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1.
Br J Surg ; 104(11): 1549-1557, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28782798

RESUMO

BACKGROUND: Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. METHODS: Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. RESULTS: In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. CONCLUSION: PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Pancreaticoduodenectomia , Veia Porta/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Duração da Cirurgia , Estudos Retrospectivos
2.
Immunogenetics ; 62(1): 41-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19937016

RESUMO

Lipopolysaccharide (LPS) from gram-negative bacteria activates B cells, enabling them to proliferate and differentiate into plasma cells. This response is critically dependent on the expression of TLR4; but other genes, such as RP105 and MHC class II, have also been shown to contribute to B cell LPS response. Here, we have evaluated the role of genetic control of the B cell response to LPS at the single cell level. We compared the response to LPS of peritoneal cavity (PEC) and splenic B cells on the BALB/c genetic background (LPS-low responder) to those on the C57BL/6J background (LPS-high responder) and their F1 progeny (CB6F1). Both PEC and splenic B cells from B6 exhibited 100% clonal growth in the presence of LPS; whereas, BALB/c PEC and splenic B cells achieved only 50% and 23% clonal growth, respectively. Adding CpG to the LPS stimulus pushed PEC B cell clonal growth in the low responder strain BALB/c up to 90%, showing that the nonresponse to LPS is a specific effect. Surprisingly, PEC B cells on the F1 background behaved as high responders, while splenic B cells behaved as low responders to LPS. The data presented here reveals a previous unsuspected behavior in the genetic control of the B cell response to LPS with an opposing impact in splenic versus peritoneal cavity B cells. These results suggest the existence of an, as yet, unidentified genetic factor exclusively expressed by coelomic B cells that contributes to the control of the LPS signaling pathway in the B lymphocyte.


Assuntos
Linfócitos B/imunologia , Regulação da Expressão Gênica , Lipopolissacarídeos/imunologia , Peritônio/imunologia , Baço/citologia , Animais , Linfócitos B/metabolismo , Cruzamentos Genéticos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peritônio/citologia , Baço/imunologia
3.
J Viral Hepat ; 17(5): 336-44, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19678893

RESUMO

Reducing the dose of drug affects treatment efficacy in pegylated interferon (Peg-IFN) and ribavirin combination therapy for patients with hepatitis C virus (HCV) genotype 1. The aim of this study was to investigate the impact of drug exposure, as well as the baseline factors and the virological response on the treatment efficacy for genotype 2 patients. Two-hundred and fifty patients with genotype 2 HCV who were to undergo combination therapy for 24 weeks were included in the study, and 213 completed the treatment. Significantly more patients who achieved a rapid virological response (RVR), defined as HCV RNA negativity at week 4, achieved a sustained virological response (SVR) (92%, 122/133) compared with patients who failed to achieve RVR (48%, 38/80) (P < 0.0001). Multivariate logistic-regression analysis showed that only platelet counts [odds ratio (OR), 1.68; confidence interval (CI), 1.002-1.139] and RVR (OR, 11.251; CI, 5.184-24.419) were independently associated with SVR, with no correlation being found for the mean dose of Peg-IFN and ribavirin for RVR and SVR. Furthermore, in the stratification analysis of the timing of viral clearance, neither mean dose of Peg-IFN (P = 0.795) nor ribavirin (P = 0.649) affected SVR in each group. Among the patients with RVR, the lowest dose group of Peg-IFN (0.77 +/- 0.10 microg/kg/week) and ribavirin (6.9 +/- 0.90 mg/kg/day) showed 100% and 94% of SVR. Hence, RVR served as an important treatment predictor, and drug exposure had no impact on both SVR and RVR in combination therapy for genotype 2 patients.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , RNA Viral/sangue , Proteínas Recombinantes , Resultado do Tratamento , Carga Viral
4.
J Viral Hepat ; 16(8): 578-85, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19552663

RESUMO

Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN alpha-2b during the first 12 weeks was the independent factor for c-EVR (P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving > or = 1.2 microg/kg/week of Peg-IFN, and declined to 38% at 0.9-1.2 microg/kg/week, and 22% in patients given <0.9 microg/kg/week (P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 (P < 0.0001) and SVR (P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Idoso , Relação Dose-Resposta a Droga , Feminino , Genótipo , Hepacivirus/genética , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , RNA Viral/sangue , Proteínas Recombinantes , Resultado do Tratamento
5.
Dis Esophagus ; 21(4): 355-63, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18477259

RESUMO

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30-40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (kappa) statistics for multiple raters. The kappa-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The kappa-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275-0.315, with a standard error of 0.083-0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis.


