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31.
YC-1, a novel activator of platelet guanylate cyclase 总被引:11,自引:0,他引:11
YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC- 1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo. 相似文献
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FN Engsig LH Omland MV Larsen LD Rasmussen T Qvist J Gerstoft N Obel 《HIV medicine》2010,11(7):457-461
Objectives
According to the Swiss Federal Commission for HIV/AIDS, HIV‐infected patients on successful antiretroviral treatment have a negligible risk of transmitting HIV sexually. We estimated the risk that patients considered to have an undetectable viral load (VL) are actually viraemic.Methods
A Danish, population‐based nationwide cohort study of HIV‐infected patients with VL <51 HIV‐1 RNA copies/mL for more than 6 months was carried out for the study period 2000–2008. The observation time was calculated from 6 months after the first VL <51 copies/mL to the last measurement of VL or the first VL >50 copies/mL. The time at risk of transmitting HIV sexually was calculated as 50% of the time from the last VL <51 copies/mL to the subsequent VL if it was >1000 copies/mL. The outcome was the time at risk of transmitting HIV sexually divided by the observation time.Results
We identified 2680 study subjects contributing 9347.7 years of observation time and 56.4 years of risk of transmitting HIV (VL>1000 copies/mL). In 0.6% [95% confidence interval (CI) 0.5–0.8%] of the overall observation time the patients had VL >1000 copies/mL. In the first 6 months this risk was substantially higher (7.9%; 95% CI 4.5–11.0%), but thereafter decreased and was almost negligible after 5 years (0.03%; 95% CI 0.0–0.2%). The risk was higher in injecting drug users, but otherwise did not differ between subgroups of patients.Conclusion
The risk of viraemia and therefore the risk of transmitting HIV sexually are high in the first 12 months of successful antiretroviral treatment, but thereafter are low. 相似文献36.
Kimme-Smith C; Duerinckx AJ; Kaiser S; Jones JP; Tessler FN; Bassett LW 《Radiology》1989,172(2):449-452
The frequency responses of nine real-time mechanical probes and two pulsed Doppler probes from four manufacturers were measured. The reflected frequency was measured in a clinical environment by evaluating the pulser, transducer assembly, and receiver as a system. Two independent systems were used for these measurements: a spectrum analyzer and a data acquisition system that computed the fast Fourier transform of the reflected waveform. Results showed that probe frequency (calibrated by the manufacturer in the transmit mode with a hydrophone) was as much as 30% higher than that found by means of frequency measurement procedures with the probe attached to the ultrasound system and evaluated in the receive mode. Such large discrepancies indicate that if acceptance testing of the frequency spectrum is not performed at a clinical facility, prolonged clinical evaluation of new equipment should be arranged. 相似文献
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Zhang JW; Song WF; Zhao YJ; Wu GY; Qiu ZM; Wang FN; Chen SS; Stamatoyannopoulos G 《Blood》1993,81(6):1624-1629
We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that is associated with elevated fetal hemoglobin in the adult. The propositus is a homozygote from the Yunnan province of China. The deletion spans about 90 kb of DNA and removes the A gamma, delta, and beta-globin genes. The 5' breakpoint of the deletion is located about 0.13 kb upstream from the A gamma-globin gene, whereas the 3' breakpoint is located about 66 kb downstream from the beta-globin gene, about 13 kb upstream from the breakpoint of the Chinese (A gamma delta beta)zero-thalassemia. Heterozygotes for this Yunnanese form of (A gamma delta beta)zero-thalassemia express between 9% and 17% of fetal hemoglobin, whereas the homozygote present with a mild anemia (Hb = 10.7 g/dl). Comparison of the sites of 3' breakpoints of the Yunnanese and the Chinese (A gamma delta beta)zero-thalassemia mutants is compatible with the hypothesis that an enhancer element is located between the 3' breakpoints of these two mutants. Juxta-position to the G gamma gene of this element may be responsible for the efficient gamma-gene expression in the Yunnanese mutant. 相似文献
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Antimicrobial and antispasmodic activity of leaf extract and fractions of Stachytarpheta cayennensis
TC Okoye PA Akah CO Okoli AC Ezike FN Mbaoji 《Asian Pacific journal of tropical medicine》2010,3(3):189-192
ObjectiveTo investigate the antimicrobial activity of the methanol leaf extract (ME), n-hexane fraction (HF), ethylacetate fraction (EF) and methanol fraction (MF), of Stachytarpheta cayennensis C. Rich (verbenaceae) as well as to ascertain the antispasmodic effects of the ME and the various fractions (HF, EF and MF) on acetylcholine (Ach) and histamine (H) induced contractions on isolated guinea pig ileum.MethodsThe in vitro agar well diffusion method was used for the antimicrobial studies while the isolated tissue method was employed for the antispasmodic test. Organisms used were all clinical isolates of Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella paratyphi, Candida albicans and Aspergillus niger.ResultsThe extract and fractions exhibited dose dependent inhibition against all the bacteria tested and also exhibited insignificant antifungal activity against Candida albicans and Aspergillus niger. The minimum inhibitory concentration (MIC) of the extract and fractions (mg/mL) on Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella paratyphi respectively were ME 5.62, 14.12, 22.38, 2.11; EF 1.25, 6.30, 9.40, 9.40 and MF 3.98, 8.81, 39.80, 21.13. The n-hexane fraction exhibited MIC of 1.07 mg/mL against only Bacillus subtilis. The extract and fractions exhibited significant (P< 0.05) dose dependent attenuation of contractions induced by acetylcholine and histamine on isolated guinea pig ileum. Concentrations of the extract and fractions (μg/mL) which evoked 50% inhibition of maximal response exhibited by Ach were ME 0.64, HF 0.16, EF 0.08 and MF 0.15, while that of histamine included ME 5.12, HF 0.16, EF 0.04 and MF 0.64. Preliminary phytochemical studies on the extract and fractions indicated the presence of carbohydrates, alkaloids, saponins, flavonoids, steroids and terpenoids.ConclusionsThe extract and fractions of Stachytarpheta cayennensis possessed both antibacterial and antispasmodic effects confirming the claimed use in folkloric medicine for wound healing and gastrointestinal ulceration. 相似文献