Pharmacokinetics of aditoprim and trimethoprim in buffalo calves

Pharmacokinetic parameters of two antifolates, trimethoprim and aditoprim, were studied in buffalo calves. The elimination half-life of aditoprim (6.14 h) was nearly twice as long as that of trimethoprim (3.08 h) and compares well with values observed in heifers. This longer half-life of aditoprim is a result of its much larger distribution volume (four to five times larger) because the clearance of aditoprim was about twice as high as that of trimethoprim. The longer half-life of aditoprim is expected to give a longer duration of in vivo bacteriostatic activity than that of trimethoprim.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Using psychometric ability to improve education in ultrasound-guided regional anaesthesia: a multicentre randomised controlled trial

The learning curve for novices developing regional anaesthesia skills, such as real-time ultrasound-guided needle manipulation, may be affected by innate visuospatial ability, as this influences spatial cognition and motor co-ordination. We conducted a multinational randomised controlled trial to test if novices with low visuospatial ability would perform better at an ultrasound-guided needling task with deliberate practice training than with discovery learning. Visuospatial ability was evaluated using the mental rotations test-A. We recruited 140 medical students and randomly allocated them into low-ability control (discovery learning), low-ability intervention (received deliberate practice), high-ability control, and high-ability intervention groups. Primary outcome was the time taken to complete the needling task, and there was no significant difference between groups: median (IQR [range]) low-ability control 125 s (69–237 [43–600 s]); low-ability intervention 163 s (116–276 [44–600 s]); high-ability control 130 s (80–210 [41–384 s]); and high-ability intervention 177 s (113–285 [43–547 s]), p = 0.06. No difference was found using the global rating scale: mean (95%CI) low-ability control 53% (95%CI 46–60%); low-ability intervention 61% (95%CI 53–68%); high-ability control 63% (95%CI 56–70%); and high-ability intervention 66% (95%CI 60–72%), p = 0.05. For overall procedure pass/fail, the low-ability control group pass rate of 42% (14/33) was significantly less than the other three groups: low-ability intervention 69% (25/36); high-ability control 68% (25/37); and high-ability intervention 85% (29/34) p = 0.003. Further research is required to determine the role of visuospatial ability screening in training for ultrasound-guided needle skills.     

Plant from New-Caledonia. Alkaloids of Melodinus reticulatus

(-)Tabersonine and (-)-11-methoxytabersonine were isolated from fruits of Melodinus reticulatus. Stems and leaves contain uvaol and eight alkaloids, five of which were previously described: (-)tabersonine, venalstonidine, kopsinine, venalstonine and its 3-oxoderivative. Three are new: 19-hydroxyvenalstonine, 19-hydroxyvenalstonidine and 3-oxovenalstonidine.     

稳定型圆锥角膜患者植入新型Phakic角膜接触镜的视觉效果分析

目的：评估可植入式Phakic角膜接触镜治疗稳定型圆锥角膜患者的疗效、安全性、稳定性和可预测性。

方法：共14例患者采用植入式Phakic角膜接触镜(IPCL)矫正屈光不正,测量了未矫正视力、最佳矫正视力、离焦曲线、对比敏感度、屈光度及可能的副作用。评估结果超过6mo。

结果：平均等效球镜度(SE)和散光在术后6mo末次检查时由术前-6.94±2.79 DS和-4.24±1.42 DC分别变为术后-0.23±0.43 DS和-1.05±0.49 DC。术前平均Snellen视力为0.18±0.10。6mo内未矫正视力和最佳矫正视力平均值分别为0.13±0.10和0.05±0.15。平均安全指数为1.11。所有眼视力均无降低,其中22眼视力提高超过1行。20眼(71.4%)屈光度在0.50 D以内,27眼(96.42%)在±1.00 D以内。术后1wk至6mo,屈光度变化为-0.23±0.43(范围： -1.00至+0.75)。6mo内角膜内皮细胞(ECL)丢失率小于5%。术后6mo眼压(IOP)为11.32±2.28 mmHg。

结论：Toric植入式Phakic角膜接触镜在矫正与稳定圆锥角膜相关的近视和近视散光方面具有有效性、安全性和可预测性。     

Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10⁻⁵ in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17–28, 2019. © 2018 Wiley Periodicals, Inc.