Assuntos
Esofagite Péptica/classificação , Esofagite Péptica/diagnóstico , Esofagoscopia , Variações Dependentes do Observador , Adulto , Idoso , Esofagite Péptica/patologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
6.
J Clin Invest ; 70(5): 1128-30, 1982 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6290537

RESUMO

Bile acids in the spent medium for the cell culture were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry to determine whether human hepatoblastoma cell line could synthesize bile acids. Cholic, chenodeoxycholic, and lithocolic acids were found in the culture medium, and a portion of chenodeoxycholic acid and all of lithocholic acid were sulfated. Since the cells had been cultured in serum-free medium, it is clear that the bile acids were newly synthesized and sulfated by the cultured cells. Chenodeoxycholic acid was the main bile acid in the medium, suggesting that the cell line might predominantly synthesize chenodeoxycholic acid. On the other hand, the cells had fetal or hepatoma characters such as marked alpha-fetoprotein production. These results suggest that fetal or hepatoma type bile acid metabolism might occur in the cell line, and that the established cell line could be an useful in vitro model for the study of bile acid metabolism in hepatoma.


Assuntos
Ácidos e Sais Biliares/biossíntese , Carcinoma Hepatocelular/metabolismo , Animais , Ácidos e Sais Biliares/análise , Carcinoma Hepatocelular/análise , Linhagem Celular , Células Cultivadas , Ácido Quenodesoxicólico/análise , Cromatografia Gasosa , Ácido Desoxicólico/análise , Humanos , Neoplasias Hepáticas , Ratos , Fatores de Tempo
7.
J Phys Condens Matter ; 18(26): 6033-44, 2006 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-21690816

RESUMO

X-ray diffraction of Ce(3+)-doped SrMgF(4) (SMF:Ce) crystals shows a superlattice structure, reflecting the distribution of Ce(3+) polyhedra centres observed in optical experiments. Optical absorption bands and fluorescence bands from the Ce(3+) polyhedra centres overlap in the vacuum ultraviolet (VUV) and ultraviolet (UV) regions, respectively, so that wide pumping and tuning ranges are expected for laser operation. The SMF:Ce crystals, as well as the isomorphous BaMgF(4), are candidates for a tunable laser gain material with nonlinear properties. The optical absorption, excitation, and fluorescence bands observed in the SMF:Ce crystals at low temperatures are ascribed to five distinct fluorescent centres. Three centres have well-known Ce(3+) optical characters, for example, fluorescence with double peaks separated by 2000 cm(-1) and five resolved absorption/excitation bands. These centres are assigned to Ce(3+)-polyhedra classified by weak and strong crystal fields as a consequence of the superlattice structure. The other two fluorescence bands observed in the visible region have 1.5-2 times larger linewidths than those of the former three bands. These bands are interpreted as optical transitions from complexes consisting of Ce(3+) and one or two electrons trapped at a vacancy of the nearest neighbour F(-) ligand ions.

8.
Biochim Biophys Acta ; 540(2): 231-7, 1978 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-26419

RESUMO

The neutral lipid accumulation in myo-inositol deficient Saccharomyces carlsbergensis results at least partly from an enhancement of acetyl CoA carboxylase activity due to the high level of fructose 1,6-biphosphate which activates acetyl CoA carboxylase, and due to the low level of citrate which counteracts the activation [4]. In an attempt to explore the effect of myo-inositol deficiency on the metabolic fluxes, various enzyme activities were compared between the myo-inositol supplemented and deficient cells. The activities of phosphofructokinase and ATP-citrate lyase increased by 74 and 83%, respectively. The activity of glucose-6-phosphate dehydrogenase was unchanged. Unlike acetyl CoA carboxylase, elimination of low molecular effectors had no influence on their activities. The thermostability of phosphofructokinase (at 53 degrees C) increased, while that of aldolase (at 48 degrees C) greatly decreased due to the deficiency. The thermostability of glucose-6-phosphate dehydrogenase (at 52 degrees C) was also unchanged.


