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A CLINICAL STUDY ON PALITYA W.S.R. TO PREMATURE GRAYING OF HAIR AND ITS MANAGEMENT WITH NIMBABEEJA TAILA NASYA AND BHRUNGARAJADI RASAYANA

1. A CLINICAL STUDY ON PALITYA W.S.R. TO PREMATURE GRAYING OF HAIR AND ITS MANAGEMENT WITH NIMBABEEJA TAILA NASYA AND BHRUNGARAJADI RASAYANA

2. INTRODUCTION Palitya is derived from the word palita , which means kasha paka . Heefueleb kesÀMem³e MegkeÌuelee e ( Yo.ratra . 61/1) Graying of hair or whitening of hair is termed as palita . Acharya Charaka described in trimarmiya adhyaya , Acharya Vagbhata & Sarangadhara described in sirokapalagata roga and Acharya sushruta , Madhavakara , Yogaratnakara , Bhavaprakasha described under Kshudraroga adhikara .

3. Definition lespees DeefveueeOew : men kesÀMeYetefceb oOJeeDeeMeg kegÀ³ee&led Keueefle vejm³e e efkeÀeeq ®® ebleg oiOJee Heeefueleeefve kegÀ³e&eoefjÒeYelJevJeb ®e efMejes©neCeeced ee ( ch . chi. 26/132) Means the body heat joined with vata etc. burns the hair ground shortly and thus causes baldness if the burning is slightly producers whiteness for greying of hair

4. Nidana   MeeskeÀÞece¬eÀesOekeÀ =le: Meefjjes < cee efMejesiele : e kesÀMeeved meoes <e: He®eefle Heeefueleb mecYeJel³ele: (Ast.hru. Uttarasthana 23/29) It means heat of the body reaching the head due to grief, Physical exertion & anger, vitiating the doshas make the hairs grey , Palitya is thus produced. Lakshana leÜeleelmHegÀefìleb M³eeJeb Kejb ©# eb peueÒeYeced e efHelleelmeoenb HeerleeYeb , keÀHeÀeled eqmveiOeb efJeJeÉef×celed ee mLetueb megMegkeÌueb , meJezmleg efJeÐeeܳeeefceÞeue#eCeced e MesMes©peesÓJeb ®e Dev³eefÜJeCe& mHeMe&veemenced ee Ast.hrs. Uttasthana 23/30-31.

5. The sign and symptoms are Sphutita Shyaba Khara Ruksha Jalaprabha Daha Pittabha Snigdha Vivrudhasthula Sukla

6. Ayurveda accounts for two types of palitya i.e. Akalaja (premature grey hair) Kalaja (senile grey hair) Palitya i.e premature graying of hair is a burning cosmetic issue in present era. When graying begins before the usual age of onset, it is termed as premature graying of hair. The onset and progression of graying correlate very closely with chronological aging and occur in varying degrees in all indivisuals eventually, regardless of gender or race.

7. INCIDENCE & PREVALANCE Palitya is common in young age between 20-30 years age group. Even in children also the incidences are increasing day by day. Hair is said to have grayed prematurely if it occurs before the age of 20 years in whites, before 25 years in Asians and before 30 years in Africans. The prevalence of premature greying of hair is found to be 1.2% The prevalence was higher among female as compared to male.

8. NEED OF THE STUDY Premature greying aids to embracement & social stigma. Current treatment available are not much satisfactory to cure, check or prevent this problem. Treatment of Palitya as mentioned in Ayurveda includes sodhana & samanachikitsa . Hence, aiming to derive a new treatment modality for Palitya (Premature greying of hair) this research has been proposed. So in order to obtain an safe and cost effective remedy this problem has been selected

9. PREVIOUS RESEARCH WORK DONE:- Evaluation of Bhrungarajatailanasya with and without Bhrungarajadirasayana in the management of Akala Palitya a comparative study by Dr. Lokanath J Avadhani , Rajiv Gandhi University of Health Science, Bengaluru 2011-12 Clinical management of Akala Palityam (Gray hair) with Triphaladilepam with and without Nimbabeejataila Nasyam by Dr. Lavudya Kamala Kumari , N.T.R. University of Health Science, B.R.K.R.GOVT. Ayurvedic College & Hospital, Erragadda , Hyderabad 2005 Study of Khalitya&Palitya with special emphasis on etiopathogenesis by Dr. Vishakha D Pathak , Tilak Maharastra University, Pune .

