RESUMO
This paper presents the design and characteristics of a five-fingered haptic interface robot named HIRO III. The aim of the development of HIRO III is to provide a high-precision three-directional force at the five human fingertips. HIRO III consists of a 15-degrees-of-freedom (DOF) haptic hand, a 6-DOF interface arm, and a control system. The haptic interface, which consists of a robot arm and hand, can be used in a large workspace and can provide multipoint contact between the user and a virtual environment. However, the following problems peculiar to a multi-DOF robot have arisen: a large amount of friction, a backlash, and the presence of many wires for many motors and sensors. To solve these problems, a new mechanism and a wire-saving control system have been designed and developed. Furthermore, several experiments have been carried out to investigate the performance of HIRO III. These results show the high-precision force display and great potential of HIRO III.
RESUMO
BACKGROUND: Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus. OBJECTIVE: To evaluate the effect of angiotensin II receptor blockade on cardiac function and fine structures in diabetes. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 30), a model of spontaneously developing diabetes mellitus, and their diabetes resistant counterparts (n = 20) were used. At 30 weeks of age, when the OLETF rats show hyperglycaemic obesity with hyperinsulinaemia, the animals were divided into two groups and given candesartan, an angiotensin II receptor blocker, 0.2 mg/kg/day, or vehicle for six weeks. Capillary density was evaluated in the left ventricular myocardium by electron microscopy, matrix metalloproteinase (MMP) activity by zymography, and cytokines by reverse transcriptase polymerase chain reaction. RESULTS: Compared with the control rats, the OLETF rats at 36 weeks showed decreased peak negative dP/dt (mean (SD): 2350 (250) v 3492 (286) mm Hg/s) and increased cardiomyocyte diameter (24.3 (0.6) v 18.9 (0.6) microm) (both p < 0.05). Thickening of the capillary basement membranes and decreased capillary density were observed. Angiotensin receptor blockade improved almost all the haemodynamic variables, and the histological findings became similar to those of the controls. Angiotensin receptor blockade also activated MMP-2 and prevented an increase of inflammatory cytokines, especially interleukin (IL)-1beta and IL-6, in the diabetic heart. CONCLUSIONS: Angiotensin II receptor blockade preserved left ventricular diastolic function. It was also potent at improving cardiomyocyte diameter and the thickening of the capillary basement membrane, increasing MMP-2 activity, and decreasing inflammatory cytokines. With all these changes, candesartan could contribute to cardioprotection in diabetes mellitus.
Assuntos
Angiotensina II/antagonistas & inibidores , Antagonistas de Receptores de Angiotensina , Benzimidazóis/uso terapêutico , Angiopatias Diabéticas/prevenção & controle , Tetrazóis/uso terapêutico , Disfunção Ventricular Esquerda/prevenção & controle , Animais , Compostos de Bifenilo , Glicemia/metabolismo , Peso Corporal , Capilares , Citocinas/antagonistas & inibidores , Angiopatias Diabéticas/fisiopatologia , Heme Oxigenase (Desciclizante)/metabolismo , Imuno-Histoquímica , Masculino , Metaloproteinases da Matriz/metabolismo , Tamanho do Órgão , Ratos , Ratos Endogâmicos OLETF , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND AND AIM: Complement receptor type 1 (CR1) is a transmembrane protein, and human erythrocyte CR1 (E-CR1) is involved in the transport of circulating immune complexes (IC) from the circulation to the reticuloendothelial system, including the liver and spleen. In chronic viral hepatitis, increased levels of IC containing viral particles and an association with various extrahepatic manifestations have been reported. However, regulatory mechanisms for IC levels are not fully understood. PATIENTS/SUBJECTS AND METHODS: We analysed IC, E-CR1, and quantitative polymorphism of the CR1 gene in 149 patients with chronic viral liver diseases and in 64 normal blood donors using an enzyme linked immunosorbent assay, radioimmunoassay, and polymerase chain reaction-restriction fragment length polymorphism, respectively. We also analysed the effect of CR1 gene polymorphism on IC binding to E-CR1 using molecular methods. RESULTS: E-CR1 levels in patients with chronic hepatitis and chronic viral liver diseases as a whole correlated inversely with increased levels of IC. Moreover, significantly high levels of IC were observed in patients with chronic hepatitis C (CH-C) who were homozygous for the E-CR1 low density allele. We also found low levels of E-CR1 in liver cirrhosis and CH-C but not in CH-B. Low levels of E-CR1 in CH-C were observed, even after considering the polymorphism of the CR1 gene. Finally, we demonstrated CR1 gene polymorphism dependent binding of hepatitis virus containing IC. CONCLUSIONS: Our results emphasise the important role of E-CR1 in clearance of IC from the circulation and the acquired, rather than inherited, decrease in E-CR1 in chronic viral liver diseases, especially of type C.