Assuntos
Inositol/metabolismo , Saccharomyces/enzimologia , ATP Citrato (pro-S)-Liase/metabolismo , Acetil-CoA Carboxilase/metabolismo , Citrato (si)-Sintase/metabolismo , Estabilidade de Medicamentos , Frutose-Bifosfato Aldolase/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glicólise , Fosfofrutoquinase-1/metabolismo , Temperatura
9.
Biochim Biophys Acta ; 531(2): 197-205, 1978 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-214137

RESUMO

myo-Inositol deficiency in rats produced an overaccumulation of triacylglycerols in the liver due to stimulated lipolysis in the adipose tissue (Hayashi, E., Maeda, T. and Tomita, T. (1974) Biochim. Biophys. Acta 360, 134--155). The mechanism of the enhancement in lipolysis has now been investigated. The lipolytic response to adrenalin, corticotropin and insulin of the epididymal adipose tissue did not change due to the deficiency, but hormone-sensitive lipase activity, plasma adrenalin level and blood pressure were higher in the deficient rats. Adrenalectomy had no influence, but administration of sympathetic nervous blockers (reserpine, hexamethonium and bupranolol) inhibited the liver lipid deposition and an increase of serum free fatty acids in the deficient rats. These results indicate that the enhancement in lipolysis is mediated by an excitation of sympathetic nerve terminals innervating in the adipose tissues.


Assuntos
Tecido Adiposo/metabolismo , Inositol/deficiência , Mobilização Lipídica , Fígado/metabolismo , Tecido Adiposo/efeitos dos fármacos , Adrenalectomia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Bupranolol/farmacologia , Epinefrina/farmacologia , Compostos de Hexametônio/farmacologia , Insulina/farmacologia , Lipase/metabolismo , Mobilização Lipídica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Ratos , Reserpina/farmacologia , Triglicerídeos/metabolismo
10.
Biochim Biophys Acta ; 841(2): 229-31, 1985 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-4016150

RESUMO

The formation of chenodeoxycholic acid via 7-ketolithocholic acid by rat liver preparations was examined in vitro. Results showed that a rat liver preparation reduced 7-ketolithocholic acid mainly to chenodeoxycholic acid and to ursodeoxycholic acid in a smaller amount, and that the reductase required NADPH but not NADH as coenzyme and was mainly localized in the microsomes.


Assuntos
Ácido Quenodesoxicólico/biossíntese , Ácido Litocólico/análogos & derivados , Fígado/metabolismo , Animais , Técnicas In Vitro , Cinética , Ácido Litocólico/metabolismo , Masculino , Microssomos Hepáticos/metabolismo , NADP/metabolismo , Oxirredução , Ratos , Ratos Endogâmicos
11.
Am J Clin Nutr ; 29(10): 1167-74, 1976 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-973605

RESUMO

Sumo is an ancient sport in Japan and there are at present over 800 professional sumo wrestlers (rikishis). After entrance into the wrestler society a wrestler takes strenuous daily training together with a very high calorie diet (more than 5,000 cal). Frequency of food intake is twice a day. The average diet of Japanese people contains of 2,279 calories and the meal frequency is generally three times a day. In 96 wrestlers average actual body weight and modified Broca index was 100.4 kg and 143.5%, respectively. In this group the prevalence of overweight with obesity, overweight without obesity, nonoverweight with obesity, and nonoverweight without obesity was 53.4, 39.1, 1.0, and 6.5%, respectively. Also mean serum levels of triglyceride, phospholipid, uric acid, and total protein were significantly higher than those obtained in 89 age-matched healthy males. The incidence of diabetes mellitus, gout, and hypertension in wrestlers was 5.2, 6.3, and 8.3%, respectively, all values being considerably higher than in controls. Weight correlated significantly with skinfold thickness, diastolic blood pressure, total cholesterol, and uric acid in each group. Multiple regression analyses were made treating weight or uric acid as dependent variables in both groups. Obesity, hyperlipidemia, and hyperuricemia in wrestlers were presumed to be caused chiefly by the high calorie diet and partially by the infrequent meal intake.


