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Lithium/DMSO is superior to ketoconazole 2% (Nizoral)


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Ann Dermatol Venereol. 2007 Apr;134(4 Pt 1):347-51.

[Lithium gluconate 8% in the treatment of seborrheic dermatitis]

 

 

Dr?no B, Blouin E, Moyse D.

 

D?partement de Dermatologie, CHU de Nantes, 44035 Nantes Cedex. bdreno@wanadoo.fr

 

 

Seborrheic dermatitis is a chronic from of inflammatory dermatitis characterized by erythema and desquamation with predominant localization on the face (nasolabial folds, eyebrows, hair-line and ears). It appears to be caused by proliferation of Malassezia yeasts. Lithium gluconate 8% gel (Lithioderm 8% gel) is the only drug containing topical lithium salt commercially available in France for the treatment of seborrheic dermatitis. The mechanism of action of topical lithium is not well known; it may act through anti-inflammatory and antifungal action. Efficacy and safety were assessed in 2 clinical studies, one versus placebo and the other versus ketoconazole 2% foaming gel using the same principal criterion defined as the rate of patients showing complete remission after 2 months of treatment (complete disappearance of both erythema and desquamation). Lithium gluconate 8% was significantly more effective than placebo and than ketoconazole 2% foaming gel and was well tolerated. Adverse events observed were cutaneous (burning sensation, erythema and pruritus), for the most part of mild severity. No cutaneous side effects contributed to those reported with the use of systemic lithium in psychiatric disorders were noted. Pharmacokinetic studies have shown that systemic absorption after topical application is low. Lithioderm 8% gel is applied twice daily over a recommended period of 2 months. It constitutes a new alternative in the treatment of facial seborrheic dermatitis, regardless of severity.

 

 

 

Br J Dermatol. 2003 Jun;148(6):1230-6.

Lithium gluconate 8% vs ketoconazole 2% in the treatment of seborrhoeic dermatitis: a multicentre, randomized study.

Dreno B, Chosidow O, Revuz J, Moyse D; STUDY INVESTIGATOR GROUP.

 

Clinique Dermatologique, CHU Nantes, H?tel Dieu, BP 1005, 44305 Nantes cedex, France. bdreno@wanadoo.fr

Abstract

 

BACKGROUND: Lithium significantly improved seborrhoeic dermatitis symptoms in comparison with placebo. Objectives This randomized controlled trial was designed to show a non-inferiority of 15% (primary end-point) of lithium gluconate 8% ointment compared with ketoconazole 2% emulsion. METHODS: The study population comprised out-patients who had facial seborrhoeic dermatitis for at least 2 months, with moderate to severe erythema and desquamation at inclusion. The primary end-point was complete remission, defined as the disappearance of both erythema and desquamation. The non-inferiority of lithium was assessed on the 95% confidence interval (CI) of the difference between treatments. RESULTS: The intent-to-treat analysis (ITT) involved 288 patients and the per protocol (PP) analysis 269 patients. Treatment groups were comparable at baseline on age, sex, disease duration and symptoms. For the main criterion, the success rate was 52.0% (lithium) vs. 30.1% (ketoconazole) in the ITT population and 53.2% (lithium) vs. 30.7% (ketoconazole) in the PP population. The non-inferiority of lithium was demonstrated with differences of 21.9% (95% CI 10.0-33.7%) and 22.5% (95% CI 10.2-34.8%), respectively, in the ITT and PP population. As the lower limit of the 95% CI was > 0, the superiority of lithium was shown. Lithium also showed better results on other symptoms: burning and dryness. Adverse events were reported by 26.3% (lithium) and 25% (ketoconazole) of patients. CONCLUSIONS: Lithium was 22% more effective than ketoconazole in giving complete remission of seborrhoeic dermatitis, with comparable safety.

 

 

Proc Natl Acad Sci U S A. 2003 May 13;100(10):5834-9.

A Wnt- and beta -catenin-dependent pathway for mammalian cardiac myogenesis.

Nakamura T, Sano M, Songyang Z, Schneider MD.

 

Center for Cardiovascular Development and Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

 

Acquisition of a cardiac fate by embryonic mesodermal cells is a fundamental step in heart formation. Heart development in frogs and avians requires positive signals from adjacent endoderm, including bone morphogenic proteins, and is antagonized by a second secreted signal, Wnt proteins, from neural tube. By contrast, mechanisms of mesodermal commitment to create heart muscle in mammals are largely unknown. In addition, Wnt-dependent signals can involve either a canonical beta-catenin pathway or other, alternative mediators. Here, we tested the involvement of Wnts and beta-catenin in mammalian cardiac myogenesis by using a pluripotent mouse cell line (P19CL6) that recapitulates early steps for cardiac specification. In this system, early and late cardiac genes are up-regulated by 1% DMSO, and spontaneous beating occurs. Notably, Wnt3A and Wnt8A were induced days before even the earliest cardiogenic transcription factors. DMSO induced biochemical mediators of Wnt signaling (decreased phosphorylation and increased levels of beta-catenin), which were suppressed by Frizzled-8Fc, a soluble Wnt antagonist. DMSO provoked T cell factor-dependent transcriptional activity; thus, induction of Wnt proteins by DMSO was functionally coupled. Frizzled-8Fc inhibited the induction of cardiogenic transcription factors, cardiogenic growth factors, and sarcomeric myosin heavy chains. Likewise, differentiation was blocked by constitutively active glycogen synthase kinase 3beta, an intracellular inhibitor of the Wntbeta-catenin pathway. Conversely, lithium chloride, which inhibits glycogen synthase kinase 3beta, and Wnt3A-conditioned medium up-regulated early cardiac markers and the proportion of differentiated cells. Thus, Wntbeta-catenin signaling is activated at the inception of mammalian cardiac myogenesis and is indispensable for cardiac differentiation, at least in this pluripotent model system.

