RESUMO
BACKGROUND AND OBJECTIVES: Leprosy is yet an important infectious disease in Brazil. The objective of this study was to determine the frequency of leprosy among children and adolescents in a countryside city from Legal Amazon region. RESULTS: there was a high frequency of Hansen's disease among children from 5 to 9 years-old, predominantly females, with multibacillary form, and dimorphous types. CONCLUSION: due to late diagnosis and higher frequency of treatment abandonment leprosy is a serious public health problem among children and adolescents is this small city.
Assuntos
Hanseníase Multibacilar/embriologia , Hanseníase/epidemiologia , Adolescente , Distribuição por Idade , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Lactente , Masculino , PrevalênciaRESUMO
We determined if the increased vascular responsiveness to endothelin-1 (ET-1) observed in male, but not in female, DOCA-salt rats is associated with differential vascular mRNA expression of ET-1 and/or ET A/ET B receptors or with functional differences in Ca2+ handling mechanisms by vascular myocytes. Uninephrectomized male and female Wistar rats received DOCA and drinking water containing NaCl/KCl. Control rats received vehicle and tap water. Blood pressure and contractile responses of endothelium-denuded aortic rings to agents which induce Ca2+ influx and/or its release from internal stores were measured using standard procedures. Expression of mRNA for ET-1 and ET A/ET B receptors was evaluated by RT-PCR after isolation of total cell RNA from both aorta and mesenteric arteries. Systolic blood pressure was higher in male than in female DOCA rats. Contractions induced by Bay K8644 (which activates Ca2+ influx through voltage-operated L-type channels), and by caffeine, serotonin or ET-1 in Ca2+-free buffer (which reflect Ca2+ release from internal stores) were significantly increased in aortas from male and female DOCA-salt compared to control aortas. DOCA-salt treatment of male, but not female, rats statistically increased vascular mRNA expression of ET-1 and ET B receptors, but decreased the expression of ET A receptors. Molecular up-regulation of vascular ET B receptors, rather than differential changes in smooth muscle Ca2+ handling mechanisms, seems to account for the increased vascular reactivity to ET-1/ET B receptor agonists and higher blood pressure levels observed in male DOCA-salt rats.
Assuntos
Cálcio/metabolismo , Endotelina-1/genética , Hipertensão/metabolismo , Receptores de Endotelina/metabolismo , Caracteres Sexuais , Vasoconstrição , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil) , Animais , Cafeína/farmacologia , Agonistas dos Canais de Cálcio/farmacologia , Desoxicorticosterona , Feminino , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We determined if the increased vascular responsiveness to endothelin-1 (ET-1) observed in male, but not in female, DOCA-salt rats is associated with differential vascular mRNA expression of ET-1 and/or ET A/ET B receptors or with functional differences in Ca2+ handling mechanisms by vascular myocytes. Uninephrectomized male and female Wistar rats received DOCA and drinking water containing NaCl/KCl. Control rats received vehicle and tap water. Blood pressure and contractile responses of endothelium-denuded aortic rings to agents which induce Ca2+ influx and/or its release from internal stores were measured using standard procedures. Expression of mRNA for ET-1 and ET A/ET B receptors was evaluated by RT-PCR after isolation of total cell RNA from both aorta and mesenteric arteries. Systolic blood pressure was higher in male than in female DOCA rats. Contractions induced by Bay K8644 (which activates Ca2+ influx through voltage-operated L-type channels), and by caffeine, serotonin or ET-1 in Ca2+-free buffer (which reflect Ca2+ release from internal stores) were significantly increased in aortas from male and female DOCA-salt compared to control aortas. DOCA-salt treatment of male, but not female, rats statistically increased vascular mRNA expression of ET-1 and ET B receptors, but decreased the expression of ET A receptors. Molecular up-regulation of vascular ET B receptors, rather than differential changes in smooth muscle Ca2+ handling mechanisms, seems to account for the increased vascular reactivity to ET-1/ET B receptor agonists and higher blood pressure levels observed in male DOCA-salt rats
Assuntos
Animais , Masculino , Feminino , Ratos , Desoxicorticosterona , Endotelina-1 , Hipertensão , Receptores de Endotelina , Cloreto de Sódio , Vasoconstrição , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro , Caracteres SexuaisRESUMO
We previously demonstrated a differential activation of the endothelin-1 (ET-1) pathway in male and female deoxycorticosterone (DOCA)-salt hypertensive rats, with the male rats exhibiting marked alterations in vascular and pressor responses to ET-1 and Suc-[Glu,(9)Ala(11,15)]-ET-1(8-21) (IRL-1620), an ET(B) agonist. Mechanisms underlying these gender differences are unclear, and we hypothesized that the ovarian hormones attenuate vascular ET(B) responses in female DOCA-salt rats. Female Wistar rats were randomized in 3 groups: sham-operated, ovariectomized (OVX), and OVX plus hormone replacement with estradiol (E) or estradiol/progesterone (EP). Two weeks later, rats were uninephrectomized and further randomized in DOCA-salt (subcutaneous injections of desoxycorticosterone and drinking water containing NaCl/KCl) and control normotensive (subcutaneous injections of vehicle and tap water). Blood pressure was evaluated both by direct and standard tail-cuff methods. Responses to IRL-1620 were evaluated in vivo/in situ in the mesenteric microcirculation. mRNA expression of ET-1 and ET(A/B) receptors was evaluated in mesenteric arteries by reverse transcription-polymerase chain reaction and expressed relative to GAPDH. OVX-DOCA rats developed a more severe form of hypertension than did DOCA rats. Treatment with E or EP restored