Assuntos
Obesidade , Esportes , Luta Romana , Adolescente , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Proteínas Sanguíneas/metabolismo , Composição Corporal , Constituição Corporal , Estatura , Humanos , Japão , Metabolismo dos Lipídeos , Masculino , Obesidade/etiologia , Obesidade/metabolismo , Dobras Cutâneas , Medicina Esportiva , Ácido Úrico/sangue
12.
Mech Ageing Dev ; 10(1-2): 81-92, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-221757

RESUMO

A comparison of results obtained from studies of the intracellular fractions of the tissues of liver, brain and heart of "young" (1-2 months), "old" (24-27 months) and "senile" (34-37 months) rats showed that the ratios of three enzymes, acid phosphatase, beta-N-acetylglucosaminidase and acid RNase of the liver and heart were very similar and their activities decreased with age. On the other hand, the protein content is the supernatant of the liver, and acid DNase activities in the supernatant of the brain increased significantly with age. When the 24-27 month and 34-37 month old rats were compared, the ratios of the total activities of liver beta-N-glucosaminidase and brain acid DNase in the supernatant and the specific activities of brain beta-N-glucosaminidase in the microsomal fraction increased significantly.


Assuntos
Envelhecimento , Encéfalo/enzimologia , Hexosaminidases/metabolismo , Fígado/enzimologia , Miocárdio/enzimologia , Monoéster Fosfórico Hidrolases/metabolismo , Fosfatase Ácida/metabolismo , Animais , Desoxirribonucleases/metabolismo , Lisossomos/enzimologia , Masculino , Microssomos/enzimologia , Ratos , Ribonucleases/metabolismo
13.
Atherosclerosis ; 39(4): 453-61, 1981 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7259825

RESUMO

In spontaneously hypertensive rats, prolonged hypertension caused a decrease in aortic cholesterol esterase activity with N-acetyl-beta-D-glucosaminidase activity increased and acid phosphatase activity unchanged [3]. The present study was undertaken to compare these changes with those caused by other experimentally induced types of hypertension. Treatment with DOCA-salt for one month significantly elevated both aortic cholesterol esterase and acid phosphatase activities. In contrast, to spontaneous hypertension, venous changes were also observed. An intake of 1% NaCl ad libitum produced results similar to those with the DOCA-salt treatment, despite the fact that blood pressure did not increase. This suggested that humoral factors were the main cause of the elevated enzyme activities in DOCA-salt hypertension. In rats made hypertensive by unilateral renal arterial constriction with contralateral nephrectomy (one clip--one kidney hypertension) or without contralateral nephrectomy (one clip--two kidney hypertension), aortic cholesterol esterase activities were unchanged, while aortic N-acetyl-beta-D-glucosaminidase, and aortic and venous acid phosphatase activities were increased. These results show distinct differences in the response of lysosomal enzymes during the three hypertensive states.


Assuntos
Aorta/enzimologia , Hidrolases de Éster Carboxílico/sangue , Hipertensão/enzimologia , Lisossomos/enzimologia , Esterol Esterase/sangue , Acetilglucosaminidase/sangue , Fosfatase Ácida/sangue , Animais , Desoxicorticosterona , Hipertensão/induzido quimicamente , Hipertensão Renal/enzimologia , Masculino , Ratos , Cloreto de Sódio
14.
Atherosclerosis ; 43(2-3): 405-15, 1982 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7115469