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Eritrócitos/imunologia , Hepatite Viral Humana/imunologia , Receptores de Complemento/fisiologia , Adulto , Idoso , Doença Crônica , Feminino , Hepatite Viral Humana/genética , Humanos , Cirrose Hepática/imunologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Receptores de Complemento/genéticaRESUMO
In failing hearts, cardiomyocytes degenerate and interstitial fibrosis, which indicates cardiomyocyte loss, becomes more prominent in the myocardium. However, the precise mechanism of cardiomyocyte degeneration that leads to cell death is still unclear, although it is presumed that lysosomal function and autophagy play an important role because lysosomal activity increases under stress such as hypoxia. Myocardium that had been resected during partial left ventriculectomy performed in patients with dilated cardiomyopathy (DCM) was examined. Under light microscopy, some cardiomyocytes had a marked scarcity of myofibrils and had prominent cytoplasmic vacuolization. Atrophic and degenerated cardiomyocytes were often observed adjacent to replacement fibrotic tissue. Immunohistochemistry showed positivity for lysosome-associated membrane protein and a lysosomal catheptic enzyme in vacuoles of various sizes in the cardiomyocytes and these lysosomal markers were markedly increased in atrophic and degenerated cardiomyocytes. Electron microscopy revealed that degenerated cardiomyocytes had many vacuoles containing intracellular organelles, such as mitochondria, and were considered to be autophagic vacuoles. In DCM hearts, autophagy appeared to be associated not only with degradation of damaged intracellular organelles but also with progressive destruction of cardiomyocytes. It is possible that autophagic degeneration is one of the mechanisms of myocardial cell death.
Assuntos
Cardiomiopatia Dilatada/patologia , Lisossomos/fisiologia , Miocárdio/patologia , Adulto , Antígenos CD/metabolismo , Cardiomiopatia Dilatada/enzimologia , Cardiomiopatia Dilatada/etiologia , Catepsina D/metabolismo , Compartimento Celular , Morte Celular , Feminino , Humanos , Imuno-Histoquímica , Proteínas de Membrana Lisossomal , Lisossomos/enzimologia , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/patologia , Miocárdio/ultraestrutura , Vacúolos/patologia , Vacúolos/ultraestruturaRESUMO
BACKGROUND: Platelet aggregation, blood coagulation, and fibrinolysis play a pivotal role in the pathogenesis of unstable angina. METHODS: Platelet aggregability was examined on admission and after 2 weeks of treatment in 22 patients with unstable angina, in particular with regard to small-sized platelet aggregates, plasma tissue factor (TF) antigen levels as a marker of blood coagulation, and plasma plasminogen activator inhibitor (PAI) activity levels as an indicator of fibrinolysis. We also examined the same parameters in 19 patients with stable exertional angina and 17 patients with chest pain syndrome. RESULTS: The number of small-sized platelet aggregates increased more significantly in the unstable angina group than in the stable exertional angina and chest pain syndrome groups. In the unstable angina group, the number of small-sized platelet aggregates decreased significantly after 2 weeks of treatment, but was still higher than that in the stable exertional angina and chest pain syndrome groups. Plasma TF antigen and PAI activity were higher in the unstable angina group than in the stable exertional angina and chest pain syndrome groups. TF and PAI activity decreased to normal ranges after 2 weeks of treatment in the unstable angina group. There were significant positive correlations among the three parameters on admission. CONCLUSIONS: It was demonstrated that small-sized platelet aggregates, plasma TF antigen and PAI activity levels increased concomitantly in the unstable angina group. While the blood coagulation and fibrinolytic parameters decreased after stabilization of the clinical symptoms, platelet hyperaggregability still persisted. These results suggest that continuous antiplatelet therapy is essential for the treatment of unstable angina.
