Evaluation of mild hyperhomocysteinemia during the development of atherosclerosis in apolipoprotein E-deficient and normal mice.

We focused on the effect of mild hyperhomocysteinemia (HHcy) on the development of atherosclerosis, using apolipoprotein E-deficient (apoE(-/-)) and normal mice. Mice received diets enriched in methionine with low or high levels of folate, B(12) and B(6) (diets B and C, respectively), and diet only with low levels of folate, B(12) and B(6) (diets D), to induce mild HHcy. Normal mice fed on diets B, C and D presented mild HHcy, but they did not develop atherosclerotic lesions after 24 weeks of diet. In addition, increased endoplasmic reticulum stress was present in normal mice fed on diet B, compared to others groups. ApoE(-/-) mice fed on diet B for 20 weeks presented the greatest atherosclerotic lesion area at the aortic sinus than other groups. These results suggest that the methionine may have a toxic effect on endothelium, and the B-vitamins addition on diet may have a protective effect in the long term, despite the increase on homocysteine levels. Mild HHcy accelerated the development of atherosclerosis in apoE(-/-) mice, and supplementation with B-vitamins is important for prevention of vascular disease, principally in the long term.

Assessment of serum chromogranin-A as prognostic factor in high-risk prostate cancer.

PURPOSE: The presence of neuroendocrine differentiation may play a key role in androgen-independent tumor progression. The prognostic significance of plasma chromogranin-A (CgA) was assessed in a series of consecutive patients with high-risk prostate cancer (PCa). PATIENTS AND METHODS: Twenty-three patients presenting high-risk PCa and 8 healthy individuals, as control group, had their blood samples collected to evaluate CgA, free and total prostate specific antigen, and free and total testosterone in a pilot study. The correlations of serum CgA levels with PSA, testosterone, Gleason score, number of foci of hypercaptation in bone scan, age, and outcomes were evaluated at baseline and after 12 months. RESULTS: Patients with PCa had significantly higher levels of plasma CgA (mean, 8.7; range, 1.9-73) than healthy patients (mean, 3.45; range, 0.6-5.6), P = 0.02. Analyzing only the patients group through correlation of the ranks, it was observed that CgA has low, insignificant correlations with PSA (P = 0.07) and with metastatic extension (P = 0.09). No association was found between the plasma CgA levels and the Gleason score (P = 0.20), age (P = 0.15), or disease progression (P = 0.27). CONCLUSION: The serum levels of CgA were significantly increased in the group with PCa compared with the healthy group. However, there were low correlations between serum CgA and known prognostic factors (such as total and free PSA, age, Gleason score, and bone metastases) or clinical deterioration. Although future studies are needed with larger samples and longer follow-up, the presented data envisage a limited role to serum CgA as high-risk PCa prognostic factor.

Insuficiência renal crônica e hormônio de crescimento: efeitos no eixo GH-IGF e na leptina / Chronic renal failure and growth hormone: effects on GH-IGF axis and leptin

OBJETIVO: Avaliar as alterações de IGF-1, IGFBP-3, leptina e insulina após o uso de doses de reposição de hormônio de crescimento recombinante humano (rhGH) em crianças baixas pré-púberes com insuficiência renal crônica (IRC). CASUíSTICA E MÉTODOS: Em 11 crianças (3F:8M), com idade média de 9,6 anos, em uso de rhGH (0,23mg/Kg/semana) por 12 meses, foram dosados (antes, 6 e 12 meses após o início do tratamento com rhGH) leptina, insulina, glicemia, IGF-1 e IGFBP-3. RESULTADOS: As concentrações séricas de leptina, insulina e glicemia não variaram significativamente no decorrer do uso do rhGH, sendo observado o padrão de leptina e glicemia normais, com hiperinsulinemia. Houve aumento significativo da IGF-1 e IGFBP-3 durante o uso do rhGH. CONCLUSÕES: O uso de doses de reposição de rhGH durante 12 meses em um grupo selecionado de crianças com IRC propiciou aumento significativo da concentração sérica de IGF-1 e IGFBP-3, com leptinemia normal e resistência insulínica.