10. 4 . A clinical study to assess the efficacy of pratimarshanasya in prevention of Akala Palitya W.S.R. to premature greying of hair by Dr. Sagar Sharma, Rajiv Gandhi University of Health Sciences, Karnataka. Sri Jagadguru Gavisiddheswar Ayurvedic Medical College & Hospital, P.G. studies & Research centre, Gavinath Campus, Koppal , Karnataka (2013-14)

11. AIM AND OBJECTIVE OF THE STUDY AIM - A clinical study on palitya w.s.r to Premature greying of hair and its management with nimbabeeja taila nasya and bhrungarajadi rasayana . OBJECTIVE - Review of literature of the disease both for ancient and modern point of view and research of the drug. To evaluate the efficacy of nimbabeeja taila & bhrungarajadi rasayana in the management of Palitya . To evaluate the efficacy of Nimbabeeja taila nasya in the management of palitya

12. HYPOTHESIS It is presumed that Nimababeeja taila & bhrungarajadi rasayana described by Bhaisajyaratnavali can effectively control the clinical symptoms of palitya . (Ref- Nimababeej ataila – Bhaisajya Ratnavali , Kshudraroga 60/80 Bhrungarajadirasayana-BhaisajyaRatnavali , Rasanayanadhikara73/28-29) PURPOSE OF MEDICINE USE – The need has already been felt to develop certain ayurvedic treatment for the better management of palitya which could be safe, effective, cost-effective readily available and without any side effect. So, keeping all the fact in mind I have taken this formulation Nimbabeeja taila and Bhrungarajadi rasayana .

13. MATERIAL AND METHODS- DRUG REVIEW The raw drugs will be purchased from local market . The trial drug Nimbabeeja taila and Bhrungarajadi rasayana will prepared in G.A.M,PURI pharmacy attached to Dept. of R.S.B.K .

14. Nimbabeejataila efvecyem³e efyepeeefveefnYeeefJeleeefve Ye=²mlelees ³esve leLeeçmevem³e e lewuevleg les< eebefJeeflenefvle vem³eeod ogiOeecyegYeesÊegÀ : Heefuelebmecgeuecedee (Bha.Ra-60/80-Cakradatta) Ingredient Nimbabeeja Asana Bhrungaraja DOSAGE- 2bindu in each nostrils Bhavana Dravya 1-1 Day

15. Bhrungarajadi rasayana Í} MCeerke = Àleb Ye=²jpem³e ® egCe&b efleueeOe&kebÀ ® eeeceuekeÀe ×& keÀáe meMeke&Àjb Ye#e³elees ieg [ wJee & velem³e jesieevepejevece =l³eg: ~~28~~ DevOe : HeM³esodiecevejefnlees celleceele²ieeceer cetkeÀesJeeiceerÞeæJeCejefnleesotjMeyoevegmeejer veer©*dcel³eex YeJeefleHeefueleesveeruepeercetuekesÀMees peerCe&e ovl³ee: HegvejefHeveJee : # eerjieewjeYeJeefvle ~~29~~ ( Bha.Ra 73/28-29 Cakradatha )

16. Ingredient Bhrungaraj Chruna - 1PART Krushna Tila Chruna -1/2 PART Amalaki Churna -1/2 PART Anupana : Sarkara or Guda DOSAGE- 5gm b.i.d Duration: 3 months Follow up in every 1 month

17. DIAGNOSTIC CRITERIA- Inclusion criteria Patients having features of Akala Palitya . Patients to age group of 20-30years Patients yogya for nasya and rasayana . Exclusion criteria Patients with age below 20 years and above 30 years Patients ayogya for nasya and rasayana . Infection diseases of scalp like Alopecia areata . Akala Palitya associated with the diseases of pigmentation like vitiligo , leprosy and Albinism. Any other systemic diseases. Subjects with hormonal diseases and hereditary disorders.