RESUMO

Sex differences in aortic cholesterol esterase activity and changes in the activity following castration and gonadal hormone treatment were investigated in rats. Differences in the enzyme activity were apparent after 2.5 months and became most significant after 6 months. The activity in the aorta and the liver was significantly higher in female rats. Prepubertal orchiectomy increased the aortic activity, feminizing the type of metabolism, whereas postpubertal orchiectomy, and both pre- and postpubertal ovariectomy induced no change in the activity. The administration of testosterone to female rats significantly decreased the aortic activity, masculinizing the type of metabolism. However, the administration of testosterone or of 17 beta-estradiol to male rats had no effect. These results suggest (1) that there are clear sex differences in aortic cholesterol esterase activity, (2) that prepubertal exposure to androgens plays a critical role in the sexual differentiation in aortic and hepatic cholesterol ester metabolism, and (3) that the administration of testosterone can temporarily masculinize the type of metabolism. These results partly explain the sexual differences in susceptibility to atherosclerosis.


Assuntos
Aorta/enzimologia , Hidrolases de Éster Carboxílico/metabolismo , Castração , Caracteres Sexuais , Esterol Esterase/metabolismo , Envelhecimento , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Estradiol/farmacologia , Feminino , Fígado/enzimologia , Masculino , Ratos , Ratos Endogâmicos , Testosterona/farmacologia
15.
Atherosclerosis ; 37(3): 409-22, 1980 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-6257251

RESUMO

Spontaneously hypertensive rats (SHRSP and SHR) and normotensive WKR were treated with hypotensive drugs, and arterial and venous enzyme activities were compared between treated and nontreated hypertensive groups. With the 4 month experiment, cholesterol esterase activity in the aorta from hypertensive SHRSP and SHR was significantly lower than that in the respective treated groups, whereas venous activity did not differ. By contrast, aortic NAGA activity was significantly higher in the hypertensive groups without any changes in venous activity. Acid phosphatase activity was unaltered. No effects of treatment were observed in the normotensive WKR. Accompanying a decrease in aortic cholesterol esterase, there was a marked increase in aortic cholesteryl esters accompanying hypertension. Aortic phosphodiesterase activity was significantly elevated in the hypertensive SHRSP and SHR compared with the respective treated groups. These results suggest that hypertension of long duration specifically decreased aortic cholesterol esterase activity with a consequent accumulation of cholesteryl esters in the aorta, and that this hemodynamic effect seemed to be partly mediated by cyclic AMP with an effect on the lysosomal membrane. These results could provide the biochemical bases for the relationship between hypertension and atherosclerosis.


Assuntos
Acetilglucosaminidase/metabolismo , Fosfatase Ácida/metabolismo , Aorta Abdominal/enzimologia , Hidrolases de Éster Carboxílico/metabolismo , Hexosaminidases/metabolismo , Hipertensão/enzimologia , Esterol Esterase/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Animais , Pressão Sanguínea , Ésteres do Colesterol , Hipertensão/tratamento farmacológico , Masculino , Meticlotiazida/uso terapêutico , Ratos , Reserpina/uso terapêutico
16.
Br J Pharmacol ; 53(2): 207-15, 1975 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-238699

RESUMO

1 Some pharmacological properties of surugatoxin (SGTX), a purified toxic substance from the Japanese ivory mollusc (Babylonia japonica), have been investigated. SGTX (50 nmol/kg i.v.) produced a prolonged fall of blood pressure in anaesthetized cats. This hypotensive effect was neither blocked by atropine and propranolol nor by spinal cord transection. 2 SGTX (37-50 nmol/kg i.v.) inhibited the hypertensive and hypotensive response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) and to electrical stimulation of the splanchnic and vagal nerve, whereas it usually augmented the hypertensive response to adrenaline and to 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) in anaesthetized cats. 3 Close intra-arterial injection of SGTX (6.2-12.3 nmol/kg) to the superior cervical ganglion blocked the contractile response of the nictitating membrane to preganglionic stimulation of cervical sympathetic nerve or injected DMPP, but not to postganglionic stimulation or to injected adrenaline and McN-A-343. 4 SGTX affected neither the indirectly nor the directly stimulated response of the rat isolated phrenic nerve-diaphragm at concentrations less than 12.3 mum. 5 The effect of SGTX on the contractile response to some agonists and on the twitch response to transmural stimulation in the guinea-pig isolated ileum was investigated. At less than 12.3 mumSGTX did not depress responses to acetylcholine or histamine. The curves for nicotine- and DMPP-induced contractions were shifted to the right and depressed gradually as the concentration of SGTX was increased (12.3 nm-1.23 mum). SGTX partially inhibited the contraction induced by 5-hyroxytryptamine and the transmurally-stimulated twitch response. 6 These results suggest that SGTX has a ganglion-blocking action. The mode of anti-nicotinic action of SGTX in the guinea-pig isolated ileum seems to differ from that of hexamethonium and tetraethylammonium and to resemble more closely that of mecamylamine.


