ABSTRACT Objective: This study aimed to evaluate whether the therapeutic use of caffeine for premature newborns is associated with changes in sleep habits and the presence of obstructive sleep apnea in childhood. Methods: This is a cross-sectional single-center study in which the caretakers of 87 children aged 5–10 years, born full-term or preterm, treated or not with caffeine in the neonatal period, answered questionnaires to screen for obstructive sleep apnea (Pediatric Obstructive Sleep Apnea Screening Tool [PosaST]) and to characterize the sleep habits (Children's Sleep Habits Questionnaire [CSHQ]) of their children. ANOVA and linear regression tests were performed to verify possible differences between the groups. Results: Children born prematurely who were treated with caffeine woke up significantly later on weekdays than those born at term (09h±00h58 and 07h43±1h15, respectively, p=0.022) and had longer total daily sleep time also compared to those born at term (10h24±1h08 and 09h29±1h08, respectively, p<0.001). There was no significant difference between the three groups in overall PosaST and CSHQ scores. Conclusions: Caffeine use in the neonatal period did not impair sleep habits later in life and did not lead to increased obstructive sleep apnea scores in prematurely born children compared to those born at term.

RESUMO Objetivo: Avaliar se o uso terapêutico de cafeína para recém-nascidos prematuros se associa a alterações nos hábitos de sono e à presença de apneia obstrutiva do sono na infância. Métodos: Este é um estudo unicêntrico transversal no qual os responsáveis por 87 crianças com idades entre cinco e dez anos, nascidas a termo ou pré-termo e tratadas ou não com cafeína no período neonatal responderam a questionários para triagem de apneia obstrutiva do sono (Pediatric Obstructive Sleep Apnea Screening Tool – PosaST) e para a caracterização dos hábitos de sono (Children's Sleep Habits Questionnaire – CSHQ) de seus filhos. Foram realizados testes de variância (ANOVA) e de regressão linear para verificar possíveis diferenças entre os grupos. Resultados: As crianças nascidas prematuras que foram tratadas com cafeína acordaram significativamente mais tarde nos dias de semana do que as nascidas a termo (09h±00h58 e 07h43±1h15, respectivamente, p=0,022) e tiveram maior tempo total de sono diário também comparadas às nascidas a termo (10h24±1h08 e 09h29±1h08, respectivamente, p<0,001). Não houve diferença significativa entre os três grupos na pontuação geral dos questionários PosaST e CSHQ. Conclusões: O uso de cafeína no período neonatal não prejudicou tardiamente os hábitos de sono e não levou ao aumento dos escores de apneia obstrutiva do sono de crianças nascidas prematuras quando comparadas com crianças nascidas a termo.

RESUMO Considerando o envelhecimento como um fenômeno em que há um declínio nos processos essenciais a sobrevivência celular, investigamos as vias autofágica e proteassômica em três grupos: jovens, idosos e longevos. O perfil de expressão dos genes relacionados à via autofágica foi analisado em sangue periférico, e a quantificação do proteassoma realizada em plasma. Não foram encontradas alterações significativas nas concentrações plasmáticas de proteassoma ou na correlação entre as concentrações de proteassoma e as idades. No entanto, alguns genes relacionados a autofagia e / ou apoptose foram expressos diferencialmente. Além disso, as análises de rede e de enriquecimento mostraram uma interação entre quatro dos cinco genes diferencialmente expressos e a associação desses ao processo transcricional. Considerando que os indivíduos longevos mantiveram tanto a expressão de genes ligados à maquinaria autofágica, quanto os níveis de proteassoma quando comparados aos idosos, concluímos que esses fatores poderiam ser considerados cruciais para o envelhecimento bem-sucedido.

ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

RESUMO A doença de Pompe é uma doença hereditária causada pela deficiência da enzima alfa-glicosidase ácida (GAA). Estudo observacional foi realizado, em um único centro, para determinar a prevalência da doença de Pompe de início tardio (LOPD) em uma população brasileira de alto risco, usando teste em gota seca (DBS) como ferramenta principal de triagem para detectar a deficiência da GAA. DBS foi coletado para avaliar a atividade da GAA em 24 pacientes com fraqueza muscular de cinturas “não explicada” sem miopatia vacuolar na biópsia muscular. As amostras com atividade enzimática reduzida foram também submetidas a análise de mutações no gene GAA. Dos 24 pacientes com DBS, baixa atividade da enzima GAA (NaG/AaGIA: 40.42; %INH: 87.22%) foi encontrada em um paciente (4.2%). Nessa paciente, a análise genética confirmou duas mutações em heterozigose composta no gene GAA (c.-32-13T > G/p.Arg854Ter). Nossos resultados confirmam que LOPD deve ser investigada quando a manifestação clínica é uma fraqueza muscular de cinturas “não explicada”, mesmo na ausência de miopatia vacuolar na biópsia muscular.