Assuntos
Angina Instável/sangue , Coagulação Sanguínea/fisiologia , Trombose Coronária/complicações , Fibrinólise/fisiologia , Inativadores de Plasminogênio/sangue , Agregação Plaquetária/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Instável/tratamento farmacológico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tromboplastina/imunologiaRESUMO
Partial left ventriculectomy (PLV) can be used to treat refractory congestive heart failure caused by dilated cardiomyopathy (DCM). In order to understand the relationship between the underlying myocardial injury and early clinical outcomes after PLV, histopathologic, immunohistochemical and virologic studies of the resected myocardium were performed. The posterolateral left ventricular walls from 27 patients with idiopathic DCM were examined. Cardiomyocyte diameter, degree of myocardial fibrosis, degree of cardiomyocyte degeneration, and degree of inflammatory cell infiltration were compared with mortality rates. Polymerase chain reaction was performed to detect enterovirus genome in the myocardium. Some patients had inflammatory cell infiltrates with focal accumulations of lymphocytes and macrophages, including both cytotoxic/suppressor T-cells and helper/inducer T-cells. The number of inflammatory cells (activated lymphocytes plus macrophages/mm2) was significantly greater in patients who died of cardiac insufficiency after surgery (27.8 +/- 5.7; n = 7) than in the survivors (11.1 +/- 2.5; n = 15). There was no significant difference in the degree of myocardial fibrosis, cardiomyocyte diameter or degree of cardiomyocyte degeneration between the 2 groups. Enterovirus genome was detected in the myocardium of 9 (38%) of 24 patients examined and 5 of these enterovirus-positive hearts had severe inflammatory cell infiltrates (37.9 +/- 2.5/mm2). Early survival in patients undergoing PLV for DCM is significantly affected by the degree of myocardial inflammation, so patients with more severe or ongoing inflammation may have poor clinical outcomes. Chronic myocarditis may play an important role in the etiology and pathophysiology of idiopathic DCM.
Assuntos
Cardiomiopatia Dilatada/cirurgia , Quimiotaxia , Ventrículos do Coração/cirurgia , Miocardite/patologia , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/patologia , DNA Viral/análise , Enterovirus/genética , Feminino , Ventrículos do Coração/patologia , Humanos , Imuno-Histoquímica , Leucócitos/fisiologia , Macrófagos/fisiologia , Masculino , Pessoa de Meia-Idade , Miocardite/mortalidade , Miocardite/virologia , Prognóstico , Resultado do TratamentoRESUMO
A recently developed platelet aggregometer using a laser light scattering method is capable of monitoring the increase in size of small-sized platelet aggregates (diameter 9-25 microm), which cannot be detected with the conventional methods. Whether coronary spasm can cause platelet aggregation in the coronary circulation is unknown. We investigated platelet aggregation, especially small-sized platelet aggregates, simultaneously in the coronary sinus and the aortic root in 18 patients with coronary spastic angina before and after a left coronary artery spasm induced by intracoronary injection of acetylcholine, and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid right atrial pacing. Platelet aggregation in 12 patients with chest pain syndrome was also examined before and after coronary spasms provoked by acetylcholine. The number of small-sized platelet aggregates increased significantly in the coronary sinus [2.0+/-0.6 x 104 to 4.1+/-1.0 x 104 (V), P<.01] and in the aortic root [1.7+/-0.6 x 104 to 3.2+/-0.6 x 104 (V), P<.05], and the coronary sinus-arterial difference in the number of small-sized platelet aggregates [2.3+/-1.9 x 103 to 1.1+/-0.4 x 104 (V), P<.01] increased significantly after attacks in the coronary spastic angina group, but remained the same in the stable exertional angina group after attacks and in the chest pain syndrome group after the administration of acetylcholine. Therefore, we can conclude that acute myocardial ischemia induced by coronary spasm causes platelet aggregation in the coronary circulation.
