Changes in serum free testosterone, sleep patterns, and 5-alpha-reductase type I activity influence changes in sebum excretion in female subjects.

BACKGROUND/PURPOSE: Sebum is thought to play an important role in acne vulgaris and sebum excretion rate (SER) is often used as a marker of efficacy in acne studies. This study explored factors that could induce intra-subject variability in SER. METHODS: SER was measured twice, 7 days apart, on the forehead of 40 healthy subjects. At each visit, the following parameters were also evaluated: serum androgen levels, 5-alpha-reductase type I gene expression, forehead temperature, sleep habits, diet, facial washing routine, and UV exposure. RESULTS: There was a positive correlation between the time subjects fell asleep on Day 0 and the change in SER for the left (P = 0.010; R = 0.402) and right sides (P = 0.002; R = 0.467) of the forehead. There was a significant inverse correlation between SER and 5-alpha-reductase type 1 expression and between free testosterone levels and 5-alpha-reductase type 1 expression. In sub-analyses performed on men and women, these correlations were only significant for women. CONCLUSION: Variations in sleep patterns, free testosterone, and 5-alpha-reductase type 1 activity are associated with changes in sebum excretion in women. This could explain some of the inter-subject variability in SER measured between visits in clinical studies.

Remission of systemic lupus and overlap syndrome after interferon therapy for chronic C hepatitis

O lúpus eritematoso sistêmico (LES) e a doença indiferenciada do conjuntivo são síndromes auto-imunes sistêmicas de etiologia complexa. Sua patogênese envolve fatores hormonais, ambientais e genéticos. Hepatite C tem sido diagnosticada com frequência crescente em pacientes com quadros de auto-imunidade. Os efeitos do interferon-alfa, antiviral usado rotineiramente na hepatite C, no sistema imunológico de pacientes com LES ou doenças correlatas tem constituído matéria de debate. Descrevem-se aqui duas pacientes com doenças auto-imunes que tiveram a doença básica melhorada após o uso de interferon-alfa para tratamento de hepatite C. A primeira paciente, 52 anos, branca, apresenta quadro de LES com artralgias, proteinúria, leucopenia, anticorpos antinucleares e anti-DNA desde 1996. Em diversas ocasiões esteve internada para corticoterapia endovenosa e imunossupressores. Na evolução, em novembro de 1996, apresentou elevação discreta de transaminases. Hepatite C foi diagnosticada através de sorologia, PCR e biópsia hepática. A terapêutica com interferon-alfa por seis meses foi altamente efetiva na hepatopatia. Concomitantemente, houve remissão clínico-laboratorial do LES. A segunda paciente, branca, 29 anos, apresenta quadro compatível com doença indiferenciada do conjuntivo desde 1990. Clinicamente, cursava com poliartralgias, neurite óptica, síndrome cerebelar, lapsos de memória recente e miopatia. Não havia marcadores sorológicos específicos de auto-imunidade. Em 1994, apresentou grande elevação de enzimas hepáticas. Hepatite C foi confirmada por PCR e biópsia hepática. O tratamento com interferon-alfa em 1995 foi eficaz na hepatite C, incluindo repetida negatividade na PCR, e também no quadro auto-imune. Em 1997 e 1999, os sintomas desmielinizantes recidivaram, mas foram responsivos a corticoterapia. A função permanece normal, com PCR negativo para HCV. Os efeitos do interferon-alfa no sistema imune são múltiplos e complexos. Em transplantados renais, seu uso na hepatite C pode causar rejeição do enxerto. Entretanto, possui, confirmadamente, ação antiproliferativa na leucose de células cabeludas e hemangiomas. De acordo com um estudo russo, o uso de interferons, principalmente se associados a ciclofosfamida, parece ser benéfico no LES. Por outro lado, outros relatos associam o interferon-alfa a induções de LES. Nas duas pacientes aqui reportadas, um potencial efeito imunosssupressor do alfa-interferon parece ter predominado

Expression of the catalytic activity of plasminogen activator under physiologic conditions.

We have investigated the factors governing the plasminogen-dependent fibrinolysis catalyzed by the serine proteinase, plasminogen activator (EC 3.4.21.-), under physiologic conditions. We found that live rabbit fibroblasts digested much less fibrin than predicted by cell-free assay of the secreted plasminogen activator. The reduced catalytic activity of plasminogen activator expressed by cells growing on fibrin was regulated by the salt concentration of culture medium. The plasminogen activators of cells from several mammalian species were inhibited by physiologic salt concentrations (0.15 M NaCl) in cell-free assays. CaCl2 and KCl, but not D-glucose, were also effective inhibitors. The catalytic activity of purified human urokinase and of plasmin was unaffected by increased ionic strength. Plasminogen activators secreted both spontaneously and in response to stimulation by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate, were inhibited by 0.15 M NaCl. Physiologic salt concentration appeared to function by interacting with plasminogen activator, or plasminogen, and a third component, possibly a reversible inhibitor. One consequence of this regulation of plasminogen activator under physiologic conditions is the limitation of plasminogen-dependent fibrin degradation by living cells.