RESUMO
Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.
Assuntos
Barorreflexo , Sepse , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Frequência Cardíaca , Rim , Ratos , Ratos Wistar , Sistema Nervoso SimpáticoRESUMO
Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.
RESUMO
Osteogenesis imperfecta (OI) is a Mendelian disease with genetic heterogeneity characterized by bone fragility, recurrent fractures, blue sclerae, and short stature, caused mostly by mutations in COL1A1 or COL1A2 genes, which encode the pro-α1(I) and pro-α2(I) chains of type I collagen, respectively. A Brazilian family that showed variable expression of autosomal dominant OI was identified and characterized. Scanning for mutations was carried out using SSCP and DNA sequence analysis. The missense mutation c.3235G>A was identified within exon 45 of the COL1A1 gene in a 16-year-old girl diagnosed as having OI type I; it resulted in substitution of a glycine residue (G) by a serine (S) at codon 1079 (p.G1079S). The proband's mother had the disease signs, but without bone fractures, as did five of nine uncles and aunts of the patient. All of them carried the mutation, which was excluded in four healthy brothers of the patient's mother. This is the first description in a Brazilian family with OI showing variable expression; only one among seven carriers for the c.3235G>A mutation developed bone fractures, the most striking clinical feature of this disease. This finding has a significant implication for prenatal diagnosis in OI disease.
Assuntos
Colágeno Tipo I/genética , Mutação de Sentido Incorreto/genética , Osteogênese Imperfeita/genética , Adolescente , Adulto , Idoso , Substituição de Aminoácidos/genética , Sequência de Bases , Brasil , Criança , Cadeia alfa 1 do Colágeno Tipo I , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Polimorfismo Conformacional de Fita Simples/genéticaRESUMO
Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c.1875+1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.
Assuntos
Colágeno Tipo I/genética , Mutação , Osteogênese Imperfeita/genética , Splicing de RNA/genética , Adolescente , Densidade Óssea , Brasil , Cadeia alfa 1 do Colágeno Tipo I , Análise Mutacional de DNA , Humanos , MasculinoAssuntos
Humanos , Vitiligo/diagnóstico , Vitiligo/etiologia , Vitiligo/psicologia , Vitiligo/terapiaRESUMO
BACKGROUND: Myocardial infarction is an important cause of heart failure because it cause tissue loss and contractility disturbances. In chronically infarcted hearts the increase in the collagen content in the extracellular matrix of the surviving viable myocardium has been considered a major factor contributing to development of heart failure. Postinfarction neuroendocrine activation involving the renin-angiotensin system has been implicated in this cardiac fibrosis. METHODS AND RESULTS: As collagen synthesis and degradation are dynamic processes and postinfarction remodeling is a time-dependent phenomenon, rats submitted to coronary artery ligation to produce myocardial infarction were treated with captopril after infarction (30 mg/kg, intraperitoneally, daily) to investigate whether blockade of the renin-angiotensin system can prevent postinfarction myocardial hypertrophy and reactive fibrosis. Groups of rats with myocardial infarction were treated with captopril throughout the protocol period (6 weeks), or during the first 3 weeks after infarction (early therapy), or only during the last 3 weeks of the protocol (late therapy). Untreated groups of rats with or without myocardial infarction were used as control subjects. All animals were killed 6 weeks after surgery to evaluate hypertrophy of heart chambers and collagen deposition in the right ventricle wall and in surviving left ventricular muscle. Protein and hydroxyproline concentrations were assayed biochemically in these tissue homogenates. Only rats with an infarct covering 20 to 40% of the left ventricular surface were included in the study. In the control uninfarcted group (n = 12), hydroxyproline content was 152 +/- 12 micrograms in the right ventricle and 370 +/- 30 micrograms in the left ventricle. These values increased (P < .05) to 232 +/- 13 and 630 +/- 46 micrograms, respectively, in the group with myocardial infarction (n = 8) without treatment. These values were significantly reduced (P < .05) to 160 +/- 9 micrograms in the right ventricle and 