Assuntos
Vasoespasmo Coronário/sangue , Agregação Plaquetária , Acetilcolina , Adulto , Idoso , Aorta , Coleta de Amostras Sanguíneas , Dor no Peito/sangue , Estudos de Coortes , Angiografia Coronária , Circulação Coronária , Vasoespasmo Coronário/induzido quimicamente , Vasoespasmo Coronário/diagnóstico por imagem , Feminino , Humanos , Ácido Láctico/sangue , Lasers , Masculino , Pessoa de Meia-Idade , Espalhamento de RadiaçãoRESUMO
It has been documented that the serum complement activities measured by hemolytic assay (CH50) are decreased after storage of sera at a low temperature in some patients with chronic hepatitis C. However, the mechanism of this phenomenon has not been identified yet. Here, we tried to elucidate factors involved in the cold activation of complement (CAC). To clarify what pathway is activated in CAC, we measured complement cleavage products after cold storage of sera. C4d increased significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not increase in any of the groups. In order to determine whether IgG or IgG complex is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel beads, and all of them retained hemolytic activities to some extent after cold storage. Column chromatography through Superose 6HR of CAC-positive serum identified the fractions containing molecules that induced CAC in normal serum, which were depleted by treatment with protein G Sepharose. In conclusion, CAC in hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex produced in hepatitis C virus infection may be an important factor in inducing CAC, a common extrahepatic manifestation of hepatitis C.
Assuntos
Ativação do Complemento/fisiologia , Hepatite C Crônica/imunologia , Imunoglobulina G/imunologia , Adulto , Idoso , Temperatura Baixa , Ensaio de Atividade Hemolítica de Complemento , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This report describes a case of cardiomyopathy with a novel point mutation of mitochondrial DNA coding lysine tRNA in association with severe ultrastructural alterations of the mitochondria in the cardiomyocytes. Abnormalities of energy production and/or abnormal protein synthesis because of the mutation of mitochondrial DNA may have played an important role in the pathogenesis of this case, which showed severe cardiomyocyte degeneration and deterioration from hypertrophic cardiomyopathy to severe dilated cardiomyopathy.
Assuntos
Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/etiologia , Criança , Análise Mutacional de DNA , DNA Mitocondrial/genética , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Miocárdio/citologia , Mutação Puntual , RNA de Transferência de Lisina/genéticaRESUMO
The soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein (SNAP) receptor (SNARE) hypothesis has been applied to exocytosis in salivary glands. The expression of SNARE proteins has not been well investigated in the parotid gland. In this study, the mRNA expression of SNAREs and membrane-fusion-related proteins were investigated in the rat parotid by reverse transcriptase-polymerase chain reaction (RT-PCR). All syntaxins except syntaxin 1, and the vesicle-associated membrane proteins (VAMP) except VAMP-7, NSF, SNAP-23 and alpha-SNAP, were expressed for the SNAREs in rat parotid. Synaptotagmins 3, 4 and 11, Munc18s (1, 2 and 3), syncollin, prenylated Rab acceptor (PRA1), zygin 1, pantophysin and cellugyrin, which are the other membrane-fusion-related proteins, were also detected, but neither Rim nor rabphilin 3A, which have high specificity of binding to Rab 3A, were found. mRNA expressions of many SNAREs and of the membrane-fusion-proteins suggest novel interactions for the regulation of salivary exocytosis.
