Code No: R9501 Jawaharlal Nehru Technological University Hyderabad B.Pharmacy III Year II Semester Examinations April/May-12 April/May - 2012 Answer any FIVE Questions All Questions carry equal marks Discuss the role of parameters like lipophilicity, chelation and hydrogen bonding in biological activity ofdrug. Explain the concept of prodrug with examples. Write the
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Microsoft word - hair nutrition
A Nanogen Briefing for the Scientific Community
by Toby Cobbledick
Nutrition is a complex subject as the effects of correct nutrition are indirect and slow to appear. This is particularly true for hair which
is slow to respond to any form of treatment. Correct nutrition has been shown by many trials to be essential for healthy hair growth,
and conversely many deficiencies correlate with hair loss. Hair nutrition is therefore a vital part of any treatment regime. A truly
systematic and rigorous approach must be taken when formulating a nutritional supplement for hair due the many factors that affect
the eventual efficacy of the treatment. Several of these factors are discussed with applicable examples to demonstrate the importance
of careful formulation.
additional consideration is the selective inhibition of the two isoforms of 5α reductase. It has been shown in limited in vitro The fact that hair growth requires complex nutrients and a ready tests that both isoforms may be inhibited by lipid-rich saw supply of oxygen is well documented, but often overlooked. palmetto extracts, however there has been no study finding a Perhaps because the effects are indirect and difficult to measure, measurable effect on both isoforms from the whole fruit form. Of comparatively few studies have trialled ingredients and course the whole fruit contains all of the components of the combinations of ingredients to maintain or promote hair growth. extract and so theoretically would have the same effect, however It is not surprising then that many respectable manufacturers of nutritional supplements do not consider the importance of bioavailability, balancing elements with shared uptake pathways, and fail to ensure that no component has a negative effect on the Bioavailability
absorption or action of other components in the formula. Just as surely as hair will not begin to grow without appropriate Many common vitamins and all amino acids exist as multiple growth factors and external stimuli, hair will not continue to grow isomers, however it is rare that both or even all forms are equally without adequate circulation and nutrition. A balanced, available to human metabolism. The chirality of amino acids is bioavailable formula to protect and maintain hair growth is vital. well established, as is the dramatic difference between left and right enantiomers in the human body. On the whole, humans can only metabolise left or L enantiomers, such as L-Cysteine. R-Cysteine is not taken up or commonly metabolised, therefore Concentration
commonly used racemic mixtures of the two forms are only half There is a habit among supplement formulators to include the maximum possible level of everything, “bigger is better” and they Vitamins, such as vitamin B6 also have several forms, pyridoxine want their label to look better than the next one. is the form of vitamin B6 most commonly used in nutritional supplements, however it is not the bio-active form. Instead it It is well known that this is not necessarily correct. The most must be phosphorylated to become pyridoxal 5 phosphate, which obvious and common example in hair loss supplements is saw is active as an enzyme cofactor for many reactions, and is palmetto. Opinions vary about the efficacy of saw palmetto in important for uptake of other nutrients as well. The vivo, but there is strong evidence from tissue sample phosphorylation reaction to activate pyridoxine takes energy and experiments that saw palmetto inhibits the 5α reductase enzyme a certain set of conditions, and therefore not all the pyridoxine responsible for converting testosterone to dihydrotestosterone. taken in a supplement is used. A more efficient alternative is to Component analysis shows that certain fatty acids but use pyridoxal 5 phosphate in the supplement, so the bio-active particularly lauric acid and oleic acid are responsible for the form is immediately available, requiring no energy, and minimal activity of saw palmetto. Saw palmetto extract is a refined version of the whole fruit form, and retains a high percentage of the fatty acid content whilst removing other less useful Bioavailability is not just controlled by isomeric forms. Nutrient uptake is complex, and there are many surprising instances where one nutrient is dramatically affected – either negatively or Therefore it is apparent that a significantly lower dose of the positively, by a completely different nutrient in the formula. extract is required to deliver the same levels of active fatty acids, Pyridoxal 5 phosphate increases L-cysteine incorporation into one calculation estimates that 320mg of extract would have the keratin, however as pyridoxal 5 phosphate may be a cofactor of fatty acid component of 1500mg of the whole fruit form. An 2010 Copyright Nanogen Hair