520 +/- 40 micrograms in the left ventricle in the group with myocardial infarction treated with captopril for 6 weeks. The percentage decreases in collagen content and myocardial weight produced by captopril were similar. Thus, hydroxyproline concentration (mg hydroxyproline muscle), which increases significantly in both ventricles after myocardial infarction, was not modified by captopril therapy. Protein concentration in the right and left ventricular muscles decreased after myocardial infarction. This decrease was enhanced in the infarcted groups submitted to captopril treatment, mainly in the group treated for 6 weeks. Lesser effects on hypertrophy and hydroxyproline content were observed in the groups of rats treated with captopril in only the earlier or later phase of infarction. CONCLUSIONS: It is concluded that captopril reduces similarly postinfarction hypertrophy and collagen deposition in surviving myocardium. These effects, although less intense, also occur when the drug is used for a short period immediately after myocardial infarction or when used later, when ventricular remodeling is almost fully developed.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Cardiomegalia/prevenção & controle , Colágeno/efeitos dos fármacos , Infarto do Miocárdio/patologia , Miocárdio/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Captopril/uso terapêutico , Cardiomegalia/etiologia , Cardiomegalia/patologia , Colágeno/análise , Modelos Animais de Doenças , Fibrose , Masculino , Infarto do Miocárdio/complicações , Miocárdio/química , Ratos , Ratos WistarRESUMO
PURPOSE: To determine angiotensin converting enzyme (ACE) activity in the heart of infarcted rats and to investigate the effects of captopril and losartan on the post-infarction remodeling process. METHODS: Myocardial infarction (MI) was produced in Wistar rats by ligature of the left coronary artery. Control rats (Con) underwent a sham surgery. MI and Con rats remained untreated or were treated with captopril (30 mg/kg/day) or losartan (15 mg/kg/day) for 30 days. ACE activity was determined in right (RV) and left ventricular (LV) muscles and in the scar tissue. The effects of captopril therapy was also investigated in the hydroxiproline (OH-Pro) and protein in RV and LV. RESULTS: ACE activity increased 25% in the RV and 70% in the remaining LV muscle. The highest ACE activity was found in the scar tissue, where it was 4.5 times the value of the LV muscle (420 +/- 68 vs 94 +/- 8 nmoles/g/min; P < 0.01). An increase of the end-diastolic pressure and of the muscle mass was found in the RV and LV of MI rats. Captopril and losartan treatments were equally efficient to attenuate these parameters in both ventricles. Captopril also reduced the total OH-Pro content in the RV and LV muscles. The Prot concentration was significantly reduced in the myocardium of MI rats, an effect enhanced by captopril therapy. CONCLUSION: The AII concentration in the blood draining from the scar to the surrounding muscle is probably high. It is likely that this elevated local generation of AII contributes to hypertrophy and to collagen deposition. The effects of ACE inhibitors on remodeling are likely to depend on the reduction of the locally generated AII.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Coração/fisiologia , Losartan/farmacologia , Infarto do Miocárdio/fisiopatologia , Peptidil Dipeptidase A/fisiologia , Angiotensina II , Animais , Ventrículos do Coração/química , Hemodinâmica/efeitos dos fármacos , Hidroxiprolina/análise , Masculino , Proteínas/análise , Ratos , Ratos Endogâmicos , Ratos Wistar , VasoconstritoresRESUMO
Histamine levels of several organs from mice chronically infected with a myotropic strain of Trypanosoma cruzi were determined by bioassay. An increase in histamine content was observed in stomach, small intestine, colon, heart and skeletal muscle, when compared with noninfected weight and age-matched mice. These results suggest that mast cells, the main storage site of peripheral histamine, can play a role in the inflammatory and/or immunologic components of experimental trypanosomiasis.
Assuntos
Doença de Chagas/metabolismo , Histamina/metabolismo , Animais , Feminino , Masculino , Mastócitos/metabolismo , CamundongosRESUMO
Os autores apresentam um caso de sarcoidose com envolvimento cutaneo, osseo, e de linfonodos para-hilares, numa paciente do sexo feminino