conclusion: Diagnosis and treatment approaches of orbital metastases arecomplex and require an experienced multidisciplinary team.

Key words : Breast cancer; orbital metastases .


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INTRODUCTION:

The most common sites of breast cancer metastasis are the lungs, bones, and liver , but the

orbit is an infrequent location and a comparatively rare site of distribution among the ocular area

structures. The frequency of intra-orbital metastasis in systemic cancer is a controversial topic:

some authors relate an incidence of up to 30% [ 1]; others believe it occurs in approximately 2%

to 3% of cases [ 2,3]. The most cases in the literature were reported in women with previous

history of breast cancer and usually extra orbital metastases were present before [4].

Once diagnosis is confirmed treatment for patients with orbital metastases is

multidisciplinary and aims to preserve patients quality of life and visual function [4].

We report a case of orbital metastases in a patient with newly diagnosed breast cancer. The

diagnosis, treatment and prognosis concepts of orbital metastases will be reported.

CASE REPORT : A 75 year old woman suffered a pathologic right humerus fracture. Clinical examination

revealed skin retraction and a lesion of 2 cm in the right breast. At the Breast Unit our patient

underwent standard pre-operative investigations -mammography, ultrasound examination and

biopsy of the lesion - showing a ductal adenocarcinoma of the breast . Immunohistochemical

evaluation was positive for estrogen receptor (ER: 90%) and progesterone receptor (PgR: 90%).

Human Epidermal Growth Factor Receptor 2 (HER2) was negative.

Breast carcinoma metastatic to the right humerus bone was confirmed histopathologically.

The patient presented, also an exophthalmos [figure1], without decreased visual acuity in her

right eye. There were no clinical signs of neuromuscular dysfunction of the eye or any other

neurological disorder. Ophthalmologic examination was normal.


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Figure 1:Axial view shows right exophthalmos .A computed tomography (CT ) and Magnetic resonance imaging (MRI )of the orbit and head

were performed, both showing a solid, intra-orbital, extra-bulbar, 3 2 cm mass, occupying the

inferior quadrant of the right orbit [figure 2,3 and 4]. A Thoracic abdominal-pelvic CT relievedmultiple bone metastases.

Figure 2 :

The axial CT scan shows intra-orbital mass,occupying the inferior quadrant of the right orbit

Figure 3:

Orbital MRI of the patient before treatment


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reveals intraorbital mass of the right orbit .

Figure 4:

The coronal orbital MRI reveals intraorbital mass

of the right orbit .

The patient received hormonal therapy, consisting of daily tamoxifen 20 mg per day; in

addition bisphosphonate treatment with 4 mg zolendronate per month was initiated. Due to

progression, after 11 months, of bone disease hormonal therapy was switched to Paclitaxelweekly in a dose of 80 mg/m.

Further metastatic bone lesions developed in the spine and the patient received analgesic

radiotherapy (8 Gy) to the lumbar spine.

DISCUSSION :

Intraorbital metastasis of breast cancer is rare, it represent 3 to 10% of all ocular metastases

[1]. Metastases to the eye and orbit have been described for a variety of solid tumors, but breast

carcinoma accounts for the majority of ocular and orbital metastases [4,5,6], followed by lung,

prostate, gastrointestinal, kidney and skin (melanoma) cancers [7,3].

Breast cancer tends to metastasize to the orbit and intraoculair. The orbital metastases from

breast cancer involves predominantly the lateral and superior quadrants [7] and tend to infiltrate

the extraocular muscle and surrounding orbital fat, causing motility deficits.The most intraocular


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metastases from breast cancer is in the uvea and the choroid . The metastases to the ciliary body,

optic disk, iris, retina, and vitreous are very rare [7, 11].

Typical manifestations of orbital metastases include a palpable mass causing displacement

or proptosis of the globe , exophthalmos ( as in our case), pain, inflammation, bone involvement,

chemosis and eyelid swelling [8] ,but the prevalent symptom is diplopia because of the

preference of metastases breast cancer to extra-ocular muscle causing a mobility deficits.

The diagnosis can be suspected by imaging studies [9], such CT- scan and MRI of the

orbits, but the correct diagnosis requires an orbital biopsy. The fine needle aspiration biopsy of

the orbital metastasis allows the diagnostic in almost 90% of the cases. However, in patients with

known metastatic cancer, as in our case, the orbital biopsy may be avoided if there is a strong

clinical and imaging suspicion for metastatic disease. The orbital biopsy should only be done in

patients with no known previous history of cancer and in patients in whom the orbit is the onlysite of suspected metastasis [7].

In our case, orbital metastasis occur in a newly diagnosis breast cancer unlike most of the

cases reported in the literature. Indeed, the most cases reported in women with previous history

of breast cancer and usually extra orbital metastases were present before and this situation was

explained by the increase of survival of the patients.

Management of orbital metastases remains a difficult task. There is naturally no consensus

or any guidelines for the optimal management of patients with orbital metastasis. Treatment for

orbital metastases is inevitably palliative and aims at improving patient's quality of life and

restore or preserve visual function. Once diagnosis is confirmed the treatment for patients with

orbital metastases is multidisciplinary and may include radiotherapy, systemic chemotherapy,

hormonal therapy, or surgery in selected patients.

The main treatment option is radiotherapy, with high rates (60%80%) of clinicalimprovement of local symptoms and vision [4, 8]; it improves symptoms in 80% of cases and

restores vision in some cases [10]. However, the radiotherapy side effects such as radiation

retinopathy and cataract formation must be balanced against the overall prognosis and survival

of the individual patient [11,12].The radiotherapy has not be done in our case ,because her visual

function was normal and she had multiple metastases.


