7-甲氧基-4′-羟基-3′-二乙胺甲基异黄酮(MHDF)对大鼠血流动力学和主动脉的作用

本实验观察了MHDF对整体大鼠血流动力学和离体大鼠胸主动脉的作用。结果表明iv MHDF(3～12.8 mg/kg)能降低大鼠左心室±dp/dt_max,V_max,V_pm和LVSP,延长T-dp/dt_max,减慢心率。MHDF还能舒张大鼠胸主动脉,ED₅₀为6.5×10^-6mol/L;非竞争拮抗NA和CaCl₂致主脉收缩,pD₂′为3.11±0.21和3.73±0.07;抑制高K⁺致主动脉收缩,IC₅₀为1.76×10^-5mol/L。提示MHDF对血管的作用与α受体阻断剂不同,而可能与钙拮抗有关。     

Effects of hepatic arterial yttrium-90 microsphere administration alone and combined with regional bromodeoxyuridine infusion in dogs

Brachytherapy by embolization with radiotherapeutic microspheres following intraarterial infusion of a radiosensitizer represents an attempt to combine several selective modalities into a more potent, focused attack on regionally confined tumors. In pursuit of this goal, we examined the ability of foxhounds with surgically implanted hepatic arterial (HA) delivery systems to tolerate a clinically relevant dosage of HA yttrium-90 (Y-90) by microsphere administration either alone or preceded by a 28-day constant HA infusion of either 5-bromo-2'-deoxyuridine (BUDR) or a control solution. Five dogs received BUDR (10 mg/kg/day) and five a control buffer infusion for 28 days immediately prior to the administration of Y-90-coated 15 micron resin microspheres (equivalent of 5000 rads to the entire liver) to each dog on day 31. In all animals, blood counts, bilirubin, amylase, appetite, weight, and behavior remained unchanged. Dogs receiving the microspheres after buffer infusion alone exhibited no hepatic enzyme alanine aminotransferase or alkaline phosphatase elevation. Alanine aminotransferase and alkaline phosphatase levels both rose during the third week of BUDR infusion, and while subsequent microsphere administration further increased enzyme levels, these levels had largely normalized by necropsy on day 82. At necropsy, the type and degree of hepatic toxicity among the animals receiving radioactive microspheres was comparable to that previously described in patients receiving external beam hepatic irradiation at conventional doses (2000-3000 rads). Also noted was a radiation-induced cholecystitis (due in large part to the gallbladder's total reliance on the hepatic artery for blood supply). One resin microsphere dog exhibited a small quantity of microspheres in the lungs causing focal radiation-induced granulomas suggesting the need to assess shunting of microspheres through the liver in clinical studies. Thus, HA Y-90 microspheres with BUDR can produce acceptable, nonlethal, and tolerable toxicities in this dog model suggesting that clinical studies of this combination are not likely to be contraindicated by synergistic toxicity. Although HA BUDR did not contribute significantly to the toxicity of the Y-90 microspheres, HA BUDR by itself administered uninterrupted for 4 weeks may, like HA FUDR (clinically), cause chemical hepatitis/cholangitis. The unexpected fragmentation of the resin spheres (albeit without myelosuppression) has led us to begin studies with a recently developed nondisruptible glass microsphere (ThereSphere) in which the Y-90 is part of the glass matrix and cannot leach.(ABSTRACT TRUNCATED AT 400 WORDS)     

Detailed Diurnal Rhythm of Sensitivity to Melatonin Injections in Turkish Hamsters, Mesocricetus brandti

A diurnal rhythm of sensitivity to exogenous melatonin was defined in adult male Turkish hamsters, Mesocricetus brandti. Melatonin was administered daily by subcutaneous injections (15 micrograms in 0.1 ml 10% ethanolic saline) for 10 weeks in animals exposed to 16 L:8 D. As in golden and Djungarian hamsters, two periods of melatonin sensitivity were identified. The first, in late afternoon, persisted for 6 hr, from 7 hr to 1 hr before lights off. The second period was briefer, of only 2 hr duration in the late night, terminating at the time of lights on. Melatonin injections given during these sensitive periods promoted testicular regression in most animals; melatonin administered at other times of the day was without effect on testicular function in most animals of these groups. Gonadal regression induced by properly timed melatonin injections was rapid, in many groups nearly complete in 6 to 7 weeks. The results are discussed in relation to the function of pineal melatonin in photoperiodic time measurement in hamsters.     

Rapid expansion and IL-4 expression by Leishmania-specific naive helper T cells in vivo

CD4 T cells are pivotal for effective immunity, yet their initial differentiation into effector subsets after infection remains poorly defined. We examined CD4 T cells specific for the immunodominant Leishmania major LACK antigen using MHC/peptide tetramers and IL-4 reporter mice. Comprising approximately 15 cells/lymph node in naive mice, LACK-specific T cells expanded over 100-fold, and 70% acquired IL-4 expression by 96 hr. Despite their pathogenic role in susceptible mice, LACK-specific precursor frequency, expansion, and IL-4 expression were comparable between susceptible and resistant mice. When injected with unrelated antigen, Leishmania efficiently activated IL-4 expression from naive antigen-specific T cells. CD4 subset polarization in this highly characterized model occurs independently from IL-4 expression by naive T cells, which is activated indiscriminately after parasitism.     

