Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.
Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.
Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively. 相似文献
We evaluated a 1-year course of a newly developed immunosuppressant, mizoribine (at a dosage of 3 mg/kg body weight per day),
in nine children with steroid-dependent nephrotic syndrome. Steroid treatment could be discontinued in two patients and the
maintenance dosage of steroid could be reduced to less than half of that given before mizoribine therapy in a third. There
were no beneficial effects in the remaining six patients. No adverse effects of mizoribine were observed during the course
of therapy.
Received September 20, 1996; received in revised form and accepted April 24, 1997 相似文献
This study was designed to determine the influence of ileal pouch capacity and anal sphincteric function on the clinical outcome
after ileal pouch-anal anastomosis. A total of 24 patients who had undergone ileal pouch-anal anastomosis (J pouch) for ulcerative
colitis were studied. The 24-hour stool frequency was found to be inversely correlated with the sensitivity threshold volume
(STV), maximal tolerance volume (MTV), and distensibility, but was independent of the maximal resting pressure and maximal
squeeze pressure. Patients experiencing nocturnal fecal incontinence had maximal resting pressures that were significantly
lower than those of nocturnally continent patients. Among the patients with fecal incontinence, those with frequent soiling
had lower resting pressures, STV, and distensibility than the patients with intermittent spotting. In addition, the STV in
patients needing nocturnal evacuation were lower than those of patients who did not evacuate after falling asleep. The conclusions
are as follows. Both stool frequency and the need for nocturnal pouch evacuation correlated directly with pouch volume. Anal
incontinence was more common in patients with low internal sphincteric function. In addition, frequent and gross nocturnal
incontinent patients demonstrate a worse function in both the anal sphincter and reservoir than those with intermittent spotting. 相似文献
We describe the case of a 61-year-old woman diagnosed with primary Sj?gren's syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of recurrent purpuric rashes. Her two daughters had previously been diagnosed with other autoimmune diseases. One daughter had Graves' disease and the other had Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was made based on dryness of mucous membranes, Shirmer test, and parotid sialography. Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may develop other autoimmune diseases. This case aids understanding of the immune pathogenesis and genetic background of SS. 相似文献
Objective. To clarify the MRI features of parasymphyseal insufficiency fractures of the os pubis. Design and patients. MRI was performed in four postmenopausal women with parasymphyseal insufficiency fractures. The diagnosis was confirmed with
plain films in every patient. T1-weighted and T2-weighted images were obtained in four patients using a 1.5-T unit. Postcontrast
T1-weighted imaging was also done in three patients. Results and conclusions. MRI of pubic parasymphyseal insufficiency fracture characteristically demonstrates a hyperintense mass lesion with a hypointense
rim on T2-weighted imaging, showing peripheral and septal enhancement after contrast administration. It is important to have
this entity in mind in patients with osteoporosis, especially in patients with a history of pelvic irradiation for malignant
disease, so as not to misinterpret it as a chondroid tumor or bone metastasis. 相似文献
The serum triglyceride concentration (TG) tested in health checks after meals cannot properly sort out hypertriglyceridemia with reference to the upper normal limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society, because TG goes up considerably after a meal. In our survey of a large number of health check examinees (free of abnormal biochemical data other than TG and diseases under medical treatment), the mean (M) of fasting TG + 2 standard deviations (SD) was close to 150 mg/dl. When the screening level was set at M + 2SD for each time span after a meal, the ratio of the screened was distributed between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on fasting. Accordingly, the nearest round number ending with zero for the first digit is suggested to be of practical use for the screening level of after-meal TG. The average TG in females was definitely lower than that of males, though proportionately increasing with age. The ratio of the screened among females aged between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively. 相似文献
Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but
no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53
expression of proximal and distal gastric cancer concerning histopathology and prognosis.
Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical
methods.
Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher
than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference
between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology
of gastric cancer.
Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer. 相似文献