blood pressure to levels observed in DOCA rats. In the mesentery, IRL-1620 induced vasodilatation in control rats, a mild vasoconstriction in DOCA rats, and marked vasoconstriction in OVX-DOCA rats. Both E and EP decreased IRL-1620-induced vasoconstriction in the DOCA group. In the normotensive group, OVX did not change blood pressure or IRL-1620-induced vasodilation. Removal of the ovaries increased ET-1 mRNA in arteries from DOCA and control rats, although treatment with E or EP reversed these changes. Vascular ET(B) receptor mRNA levels were greatly enhanced in OVX-DOCA but not OVX-control rats. Hormone replacement with E or EP restored ET(B) receptor expression in the DOCA group. A greater blood pressure-lowering effect of bosentan (ET(A)/ET(B) blocker) was observed in OVX-DOCA rats. The observation that OVX worsens hypertension as well as the altered ET(B) receptor-mediated responses and the effects of bosentan in female DOCA rats supports our suggestion that the ovarian hormones modulate ET-1/ET(B) receptor vascular responses/expression in DOCA-salt hypertension.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotelina-1/farmacologia , Estradiol/farmacologia , Hipertensão/fisiopatologia , Progesterona/farmacologia , RNA Mensageiro/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Desoxicorticosterona/administração & dosagem , Endotelina-1/genética , Endotelinas/farmacologia , Estradiol/sangue , Feminino , Hipertensão/induzido quimicamente , Hipertensão/genética , Técnicas In Vitro , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Ovariectomia , Fragmentos de Peptídeos/farmacologia , Potássio na Dieta/administração & dosagem , Progesterona/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cloreto de Sódio na Dieta/administração & dosagem , Fatores de Tempo , Útero/crescimento & desenvolvimento , Vasoconstrição/efeitos dos fármacosRESUMO
In experimental models of hypertension, blood pressure reaches a higher level in male than in female rats. Because endothelin-1 (ET-1) seems to play a role in blood pressure elevation in deoxycorticosterone acetate (DOCA)-salt hypertension, we hypothesized that male DOCA-salt rats would display a greater vascular responsiveness to ET-1 than female DOCA-salt rats. Male and female Wistar rats were uninephrectomized, received DOCA injections (50 mg/kg/week) and water plus 1.0% NaCl/0.2% KCl. Control rats received vehicle and tap water. Responses to ET-1, norepinephrine (NE), serotonin (5-HT), IRL-1620, a selective endothelin-B- (ET(B)) receptor agonist, and acetylcholine (ACh) were evaluated in isolated aortic rings and also in vivo in the mesenteric microcirculation. Endothelium-intact aortas from male and female DOCA rats displayed increased sensitivity (p < 0.05) to NE and 5-HT, but decreased relaxation to ACh in comparison to aortas from respective control male and female rats. Endothelium-denuded, but not endothelium-intact, arteries from male DOCA rats displayed increased sensitivity (-log EC20) to ET-1, but no changes in ET-1 sensitivity were observed in female DOCA aortas. IRL-1620 induced contraction in male DOCA aortas, but not in female DOCA or control endothelium-denuded aortas. In the microcirculation, IRL-1620 induced vasodilation in male and female control rats, but marked vasoconstriction in male DOCA and minimal changes in vessels diameter in female DOCA rats. Bosentan, an ET(A)/ET(B)-receptor antagonist, induced a greater decrease in mean arterial blood pressure in male than in female DOCA-salt hypertensive rats. These data support the hypothesis that DOCA-salt rats exhibit gender differences in ET-1 vascular reactivity, which probably result from functional changes in ET(B)-receptors. The increased ET(B) responses in male DOCA-salt hypertensive rats may play a role in their higher blood pressure levels.
Assuntos
Desoxicorticosterona/farmacologia , Endotelina-1/farmacologia , Hipertensão/fisiopatologia , Cloreto de Sódio/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Endotelinas/farmacologia , Feminino , Técnicas In Vitro , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Caracteres SexuaisRESUMO
AIMS: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. METHODS: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. RESULTS: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy. CONCLUSIONS: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.
Assuntos
Consumo de Bebidas Alcoólicas/sangue , Anti-Infecciosos/sangue , Cirrose Hepática Alcoólica/fisiopatologia , Hepatopatias/fisiopatologia , Metronidazol/análogos & derivados , Metronidazol/sangue , Adolescente , Adulto , Idoso , Anti-Infecciosos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Humanos , Cirrose Hepática Alcoólica/sangue , Hepatopatias/sangue , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-IdadeRESUMO
AIMS: To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis. METHODS: Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion. RESULTS: Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion. CONCLUSIONS: Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.
Assuntos
Hepacivirus , Hepatite C/sangue , Fígado/metabolismo , Metronidazol , Adulto , Feminino , Hepacivirus/imunologia , Hepatite C/diagnóstico , Hepatite C/imunologia , Humanos , Testes de Função Hepática , Masculino , Metronidazol/sangue , Metronidazol/metabolismo , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side-effects. The aim of this study was to investigate the effects of a 5-day administration of omeprazole on metronidazole pharmacokinetics. METHODS: Fourteen healthy male volunteers were selected. The study had an open, randomized, two-period crossover design with a 21-day washout period between the phases. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reversed-phase HPLC with ultraviolet detection. RESULTS: Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole. CONCLUSION: Our results indicate that short-term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.