Assuntos
Toxinas Marinhas/farmacologia , Moluscos/fisiologia , Acetilcolinesterase/metabolismo , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Gatos , Depressão Química , Estimulação Elétrica , Feminino , Bloqueadores Ganglionares/farmacologia , Íleo/efeitos dos fármacos , Técnicas In Vitro , Indóis/farmacologia , Inositol/análogos & derivados , Inositol/farmacologia , Masculino , Venenos de Moluscos , Ácidos Nicotínicos/antagonistas & inibidores , Membrana Nictitante/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , Pteridinas/farmacologia , Estimulação Química
17.
Br J Pharmacol ; 84(3): 765-71, 1985 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3986434

RESUMO

The action of adenosine on the myenteric plexus-longitudinal muscle strips from guinea-pig ileum to high frequency electrical field stimulation (10 Hz) was investigated. Electrically induced contractions were reduced markedly by tetrodotoxin (0.2 microM) and atropine (1 microM), and partially by noradrenaline (3 microM) and morphine (3 microM). Adenosine, adenosine 5'-monophosphate (AMP) and adenosine triphosphate (ATP) produced a concentration-dependent inhibition of the high frequency contractions over the range of 0.1-100 microM, the most potent being adenosine. The concentration-response curve for adenosine was significantly shifted to the left by dipyridamole (10 nM), while dipyridamole at higher concentrations (30 nM-10 microM), depressed the contraction markedly by itself. Dipyridamole decreased [3H]-adenosine uptake into strips of ileum in a concentration-dependent manner. There was a significant correlationship between the reduction of adenosine uptake and the inhibition of the contraction induced by dipyridamole (r = 0.970). In strips desensitized to adenosine or treated with adenosine deaminase, the inhibitory effect of dipyridamole was significantly reduced. The present investigation revealed that adenosine depressed responses of guinea-pig ileum to high frequency electrical stimulation and suggested that the inhibitory effect of dipyridamole may be closely associated with the behaviour of endogenous adenosine or related compounds.


Assuntos
Adenosina/farmacologia , Dipiridamol/farmacologia , Músculo Liso/efeitos dos fármacos , Adenosina/metabolismo , Adenosina Desaminase/farmacologia , Animais , Atropina/farmacologia , Interações Medicamentosas , Estimulação Elétrica , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiologia
18.
Br J Pharmacol ; 63(3): 457-64, 1978 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-667489

RESUMO

1 Electrically (30 Hz) induced contractions of guinea-pig isolated ileal longitudinal muscles were reduced by tetrodotoxin (1 micron), adenosine (30 micron) and morphine (10 micron). 2 When stimulated with 10 or 30 Hz for 10 s at 1 min intervals, a progressive decline of amplitude of the contraction was seen (development of tachyphylaxis). At this time, the contractile response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10 micron) was also greatly reduced. 3 The smaller responses to electrical stimulation and DMPP during tachyphylaxis were restored to their initial amplitude by the addition of theophylline (10 micron). The appearance of tachyphylaxis was prevented by pretreatment with theophylline (1 to 10 micron) and was greatly accelerated by pretreatment with dipyridamole (0.1 1 micron). 4 In [14C]-choline or [3H]-adenosine preloaded muscle strips, electrical stimulation (30 Hz) increased the 14C- or 3H-output, the effect being sensitive to tetrodotoxin blockade. The tachyphylaxis to electrical stimulation was accompanied by a considerable and sustained increase in 3H-output, an effect that was accelerated by dipyridamole (1 micron). The 14C-output initially increased but fell off gradually with the development of tachyphylaxis at which time theophylline (30 micron) reversed the fall. 5 There was a marked increase in the proportion of released [3H]-adenosine to its derivatives during the development of tachyphylaxis. Approximately 60% of the released total radioactivity after tachyphylaxis was found to be [3H]-adenosine. 6 These results suggest that the development of tachyphylaxis may be closely associated with the release of endogenous adenosine derivatives (mostly adenosine) which have presynaptic inhibitory actions on the cholinergic elements in guinea-pig ileum.