ABSTRACT Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with “unexplained” limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an “unexplained” limb-girdle weakness even without vacuolar myopathy in muscle biopsy.

The present study evaluated the effects of postnatal intermittent hypoxia on locomotor activity and neuronal cell survival in early adulthood rats. During a critical period of brain development on postnatal day (PD) 7-11, male rat pups were exposed to intermittent hypoxia and randomly assigned to three experimental groups: (1) intermittent hypoxia, (2) normoxia, and (3) control (unhandled). One and a half months later on PD56, a behavioral test was conducted, and cell survival was estimated in the hilus, dental gyrus, and CA1 and CA3 subfields of the hippocampus, nucleus accumbens shell and core, dorsal and ventral striatum, and prefrontal cortex. Our results showed that intermittent hypoxia produced hyperactivity that correlated well with psychomotor agitation observed in patients with schizophrenia. Moreover, post-hypoxic rats exhibited a reduction of the number of neurons in the hilar region of the hippocampus and dorsal striatum, structures that have been neuropathologically associated with schizophrenia.These findings suggest that intermittent hypoxia can modify the pattern of locomotor activity and selectively affect neurons in rats tested in early adulthood.

OBJECTIVES: This study evaluated the effect of Continuous Positive Airway Pressure treatment on oxidative stress parameters and the quality of life of elderly patients with obstructive sleep apnea syndrome. METHODS: In total, 30 obstructive sleep apnea syndrome patients and 27 subjects without obstructive sleep apnea syndrome were included in this study. Both groups underwent quality of life and oxidative stress evaluations at baseline and after six months. Polysomnography was performed in both groups at baseline and a second time in the obstructive sleep apnea syndrome group after six months of Continuous Positive Airway Pressure treatment. All of the variables were compared between the control and obstructive sleep apnea syndrome groups in this prospective case-control study. RESULTS: The baseline concentrations of the antioxidant enzyme catalase were higher in the obstructive sleep apnea syndrome group than the control group. After Continuous Positive Airway Pressure treatment, the obstructive sleep apnea syndrome group exhibited a reduction in the level of oxidative stress, as indicated by a decrease in the level of lipid peroxidation measured by the malondialdehyde (MDA) concentration [pre: 2.7 nmol malondialdehyde/mL (95% 1.6-3.7) vs. post: 1.3 nmol MDA/mL (0.7-1.9), p<0.01]. Additionally, improvements were observed in two domains covered by the SF-36 questionnaire: functional capacity [pre: 77.4 (69.2-85.5) vs. post: 83.4 (76.9-89.9), p = 0.002] and pain [pre: 65.4 (52.8-78.1) vs. post: 77.8 (67.2-88.3), p = 0.004]. CONCLUSION: Our study demonstrated that the use of Continuous Positive Airway Pressure to treat obstructive sleep apnea syndrome in elderly patients reduced oxidative stress and improved the quality of life.

Fabry Disease, an X-linked inborn error of metabolism, is characterized by progressive renal insufficiency, with cardio and cerebrovascular involvement. Homocysteine (Hcy) is considered a risk factor for vascular diseases, but the mechanisms by which it produces cardiovascular damage are still poorly understood. Regarding the vascular involvement in FD patients, the analysis of factors related to thromboembolic events could be useful to improving our understanding of the disease. The aim of this study was to evaluate plasma Hcy and other parameters involved in the methionine cycle, as well as oxidative stress markers. The sample consisted of a group of 10 male FD patients and a control group of 8 healthy individuals, paired by age. Venous blood was collected for Hcy determination, molecular analysis, identification of thiobarbituric acid reactive substances, total glutathione and antioxidant enzymes activity, as well as vitamins quantification. Comparative analysis of FD patients versus the control group indicated hyperhomocysteinemia in 8 of the 10 FD patients, as well as a significant increase in overall glutathione levels and catalase activity. It is inferred that FD patients, apart from activation of the antioxidant system, present increased levels of plasma Hcy, although this is probably unrelated to common alterations in the methionine cycle.