18. PLAN OF PROTOCOL Plan of study Comparative clinical trial study will be undertaken to co-relate the clinical effect of the trial drug. In the present study 60 clinically diagnosed patient of either sex of palitya are selected from OPD/IPD of G.A.M. & Hospital Puri. A regular record of assessment of all the patient will be maintained according to the format prepared for the purpose. Group- A -30 Patients will be treated with both nimbabeeja taila nasya and Bhrungarajadi rasayana internally. Goup-B-30 patients will be treated with nimbabeeja taila nasya Types of study –clinical study

19. STUDY DESIGN- SINGLE GROUP DESIGN- BT = Before treatment AT= After treatment

20. DOUBLE GROUP DESIGN- ASSESSMENT CRITERIA Assessment will be made by assessment scale availing subjective parameters & objective parameters.

21. Objective Parameters Sphutita (absent or present) Khara (absent or present) Ruksha (absent or present) Sukla (absent or present)

22. Hair Count A new scoring system (Graying severity score, GSS) was devised to evaluate the external of graying taking into account five representative sites from the scalp by two independent investigation and analysed for agreement GSS ranged from 0 to 15 that was further graded as mild, moderate and severe. 5zones- Frontal, vertex, right, left, occipital A 1cm 2 area was washed with a skin marker and the hair within this square was cropped to approximately 1mm above scalp surface. These five squares were then photographical and projected on the computer screen to count the numbers of white and black hair.

23. Based on the hair count, a score was assigned to each zone a/c to the percentage of grey hair in each square. This was calculated and scored as Score-1-- 10% grey hair/cm 2 Score-2 -- 10%-30% gray hair/cm 2 Score-3-- more than 30% gray hair/cm 2 The GSS was finally calculated for each patient by taking a sum of the scores a the five represent sites. Thus the maximum attainable score for a patient was 15 (3X5) The objective scores were further graded as; Mild (a score of 0-5) Moderate (Score of 6-10) Severe (Score of 11-15)

24. INVESTIGATION :- D.C T.L.C E.S.R Haemoglobin F.B.S P.P.B.S T 3 ,T 4 ,TSH Vitamine-B 12 , D

25. PRESENTATION OF RESEARCH WORK The whole research work will be presented in the form of binding thesis with suitable language by the following parts and chapters. Part-1 Introduction Review of Literature Ayurvedic Review of disease Modern Review of disease Part-2 Clinical Study Materials and methods Drug Review Observation and Statistical evaluation

26. Part-3 Discussion Summery and Conclusion Part-4 Reference Bibliography Appendix REFERENCE Acharya Charaka – Chikitsa sthana – Trimarmiyaadhyaya (26 chapter) Acharya Shushruta – Nidanasthana – Kshudraroga adhyaya (13 chapter) Acharya Vagvatta – Uttarasthana – siroroga vigyana (23 chapter) Acharya Vagvatta – Uttarasthana – siroroga pratisetha (24 chapter) Acharya Madhavakara – Nidana sthana – Kshudraroga Adhyaya (55 chapter) Acharya Sarangadhara – Purva khanda – Sirakalagataroga (7 th chapter) Bhaisajya Ratnavali – Kshudraroga adhihara (60 no. chapter) Bhavaprahasha – Kshudraroga adhikara (61 no. chapter) Yogaratnahara – Kshudraroga adhihara (40 no. chapter)

27. SUMMARY AND CONCLUSION It has been hope that present study will bring out a new standard, effective and successful treatment for Palitya .

