RESUMO
BACKGROUND: Increased level of hydrogen sulphide (H2 S) in sputum is reported to be a new biomarker of neutrophilic airway inflammation in chronic airway disorders. However, the relationship between H2 S and disease activity remains unclear. OBJECTIVE: We investigated whether H2 S levels could vary during different conditions in asthma. METHOD: H2 S levels in sputum and serum were measured using a sulphide-sensitive electrode in 47 stable asthmatic subjects (S-BA), 21 uncontrolled asthmatic subjects (UC-BA), 26 asthmatic subjects with acute exacerbation (AE-BA) and 15 healthy subjects. Of these, H2 S levels during stable, as well as exacerbation states, were obtained in 13 asthmatic subjects. RESULTS: Sputum H2 S levels were significantly higher in the AE-BA subjects compared to the UC-BA and healthy subjects (P < .05). However, serum H2 S levels in the AE-BA subjects were lower than in the S-BA subjects (P < .001) and similar to those in healthy subjects. Thus, the sputum-to-serum ratio of H2 S (H2 S ratio) in the AE-BA subjects was significantly higher than in the S-BA, UC-BA and healthy subjects (P < .05). Among all subjects, sputum H2 S levels showed a trend to decrease with FEV1 %predicted and significantly positive correlations with sputum neutrophils (%), sputum IL-8 and serum IL-8. A multiple linear regression analysis showed that sputum H2 S was independently associated with increased sputum neutrophils (%) and decreased FEV1 %predicted (P < .05). The cut-off level of H2 S ratio to indicate an exacerbation was ≥0.34 (area under the curve; 0.88, with a sensitivity of 81.8% and specificity of 72.7%, P < .001). Furthermore, half of the asthmatic subjects with H2 S ratios higher than the cut-off level experienced asthma exacerbations over the following 3 months after enrolment. CONCLUSIONS: The H2 S ratio may provide useful information on predicting future risks of asthma exacerbation, as well as on obstructive neutrophilic airway inflammation as one of the non-Th2 biomarkers, in asthma.
Assuntos
Asma/imunologia , Asma/metabolismo , Biomarcadores , Sulfeto de Hidrogênio/metabolismo , Escarro/metabolismo , Adulto , Idoso , Asma/diagnóstico , Estudos Transversais , Citocinas/metabolismo , Progressão da Doença , Feminino , Humanos , Sulfeto de Hidrogênio/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Curva ROC , Testes de Função Respiratória , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismoRESUMO
BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m-2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80-120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Oxônico/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Tegafur/administração & dosagem , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Administração Intravenosa , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Tegafur/efeitos adversos , Resultado do Tratamento , GencitabinaRESUMO
Insulin-like growth factor-1 (IGF-1) is one of the important factors for growth, milk production and reproductive functions and mainly released from the liver in response to growth hormone (GH) via GH receptor (GHR) in cattle. Recently, some single nucleotide polymorphisms (SNPs) were identified in the bovine GHR gene. Some GHR-SNPs were shown to be related to plasma IGF-1 concentration in cattle. Hence, the capacity to IGF-1 production in the liver might be affected by GHR-SNP and associated with performance in the future. This study examined whether GHR-SNP is associated with IGF-1 production in the liver of pre-pubertal heifers. In 71 Holstein calves, blood samples for genomic DNA extraction were obtained immediately after birth. To genotype the GHR-SNPs in the promoter region, polymerase chain reaction (PCR) products were digested with restriction enzyme NsiI (cutting sites: AA, AG and GG). All heifers at 4 months of age were intramuscularly injected with 0.4 mg oestradiol benzoate. Blood samples were obtained from the jugular vein just before (0 h) and 24 h after injection. The number of AA, AG and GG at the NsiI site was 0, 17 and 54 respectively. In AG and GG, plasma GH concentrations were higher pre-injection than 24 h post-injection (p < 0.01). Moreover, plasma GH concentrations in AG post-injection were higher than in GG (p < 0.05). In contrast, the GG genotype exhibited higher plasma IGF-1 concentrations in pre-injection than post-injection (p < 0.01), although oestradiol did not change IGF-1 concentration in the AG genotype. We conclude that the GG polymorphism in the promoter region of GHR is associated with a higher potential capacity of IGF-1 production in the liver of cattle.