Assuntos
Proteínas de Ligação ao Cálcio , Proteínas de Transporte/biossíntese , Fusão de Membrana , Proteínas de Membrana/biossíntese , Glândula Parótida/metabolismo , Saliva/metabolismo , Proteínas de Transporte Vesicular , Animais , Exocitose , Expressão Gênica , Masculino , Glicoproteínas de Membrana/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Proteínas Qa-SNARE , Proteínas R-SNARE , RNA Mensageiro/análise , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas SNARE , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida , Sinaptotagminas , Sintaxina 1Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Enalapril/uso terapêutico , Fibrinólise/efeitos dos fármacos , Losartan/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Método Duplo-Cego , Enalapril/efeitos adversos , Feminino , Humanos , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Inativadores de Plasminogênio/sangue , Terapia Trombolítica , Tromboplastina/metabolismo , Ativador de Plasminogênio Tecidual/sangueRESUMO
We report a chronic hepatitis B virus (HBV) carrier with non-Hodgkin lymphoma (NHL) who developed HBV hepatitis following conventional dose chemotherapy and was successfully treated with lamivudine and glycyrrhizin. A 55 year-old male patient with primary testicular NHL (diffuse large B-cell type) relapsed. During the salvage chemotherapy, the patient showed elevated serum levels of transaminase and HBV-DNA due to HBV reactivation. Treatment with lamivudine, an antiviral nucleoside analog, was started at a dose of 100mg/day. Shortly after the treatment the HBV-DNA level was suppressed, and sustained elevation of transaminase levels were normalized after additional treatment with glycyrrhizin. This experience suggests that lamivudine combined with glycyrrhizin may be effective for controlling HBV replication and treating chemotherapy-induced HBV hepatitis in chronic HBV carriers with NHL.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Ácido Glicirrízico/administração & dosagem , Hepatite B/induzido quimicamente , Hepatite B/tratamento farmacológico , Lamivudina/administração & dosagem , Linfoma não Hodgkin/virologia , Inibidores da Transcriptase Reversa/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Doença Crônica , DNA Viral/sangue , Quimioterapia Combinada , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/crescimento & desenvolvimento , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/virologia , Ativação Viral/efeitos dos fármacosRESUMO
Lipopolysaccharide (LPS) of Burkholderia cepacia was purified by the conventional phenol-water extraction method (preparation BcLPS-1), followed by enzymatic treatments with DNase, RNase, trypsin, and proteinase K (preparation BcLPS-2), and finally by deoxycholate-phenol-water extraction (preparation BcLPS-3). Cells of LPS-hyporesponsive C3H/HeJ mice were activated by both the BcLPS-1 and the BcLPS-2 preparations but barely activated by BcLPS-3. When LPS-responsive C3H/HeN mice were used as targets, endotoxic activities such as lethal toxicity to galactosamine-sensitized mice, mitogenicity to spleen cells, and activation of macrophages to induce tumor necrosis factor alpha and interleukin-6 (IL-6) were strongly exhibited even by highly purified BcLPS-3 at levels comparable to those of the highly active enterobacterial LPS of Salmonella enterica serovar Abortus-equi (SaeLPS), used as the control. The ability of BcLPS-3 to activate murine macrophages for induction of IL-1beta was, however, much weaker than that of SaeLPS. Both accumulation of pro-IL-1beta protein and expression of IL-1beta mRNA in macrophages by stimulation with BcLPS-3 were much weaker than by stimulation with SaeLPS. These results indicate that LPS of B. cepacia has the potential to play a role as a pathogenic factor with strong activity comparable to that of usual enterobacterial LPS, but unlike the latter, this LPS has a relative lack of ability in the activation of murine macrophages to induce IL-1beta. The lack of IL-1beta-inducing ability appears to be caused by incomplete signal transduction somewhere in the upstream step(s) of IL-1beta gene transcription.
Assuntos
Burkholderia cepacia/imunologia , Interleucina-1/biossíntese , Lipopolissacarídeos/imunologia , Ativação de Macrófagos , Macrófagos Peritoneais/imunologia , Animais , Infecções por Burkholderia/imunologia , Infecções por Burkholderia/microbiologia , Galactosamina/farmacologia , Interleucina-1/genética , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Baço/citologia , Baço/imunologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
TT virus (TTV) is much more prevalent than we once imagined. With the use of primers designed from the noncoding regions, a more than 90% rate of TTV infection in the general population by polymerase chain reaction (PCR) has been reported, showing that nonparenteral transmission must play an important role to its epidemiology. We considered that TTV may be secreted through bile juice into feces to establish nonparenteral infection. Paired bile juice and serum samples were obtained from 26 patients who were receiving bile drainage. Feces were also recovered after the drainage tube was removed. TTV DNA was detected from 22 patients in serum (84.6%), and they were all TTV DNA positive in bile juice. Most feces samples recovered from TTV-positive patients were also TTV DNA positive. Secretion of TTV into bile juice appears to be common, and this could play an important role to its transmission and its epidemiology.