Effectiveness of female and male condoms in preventing exposure to semen during vaginal intercourse: a randomized trial.

OBJECTIVES: Comparison of male condom (MC) vs. female condom (FC) with respect to self-reported mechanical and acceptability problems and semen exposure using prostate-specific antigen (PSA) as an objective biological marker and evaluation of the effect of an educational intervention on self-reported problems and semen exposure, by condom type. DESIGN: Randomized crossover trial. METHODS: Four hundred women attending a family planning clinic in Brazil were randomized and either received in-clinic instruction or were encouraged to read the condom package insert; all used two FCs and two MCs. We measured the rates of self-reported user problems with MC and FC use and the rates of semen exposure during use (assessed by testing vaginal fluid for PSA). RESULTS: The educational intervention group reported fewer problems with either condom as compared with the control group (p = .0004, stratified by condom type). In both groups, self-reported problems were more frequent with FC use than with MC use (p < .0001, stratified by intervention). The educational intervention did not significantly reduce semen exposure. Overall, semen exposure occurred more frequently with FC use (postcoital PSA, > 1 ng/mL; 22%) than with MC use (15%); the difference, however, was small and nonsignificant for high PSA levels (> or = 150 ng/mL; 5.1% for FC vs. 3.6% for MC). CONCLUSIONS: In this study, the FC was less effective than the MC in preventing semen exposure during use and led more frequently to self-reported user problems. Both devices were highly protective against "high-level" semen exposure, as measured by postcoital PSA levels in vaginal fluid. In-clinic education may reduce user problems and increase acceptability and use of both devices.

[Chronic renal failure and growth hormone: effects on GH-IGF axis and leptin]. / Insuficiência renal crônica e hormônio de crescimento: efeitos no eixo GH-IGF e na leptina.

AIM: To analyze the changes in IGF-1, IGFBP-3, leptin and insulin after replacement doses of recombinant human growth hormone (rhGH) in short prepubertal children with chronic renal failure (CRF). PATIENTS AND METHODS: Eleven children (3F:8M), with mean age of 9.6 years, were treated with rhGH (0.23 mg/Kg weekly for 12 months). Serum leptin, insulin, glucose, IGF-1 and IGFBP-3 were measured before, 6 and 12 months after beginning rhGH treatment. RESULTS: The serum levels of leptin, insulin and glucose did not vary during the treatment; normal leptin and glucose levels and high insulin were observed. There was a significant increment of IGF-1 and IGFBP-3 during the use of rhGH. CONCLUSIONS: The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.

Diagnosis of 5alpha-reductase type 2 deficiency: contribution of anti-Müllerian hormone evaluation.

AIM: To evaluate anti-Müllerian hormone (AMH) levels in patients with clinical and molecular diagnosis of 5alpha-reductase 2 deficiency. PATIENTS AND METHODS: Data from 14 patients whose age ranged from 21 days to 29 years were analyzed according to age and pubertal stage. Sexual ambiguity was rated as Prader III in 11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum levels were measured in all but two patients, who had been previously submitted to gonadectomy; T and DHT were also measured in 20 age-matched controls. RESULTS: Gonadotropin levels were normal in all but one patient who retained gonads (six of whom had reached puberty) and T/DHT ratio was elevated in all patients when compared to controls. All prepubertal patients had AMH levels < -1 SD for age, while most pubertal patients had AMH levels compatible with pubertal stage. CONCLUSIONS: Prepubertal patients with 5alpha-reductase 2 deficiency have AMH values in the lower part of the normal range. These data indicate that T does not need to be converted to DHT to inhibit AMH secretion by Sertoli cells.

