华蟾蜍毒素对离体豚鼠输精管的作用

华蟾蜍毒素(华蟾素)使离体豚鼠输精管产生剂量依赖性收缩反应,利血平化豚鼠输精管及冷藏输精管对华蟾素反应减弱。给酚妥拉明、维拉帕米后,输精管对华蟾素反应均受抑制,溴苄胺可使反应潜伏期缩短。结果提示华蟾素收缩输精管反应可能与其促进肾上腺素能神经末稍NA释放有关。     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Case-control study of prenatal ultrasonography exposure in children with delayed speech.

OBJECTIVE: To determine whether there is an association between prenatal ultrasound exposure and delayed speech in children. DESIGN: Case-control study. SETTING: Network of community physicians affiliated with the Primary Care Research Unit, University of Calgary. SUBJECTS: Thirty-four practitioners identified 72 children aged 24 to 100 months who had undergone a formal speech-language evaluation and were found to have delayed speech of unknown cause by a speech-language pathologist. For each case subject the practitioners found two control subjects matched for sex, date of birth, sibling birth order and associated health problems. MAIN OUTCOME MEASURES: Rates of prenatal ultrasound exposure and delayed speech. RESULTS: The children with delayed speech had a higher rate of ultrasound exposure than the control subjects. The findings suggest that a child with delayed speech is about twice as likely as a child without delayed speech to have been exposed to prenatal ultrasound waves (odds ratio 2.8, 95% confidence limit 1.5 to 5.3; p = 0.001). CONCLUSION: An association between prenatal ultrasonography exposure and delayed speech was found. If there is no obvious clinical indication for diagnostic in-utero ultrasonography, physicians might be wise to caution their patients about the vulnerability of the fetus to noxious agents.     

Perforin- and Fas-dependent mechanisms of natural killer cell-mediated rejection of incompatible bone marrow cell grafts

Natural killer (NK) cells eliminate target cells infected with intracellular pathogens and tumor cells by employing the granule exocytosis and death receptor pathways. They also mediate the acute rejection of incompatible bone marrow cell (BMC) grafts. However, the cytotoxic mechanisms employed during acute BMC graft rejection are obscure. Throughout these studies, BMC graft rejection was compared between two inbred strains of mice: 129 mice, which apparently use perforin- and Fas-dependent cytotoxicity, and C57BL/6 (B6) mice, which are able to exploit perforin- and/or Fas-independent mechanisms. Using perforin-knockout (PKO) mice, we have determined that the granule exocytosis pathway can play a major role in NK cell-mediated rejection of allogeneic and MHC class I-deficient BMC, depending upon the genetic background of the recipient and the environmental housing conditions. Although the granule exocytosis pathway seems to be the most potent cytolytic mechanism of NK cell-mediated rejection, alternative perforin-independent mechanisms, such as death receptor-induced apoptosis, also exist. By preventing both perforin- and Fas-mediated interactions concurrently, we observed that 129 mice were impaired in mediating MHC class I-deficient BMC rejection, while B6 mice maintained strong rejection capacities. The administration of neutralizing TNF antibodies to B6PKO mice before challenging with Fas and MHC class I double-deficient BMC still did not reverse rejection. Thus, our studies reveal the relative importance of perforin-, Fas-, and TNF-based cytotoxicity in NK cell-mediated rejection of incompatible BMC.     

HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viremia

Many patients infected with HIV do not achieve or maintain virologic suppression below levels of detection while on potent combination antiretroviral therapy. The likelihood of emergence of incident mutations conferring reduced antiretroviral drug susceptibility was estimated among patients maintained on a stable regimen with ongoing detectable plasma HIV RNA levels. Ninety-eight HIV-infected patients were identified who had 2 genotypic antiretroviral resistance tests available. Poisson log-linear regression models were used to identify predictors and estimate incidence rates of number of acquired antiretroviral drug resistance mutations per person-year. At the 1st resistance test, 88% of patients had evidence of at least 1 mutation. Sixty percent of patients acquired at least 1 new mutation during a median of 9.3 months between consecutive resistance tests, with an incidence rate of 1.61 acquired mutations per person-year (95% CI: 1.36-1.90). Predictors of resistance evolution included average plasma HIV RNA level, HIV RNA slope, and number of mutations detected at the 1st resistance test. The likelihood of acquiring drug resistance mutations while remaining on potent combination antiretroviral therapy that does not confer complete suppression of HIV replication is relatively low and depends on the level of viral replication and prior resistance.