Assuntos
Bile/virologia , Fezes/virologia , Torque teno virus/isolamento & purificação , Infecções por Vírus de DNA/transmissão , DNA Viral/análise , Humanos , Reação em Cadeia da Polimerase , Torque teno virus/genéticaRESUMO
Interferon-alpha (IFN-alpha) has been widely used for treatment of chronic hepatitis C in Japan. In general, cardiovascular adverse reactions are rare in association with IFN-alpha therapy. Here, a 64-year-old man with chronic active hepatitis C complained of fatigue, palpitation and depression, and developed atrial fibrillation with prominent negative T waves during IFN-alpha therapy. Echocardiogram showed septal and apical hypertrophy. Three days after discontinuation of IFN-alpha, subjective symptoms and atrial fibrillation subsided. It is unclear whether or not IFN-alpha induced the giant negative T waves with apical hypertrophy. We might observe the developing course of hepatitis C virus (HCV)-related myocardial hypertrophy by chance. Cardiovascular toxicity should be carefully monitored during IFN-alpha therapy even in patients with minor cardiac disease, such as premature ventricular contracture (PVC) and mild hypertension.
Assuntos
Antivirais/efeitos adversos , Fibrilação Atrial/induzido quimicamente , Complexos Atriais Prematuros/induzido quimicamente , Eletrocardiografia , Hepatite C Crônica/tratamento farmacológico , Hipertrofia Ventricular Esquerda/complicações , Interferon-alfa/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Antivirais/uso terapêutico , Fibrilação Atrial/etiologia , Complexos Atriais Prematuros/etiologia , Fármacos Cardiovasculares/uso terapêutico , Hepatite C Crônica/complicações , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/virologia , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Taquicardia/induzido quimicamente , UltrassonografiaRESUMO
Oxidized low-density lipoproteins are important in the progression of atherosclerosis. Autoantibodies against malondialdehyde-modified low-density lipoproteins have been reported to be predictive of the progression of atherosclerosis. This study sought to examine whether plasma levels of autoantibodies against oxidized low-density lipoprotein increase in the coronary circulation in patients with coronary spastic angina. The authors examined plasma antioxidized low-density lipoprotein antibody levels (activity unit values (AcU)/mL) simultaneously in the coronary sinus and the aortic root in 20 patients with coronary spastic angina, 23 patients with stable exertional angina, and 15 control subjects by measuring plasma levels of immunoglobulin G (IgG) autoantibodies against malondialdehyde-modified low-density lipoproteins by enzyme-linked immunosorbent assay. The plasma antioxidized low-density lipoprotein antibody levels (AcU/mL) in the coronary sinus increased in coronary spastic angina (38 +/- 16) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < or = 0.0001). The levels (AcU/mL) in the aortic root also increased in coronary spastic angina (33 +/- 12) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < 0.005). Furthermore, the coronary sinus-arterial differences of the levels (AcU/mL) were also higher in coronary spastic angina (5 +/- 9) than in stable exertional angina (0 +/- 6) and healthy subjects (-1 +/- 5) (p < 0.05). The generation of malondialdehyde-modified low-density lipoproteins is reported to be associated with atherothrombosis. These findings suggest that elevated levels of autoantibodies against malondialdehyde-modified oxidized low-density lipoproteins in coronary circulation are associated with the development of atherothrombosis from the progression of atherosclerosis rather than with the extent of coronary atherosclerosis in patients with coronary spastic angina.
Assuntos
Angina Pectoris Variante/imunologia , Autoanticorpos/imunologia , Circulação Coronária/imunologia , Lipoproteínas LDL/imunologia , Acetilcolina/administração & dosagem , Administração Sublingual , Adulto , Idoso , Angina Pectoris Variante/sangue , Angina Pectoris Variante/diagnóstico , Biomarcadores/sangue , Cateterismo Cardíaco , Angiografia Coronária , Vasos Coronários , Diagnóstico Diferencial , Progressão da Doença , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Injeções Intra-Arteriais , Masculino , Malondialdeído/imunologia , Pessoa de Meia-Idade , Nitroglicerina/administração & dosagem , Oxirredução , Vasodilatadores/administração & dosagemRESUMO
It is well known that there are circadian rhythms of 2-deoxyglucose uptake and neuronal firing in the rat suprachiasmatic nucleus (SCN) during fetal and early postnatal periods. A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 function as positive regulators and three mPeriod (mPer) genes play a role in negative feedback. Per genes expression occurs not only in the adult SCN but also in the fetal SCN. However, the developmental change in these genes remains unclear. In this experiment, we examined the day--night pattern of expression of Per1 and Per2 mRNA in the mouse SCN and cerebral cortex on embryonic day 17, postnatal day 3, and in young adult mice under a light-dark cycle. Daily rhythms of mRNA content were observed in mPer1 but not mPer2 in the fetal SCN. Interestingly, the expression of mPer2 in the SCN was high throughout the entire day, and a significant daily rhythm of this gene was observed on postnatal day 6. The expression pattern of SCN mPer1 in constant darkness was similar to that seen in the light-dark cycle. The present results suggest that the daily oscillation of mPer1 but not of mPer2 in the SCN in fetal and early postnatal mice may be associated with the daily rhythms of 2-deoxyglucose uptake and neuronal firing.