Perda do ritmo circadiano do TSH como variável prognóstica em pacientes críticos / Loss of circadian rhythm of TSH as outcome sacdor in critically ill patients

Foram estudados 75 pacientes consecutivamente internados na UTI, dos quais 45 eram do sexo feminino e 30 do sexo masculino. A idade variou de 23 a 69 anos. Todos eram portadores de patologias graves que exigiam algum tipo de cuidado intensivo. No primeiro dia da internaçäo foram colhidas amostras de sangue para dosagem de TSH às 8h da manha (TSH8) e à 1 hora da madrugada (TSH1). Os pacientes foram divididos em dois grupos: o Grupo A com 54 pacientes que sobreviveram à internaçäo, e o Grupo B com 21 pacientes que vieram a falecer durante a internaçäo na UTI. Os pacientes do Grupo A apresentaram um TSH(8) médio de 1,19 + 0,14 mU/L e um TSH(1) de 1,41 + 0,14 mU/L. Já o Grupo B apresentou um TSH(8) médio de 1.08 + 0,24 mU/L e um TSH(1) de 1,31 + 0,28 mU/L. Os pacientes do Grupo A (sobreviventes) apresentaram diferenças estatisticamente significantes nos valores de TSH(8) em relaçäo aos valores de TSH(1). Contrariamente, no Grupo B (Nao sobreviventes) os valores de TSH(8) e TSH(1) näo diferiram estatisticamente. Foi realizada também uma análise de regressäo logística combinada dos dados de TSH(8) e de TSH(1) em relaçäo ao número de sobreviventes (P) e näo-sobreviventes (1-P). Foi utilizado o modelo: Log (P/1-P)=a + Beta1 *TSH(8)) + (Beta2 *TSH(1)). A análise resultou com uma estimativa de mortalidade de somente 56 por cento o que expressa um baixo poder de discriminaçäo entre sobreviventes e näo-sobreviventes. Conclui-se que a despeito da demonstraçäo de uma depressäo do surto noturno de TSH em pacientes críticos, esta variável, isoladamente, carece de poder discriminatório. Nesta série o sistema APACHE-II se mostrou superior. A inclusäo de T3,T4 e cortisol além do TSH na análise de regressäo logística poderia atingir maior precisäo, para ser usada, possivelmente, como um índice Prognóstico Endócrino.

Avaliaçäo clínica de um ensaio sensível de TSH na definiçäo do estado tiroidiano / Clinical evaluation of the sensitive assay of TSH in determination of the thyroid condition

O uso rotineiro de ensaios sensíveis para determinaçäo de TSH, recentemente introduzidos em nosso meio, trouxe grande melhora no diagnóstico de hipertiroidismo. No entanto, estes ensaios possuem limitaçöes, pois TSH em nível baixo mas näo detectável tem sido descrito em várias eventualidades que näo representam estado de hipertiroidismo. Condiçöes ambientais, particularmente a iodemia, podem interferir nos valores de normalidade do método. Assim, determinamos os parâmetros do ensaio de TSH em nosso meio a partir de dosagens de TSH, T4I, AcTg e AcTPO realizados em 91 voluntários normais. Selecionamos, das 1538 dosagens de rotina realizadas durante o ano de 1992 em nosso laboratório, os 94 pacientes com TSH inferior ao nosso limite inferior de normalidade mas näo suprimido. Destes indivíduos obtivemos pelo menos outras 2 avaliaçöes hormonais com dosagens de TSH e acompanhamento clínico de Mo=1 ano em 74 casos. Determinamos assim as causas de TSH subnormal em nosso meio, observando tratar-se principalmente de pacientes admitidos em U.T.I. por doenças críticas (32 por cento dos casos); indequadamente tratados com hormônios ou drogas anti-tiroidianas (26 por cento) e indivíduos eutiroidianos (14 por cento). Concluimos que nosso ensaio de TSH permite definiçäo do estado tiroidiano com segurança, necessitando de complementaçäo com T4I em menos de 6 por cento dos pacientes