The role of oxidative damage in poor scalp health: ramifications to causality and associated hair growth.

The oxidative stress element of unhealthy scalp leads to compromised pre-emergent hair formation and poorly formed hair as it grows. Only cosmetic solutions can minimize the impact of unhealthy hair and to achieve healthy looking and feeling hair, the scalp health must be normalized first. The objectives of this research were to both investigate whether oxidative stress was a relevant aetiological element in scalp dandruff and seborrhoeic dermatitis and whether scalp condition affects the quality of hair that grows from it. Further, this research was designed to determine whether an effective anti-dandruff shampoo would repair and protect the scalp and pre-emergent hair from oxidative stress. This study demonstrated that oxidative stress is an aetiological element relevant to the dandruff condition and that a potentiated ZPT shampoo effectively improves scalp condition, including a reduction in oxidative stress. The compromised hair condition associated with dandruff is concomitantly improved when the scalp condition is improved. It appears that there is a direct link between hair quality and scalp health.

Therapeutic efficacy of anti-dandruff shampoos: a randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole.

OBJECTIVES: Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti-fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti-fungal shampoos are maximizing bio-availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches - maximization of bio-availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material. METHODS: The anti-fungal potency of shampoos representing each of these approaches was evaluated in vitro using a standard microbiology method. Spatial delivery of ZPT particles in the follicular infundibulum was assessed in vivo using a novel confocal microscopy methodology. Clinical efficacy was assessed in a randomized, double-blind trial involving 620 male and female subjects using scalp flaking and epidermal histamine level as endpoints. RESULTS: The shampoo formula with maximized ZPT bio-availability known as the Potentiated ZPT formula exhibited greater anti-fungal potency than the Dual Active shampoo containing both ZPT and climbazole. The Potentiated ZPT formula also delivered more ZPT to the lower infundibulum than the Dual Active shampoo. A 4-week treatment with the Potentiated ZPT formula resulted in superior clinical efficacy compared with the Dual Active product at all 4 weekly time points for both flaking and epidermal histamine endpoints. CONCLUSION: These results highlight the critical role that the shampoo vehicle plays in realizing full potency of active materials. By optimizing the delivery vehicle, the enhanced anti-fungal potency and the maximized spatial delivery of active materials result in greater symptomatic improvement than a product with two active materials. The therapeutic efficacy of a product based on a complex delivery vehicle such as a shampoo must be considered from a full-product perspective rather than just the active system as the non-active components of the composition will often play a significant role in the overall product pharmacology and resultant efficacy.

The antifungal mechanism of action of zinc pyrithione.

BACKGROUND: Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT. OBJECTIVES: The objective of this study is to understand the molecular mechanism by which ZPT inhibits fungal growth, the underlying basis for its therapeutic activity. METHODS: Modern systems biology approaches, such as deletion library screening and microarray analysis, were used in combination with traditional measures of metal content, microbial growth and enzyme assays. RESULTS: It was shown that ZPT inhibits fungal growth through increased cellular levels of copper, damaging iron-sulphur clusters of proteins essential for fungal metabolism. CONCLUSIONS: The molecular basis for the antifungal activity of the commonly used active ZPT has been elucidated, more than 50 years since its introduction, as utilizing a copper toxicity mechanism that targets critical iron-sulphur proteins.

New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies.

BACKGROUND: Pathogenesis of dandruff/seborrhoeic dermatitis (D/SD) involves Malassezia yeasts, leading to the most widely accepted treatment strategy of topical application of antifungal agents, usually from rinse-off shampoos. The scalp spatial distribution of Malassezia must be mirrored by the distribution of the active agent to realize the full benefit of the active material. OBJECTIVES: Based on observations that Malassezia yeasts reside in follicular infundibula, we sought to determine whether commercial shampoo products based on the active agent zinc pyrithione (ZPT) could deliver this material to this highly restricted, but therapeutically relevant space. METHODS: Three new methods have been developed to assess ZPT active delivery to the follicular infundibulum: (i) hair plucks followed by chemical quantification of the subsurface portion; (ii) cyanoacrylate infundibular biopsies followed by chemical quantification of extracted ZPT; and (iii) confocal microscopy of infundibular spaces coupled with image analysis to yield relative quantification. RESULTS: Infundibular ZPT was detected, the quantity of which directly correlated with the consequent reduction of the infundibular Malassezia population. A commercial therapeutic shampoo delivered a disproportionately high level of ZPT to the infundibular spaces, suggesting an active mechanism to draw ZPT particles of optimum size to this space. Imaging of the infundibular ZPT in vivo allows an assessment of its state of aggregation, which would tend to minimize bioavailability. CONCLUSIONS: Effective therapeutic D/SD products must deliver the antifungal active material to the infundibulum as well as superficially on the scalp surface. This is achieved by certain therapeutic ZPT shampoos, in which the particle size of ZPT is likely to be an important factor in determining the efficiency of spatial delivery.