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However, the most patients have concomitant progressive systemic disease at diagnosis;

that why the systemic treatment is indicated especially in patients with good performance status.

So, the palliative result obtained by radiotherapy can be expected with systemic treatment

[13].The systemic chemotherapy and hormone therapy in cases of hormone-sensitive tumors is

another mainstay in the palliative setting of orbital metastases. Two cases have been reported in

the literature of response for choroidal metastasis of breast cancer; the first with transtuzumab

and vinorelbine [14] and the second with tamoxifen [15].

The surgical intervention is generally not recommended as this is not curative and may be

associated with significant ocular morbidity [10]. However, it is performed for diagnostic

purpose (biopsy) in patients with no previous history of cancer [16, 17] or as palliation in cases

of intractable ocular pain or unmanageable local hygiene due to rapid tumor growth [8].

Orbital therapy was usually effective for local palliation; however, long term survival was rare.The short-term prognosis for vision is usually good after an individualized therapeutic

approach , but the systemic prognosis is rather poor, with a median survival ranging from 22 to

31 months [range, 1-116 months] [18,7,3].

CONCLUSION:

In summary, although intraorbital metastasis of breast cancer is very rare. Patients with a

history of breast cancer presenting with ocular symptoms such as exophthalmos, ptosis,

proptosis, diplopia and pain, should alert the Oncologists and ophthalmologists to the possibility

of orbital metastases. A combination of local and systemic treatments may help preserve vision

and patients quality of life.

CONFLICT OF INTEREST :

The authors declare that they have no conflict of interest

CONSENT :

Written informed consents were obtained from the patient for publication of this case

report.

REFERENCES :


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1. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye, I: incidence in 213 patients with generalized malignancy. Am J Ophthalmol. 1967;63 :723726. [ PubMed ]

2. Milman T, Pliner L, Langer P. Breast Carcinoma Metastatic to the Orbit: An Unusually

Late Presentation. Ophthal Plast Reconst Surg. 2008;24(6):480482. doi:10.1097/IOP.0b013e31818b6adc. [ Cross Ref ]

3. Shields JA, Shields CL, Brotman HK, Carvalho C, Perez N, Eagle RC Jr. Cancermetastatic to the orbit: the 2000 Robert M. Curts Lecture. Ophthal Plast Reconst Surg.2000;17:346354. doi: 10.1097/00002341-200109000-00009. [ Cross Ref ]

4. Font RL, Ferry AP. Carcinoma metastatic to the eye and orbit. III. A Clinicopathologicstudy of 28 Cases Metastatic to the Orbit. Cancer. 1976;38:13261335. doi:

10.1002/1097-0142(197609)38:33.0.CO;2-#. [PubMed][Cross Ref]

5. Ng E, Ilsen PF. Orbital metastases. Optometry. 2010;81:647657. [PubMed]

6. de Potter P. Ocular manifestations of cancer. Curr Opin Ophthalmol. 1998;9:100104.doi: 10.1097/00055735-199812000-00018. [PubMed] [Cross Ref]

7. Ahmad SM, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr OpinOphthalmol. 2007;18:40513. [PubMed]

8. Mehdi Ahmad S, Esmaeli B. Metastatic tumors of the orbit and ocular adnexa. Curr OpinOphthalmol. 2007;18:405413. doi: 10.1097/ICU.0b013e3282c5077c. [PubMed][Cross Ref]

9. Asproudis I, Gorezis S, Charalabopoulos K, et al. Breast carcinoma metastasis to theorbit and paranasal sinuses: a case report. Exp Oncol. 2004;26:2468. [PubMed]

10. Char DH, Miller T, Kroll S. Orbital metastases: diagnosis and course. Br J Ophthalmol.1997;81:386390. doi: 10.1136/bjo.81.5.386. [PMC free article] [PubMed] [Cross Ref]

11. Amichetti M, Caffo O, Minatel E, Roncadin M, Valli MC, Lozza L, Panizzoni G. Ocularmetastases from breast carcinoma: A multicentric retrospective study. Oncol Rep. pp.761766.


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12. Glassburn JR, Klionsky M, Brady LW. Radiation therapy for metastatic disease of theorbit. Am J Clin Oncol. 1984;7:145148. doi: 10.1097/00000421-198404000-00008.[PubMed] [Cross Ref]

13. Kouvaris JR, Gkongkou PV, Papadimitriou CA, et al. Bilateral metastases to extraocularmuscles from lobular breast carcinoma. Onkologie. 2008;31:3879. [PubMed]

14. Wong ZW, Phillips SJ, Ellis MJ. Dramatic response of choroidal metastases from breastcancer to a combination of transtuzumab and vinorelbine. Breast J. 2004;10:546.[PubMed]

15. Debraj Shome, FRCS, Chaitra Jayadev, DO, Darshana Gadgil, DNB, Sundaram Natarajan, DO, and Vandana Jain, MS. Systemic chemotherapy and tamoxifen induced

regression of choroidal metastasis from a breast carcinoma in a male

16. Bellmann C, Fuss M, Holz FG, et al. Stereotactic radiation therapy for malignantchoroidal tumors. Ophthalmology. 2000;107:35865. [PubMed]

17. Talwar V, Vaid AK, Doval DC, et al. Isolated intraorbital metastasis in breast carcinoma. J Assoc Physicians India. 2007;55:4512. [PubMed]

18. Garrity JA, Henderson JW, Cameron JD. Henderson's orbital tumors. 4. New York:Raven Press; 2007. Metastatic carcinomas; pp. 313326. [PubMed].

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