Assuntos
Bovinos/genética , Fator de Crescimento Insulin-Like I/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Receptores da Somatotropina/metabolismo , Maturidade Sexual/fisiologia , Animais , Bovinos/fisiologia , Anticoncepcionais/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Genótipo , Fator de Crescimento Insulin-Like I/genética , Receptores da Somatotropina/genéticaRESUMO
This is a case report that describes 2 sisters with microcephaly, simplified gyri, and enlarged extraaxial space. Clinical features of the cases include dysmorphic features, congenital microcephaly, failure of postnatal brain growth, neonatal onset of seizures, quadriplegia, and severe psychomotor delay. Neuroradiological imaging demonstrated hypoplasia of bilateral cerebral hemispheres with enlarged extraaxial spaces, simplified gyral patterns without a thickened cortex, hypoplastic corpus callosum, and enlarged lateral ventricles, with a reduction in gray and white matter volume during the prenatal and neonatal periods. Repeat MRI revealed progressive atrophy of the cerebral gray and white matter, with enlarged lateral ventricles, although the sizes of the bilateral basal ganglia, thalamus, and infratentorial structures were relatively preserved. These neuroradiological findings imply that this disease is caused by the gene involved in neuronal and glial proliferation in the ventricular zone and in tangential neuronal migration from the ganglionic eminence. The nature of the progressive degeneration of the hemispheric structures should be clarified.
Assuntos
Cérebro/anormalidades , Microcefalia/complicações , Microcefalia/patologia , Atrofia/etiologia , Atrofia/patologia , Cérebro/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Japão , Imageamento por Ressonância Magnética , IrmãosRESUMO
AIMS: With no effective chemotherapy, the prognosis of unresectable intrahepatic cholangiocarcinoma is extremely poor. Hepatic arterial infusion of mitomycin C with degradable starch microspheres has been reported to be an effective treatment for unresectable liver metastasis. We retrospectively evaluated the efficacy and safety of this chemotherapy for treating unresectable intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: Hepatic arterial infusion chemotherapy through an implanted port system was carried out in 20 patients with unresectable intrahepatic cholangiocarcinoma. Degradable starch microspheres mixed with mitomycin C and contrast media were injected until either embolisation of the hepatic artery or influx to the gastroduodenal system was confirmed. This treatment was repeated weekly. RESULTS: Hepatic arterial infusion chemotherapy was carried out 204 times. The response rate was 50.0%. Twelve patients experienced transient epigastralgia and four experienced gastroduodenal ulcer. The time to progression was 8.3 months and the median survival time was 14.1 months. CONCLUSIONS: This chemotherapy was effective and feasible for patients with unresectable intrahepatic cholangiocarcinoma. Further study with a larger number of patients is warranted.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Artéria Hepática , Mitomicina/administração & dosagem , Amido/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Resultado do TratamentoRESUMO
A case of a 55-year-old man with descending necrotizing mediastinitis (DNM) after a tooth removal was reported. Chest computed tomography (CT) showed a fluid collection in the right thorax, in the cervical region and in the mediastinum. The patient underwent cervical drainage and thoracoscopic pleural dissective drainage. The cervical and right anterior thoracic drain was removed on the 6th day and posterior drain was removed on the 8th day after the operation. The patient was discharged on the postoperative day 13, and showed no recurrence.