Research. Al rights reserved. This paper is for internal and professional use only and should not be shared with or acted upon by consumers the enzyme responsible for incorporating L-cysteine into hair, this keratin; pantothenic acid in particular is very common in the form is unsurprising. More interesting are the studies showing that of panthenol, the conditioning agent. However a combination of both green tea and saw palmetto inhibit the absorption of iron. the two has been suggested by in vitro tests to help increase hair Whilst the mechanism for this is not entirely described, it is repair and keratinocyte proliferation[12,13]. thought to be due to the concentrations of tannic acids in both. There are also several obvious examples where two ingredients Tannic acid levels are not significantly reduced when they are act together, and these should not be ignored. For instance it is well known that vitamin B12 and iron are both necessary for Therefore a formula must be designed so not only are erythrocyte formation, and hence oxygen circulation, so it is bioavailable forms used, but the whole formula is studied for important that a supplement contain both to significantly help this negative interactions and targeted towards a particular concern. Circulation
Unfortunately a formula containing all of the nutrients necessary A final, and often overlooked, factor to consider is the circulation without a single negative interaction is rarely possible. Therefore of oxygen and nutrients to the hair. Even a perfectly balanced balance is essential, especially where nutrients compete for supplement would not be effective if there was no blood flow to the hair. Many believe that several forms of hair loss are caused or exacerbated by a deficient blood supply to the hair follicle, and Balance is not simply a matter of including every competing so it is possible that nutrients from a supplement could not reach element at the same percentage. Certain nutrients will compete the follicle in useful quantities. Therefore it may be beneficial to more successfully than others, and all elements for healthy hair increase the circulation. This can be achieved through topical are necessary at different levels. The ion uptake channel for treatments that stimulate nitric oxide production or angiogenesis. copper, zinc and magnesium ions is a useful illustration as the However a simpler solution may be to include a known stimulant balance between the three competing elements is fine, and like taurine or caffeine to increase bloodflow around the entire taking too much of one will decrease the other two. It has been shown separately that copper, zinc, and magnesium are important for hair growth. As well as their role in nutrition and The stimulatory effects of caffeine and taurine on nutrient uptake enzyme action, Copper and zinc have also both been shown to and metabolism may also be beneficial. An added consideration inhibit 5α reductase, although zinc has only been proven to is the possible effect of caffeine upon dihydrotestosterone and inhibit the type 1 isoform found in skin not hair [7,8] hair loss. Caffeine has been shown by several studies to reduce has been shown to correlate with certain diffuse alopecias in hair loss caused by dihydrotestosterone, the in vivo studies were women, but the precise cause has not been established. successful topically, but the effects of oral caffeine have not been tested at this time. Taurine has also been shown by in vitro However it would not be correct to create a supplement with testing to protect the hair from TGFβ-1 induced apoptosis. more copper, slightly less zinc, and lower magnesium content due to their proven importance. In fact as magnesium is required at higher levels around the body comparatively it should be included at a higher dose, followed by zinc, and then copper is Component Synergy
It is also vital to consider the opposite possibility in complex formulae. Combinations of nutrients may improve the results of the two nutrients separately, such as the combination of curcumin and resveratrol. Resveratrol has been extensively studied both as an anti-inflammatory and anti-angiogenic agent, however results have been limited. Curcumin has also not lived up to initial promise as an anti-inflammatory. However it has been shown that the two work synergistically in a cancer model, to decrease inflammation and possibly angiogenesis, although even in combination a significant anti-angiogenic effect in vivo seems unlikely. Correct synergy can even result in a measureable effect where neither ingredient was effective separately. L-cysteine and pantothenic acid can be useful as they are incorporated into 2010 Copyright Nanogen Hair Research. Al rights reserved. This paper is for internal and professional use only and should not be shared with or acted upon by consumers Conclusion
In spite of the paucity of clinical data in the area, it is possible 1. Marks L.S., et al., Tissue effects of saw palmetto and through careful formulation to develop a potent, bioavailable, and finasteride: use of biopsy cores for in situ quantification of balanced formula with combinations of ingredients that are likely prostatic androgens. Urology, 2001. 57(5): p. 999-1005.