28. PALITYA pejmee kesÀMeeoew MeewkeÀue³eced e DecejkeÀes <e Palitya means change of colour in hair or graying of hairs At the age old, hair turned to be white in colour . Palitya is a disease of rasadhatu drusti janya roga which is described by acharya caraka and sushruta INTRODUCTION

29. KESHA SWARUPA keÀsMee : Meer<ex cegKes MceÞeg ves$es He#ce Ye¦Jeew celeew e leveew jesceeefCe pee³evless keÀjHeeoleues efJevee e ( meejbieOej ) Human body contains hair follicles in all area except palm & sole. It is termed as different way in different area. Sirsa – Kesa Mukha – Smasru Netra – Pakhma , Bhru Rest of the body – Roma

30. KESHA UTPATI According to Maharsi Caraka :- Kesha and Roma is the mala of Asthidhatu .  According to Maharsi Sarangadhar :- Kesha is the upadhatu of majjadhatu . Roma is the mala of Asthidhatu . During Ahara poshana karna , Ahara rasa is processed by jatharagni and dhatwagni to convert in to 2 part : (1) Prasada bhaga (2) Kitta bhaga During asthidhatwagni vyapara , the poshakamshas which nurish asthidhatu are converted into 2 parts, its kittabhaga is processed by the action of malagni to produce kasha.  

31. NIDANA ¬ eÀesOeMeeskeÀÞeceke = Àle : Meefjjes < cee efMejeWiele : e efHeÊeb ®e kesÀMeeved He®eefle Heefueleb lesve pee³eles ee (su.ni 13/36) Ma. Ni. 55/32) It means heat of the body reaching the head due to anger, grief and physical exertion, vitiating the local pitta makes the hairs grey, palitya is thus produced . ¬ eÀesOeMeeskeÀ Þeceke = Àle:Mejerjes < cee efMejesiele : e EfHeÊeáe kesÀMeeveHe®eefle Heeefueleb lesve pee³eles ee (61/1) Mejerjes < cee - osneeqive : efHeÊeáe Ye^epekeÀeK³eb, le®® eefMejesieleb ¬ eÀesOelkegÀefHeleb efHeÊeb He®eeefle e MeeskesÀve ÞecesCe ®e kegÀefHelees Jee³eg:- Mejerjes < ceeCeb efMejes ve³eefle e

32. SkeÀ : ÒekegÀefHelees oes <e FlejeJeeefHe keÀesHe³esod e Fefle Je®eveeÜeleefHeÊeeY³eeb Mues < ceeb ®e keÀesefHele :, me SJe kesÀMeeveeb MeewkeÀu³eb keÀjesefle e SJeb $e³eesçefHe oes < ee : Heeefuelem³e nsleJe :– kesÀMem³e MegkeÌuelee ee (1) (61/1) Increase of vayu especially due to excess of soka and shrama , at the same time the pitta is being increased due to krodha in its ushma guna . This provoked pitta circulates through out the body through rasayani ( srota ) by the virtue of vikshepana guna of provoked vata to incease the sharira ushma . This saririka ushma reaches to shira and vitiates sthanika vata and shlesma karya . This tridoshas vitiated and graying of hair causes manifestation of palitya . On the basis of samprapti , pitta prakopaka nidana (Ref. Su. Su. 21/21), Rasadrushti (Ref. ca. su . 28/10) & ( su . Su. 24/10) and asthidrusti (ca. ci . 15/18-19) nidana can be considered as nidana of palitya .

33. Pitta Prakopaka Nidana Aharaja nidana ¬ eÀesOeMeeskeÀ Ye³ee³eemeesHeJeemeefJeoiOecewLegveesHeieceve keÀìdJecueueJeCe Leer#Ce G< Ce ueIegefJeoeefn efleuelewue efHeC³eekeÀkegÀuelLeme< e&Heele ..... Excess use of pungent ( katu ) Sour ( Amla ) Salt ( Lavana ) Excess use of Tikshna Hot ( ushma ) Light ( laghu ), vidahiarna

34. Tila Taila , pinyaka , kullatha , sarsapa , Atasi , haritasaka Godha , matsya , Aja , Abi Mamsa Dadhi , Takra , Kurchika , Mastu , Soubiraka , Suavikara Amla phala , Katbara Excess intake of Lavana & Kshara (ca. viman 1/ (17-18) Manasika nidana Krodha Shoka Viharaja nidana Ayasa Upabasa Maithuna Shrama

35. SAMPRATI GHATAKA Doshas :- Pitta-Bhrajakapitta , vata , kapha . Dushya :- Rasa, asthi dhatu . Agni :- Jatharagni , Dhatwagni . Srota :- Rasavaha , Asthivaka . Srotadrusti :- Sanga , Vimargagamana . Udhava Sthana :- Amasaya . Vyadhi adhisthana :- Keshabhumi . Roga marga :- Bahya roga marga . Sadhya asadyata :- Ekdoshaja sadhya , samipataja asadhyaya .