Assuntos
Drenagem/métodos , Mediastinite/cirurgia , Humanos , Masculino , Mediastinite/patologia , Pessoa de Meia-Idade , Necrose , ToracoscopiaRESUMO
BACKGROUND: Endotoxin (lipopolysaccharide, LPS) is a trigger of the systemic inflammatory response. We have previously found that vesnarinone and amrinone, when given before LPS, prevented cytokine production and LPS-related cardiac dysfunction. We tested the hypothesis that vesnarinone would improve intracellular Ca(2+) handling and calcium-activated contractile force after the onset of endotoxemia. METHODS AND RESULTS: Adult rabbits received a bolus injection of LPS or vehicle. Vesnarinone (3 mg/kg) was given intravenously 90 minutes later. Two hours after LPS administration, hearts were perfused in the isolated Langendorff mode. Peak left ventricular developed pressure, +/-dp/dt, oxygen consumption (MVO(2)), and ratexpressure product were evaluated in conjunction with fluorescent spectroscopic determinations of intracellular calcium concentrations (Ca(i)) and the rate of Ca(i) transient decline during diastole (tauCa). Peak left ventricular developed pressure and +/-dp/dt were significantly lower in the LPS group. These were completely restored by vesnarinone. There was significantly slower diastolic calcium removal (increased tauCa) in LPS hearts that was also corrected by vesnarinone; however, the cytosolic calcium overload characteristic of LPS hearts was only partially improved. Reduced mechanical inefficiency (the ratio of rate-pressure product to MVO(2)) and myofilament sensitivity to Ca(i) were also significantly improved by vesnarinone. CONCLUSIONS: Acute endotoxemia caused contractile protein calcium insensitivity, oxygen wastage, and abnormal calcium cycling. Vesnarinone, given in the rescue mode, normalized LPS-induced myocardial dysfunction and partially restored abnormal calcium cycling. Although the mechanisms responsible for these effects require further clarification, it appears that agents such as vesnarinone may be useful to treat inflammatory-induced myocardial dysfunction.
Assuntos
Cálcio/metabolismo , Cardiotônicos/administração & dosagem , Endotoxemia/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Quinolinas/administração & dosagem , Animais , Estimulação Cardíaca Artificial , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Corantes Fluorescentes , Compostos Heterocíclicos com 3 Anéis , Técnicas In Vitro , Infusões Intravenosas , Líquido Intracelular/metabolismo , Lipopolissacarídeos , Consumo de Oxigênio , Pirazinas , Coelhos , Função Ventricular Esquerda/efeitos dos fármacosAssuntos
Neoplasias Pulmonares/patologia , Sarcoma Sinovial/patologia , Idoso , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina/métodos , Broncoscopia , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/química , Neoplasias Pulmonares/cirurgia , Masculino , Mucina-1/análise , Proteínas de Fusão Oncogênica/metabolismo , Sarcoma Sinovial/química , Sarcoma Sinovial/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Protein kinase C (PKC) activation impairs contractility in the normal heart but is protective during myocardial ischemia. We hypothesized that PKC remains activated post-ischemia and modulates myocardial excitation-contraction coupling during early reperfusion. METHODS: Langendorff-perfused rabbit hearts where subjected to 25 min unmodified ischemia and 30 min reperfusion. Total PKC activity was measured, and the intracellular translocation pattern of PKC-alpha, -delta, -epsilon, and -eta assessed by immunohistochemistry and fractionated Western immunoblotting. The PKC-inhibitors chelerythrine and GF109203X were added during reperfusion and also given to non-ischemic hearts. Measurements included left ventricular function, intracellular calcium handling measured by Rhod-2 spectrofluorometry, myofibrillar calcium responsiveness in beating and tetanized hearts, and metabolic parameters. RESULTS: Total PKC activity was increased at end-ischemia and remained elevated after 30 min of reperfusion. The translocation pattern indicated PKC-epsilon as the main active isoform during reperfusion. Post-ischemic PKC inhibition affected mainly diastolic relaxation, with lesser effect on contractility. Both PKC inhibitors increased the Ca(2+) responsiveness of the myofilaments as indicated by a leftward shift of the calcium-to-force relationship and increased maximum calcium activated tetanic pressure. Diastolic Ca(2+) removal was delayed and the post-ischemic [Ca(2+)](i) overload further exacerbated. Depressed systolic function was associated with a lower amplitude of [Ca(2+)](i) transients. CONCLUSION: PKC is activated during ischemia and remains activated during early reperfusion. Inhibition of PKC activity post-ischemia impairs functional recovery, delays diastolic [Ca(2+)](i) removal, and increases Ca(2+) sensitivity of the contractile apparatus, resulting in impaired diastolic relaxation. Thus, post-ischemic PKC activity may serve to restore post-ischemic Ca(2+) homeostasis and attenuate contractile protein calcium sensitivity during the period of post-ischemic [Ca(2+)](i) overload.