Assuntos
Nucleotídeos de Adenina/fisiologia , Adenosina/fisiologia , Contração Muscular , Músculo Liso/fisiologia , Acetilcolina/metabolismo , Adenina/metabolismo , Nucleotídeos de Adenina/farmacologia , Adenosina/metabolismo , Adenosina/farmacologia , Animais , Dipiridamol/farmacologia , Estimulação Elétrica , Cobaias , Técnicas In Vitro , Masculino , Taquifilaxia , Teofilina/farmacologia
19.
Chest ; 114(6): 1749-55, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9872211

RESUMO

Video-assisted thoracoscopy using a miniaturized endoscope (mini-VAT) was applied for preoperative diagnosis in general thoracic surgery. Thirty-one patients, including 27 with indeterminate pulmonary nodule and 4 with suspected pleural involvement of lung cancer or metastatic pleural tumor, underwent mini-VAT. As a pilot study, 14 of the former 27 patients underwent mini-VAT while receiving general anesthesia. As a prospective study, all the remaining 17 patients underwent mini-VAT while receiving local anesthesia. Solid scopes of three different sizes, 0.9, 1.9, or 4.0 mm diameter, were used. An artificial pneumothorax for scope introduction was produced by needle thoracentesis under atmospheric pressure. Automatic cutting needle biopsy was used for tissue sampling. In the pilot study group, mini-VAT with a 4.0-mm scope provided excellent visibility and diagnostic sensitivity of 100%. This study group showed the diagnostic sensitivity of needle biopsy for pulmonary nodule to be 100%. Hemorrhages and air leaks at biopsy sites were sealed with blood coagulation in a short time. In the prospective study group, mini-VAT with a 4.0-mm scope with the patients receiving local anesthesia provided a diagnostic sensitivity of 91% for pulmonary nodule and a diagnostic accuracy of 100% for suspected pleural involvement. Causes of failure of mini-VAT with the use of local anesthesia were cough reflex during needle biopsy and incomplete lung collapse for deeply located target in two cases. The adverse effects of the mini-VAT were paradoxical respiration in two cases in which local anesthesia was used. The patients who received only local anesthesia required no chest tube drainage. Mini-VAT is a simple, minimally invasive procedure suitable as a preoperative examination technique for histologic diagnosis, evaluation of disease progression, and selection of strategy in thoracic surgery.


Assuntos
Pneumopatias/diagnóstico , Doenças Pleurais/diagnóstico , Toracoscopia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia , Desenho de Equipamento , Feminino , Humanos , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Doenças Pleurais/cirurgia , Estudos Prospectivos , Sensibilidade e Especificidade , Toracoscópios , Gravação em Vídeo
20.
J Biochem ; 108(4): 505-6, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1963427

RESUMO

Binding studies of human plasma gelsolin with ATP were done by equilibrium dialysis. Analysis of the binding data showed that plasma gelsolin had one class of ATP binding site with Kd = 2.8 x 10(-7) M, which saturated at an ATP/gelsolin ratio of 0.6. The bioluminescent assay for ATP with luciferin and firefly luciferase confirmed that the protein contained a nucleotide as ATP.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Ligação ao Cálcio/sangue , Proteínas dos Microfilamentos/sangue , Plasma/metabolismo , Gelsolina , Humanos
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