Este estudo objetivou investigar a duração do sono e fatores associados em escolares trabalhadores e não trabalhadores. Foram coletadas informações sobre o padrão do ciclo vigília/sono de 863 adolescentes de 10 a 19 anos em escolas de São Paulo, Brasil. Análises ajustadas foram aplicadas para comparação da duração do sono entre trabalhadores e não trabalhadores. O porcentual de adolescentes trabalhadores foi de 18,4% e 52% dos jovens que trabalhavam apresentaram oito ou menos horas de sono. A prevalência de baixa duração do sono foi maior nos trabalhadores dos sexos masculino (p = 0,017) e feminino (p < 0,001). Os estudantes trabalhadores apresentaram menor duração do sono mesmo com ajuste pela classe socioeconômica (p < 0,001). Apesar de existirem mais trabalhadores no turno da noite, no modelo ajustado pelo sexo e nível socioeconômico, os estudantes trabalhadores do turno da tarde apresentaram maior prevalência de baixa duração do sono (RP = 2,53; IC95%: 1,68-4,12).

The aim of this study was to investigate the duration of sleep and associated factors in working and non-working students. Data were analyzed on the sleep-wake cycle in 863 teenage students in São Paulo, Brazil. Adjusted analyses were performed to compare sleep duration in working and non-working students. 18.4% of the group worked, and 52% of the working students slept eight hours or less per night. Prevalence of short sleep duration was higher in working students of both sexes (males, p = 0.017; females, p < 0.001). Working students showed short sleep duration in the analysis adjusted for socioeconomic status, but short sleep was more frequent in older adolescents (p = 0.004) and in lower (p = 0.001) and middle (p = 0.011) socioeconomic classes. Although more working students were in night school, in the model adjusted for gender and socioeconomic status, working students in afternoon courses showed higher prevalence of short sleep duration (PR = 2.53; 95%CI: 1.68-4.12).

Este estudo objetivou investigar a duração do sono e fatores associados em escolares trabalhadores e não trabalhadores. Foram coletadas informações sobre o padrão do ciclo vigília/sono de 863 adolescentes de 10 a 19 anos em escolas de São Paulo, Brasil. Análises ajustadas foram aplicadas para comparação da duração do sono entre trabalhadores e não trabalhadores. O porcentual de adolescentes trabalhadores foi de 18,4% e 52% dos jovens que trabalhavam apresentaram oito ou menos horas de sono. A prevalência de baixa duração do sono foi maior nos trabalhadores dos sexos masculino (p = 0,017) e feminino (p < 0,001). Os estudantes trabalhadores apresentaram menor duração do sono mesmo com ajuste pela classe socioeconômica (p < 0,001). Apesar de existirem mais trabalhadores no turno da noite, no modelo ajustado pelo sexo e nível socioeconômico, os estudantes trabalhadores do turno da tarde apresentaram maior prevalência de baixa duração do sono (RP = 2,53; IC95%: 1,68-4,12).

The aim of this study was to investigate the duration of sleep and associated factors in working and non-working students. Data were analyzed on the sleep-wake cycle in 863 teenage students in São Paulo, Brazil. Adjusted analyses were performed to compare sleep duration in working and non-working students. 18.4% of the group worked, and 52% of the working students slept eight hours or less per night. Prevalence of short sleep duration was higher in working students of both sexes (males, p = 0.017; females, p < 0.001). Working students showed short sleep duration in the analysis adjusted for socioeconomic status, but short sleep was more frequent in older adolescents (p = 0.004) and in lower (p = 0.001) and middle (p = 0.011) socioeconomic classes. Although more working students were in night school, in the model adjusted for gender and socioeconomic status, working students in afternoon courses showed higher prevalence of short sleep duration (PR = 2.53; 95%CI: 1.68-4.12).

Sleep disorders have an increased incidence after menopause. The objective of this work was to evaluate the effects of isoflavone on some oxidative stress markers in postmenopausal women complaining of insomnia. Women aged between 50-65 years (n=38) were recruited and assigned to a double-blind placebo controlled study for 4 months. The treated group received 100 mg/day of isoflavones. Blood collections were conducted on three different occasions to assess total glutathione; superoxide dismutase and catalase in erythrocytes; lipid peroxidation; and homocysteine plasma concentrations. No differences between the groups were observed. However, all the patients seem to improve their oxidative stress status and homocysteine concentration after treatment. Superoxide dismutase activity was correlated with age and time of menopause at the beginning of the treatment, but these correlations were no longer observed by the end of the study. Soy isoflavones were not able to overcome the placebo effect for either oxidative stress parameters or homocysteine concentrations.