Radioterapia en la neomama reconstruida con tejido autológo: efecto en la estética, complicaciones y control local / Effects of radiotherapy on mammary reconstruction with autologous tissues

Introducción: Un subgrupo de pacientes sometidas por cáncer de mama a mastectomía y reconstrucción mamaria inmediata (RM) con colgajo miocutáneo de recto anterior del abdomen (TRAM Flap), necesitará de radioterapia externa para el control de su enfermedad. El efecto de la radiación sobre los colgajos usados para RMI esta poco dilucidado. Material y Método: Estudio retrospectivo entre abril 1994 y diciembre 2003. Se confeccionaron dos grupos. El grupo 1: Catorce (14) mujeres sometidas a mastectomía con conservación de piel y RMI con TRAM Flap pediculizado a las que se les realizó radioterapia fraccionada adyuvante. Grupo 2: Treinta mujeres (30) sometidas a mastectomía con conservación de piel y RMI con TRAM Flap pediculizado sin radioterapia adyuvante. Se compararon los resultados cosméticos, la morbilidad y el control local de la enfermedad entre ambos grupos. Resultados: El seguimiento mínimo fue de 6 meses post radioterapia y/o cirugía. En ambos grupos el resultado cosmético fue comparable. No hubo pérdida de colgajos ni reducción importante de volumen por contractura en el grupo irradiado. Dos pacientes del grupo 1 y dos pacientes en el Grupo 2 requirieron de biopsia por necrosis grasa sospechosa de recidiva tumoral. Ninguna de las 44 pacientes ha presentado recidiva locorregional. Una paciente del Grupo 2 falleció por diseminación a distancia y una se encuentra con enfermedad metastásica en tratamiento hormonal. Conclusión: Los efectos de la radioterapia sobre una neomama reconstruida con tejido autólogo son menores y sin significativa relevancia. La posibilidad de radioterapia post operatoria después de un TRAM Flap no debe ser obstáculo para la RMI.

Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea.

Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of modafinil for the treatment of residual daytime sleepiness in such patients. Patients received modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p < 0.001) and in multiple sleep latency times (MSLT) at Week 4 (p < 0.05). The percentage of patients with normalized daytime sleepiness (Epworth score < 10) was significantly higher with modafinil (51%) than with placebo (27%) (p < 0.01), but not for MSLT (> 10 min; 29% versus 25%). Headache (modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (modafinil, 12%; placebo, 3%; p = 0.024) were the most common adverse events. During modafinil or placebo treatment, the mean duration of nCPAP use was 6.2 h/night, with no significant change from baseline observed between groups. Modafinil may be a useful adjunct treatment for the management of residual daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome who are regular users of nasal continuous positive airway pressure therapy.

Dandruff has an altered stratum corneum ultrastructure that is improved with zinc pyrithione shampoo.

Transmission electron microscopy of scalp tape strips indicates that dandruff scalp possesses abnormal stratum corneum (SC) ultrastructure that is normalized by treatment with small-particle zinc pyrithione (ZPT). Similar abnormalities occur throughout the scalp of those with dandruff, even where no flaking is present. SC abnormalities are consistent with hyperproliferation, including parakeratosis, lipid droplets within corneocytes, few desmosomes, corneocyte membrane interdigitation, and excessive disorganized intercellular lipid. Reversal of SC abnormalities would require treatment of the cause(s) of dandruff, not merely flake removal. A protocol was developed to quantify scalp structural abnormalities by scoring cells from scalp tape strips for yeast number, amount of intercellular lipid, normal intercellular lipid structures, prevalence of intracellular lipid droplets, parakeratotic corneocytes, and corneocyte interdigitation. This protocol was used to compare dandruff and normal SC to dandruff SC treated with either commercial ZPT-containing shampoo or a placebo. Treatment with commercial ZPT shampoo significantly returned SC ultrastructure to normal, suggesting control of the cause of dandruff.