Assuntos
Ritmo Circadiano/genética , Proteínas Fetais/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/biossíntese , Proteínas Nucleares/genética , RNA Mensageiro/biossíntese , Núcleo Supraquiasmático/metabolismo , Fatores de Transcrição ARNTL , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas CLOCK , Proteínas de Ciclo Celular , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/metabolismo , Ritmo Circadiano/efeitos da radiação , Escuridão , Retroalimentação , Feminino , Proteínas Fetais/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos da radiação , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/biossíntese , Proteínas Circadianas Period , Gravidez , RNA Mensageiro/genética , Núcleo Supraquiasmático/embriologia , Núcleo Supraquiasmático/crescimento & desenvolvimento , Núcleo Supraquiasmático/efeitos da radiação , Transativadores/fisiologia , Fatores de Transcrição/fisiologiaRESUMO
BACKGROUND/AIMS: We investigated the prevalence of hepatitis G virus infection among inhabitants of a hepatitis C virus endemic area. METHODOLOGY: Two hundred and eighty-eight inhabitants, who underwent medical examinations for health screening, were enrolled in this epidemiological study. HGV RNA and HCV RNA were detected by polymerase chain reaction. We also examined anti-HGV envelope protein (E2) antibodies in all serum samples. RESULTS: In these 288 inhabitants, we found anti-HCV antibodies (HCV-Ab) and HCV RNA in 28.5% and 17.4%, respectively. HGV RNA and anti-HGV E2 were detected in 9 (3.1%) and 16 (5.5%), respectively. One patient was positive for both HGV RNA and anti-HGV E2. The exposure rate, expressed as the percentage of people with HGV RNA and/or anti-HGV E2, was 8.3%, which was significantly lower than the incidence of positive HCV-Ab. Of the 24 patients with HGV RNA and/or anti-HGV E2, 15 (62.5%) were positive for HCV-Ab, of those HCV RNA was detected in 9 (37.5%). Further, we found a higher prevalence of HGV exposure in patients with HCV-Ab than in those without (8.3% vs. 4.4%). CONCLUSIONS: HGV infection was not identical to the epidemic hepatitis C virus infection among inhabitants of this town, suggesting that hepatitis C virus might be less infectious than hepatitis C virus.
Assuntos
Doenças Endêmicas , Flaviviridae , Hepatite C/epidemiologia , Hepatite Viral Humana/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Anticorpos Anti-Hepatite/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangueRESUMO
To improve the efficacy of interferon (IFN) therapy for chronic hepatitis C, we proposed a therapy with twice-a-day injection of IFNbeta as the induction. To assess its biological enhancement, we compared antiviral activities in vitro using intermittent treatment schedules simulating the clinical condition. FL cells were treated with IFNbeta twice in 12 h interval (Single treatment, 1000 and 0 IU/ml; Double treatment, 500 IU/ml each) and challenged with Sindbis virus. Antiviral activities were determined with 50% cytopathic effect. Activities and mRNA expressions of 2'5'oligoadenylate synthetase (2'5'AS) were also examined. Single treatment showed its peak activity at 9 h, while Double treatment was at 3 h after the second treatment. Double treatment had a significantly higher peak activity. The up-regulated activities of 2'5'AS lasted much longer with Double treatment. The present findings demonstrated Double treatment could induce efficient biological enhancement, which is thought based on the priming effect.