OBJETIVO: Investigar a duração de sono na adolescência em diferentes níveis socioeconômicos. MÉTODO: Foram investigados 863 adolescentes de 10 a 19 anos em duas escolas de São Paulo, SP, Brasil. As coletas foram realizadas por meio de questionários para identificação de informações sobre os hábitos de sono e nível socioeconômico. RESULTADOS: A duração média de sono nos dias da semana foi de 8,83(1,87) horas e a prevalência de adolescentes com duração de sono de oito ou menos horas diárias foi de 39,0% nos dias com aula. Adolescentes da classe baixa apresentaram menor duração do sono (p = 0,043). Na análise ajustada, a idade, o nível socioeconômico e o hábito de tirar a sesta foram os principais fatores associados a poucas horas de sono. Os participantes de 18 a 19 anos apresentaram maior prevalência de poucas horas de sono em comparação aos de 10 a 11 anos (PR = 4,78; CI95%: 1,98-11,53), assim como os adolescentes da classe alta em comparação com a classe baixa (PR = 1,48; CI95%: 1,20-1,83). CONCLUSÃO: Os resultados mostraram associações entre o nível socioeconômico e os hábitos de sono de adolescentes.

OBJECTIVE: To investigate the sleep duration in adolescents of different socioeconomic status. METHOD: We investigated 863 adolescents from 10 to 19 years in two schools in São Paulo, SP, Brazil. Sleep habits data and socioeconomic status were obtained by questionnaires. RESULTS: Mean sleep duration on days of the week was 8.83(1.87) hours and the prevalence of adolescents with eight or fewer hours/day was 39.0% on school days (p = 0.043). On adjusted analysis, age, socioeconomic status and taking a nap habit were the main factors associated with few hours of sleep. Older students (aged 18 to 19 years) showed higher prevalence of few hours of sleep when compared to younger students (10 to 11 years) (RP = 4.78; IC95%: 1.98-11.53), as well as for upper class adolescents when compared to those with lower socioeconomic status. CONCLUSION: Results showed the association between socioeconomic status and adolescents' sleep/wake habits.

O presente estudo investigou fatores sócio-demográficos, de estilo de vida e gineco-obstétricos associados às concentrações séricas ou plasmáticas de homocisteína, ácido fólico, vitaminas B12 e B6 em mulheres de baixa renda de São Paulo, Brasil. Concentrações séricas de ácido fólico e vitamina B12 foram analisadas por fluoroimunoensaio; concentrações plasmáticas de homocisteína e vitamina B6, por cromatografia líquida de alta performance em fase reversa. Variáveis independentes foram inicialmente selecionadas segundo pressupostos teóricos, correlação de Pearson ou teste Kruskal-Wallis (p < 0,20). Concentrações alteradas segundo pontos de corte para homocisteína, ácido fólico, vitaminas B12 e B6 foram observadas em 20%, 6%, 11% e 67% das participantes, respectivamente. Idade foi positivamente correlacionada à vitamina B6 e homocisteína plasmáticas (p < 0,001). Índice de massa corporal foi positivamente correlacionado à vitamina B6 plasmática (p < 0,001). Modelos de regressão linear múltiplos explicaram 10,2%, 5,8%, 14,4% e 9,4% das concentrações de ácido fólico, vitamina B12, vitamina B6 e homocisteína, respectivamente. No presente estudo, variáveis sócio-demográficas, de estilo de vida e gineco-obstétricas apresentaram contribuição importante na variação das concentrações dos indicadores bioquímicos avaliados.

This study examined the socio-demographic, lifestyle, gynecological, and obstetric factors associated with serum or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6 among low-income women in São Paulo, Brazil. Serum concentrations of folic acid and vitamin B12 were measured by fluoroimmunoassay, while plasma vitamin B6 and homocysteine levels were measured by reversed-phase high performance liquid chromatography. Independent variables were initially selected by Pearson correlation or Kruskal-Wallis test (p < 0.20). Based on cut-off values, altered concentrations of homocysteine, folic acid, and vitamins B12 and B6 were found in 20%, 6%, 11%, and 67% of participants, respectively. Age was positively correlated with vitamin B6 and homocysteine plasma concentrations (p < 0.001). Body mass index was positively correlated with vitamin B6 plasma concentration (p < 0.001). Multiple linear regression models accounted for 10.2%, 5.8%, 14.4%, and 9.4% of folic acid, vitamins B12 and B6, and homocysteine plasma or serum concentrations, respectively. In this study, socio-demographic, lifestyle, gynecological, and obstetric variables showed important predictive value for serum or plasma levels of the biochemical indicators assessed.