Human and mouse alpha-synuclein genes: comparative genomic sequence analysis and identification of a novel gene regulatory element.

The human alpha-synuclein gene (SNCA) encodes a presynaptic nerve terminal protein that was originally identified as a precursor of the non-beta-amyloid component of Alzheimer's disease plaques. More recently, mutations in SNCA have been identified in some cases of familial Parkinson's disease, presenting numerous new areas of investigation for this important disease. Molecular studies would benefit from detailed information about the long-range sequence context of SNCA. To that end, we have established the complete genomic sequence of the chromosomal regions containing the human and mouse alpha-synuclein genes, with the objective of using the resulting sequence information to identify conserved regions of biological importance through comparative sequence analysis. These efforts have yielded approximately 146 and approximately 119 kb of high-accuracy human and mouse genomic sequence, respectively, revealing the precise genetic architecture of the alpha-synuclein gene in both species. A simple repeat element upstream of SNCA/Snca has been identified and shown to be necessary for normal expression in transient transfection assays using a luciferase reporter construct. Together, these studies provide valuable data that should facilitate more detailed analysis of this medically important gene.

Closing ... closing ... closed.

What can a board do when all signs point to the need to close a hospital, but its community and the state's attorney general, is not buying it? Here's some legal guidance if you're in that position.

Developmental expression of cytochrome P450 side-chain cleavage and cytochrome P450 17 alpha-hydroxylase messenger ribonucleic acid and protein in the neonatal hamster ovary.

The temporal and spatial expression of cytochrome P450 side-chain cleavage (CYP11A1) and cytochrome P450 17 alpha-hydroxylase (CYP17) mRNA and protein during thecal cell differentiation in developing hamster ovaries were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence histochemistry, respectively. Ovaries were collected from 15-day fetal through 20-day-old postnatal hamsters and used either for immunofluorescence detection of enzyme protein or RT-PCR evaluation of enzyme mRNA. Immunoreactivity of CYP11A1 first appeared in the interstitial cells on Day 10 postnatal (PN), and the intensity increased significantly with further ovarian development beyond 11 days of age. In contrast, CYP17 immunostaining was first detected in a few interstitial cells closer to large preantral follicles by Day 12 PN, and their number increased appreciably by Day 14 PN. By age 18-20 days, CYP17-positive cells were localized primarily in the thecal layer of large preantral follicles. A low level of CYP17 and CYP11A1 mRNA was present in fetal ovaries. The CYP17 mRNA levels increased sharply by Day 1 PN but decreased to a low baseline level by Day 2 PN and remained low up to Day 9 PN. Both CYP11A1 and CYP17 mRNA levels increased significantly by Day 10 PN compared to Day 9 PN; however, the increase for CYP11A1 was greater than CYP17. The CYP11A1 mRNA levels decreased noticeably on Day 11 PN and remained relatively stable until Day 14 PN; however, mRNA levels started increasing by Day 15 PN and increased sharply by Day 17 PN onward, corresponding to the increase in CYP11A1 protein in the ovarian interstitium and thecal compartments. On the other hand, CYP17 mRNA expression increased progressively through Day 12 PN. A sharp increase in CYP17 mRNA was noted on Day 13 PN in conjunction with the morphological development of thecal cells; mRNA levels remained steady afterward. The correlation of the increase in enzyme mRNA and protein, especially of CYP17, with the morphological development of thecal layers suggests that the differentiation of interstitial cells into theca may be modulated by multilayered preantral follicles, and the expression of enzyme protein occurs prior to an increase in serum LH.

Expression of P450 side-chain cleavage (CYP11A1) and P450 17alpha-hydroxylase-17/20 lyase (CYP17) messenger ribonucleic acid in hamster primary interstitial cells in vitro: differential regulation of steroidogenesis by cyclic adenosine monophosphate.