Assuntos
Cálcio/metabolismo , Proteínas Contráteis/metabolismo , Isoenzimas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/enzimologia , Proteína Quinase C/metabolismo , Alcaloides , Análise de Variância , Animais , Benzofenantridinas , Western Blotting/métodos , Diástole , Inibidores Enzimáticos/farmacologia , Imuno-Histoquímica , Indóis/farmacologia , Isoenzimas/análise , Isoenzimas/antagonistas & inibidores , Maleimidas/farmacologia , Microscopia Confocal , Perfusão , Fenantridinas/farmacologia , Proteína Quinase C/análise , Proteína Quinase C/antagonistas & inibidores , CoelhosRESUMO
Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.
Assuntos
Coração/fisiopatologia , Hemorragia/fisiopatologia , Sistema Nervoso/fisiopatologia , Vasopressinas/fisiologia , Doença Aguda , Animais , Antagonistas dos Receptores de Hormônios Antidiuréticos , Arginina Vasopressina/farmacologia , Bloqueio Nervoso Autônomo , Benzazepinas/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Desamino Arginina Vasopressina/farmacologia , Diabetes Insípido/fisiopatologia , Masculino , Ratos , Ratos Brattleboro , Ratos Endogâmicos , Receptores de Vasopressinas/agonistas , RecidivaRESUMO
The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.
Assuntos
Pressão Sanguínea , Ritmo Circadiano , Síndrome de Cushing/fisiopatologia , Adolescente , Adulto , Feminino , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/fisiopatologia , Frequência Cardíaca , Humanos , Hiperaldosteronismo/fisiopatologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêuticoRESUMO
The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.
Assuntos
Fenômenos Fisiológicos Cardiovasculares , Vasopressinas/sangue , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/antagonistas & inibidores , Derivados da Atropina/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/fisiopatologia , Carbacol/administração & dosagem , Carbacol/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Desamino Arginina Vasopressina/farmacologia , Hipertensão/fisiopatologia , Injeções Intraventriculares , Masculino , Nicotina/farmacologia , Parassimpatolíticos/farmacologia , Fentolamina/farmacologia , Fisostigmina/farmacologia , Ratos , Ratos Brattleboro , Vasopressinas/antagonistas & inibidores , Vasopressinas/farmacologiaRESUMO
The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Vasopressinas/farmacologia , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/antagonistas & inibidores , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares , Desamino Arginina Vasopressina/administração & dosagem , Diabetes Insípido/metabolismo , Diabetes Insípido/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , RatosRESUMO
We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Pressão Sanguínea , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Determinação da Pressão Arterial/métodos , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valores de Referência , População Rural , Fatores SexuaisRESUMO
The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary-adrenal axis, probably through its action on the autonomic nervous system.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Glomerulonefrite/tratamento farmacológico , Hipertensão/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisolona/uso terapêutico , Adulto , Anti-Hipertensivos/uso terapêutico , Glomerulonefrite/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Monitorização Fisiológica , Sistema Hipófise-Suprarrenal/fisiologiaRESUMO
OBJECTIVE: To examine the relationships among the circadian rhythms of blood pressure, autonomic nervous function, and physical activity of patients with varying levels of spinal cord injury. DESIGN AND METHODS: We studied 19 patients with spinal cord injury [10 tetraplegic patients with cervical cord injury (C4-C7), and nine paraplegic patients with thoracic cord injury (Th6-Th12)] compared with 16 control subjects. A new multibiomedical recorder was used to measure blood pressure (every 30 min), cardiac vagal activity (hourly frequency of R-R50), and physical activity (integrated acceleration/min) for 24 h under hospital conditions. Systemic sympathetic nervous activity and sympathoadrenal functioning were assessed by examination of hormone levels in the blood. RESULTS: Daytime and night-time values were compared; the variations in systolic and diastolic blood pressures and heart rate were slight in members of the tetraplegia group, but almost normal differences were observed in members of the paraplegia group. The circadian profile of cardiac vagal activity was normal for both patient groups, suggesting that an alteration in the sympathetic nervous rhythm had occurred in the tetraplegic patients. The plasma norepinephrine level was lower in members of the tetraplegia group than it was in members of the control group (P< 0.001), but was normal in members of the paraplegia group. The plasma level of epinephrine was lower in members of the tetraplegia (P< 0.05) and the paraplegia (P < 0.1) groups than it was in members of the control group. Daytime physical activity of members of both groups of patients was lower than that of subjects in the control group (P< 0.001 for both). CONCLUSION: The central sympathoexcitatory pathway to the upper thoracic cord plays a critical role in the maintenance of normal circadian blood pressure rhythm in humans. Motor nerve functioning and sympathoadrenal secretion are not essential to this regulation.