36. TYPES OF PALITYA According to According to According to Vagvatta :- sarangadhara :- Yogaratnakar :- Vataja (i) Kalajanita (i) vataja Pittaja (ii) Akalajanita (ii) pittaja Kaphaja (iii) kaphaja Sananipatika (iv) sannipatika Sirarujadbhaba

37. LAKSHANA leÜeleelmHegÀefìleb M³eeJeb Kejb ©# eb upeueHe^Yeced e efHeÊeelmeoenb HeerleeYeb , keÀHeÀeled eqmveiOeb efJeotef×celed ee mLegueb megMegkeÌueb , meJezmleg efJeÐee³eeefceÞeue#eCeced e MesMes©pees×gJeb ®e Dev³eefÂJeCe& mHeÀMe&vehemence ee Ast.hrs. Uttasthana 23/30-31 . JeeeflekeÀ efJe < eceb ©# eb Heerleb efHeÊeeefmeleb keÀHeÀeled e MeJe &ª HeeqvJeleb efJeÐeelmeefVeHeelemecegeqlLeleced (33) ( Yogaratnakar 40/33)

38. SADHYASADHYATA Vataja , Pittaja , Kaphaja - Sadhya Sannipatika : Asadhya Sirarujadbhaba : Asadhya CHIKITSA SUTRA Keueleew Heeefueles Jeu³eeb nefjuueeseqcve ®e MesefOeleced e vem³e JekeÀ$eefMejesçY³e²Òeosnw: mecegHee®ejsle ee (Ast.hru. Uttarasthana 24/33) Keueleew Heeefueles Jeu³eeb nefjuueeseqcve ®e MeerefOeleced e vem³eswmleswuew: MeerjesJe¬eÀÒeuesHesw½eeH³egHee®ejsle e (ca.ci.26/262-263) Treatment :- Sodhana Nasya efmej-lewue-ceo&ve Oleation on head with medicated oil cegKe-ÒeuesHe use of paste ( lepa ) on face

39. Premature greying of Hair Hair is said to greying prematurly only if greying occurs before the age of 20 years in whites , before 25 years in Asians and before 30 years in Africans. According to W.H.O incidence of premature greying of hair is common in age group of 20-30 years SKIN

40. HAIR Hair is a filamentous biomaterial that grows from follicles found in the dermis. Hair follicle :- the part beneath the skin. Hair bulb :- the part when hair is pulled from the skin. Hair follicle is located in the dermis and maintains stem cells responsible for regrowth of hair and skin

41. Hair follicle & Hair bulb

42. Hair shaft :- the hard filamentous part that extends above skin surface. Hair shaft

43. Hair growth begins inside hair follicle. Other structures :- sabeceous gland & arrector pili muscles (Responsible for hair errection , goose bumps)

44. Types of hair

45. HAIR CYCLE From the time it is formed each hair follicle undergoes a repetitive sequence of growth and rest known as the hair cycle .

46. HAIR PIGMENTATION Hair pigmentation is a process, in which there is a precise interaction in the hair follicle unit between follicular melanocytes , keratinocytes and dermal papilla fibroblasts. MELANIN :- The colour of human hair is due to pigment melanin produced by melanocytes . Melanin is produced through a multistage chemical process known as melanogenesis where the oxidation of amino acid tyrosine is followed by polymerization.

47. Function Protect underlying structure from the harmful effects of sunlight. Influence the colour of epidermis. The synthesis of melanin reaction is catalyzed by the tyrosinase , Tyrosine is found in only one specialized type of cell, the melanocyte , and in this cell melanin is found membrane-bound bodies called melanosomes .