Interstitial cells in the neonatal hamster do not respond to LH in vitro; however, side-chain cleavage (CYP11A1) and 17alpha-hydroxylase (CYP17) enzyme proteins are expressed in these cells. The objective of the study was to evaluate whether the cAMP second messenger system was active in these cells and if cAMP upregulates the levels of CYP11A1 and CYP17 mRNA. Interstitial cells (ICs) were cultured for 96 h in the presence of 5% fetal bovine serum and then cultured in serum-free medium in the presence of LH, forskolin, or 8-Br-cAMP for 24 h. The accumulation of cAMP, progesterone, and androstenedione was measured by radioimmunoassay, whereas CYP11A1 and CYP17 mRNA levels were determined by a semiquantitative reverse transcription-polymerase chain reaction and Southern hybridization analysis. LH failed to induce either progesterone or androstenedione production; however, forskolin stimulated cAMP production by interstitial cells in a dose-dependent manner. Moreover, both forskolin and 8-Br-cAMP significantly elevated the levels of CYP11A1 and CYP17 mRNA and induced progesterone synthesis by the interstitial cell monolayer. Despite the increase in CYP17 mRNA levels by 8-Br-cAMP, no appreciable change was noted in androstenedione production. These results suggest that, in vitro, a fully functional adenylate cyclase system is present in cultured interstitial cells of the neonatal hamster and that cAMP can influence the expression of CYP11A1 and CYP17 genes; however, cultured cells do not appear to express LH receptors that are functionally linked to the adenylate cyclase system. Moreover, the translation of CYP17 mRNA may require additional factors, which may originate from maturing granulosa cells.

VISTA : visualizing global DNA sequence alignments of arbitrary length.

SUMMARY: VISTA is a program for visualizing global DNA sequence alignments of arbitrary length. It has a clean output, allowing for easy identification of similarity, and is easily configurable, enabling the visualization of alignments of various lengths at different levels of resolution. It is currently available on the web, thus allowing for easy access by all researchers. AVAILABILITY: VISTA server is available on the web at http://www-gsd.lbl.gov/vista. The source code is available upon request. CONTACT: vista@lbl.gov

The business judgment rule and other protections for the conduct of not-for-profit directors.

The authors review the Business Judgment Rule as applied to a not-for-profit director's duty of care, with particular emphasis on the different forms of state statutory liability shields that serve to enhance the protections of the Rule. They also examine current trends in enforcement of breach of fiduciary duty of care standards, and provide a series of specific recommendations for not-for-profit boards to consider implementing as a means of increasing the likelihood of affording such protections to individuals serving as directors.

In vitro culture of hamster ovarian primary interstitial cells: effect of serum.

The function of ovarian interstitial cells has been largely addressed using rat theca-interstitial cell culture. However, this preparation is primarily enriched with theca and secondary interstitial cells, which make it difficult to address selectively the function of the primary interstitial cells. We have developed an in vitro culture of hamster ovarian primary interstitial cells. Cells were isolated from postnatal hamster ovaries by collagenase digestion and purified over a Percoll gradient. The preparation contained 90% viable, pure interstitial cells, which anchored to the plastic and glass culture surface in the presence of fetal bovine serum. Cell proliferation was noted in the presence of serum dosages higher than 0.2%; however, reduction of serum concentration to 0.1% or complete serum starvation did not affect cell viability but almost completely abolished cell proliferation as determined by [3H]thymidine incorporation, labeling index, and DNA content of the culture. All cells exhibited active 3beta-hydroxysteroid dehydrogenase and P450 side chain cleavage immunoreactivity, which corresponded to basal progesterone and androstenedione accumulation. Replacement of serum to starving cells resulted in the induction of the "S" phase and "M" phase specific cyclins, and resumption of cell proliferation. Our results indicate that hamster primary interstitial cells can be cultured in vitro as a monolayer, and the anchorage and proliferation of these cells depend on serum supplement; however, a viable monolayer can be maintained for several days without serum. This model will be useful for addressing the mechanisms of differentiation of ovarian interstitial cells.

The drug court. A new strategy for drug use prevention.

The concept of Drug Treatment Court is relatively new and is an innovative response by local communities to deal with the escalation of criminal activity associated with substance abuse. The frequency of repeated offenses by drug users, the overcrowding of jail space, and a diminished sense of community well-being contributed to the motivation to look for a new approach by the criminal justice system--the creation of Drug Treatment Courts. This article reviews the strategy behind this creation.