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Exercício Físico/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Adolescente , Adulto , Idoso , Aldosterona/sangue , Fator Natriurético Atrial/sangue , Epinefrina/sangue , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Renina/sangue , Estudos Retrospectivos , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/complicações , Nervo Vago/fisiopatologiaRESUMO
OBJECTIVE: Reduced baroreflex sensitivity has been reported in several kinds of human hypertension. However, the nature of the baroreceptor-heart rate reflex in hypertension due to excess mineralocorticoid has never been fully explored. PATIENTS AND METHODS: Thirty patients with primary aldosteronism, 60 patients with essential hypertension (World Health organization stages I or II) and 45 normotensive subjects were enrolled. The groups did not differ in mean age. Blood pressure was similar between patients with primary aldosteronism and those with essential hypertension. Blood pressure (Finapres) and the RR interval (ECG) were monitored continuously at rest. The closed loop gain between systolic blood pressure and RR interval variabilities was used to measure the sensitivity of the baroreceptor-heart rate reflex. RESULTS: Baroreflex sensitivity in the group with primary aldosteronism was significantly greater than in the essential hypertensive group, but did not differ significantly between the group with aldosteronism and the normotensive group. Three to four weeks after removal of an adrenal adenoma (n = 25), both systolic and diastolic blood pressure were decreased significantly in the aldosteronism group but were still higher than in the normotensive group. The baroreflex sensitivity was reduced by about 40% after adrenalectomy compared to pre-operative values. The decrease in the baroreflex gain following adrenalectomy was correlated negatively with the decrease in systolic blood pressure (r = -4.00, P=0.05). CONCLUSION: These results demonstrate that hypertension due to excess mineralocorticoids is characterized by an increase in the gain of the baroreceptor-heart rate reflex. The reduction in baroreflex gain following adrenalectomy may delay the normalization of blood pressure.
Assuntos
Hiperaldosteronismo/fisiopatologia , Hipertensão/fisiopatologia , Pressorreceptores/fisiopatologia , Adolescente , Adrenalectomia , Adulto , Idoso , Pressão Sanguínea , Frequência Cardíaca/fisiologia , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/cirurgia , Hipertensão/etiologia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine whether type A behavior, which is associated with a risk of coronary heart disease, affects left ventricular hypertrophy in patients with essential hypertension. DESIGN: Cross-sectional study of 88 untreated patients with mild to moderate essential hypertension (33 men, mean +/- SEM age 54 +/- 1 years). METHODS: We measured the type A behavior score using a standardized questionnaire, left ventricular mass index using M-mode echocardiography and 24 h mean ambulatory blood pressure (recorded every 30 min). Beat-to-beat blood pressure was also measured using a Finapres device in patients at rest and during mental stress (counting backward) to determine the blood pressure response to stress. RESULTS: The left ventricular mass index was correlated with the type A behavior score (r = 0.214, P < 0.05), age (r = 0.266, P < 0.05), 24 h mean systolic and diastolic blood pressures (r = 0.391, P < 0.001, and r = 0.382, P < 0.001, respectively), systolic blood pressure both at rest and during stress (r = 0.255, P < 0.05, and r = 0.215, P < 0.05, respectively), and the variability of both systolic and diastolic blood pressures at rest (r = 0.253, P < 0.05, and r = 0.321, P < 0.01, respectively). Stepwise multiple linear regression analysis demonstrated that age was associated with an increase in the left ventricular mass index for both sexes (P = 0.004 for males, P = 0.003 for females). The type A behavior score predicted a greater increase in left ventricular mass index in men (P = 0.018) but not in women. The 24 h mean systolic blood pressure was associated with a greater increase in left ventricular mass index in women (P < 0.001) but not in men. CONCLUSION: Type A behavior is an independent risk factor for left ventricular hypertrophy in male patients with essential hypertension.