to have good clinical outcomes. This is particularly true if 2. Abe M., et al. Pharmacologically relevant receptor binding supplements are used to support wider treatment regimes - even characteristics and 5alpha-reductase inhibitory activity of free Fatty acids contained in saw palmetto extract. Intervention utilises all of the above knowledge and technology. Biological and Pharmacological Bulletin, 2009. 32(4): p.
Nanogen have developed two targeted Intervention formulae, for Men and for Women, to give the best results possible. It is not 3. Iehlé C., et al. Human prostatic steroid 5 alpha-reductase possible, or even desirable, to include every possible anti-hair isoforms--a comparative study of selective inhibitors. loss ingredient in one tablet, as shown by issues such a Journal of Steroid Biochemistry and Molecular Biology, bioavailability and shared uptake pathways. For example, 1995. 54(5-6): p .273-279.
Intervention for Men does not contain iron or vitamin B 4. Combs, G.F. The Vitamins: Fundamental Aspects in Nutrition anaemia is rarely a cause of hair loss in men. Intervention for Women does not contain saw palmetto or green tea. As iron is 5. D'Agostini F., et al., Chemoprevention of smoke-induced especially important for women, it is vital that iron uptake is not alopecia in mice by oral administration of L-cystine and vitamin B6. Journal of Dermatological Science, 2007. 46(3):
6. Miller L.G., Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Archives of Internal Medicine, 1998. 158(20):
7. Sugimoto Y., et al., Cations inhibit specifically type I 5 alpha-reductase found in human skin. Journal of Investigative Dermatology, 1995. 104(5): p. 775-778.
8. Om A.S., Chung K.W., Dietary zinc deficiency alters 5 alpha- reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. Journal of Nutrition,1996. 126(4): p. 842-848.
9. Tataru A., Nicoara E., Idiopathic diffuse alopecias in young women correlated with hypomagnesemia. Jorunal of the European Academy of Dermatology and Venereology, 2004. 18(3): p. 393-394.
10. Aftab N., Vieira A., Antioxidant activities of curcumin and combinations of this curcuminoid with other phytochemicals. Phytotherapy Research, 2010. 24(4): p.
11. Dulak J., Nutraceuticals As Anti-Angiogenic Agents: Hopes And Reality. Journal of Physiology and Pharmacology, 2005. 56(S1): p. 51-69
12. Budde J. et al. Systemic therapy of diffuse effluvium and hair structure damage. Der Hautarzt, 1993. 44(6): p. 380-
Obrigkeit D.H., et al., Xenobiotics in vitro: the influence of L- cystine, pantothenat, and miliacin on metabolic and proliferative capacity of keratinocytes. Cutaneous and Ocular Toxicology, 2006. 25(1): p. 13-22.
14. Fischer T.W., et al., Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. International Journal of Dermatology, 2007. 46(1): p. 27-35.
15. Collin C, et al., Protective effects of taurine on human hair follicle grown in vitro. International Journal of Cosmetic Science, 2006. 28(4): p. 289-298.
2010 Copyright Nanogen Hair Research. Al rights reserved. This paper is for internal and professional use only and should not be shared with or acted upon by consumers
ATTENTION PHARMACIST: Detach “Patient’s Instructions for Use” from package insert and dispense with the product. Combivent® (ipratropium bromide and albuterol sulfate) Inhalation Aerosol Bronchodilator For Oral Inhalation Only Rx only Prescribing Information DESCRIPTION COMBIVENT Inhalation Aerosol is a combination of ipratropium bromide (as the monohydrate)