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ok great study on dermatitis of the scalp,

but i was always lead to beleive that how nizoral works to the benefit of balding men is that the Ketoconazole not only keeps the scalp healthy and clean but the antifungal agents are beleived to reduce scalp dht levels?

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It can reasonably be concluded that the clinical efficacy of ketoconazole shampoo in the treatment of AGA is primarily a function of DHT pathway disruption rather than an anti-inflammatory effect. In rat studies ketoconazole caused 5-R inhibition [28]. Furthermore, in humans ketoconazole has also been shown to inhibit the binding of 5-R to sex hormone globulins [29]. These clinical studies suggest that ketoconazole like finasteride may inhibit the production of DHT. Unlike finasteride ketoconazole has been shown to bind to human AR [30]. Thus, the effect of ketoconazole on the DHT pathway may be two-fold: inhibition of DHT and/or inhibition of DHT binding to AR. Either or both of these properties would result in reduced incidence of DHT binding to AR and inhibiting the pathway that leads to the miniaturizing of hair follicles.

 

March 04, 2001 - American Academy of Dermatology Meeting - Washington DC - Scientists working for McNeil, makers of Nizoral anti-dandruff shampoo, presented the findings of a study done on 1% Nizoral shampoo which has good news for hair loss sufferers. It has long been known that 2% prescription Nizoral has beneficial effects on Androgenic Alopecia (MPB). It however has been unclear whether the same benefits can be obtained by using the non-prescription 1% version.

In the study presented (see below), one hundred male volunteers with mild to moderate dandruff and somewhat oily scalp, were using, in a double-blind fashion, either a 1% Nizoral shampoo or a 1% zinc pyrithione shampoo, 2-3 times a week for 6 months.

Analysis of the different parameters set up in the study shows that the hair diameter gradually increased with Nizoral use (+8.46%) over a 6 month period, whereas the diameter showed a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate was reduced with Nizoral (-6.54%) while it increased with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period was reduced by 16.46% with Nizoral and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time.

 

The results are similar to a previous study done on 2% prescription strength Nizoral where it was shown that use of 2% Nizoral yielded a 7% average increase in hair shaft diameter similar to what was achieved by the control group using 2% Minoxidil and a non-medicated shampoo.

 

So for any hair loss sufferer, this research clearly indicates that using 1% or 2% Nizoral 2-3 times per week, will have positive effects on hair growth as well as controlling dandruff. It is still unclear at this time whether it's the anti-fungal properties or the anti-androgenic properties of Ketokonazole (active ingredient in Nizoral) thats responsible for the hair thickening effects, however because of the decrease in sebum rates as well, it is the authors opinion that the results are due to the anti-androgenic properties of Ketokonazole.

 

California College of Podiatric Medicine, 371 Columbus Avenue, San Francisco, CA 94133, USA.

 

Dihydrotestosterone (DHT) binding to androgen receptors (AR) in hair follicles is commonly accepted as the first step leading to the miniaturizing of follicles associated with androgenetic alopecia (AGA). Testosterone is converted to DHT by the enzyme 5alpha-reductase. Finasateride a 5alpha-reducase inhibitor blocks the production of DHT and is currently used to treat AGA. The inhibition is not complete but a reduction of DHT systemically and in the scalp is accomplished. Ketoconazole has been clinically shown to be effective in the treatment of AGA. In this paper, evidence is presented to support the hypothesis that ketoconazole 2% shampoo has a local disruption of the DHT pathway. It is proposed that using ketoconazole 2% shampoo as an adjunct to finasteride treatment could lead to a more complete inhibition of DHT and thus better treat AGA.

 

PMID: 14729013 [PubMed - indexed for MEDLINE]

 

March 04, 2001 - American Academy of Dermatology Meeting - Washington DC - Scientists working for McNeil, makers of Nizoral anti-dandruff shampoo, presented the findings of a study done on 1% Nizoral shampoo which has good news for hair loss sufferers. It has long been known that 2% prescription Nizoral has beneficial effects on Androgenic Alopecia (MPB). It however has been unclear whether the same benefits can be obtained by using the non-prescription 1% version.

In the study presented (see below), one hundred male volunteers with mild to moderate dandruff and somewhat oily scalp, were using, in a double-blind fashion, either a 1% Nizoral shampoo or a 1% zinc pyrithione shampoo, 2-3 times a week for 6 months.

Analysis of the different parameters set up in the study shows that the hair diameter gradually increased with Nizoral use (+8.46%) over a 6 month period, whereas the diameter showed a trend to decrease with zinc pyrithione use over the same period (-2.28%). The sebum excretion rate was reduced with Nizoral (-6.54%) while it increased with zinc pyrithione (+8.2%) over the same period of time. The number of hair shed over a 24-hour period was reduced by 16.46% with Nizoral and 6.02% with zinc pyrithione after 6 months. Finally, the percentage hairs in anagen phase increased by 6.4% and 8.4% respectively during the study time.

 

The results are similar to a previous study done on 2% prescription strength Nizoral where it was shown that use of 2% Nizoral yielded a 7% average increase in hair shaft diameter similar to what was achieved by the control group using 2% Minoxidil and a non-medicated shampoo.

 

So for any hair loss sufferer, this research clearly indicates that using 1% or 2% Nizoral 2-3 times per week, will have positive effects on hair growth as well as controlling dandruff. It is still unclear at this time whether it's the anti-fungal properties or the anti-androgenic properties of Ketokonazole (active ingredient in Nizoral) thats responsible for the hair thickening effects, however because of the decrease in sebum rates as well, it is the authors opinion that the results are due to the anti-androgenic properties of Ketokonazole.

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