48.   HAIR COLOUR BIOCHEMISTRY

49. NORMAL HAIR FOLLICULAR MELANIN UNIT AND MELANOGENESIS Each melanocyte is associated with five keratinocytes in the hair bulb forming a hair follicle-melanin unit. Melanogenesis in the hair is closely associated with stages of the hair cycle. Follicular menocytes are derived from immature melanoblasts that migrate from the neural crest into the skin during embryogenesis. As the hair follicle develops, the progeny of melanoblasts which proliferate in the epidermis, known as transient – amplifying melanocytes , leave that compartment and move into the developing hair follicle.

50. MELANOGENESIS :- The colour of human hair depend melanogenesis , through a process of synthesis of melanin and its subsequent distribution from the melanocyte to keratinocyte . There, menalocytes may become or remain DOPA- oxidase -positive cells (i.e. express active tyrosinase ) or remain DOPA- oxidase -negative cells (i.e. either fail to express tyrosinase or express on inactive tyrosinase ) depending on the intrafollicular compartment in which they reside. Melanocytes in the hair bulb retract their melanocyte and shut down melanogenesis towards the end of anagen . Simultaneously there is a decline in the activity on three main melanogenic enzymes :- Tyrosinase , gp 75 and dopa chrome tautomerase

51. This occurs a few days before the cessation of keratinocyte proliferation resulting in the pigment free proximal ends of shed telogen hair. During catagen , hair apoptosis occurs and quiescent hair follicle much smaller size is left telogen . Melanogenic activity restarts during early anagen with the reconstruction of the follicular melanin unit. Tyrosinase activity becomes apparent during anagen III, pigment transfer from hairbulb melanocytes to cortical keratinocytes is initiated during anagen IV and active melanogenesis continues throughout anagen V and VI, ceasing with the onset of catagen . Melanocytes are presents in two compartment of the hair follicules in the anagen hair bulb where they transfer pigment to cells that will form the hair cortex, and in the outer root sheath Grey hair follicles lack melanocytes in the hair bulb while retaining those in the outer root sheath. Hair bulb melanocytes are probably recruited from the outer root sheath melanocytes population at the onset of anagen .

52. Migration and activation of these melanocytes is possibly under unknown local signaling mechanisms like a – melanocyte stimulating hormone ( - MSH) modulation of failure of which may result in graying. The hair bulb matrix is the principle site for the fully differentiated follicular menalocyte subpopulation, these melanocytes are distributed, in particular, within the matrix above and around the upperdermalpapilla . They transfer their melanin granules to keratinocytes of the hair cortex and less so to the medulla and very rarely to the hair cuticle. Under stimulation from radiation or cytokines, the outer root sheath melanocytes may be stimulated to migrate and differentiate to naturally repigment graying hair follicles.

53. Causes of premature graying of hair Nutritional deficiencies (B 12 , D, C) Mental worries. Unhygienic condition of scalp. Heredity. Genetics. Stress (emotional & physical) Hormonal imbalance. Immune system irregularities. Thyroid disorders. Cosmetics. Radiation or chemo therapy. Drug. Pollution. Disease :-pernicious anemia Autoimmune disorder. Iron, copper, iodine – deficiency. Smoking.

54. Histopathology of greying of Hair A line across the widest part of the bulb of the hair follicle divides it into two regions. Two region A lower region of undifferentiated cells. An upper region in which the cells become differentiated to form the innersheath and the ha Below the critical level known as the line of Auber lie the matrix or the germination center of the follicle, where every cell is mitotically active and the dermal papilla. The pigmentary unit is is a pear-shaped black structure at the tip of the dermal papilla above the Auber’s line in pigmented hair where individual melanocytes cannot be distinguished. Only unpigmented and undifferentiated putative melanocyte stem cells, but not pigmented differentiated melanocytes , are normally found in the hair bulb below the line of Auber .