O presente estudo investigou fatores sócio-demográficos, de estilo de vida e gineco-obstétricos associados às concentrações séricas ou plasmáticas de homocisteína, ácido fólico, vitaminas B12 e B6 em mulheres de baixa renda de São Paulo, Brasil. Concentrações séricas de ácido fólico e vitamina B12 foram analisadas por fluoroimunoensaio; concentrações plasmáticas de homocisteína e vitamina B6, por cromatografia líquida de alta performance em fase reversa. Variáveis independentes foram inicialmente selecionadas segundo pressupostos teóricos, correlação de Pearson ou teste Kruskal-Wallis (p < 0,20). Concentrações alteradas segundo pontos de corte para homocisteína, ácido fólico, vitaminas B12 e B6 foram observadas em 20%, 6%, 11% e 67% das participantes, respectivamente. Idade foi positivamente correlacionada à vitamina B6 e homocisteína plasmáticas (p < 0,001). Índice de massa corporal foi positivamente correlacionado à vitamina B6 plasmática (p < 0,001). Modelos de regressão linear múltiplos explicaram 10,2%, 5,8%, 14,4% e 9,4% das concentrações de ácido fólico, vitamina B12, vitamina B6 e homocisteína, respectivamente. No presente estudo, variáveis sócio-demográficas, de estilo de vida e gineco-obstétricas apresentaram contribuição importante na variação das concentrações dos indicadores bioquímicos avaliados.

This study examined the socio-demographic, lifestyle, gynecological, and obstetric factors associated with serum or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6 among low-income women in São Paulo, Brazil. Serum concentrations of folic acid and vitamin B12 were measured by fluoroimmunoassay, while plasma vitamin B6 and homocysteine levels were measured by reversed-phase high performance liquid chromatography. Independent variables were initially selected by Pearson correlation or Kruskal-Wallis test (p < 0.20). Based on cut-off values, altered concentrations of homocysteine, folic acid, and vitamins B12 and B6 were found in 20%, 6%, 11%, and 67% of participants, respectively. Age was positively correlated with vitamin B6 and homocysteine plasma concentrations (p < 0.001). Body mass index was positively correlated with vitamin B6 plasma concentration (p < 0.001). Multiple linear regression models accounted for 10.2%, 5.8%, 14.4%, and 9.4% of folic acid, vitamins B12 and B6, and homocysteine plasma or serum concentrations, respectively. In this study, socio-demographic, lifestyle, gynecological, and obstetric variables showed important predictive value for serum or plasma levels of the biochemical indicators assessed.

OBJETIVOS: Determinar os valores plasmáticos de homocisteína e fator von Willebrand, como marcador de disfunção endotelial, em ratos com diabete melito induzido por estreptozotocina. MÉTODOS: Trinta e cinco ratos (rattus norvegicus albinus), machos, adultos (180-200 g), randomizados em três grupos: controle (n=10) não receberam agente ou veículo; sham (n=10) receberam solução veículo da estreptozotocina; e diabético (n=15) receberam estreptozotocina. Após oito semanas de indução do diabete melito, os animais foram pesados, anestesiados e tiveram sangue colhido da aorta abdominal para determinação dos valores de homocisteína plasmática total, fator von Willebrand e glicemia. RESULTADOS: O modelo experimental foi reprodutível em 100% dos animais. A média das concentrações plasmáticas de homocisteína foi: 7,9 µmol/l (controle); 8,6 µmol/l (sham) e 6,1 µmol/l (diabético), com diferença entre os grupos (p<0,01). Pelo método de comparações múltiplas entre os grupos, observou-se que os valores no grupo diabético foram menores que no sham (p<0,01). A média dos valores do fator von Willebrand foi 0,15 U/l (controle), 0,16 U/l (sham) e 0,18 U/l (diabético), com diferença entre os grupos (p=0,03). A média dos seus valores no grupo diabético foi maior que no grupo controle (p<0,05). No grupo diabético não houve correlação entre homocisteína e fator von Willebrand. CONCLUSÃO: No diabete melito induzido por estreptozotocina constataram-se valores reduzidos de homocisteína e elevados de fator von Willebrand, sem, contudo, haver correlações entre si e com níveis de glicemia final.