Assuntos
Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Personalidade Tipo A , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Inventário de Personalidade , Fatores de Risco , Caracteres Sexuais , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the psychobehavioral factors involved in the isolated clinic blood pressure elevation and hypertension induced by mental stress. DESIGN AND METHODS: We studied 73 untreated patients with essential hypertension defined as World Health Organization stage I or II (28 men and 45 women, mean age 55 +/- 11 years). The amount of isolated clinic blood pressure elevation was examined in terms of the difference between clinic and daytime ambulatory blood pressures. Blood pressure (measured using a Finapres device) and R-R interval (measured electrocardiographically) were continuously monitored with subjects at rest and under mental stress (counting backward) to examine the cardiovascular response to the stress. Psychobehavioral characteristics such as anger, anxiety, tension, type A behavior pattern, and nervousness were evaluated and scored using structured interviews and self-reporting questionnaires. RESULTS: The anger score was inversely correlated to the clinic-ambulatory blood pressure difference for the systolic (r = -0.308, P < 0.01) and diastolic (r = -0.233, P < 0.05) blood pressures. The score for type A behavior pattern tended to be inversely correlated to the clinic-ambulatory blood pressure difference for diastolic blood pressure (r = -0.209, P < 0.1). The nervousness score was positively correlated to stress-induced increase in the systolic (r = 0.249, P < 0.05) and diastolic (r = 0.232, P < 0.05) blood pressures. The clinic-ambulatory blood pressure difference was not related to the blood pressure rise induced by mental stress (r = 0.170 for systolic blood pressure; r = 0.112 for diastolic blood pressure). CONCLUSION: The isolated clinic blood pressure elevation and hypertension due to mental stress were related to different psychobehavioral factors.
Assuntos
Pressão Sanguínea , Emoções , Hipertensão/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/complicaçõesRESUMO
The accuracy and reliability of blood pressure (BP) values were evaluated by comparing values obtained with eight automatic or semiautomatic devices designed for home BP measurement (four microphone devices based on the Korotkoff-sound technique and four cuff-oscillometric devices) with those obtained by the auscultatory method, using a standard mercury sphygmomanometer. Systolic blood pressure (SBP) values obtained using the microphone devices coincided well with those obtained by the auscultatory method. However, these devices produced a certain proportion of errors in the measurement of diastolic blood pressure (DBP), sometimes resulting in recordings at least 25 mmHg higher than those obtained by the standard method. The most frequent causes of this phenomenon were an auscultatory (silent) gap and a weak Korotkoff sound after phase IV. A microphone device using a condenser microphone built into the manometer displayed comparatively good acoustic characteristics for determining DBP. All cuff-oscillometric devices demonstrated minimal mean differences and a constant s.d. of mean difference for DBP, with no great differences from the auscultatory method. However, mean differences and s.d.s in SBP measurements using cuff-oscillometric devices were relatively greater than those obtained using some of the microphone devices. Furthermore, the direction of the mean differences in measurements from those obtained with the auscultatory method differed. The error in relation to the auscultatory method tended to be reproducible in the same subjects with both the microphone and the cuff-oscillometric devices.(ABSTRACT TRUNCATED AT 250 WORDS)