Beckman EL-ISE电解质分析仪准确性及故障的分析判断

0 引言为了克服离子选择电极（ISE）法的微量电位信号极易受环境温度变化及电子噪声的干扰问题,该仪器采用了参考电极,把参考电极与其测定电极装在同一测量室内,保持其相同的物理环境,使干扰源对所有电极的影响相同. 以内参液作为参考电极的测量对象,测得一个参考电极电位值,再测样品的电极电位值,二者相抵就消除了所叠加的干扰信号.     

心脏直视手术围术期自体血回输335例的监护

0　引言　自体输血是采集患者体内血或回收自体失血,再输回同一患者,献血者与受血者为同一个体,既可以节约临床用血,减少患者费用,更重要是可以避免或减少同种输血传播感染性疾病.我科对335例体外循环心内直视手术患者实行自体血回输,收到较好的社会效益和经济效益.1　临床资料　1998-09/1999-02,我科心脏直视手术共445例,围术期采用自体输血335例,其中先心病226例,瓣膜手术59例,复杂心内畸形37例,冠心病、大血管13例,占同期体外循环心内直视手术75%.患者主要适应证:心脏及大血管外科手术,术前一般情况尚好,无肝、肾、呼吸功能障碍;术前检查…     

Cyclosporine metabolism by P450IIIA in rat enterocytes--another determinant of oral bioavailability?

Cyclosporine is converted to its major metabolites (M-17, M-1, and M-21) in human liver by enzymes belonging to the P450IIIA subfamily. These enzymes are also present in rat and human enterocytes; however, the possibility that CsA is metabolized in enterocytes has not been previously investigated. We therefore directly compared metabolism of 3H-CsA in microsomes prepared from liver and jejunal enterocytes. M-17, M-1, and M-21 were the major CsA metabolites produced by enterocyte microsomes. This metabolism appeared to be catalyzed by P450IIIA, because pretreatment of rats with the P450IIIA inducer dexamethasone significantly increased the rate of CsA metabolism in enterocyte microsomes and preincubation of enterocyte microsomes with anti-P450IIIA IgG inhibited the production of CsA metabolites by greater than 95%. To determine if enterocyte P450IIIA metabolizes CsA in vivo, rats were pretreated with the P450IIIA inducer dexamethasone, the P450IIIA inhibitor erythromycin, or vehicle alone. At laparotomy, 2 mg/kg of 3H-CsA was injected into a sealed loop of jejunum, and after collection of the mesenteric venous blood draining this segment for 45 min, the production of M-17 and M-1 was measured. In the control group, a mean of 3.9% of the recovered radioactivity was found as M-1 and M-17. In the rats pretreated with dexamethasone, a mean of 8.4% of the radioactivity was found as M-1 and M-17 (P less than 0.05 relative to control) and this decreased to 2.3% in the group pretreated with erythromycin (P = 0.08 relative to control). We conclude that P450IIIA in jejunal enterocytes readily metabolizes CsA. Furthermore, the metabolism of CsA by enterocytes in vivo is substantial and likely contributes to "first pass metabolism" of orally administered CsA. Our observations provide novel hypotheses to explain some important drug interactions and interpatient differences in CsA dosing requirements.     

Improving dietitians' teaching skills.

Many health professionals lack important teaching skills, perhaps adding to patient difficulties in understanding and adopting therapeutic diets. Research suggests that teaching skills improved after dietitians took a continuing education course entitled "Effective Patient Teaching." Our study tested whether dietitians' new skills would persist in the field and whether selected patient outcomes would differ as a result. Thirty staff dietitians from six urban hospitals were videotaped teaching patients, then randomly assigned to take the Effective Patient Teaching course or not (control group). Follow-up videotapes were made after 1 week, 1 month, and 3 months. After each teaching session, patient satisfaction and recall were assessed. Two judges rated 20 teaching skills, which were divided into four subsets for analysis. Repeated measures analyses of variance showed overall gains only for the group that took the Effective Patient Teaching course, which scored higher than the control group at 1 week and 1 month, but not at baseline or 3 months. Gains occurred in presentation skills and essential teaching functions. Throughout the study, interpersonal skills were high and adherence promotion skills were low for dietitians in both groups. Groups did not differ on patient satisfaction or recall. Improvements in dietitians' teaching skills translated to the field immediately after they completed the continuing education program, but not all gains were sustained after 3 months. We recommend that dietitians assess their teaching and adherence promotion skills, obtain training where warranted, and periodically reassess the application of those skills during patient teaching sessions.