OBJECTIVES: To determine the plasma homocysteine and von Willebrand factor levels as markers of endothelial dysfunction in rats with diabetes mellitus induced by streptozotocin. METHODS: Thirty-five adult male rats (Rattus norvegicus albinus) (weight between 180-200g) were randomized into three groups: control group (n=10), which received no drugs or vehicles; sham group (n=10), which received streptozotocin solution; and diabetic group (n=15), which received streptozotocin. Eight weeks after diabetes mellitus induction, the animals were weighed and anesthesized; blood samples were collected from abdominal aorta for plasma total homocysteine, von Willebrand factor and glucose levels. RESULTS: The experimental model was reproducible in 100% of animals. The mean plasma homocysteine levels were: 7.9 µmol/l (control), 8.6µmol/l (sham) and 6.1µmol/l (diabetic), with difference among the groups (p<0.01). Multiple comparison analysis among the groups showed that values in the diabetic group were lower than in the sham group (p<0.01). The mean von Willebrand factor values were 0.15 U/l (control), 0.16U/l (sham) and 0.18 U/l (diabetic), with difference among the groups (p=0.03). The mean value was higher in the diabetic group than in the control group (p<0.05). Correlation between homocysteine and von Willebrand factor was not observed in the diabetic group. CONCLUSION: Reduced homocysteine levels and increased von Willebrand factor levels were observed in diabetes mellitus induced by streptozotocin; nevertheless, there were no correlations between them and with final glucose levels.

Liver microsomal cytochrome P4502E1-dependent p-nitrophenol (PNP) hydroxylation and expression of cytochrome P4502E1 were studied in rats subjected to g-hexachlorocyclohexane (HCCH) or L-3,3,,5-triiodothyronine (T3) administration as a possible mechanism contributing to superoxide radical (O2.-) generation. HCCH treatment (a single dose of 40 mg/kg body wt) produced a 43% increase in the content of total cytochrome P450, whereas T3 (daily doses of 0.1 mg/kg body wt for two consecutive days) led to a 37% decrease. NADPH-dependent O2.- generation was elevated by HCCH and T3, expressed as either per mg of protein or per nmol of cytochrome P450, with a 135% enhancement in the O2.- production/superoxide dismutase (SOD) activity ratios being observed in both conditions. This was partly due to depression of SOD activity. Concomitantly, the molecular activity of NADPH-cytochrome p450 reductase was enhanced by 90 and 69% by HCCH and T3, respectively. In these conditions, microsomal PNP hydroxylation showed increases of 58 and 45% in HCCH- and T3-treated rats over control values, respectively, with a parallel 31% (HCCH) and 41% (T3) enhancement in the content of cytochrome P4502E1 assessed by western immunoblotting. We conclude that HCCH and T3 enhance the expression and activity of cytochrome P4502E1 and that of NADPH-cytochrome P450 reductase in rat liver, regardless of the changes in total cytochrome P450 content, representing major contributory mechanisms to microsomal NADPH-dependent O2.- generation

OBJECTIVE - To determine the prevalence of hyperhomocystinemia in patients with acute ischemic syndrome of the unstable angina type. METHODS - We prospectively studied 46 patients (24 females) with unstable angina and 46 control patients (19 males), paired by sex and age, blinded to the laboratory data. Details of diets, smoking habits, medication used, body mass index, and the presence of hypertension and diabetes were recorded, as were plasma lipid and glucose levels, C-reactive protein, and lipoperoxidation in all participants. Patients with renal disease were excluded. Plasma homocysteine was estimated using high-pressure liquid chromatography. RESULTS - Plasma homocysteine levels were significantly higher in the group of patients with unstable angina (12.7±6.7 µmol/L) than in the control group (8.7±4.4 µmol/L) (p<0.05). Among males, homocystinemia was higher in the group with unstable angina than in the control group, but this difference was not statistically significant (14.1±5.9 µmol/L versus 11.9±4.2 µmol/L). Among females, however, a statistically significant difference was observed between the 2 groups: 11.0±7.4 µmol/L versus 6.4±2.9 µmol/L (p<0.05) in the unstable angina and control groups, respectively. Approximately 24% of the patients had unstable angina at homocysteine levels above 15 µmol/L. CONCLUSION - High homocysteine levels seem to be a relevant prevalent factor in the population with unstable angina, particularly among females.