55. In gray hair, the pigmentary unit becomes fuzzy melanocytes are few and rounded and lightly pigmented oligodendritric melanocytes become detectable in the proximal hair bulb below Auber’s line. The resultant pigment loss in graying hair follicle due to a marked reduction in melanogenically active melanocytes in the hair bulb of grey anagen hair follicles is central to the pathogenesis of graying. Defective melanosomal transfer to the cortical keratinocytes or melanin incontinence due to melanocyte degenation is also believed to contribute to graying. There is autophagolysosomal degradation of melanosomes within the melanocytes itself and is usually followed by the degeneration of the melanocyte . Eventually, no melanogenic melanocytes remain in the hair bulb. True gray hair show reduced DOPA reaction (indicator of tyrosinase activity) while white hair bulbs are negative for the same.

56. Neurotransmitters Neurotransmitters is a chemical substance that act as the mediator for the transmission of nerve impulse from one neuron to another neuron. Depending upon their chemical nature. 3 types Amino acids – involved in fast synaptic transmission, inhibitory and excitatory in action Amine – involved in slow synaptic transmission, inhibitory and excitatory in action.

57. 3 . Others

58. Adrenal medularry hormones are the amine derived from catechol and these hormones are called catecholamine. 3 catecholamine are secreted by medulla. Adrenaline or epinephrine Noradrenalin or nor epinephrine Dopamine. Hormones of Adrenal medulla

59. Thyroid Hormones – leading to premature graying Both T 4 & T 3 – iodine containing derivatives of amino acid tyrosine. Iodine & tyrosine – are essential for the formation of thyroid hormones. Each thyroglobulin molecules contains 140 mollecules of amino acid tyrosine.

60. Genetics Mainly 2 genes are responsible for graying hair i.e Bcl 2 & Bcl -w. Stem cells at the base of hair follicles produce melanocytes – there are the cells that produce and store pigment in hair and skin, the death of melanocyte stem cells causes the onset of hair graying.

61. D 3 deficiency leading to premature greying of hair

62. Mode of action of Nasya : Ayurvedic According to Acharya Charaka & Vagvatta Nasa is the portal (gateway) of shiras . “ Nasa Hi shiraso dwaram ” According to Astanga Sangraha the drug administered through nostrils, reachers shringataka by Nasasrota and spreads in the murdha (Brain) taking route of Netra (eye), shrotra (ear), kantha (throat), Siramukhas (opening of the vessels) etc.   Scrapes the morbid doshas in supraclavicular region and extract them from the uttamanga . Maharsi Sushruta has explained sringataka marma as a sira marma formed by the union of siras (blood vessels) supplying to nose, ear, eye and tongue.

63. The pharmacodynamics of Nasyakarmacan be explained in light of modern anatomical and physiological studies as follows 1.Vascular pathway The nasal tissue is highly vascularized making it an attractive site for rapid and efficient systemic absorption. Rich vascular plexus permits topically administered drugs to rapidly achieve effective blood levels while avoiding intravenous catheters. Vascular path transportation is possible through the pooling of nasal venous blood into the facial vein which occurs naturally. The facial vein has no valves. It communicates freely with the intracranial circulation.It communicates through pterygoidplexus with the cavernous venous sinus Modern View

64. 2.Neurological pathway Olfactory nerve is chemoreceptor in nature. It is known that through olfactory pathway this nerve is connected with limbic system and hypothalamus which are having control over endocrine secretions.10Moreover, hypothalamus is considered to be responsible for ntegrating the functions of the endocrine system and the nervous system. Electrical stimulation of hypothalamus in animals is capable of inducing secretions in the anterior pituitary. So the drugs administratedhere stimulate the higher centers ofbrain which shows action on regulation of endocrine and nervous system functions. 3.Diffusion through nasal mucosa In the absorption of drug from the nasal cavity first step is passage through the mucus. Large and charged particles may find it more difficult to cross. But small and uncharged particles easily pass through this layer. Mechanisms for absorption of drug through the nasal mucosa include 1. Paracellular route is the first mechanism which isan aqueous route of transport. This is slow and passive route. 2. Transcellular process is the second mechanism of transport through a lipoidal route and is responsible for the transport of lipophilic drugs that show a rate dependency on their lipophilicity . Drugs also cross cell membranes by an active transport route via carrier mediated means or transport through the opening of tight junctions