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
This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared
the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University
of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the
K2HPO4 liquid phantom in 538 Americans aged 20–85 years, and with the B-MAS200 phantom in 577 Japanese aged 20–83 years. These BMD
were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111
postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared
for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower
than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6,
20.5, 38.1 mg/cm3 in women aged 20–24 years, 40–44 years, 60–64 years, respectively. In premenopausal women, BMD began to decrease at the age
of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal
women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age
in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year
in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in
Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without
fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion,
Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of
spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese
women.
Received: 18 December 1995 / Accepted: 23 September 1996 相似文献
LD78 is a cDNA newly isolated from human stimulated tonsillar lymphocytes. The expression of LD78 is related to inflammatory responses and its structure has a homology with macrophage inflammatory protein 1-alpha, which is known to have an inhibitory effect on murine CFU-S. Using a colony assay technique, we examined the effects of LD78 on human hemopoietic progenitors. The addition of doses of 100 ng/ml or more of LD78 suppressed the colony formation of KMT-2, a factor-dependent myelomonocytic cell line established from cord blood cells; this suppressive activity was neutralized by the addition of antibody against LD78. The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non-phagocytic mononuclear cells or sorted CD34+ cells. The conditioned medium of KMT-2 cells or peripheral blood mononuclear cells cultured with LD78 suppressed colony formation by CD34+ cells. From these findings, it is suggested that LD78 affects phagocytic cells and induces factors that are inhibitory for hemopoiesis. We consider LD78 to be a new cytokine that plays an inhibitory role in hemopoiesis. 相似文献
We examined the ontogeny of relaxation responses to three categories of calcium channel antagonists, represented by verapamil, diltiazem, and nifedipine, for both potential-operated (KCl-mediated) and receptor-operated channels [norepinephrine (NE)-mediated] in rat thoracic aorta. Aortic rings from 2- to 3-d, 1-wk, and 12-wk-old Sprague Dawley rats were mounted in an organ bath, bathed in Krebs' solution, and connected to a force-displacement transducer to measure isometric tension. Endothelium intact vessels at optimal passive force were exposed to a single ED50 of isotonic KCl or NE, equilibrium contraction was measured, then vessels were washed and exposed for 30 min to 1 microM verapamil, 1 microM diltiazem, or 0.1 microM nifedipine, followed by another dose of KCl or NE. Verapamil and diltiazem demonstrated significant (p less than 0.05) age-related increases in effectiveness for blocking KCl-mediated contraction [(% reduction of control contraction +/- SEM) (Verapamil: 2-3 d, 67.7 +/- 4.2; 1 wk, 72.5 +/- 1.8; 12 wk, 89.5 +/- 1.0. Diltiazem: 2-3 d, 64.6 +/- 2.9; 1 wk, 73.5 +/- 3.0; 12 wk, 83.1 +/- 1.8]. Nifedipine was equally effective at all ages: 2-3 d, 85.6 +/- 1.3; 1 wk, 90.0 +/- 1.6; and 12 wk, 91.3 +/- 1.4. Verapamil and diltiazem also showed significant age-related increases in effectiveness for blocking NE-mediated contraction (Verapamil: 2-3 d, 6.2 +/- 3.9; 1 wk, 28.0 +/- 4.8; 12 wk, 44.1 +/- 6.0. Diltiazem: 2-3 d, 8.0 +/- 3.1; 1 wk, 20.5 +/- 3.9; 12 wk, 46.5 +/- 4.8).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
For several different bone mineral measurements and various skeletal sites, we compared capability to discriminate between
women in various age decades with and without spinal fracture, and attempted to identify the most effective cutoff level in
discrimination of spinal fracture. The subjects were 88 women aged 50–59 years (including 32 with fracture), 95 women aged
60–69 years (including 54 with fracture), and 34 women aged 70–79 years (including 18 with fracture). Spinal trabecular and
cortical bone mineral density (BMD) were measured using quantitative computed tomography (CT), and spinal, radial (ultra-distal,
10% distal and 33% distal), and calcaneal BMD were measured by dual X-ray absorptiometry. These BMD values were obtained in
each subject on the same day. Three statistical techniques—Student's t-test, the logistic regression analysis, and the receiver operating characteristics (ROC) analysis— were applied and accuracy
was calculated using the various cutoff values. The capability to discriminate between women with and those without fracture
using these BMD values was different among the three age groups. In women aged 50–59 and 60–69 years, all measurements showed
good capabilities for discriminating women with fracture. In women aged 70–79 years, these measurements showed lower capability
than in those aged 50–59 and 60–69 years, but among them, the calcaneal and ultradistal radial BMD showed relatively good
capability. The 10% and 33% distal radial BMD values were not useful in the detection of the high risk women with fracture.
The cutoff BMD values for discrimination of women with fracture varied according to the sites and methods of measurement.
For each specific age group, the most suitable measurement methods and the appropriate skeletal sites should be considered,
and the effective cutoff values to discriminate those with fracture may differ according to the measurement methods, the skeletal
sites examined, and age.
Received: 5 February 1996 / Accepted: 18 June 1996 相似文献
We studied the MRI appearances of the brain in 159 patients with diabetes mellitus (DM) and 2566 agematched individuals without DM (controls). The images were reviewed for cerebral infarcts, hemorrhage, atrophy and subcortical arteriosclerotic encephalopathy. Cerebral atrophy was significantly more frequent in patients with DM than in controls (P>0.005) from the sixth to the eighth decade. The frequency of atrophy was 41.2% in the 6th decade, 60.0% in the 7th and 92.3% in the 8th decade in DM, and 19.8%, 38.9% and 56.8% respectively in controls. Unexpectedly, there was no statistically significant difference in the incidences of cerebrovascular diseases at any age. 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