High levels of fatty acids delay the recovery of intracellular pH and cardiac efficiency in post-ischemic hearts by inhibiting glucose oxidation

OBJECTIVES: This study was designed to determine if the fatty acid-induced increase in H(+) production from glycolysis uncoupled from glucose oxidation delays the recovery of intracellular pH (pH(i)) during reperfusion of ischemic hearts. BACKGROUND: High rates of fatty acid oxidation inhibit glucose oxidation and impair the recovery of mechanical function and cardiac efficiency during reperfusion of ischemic hearts. METHODS: pH(i) was measured by 31P nuclear magnetic resonance spectroscopy in isolated working rat hearts perfused in the absence (5.5 mmol/l glucose) or presence of 1.2 mmol/l palmitate (glucose+palmitate). Glycolysis and glucose oxidation were measured using [5-3H/U-14C]glucose. RESULTS: When glucose+palmitate hearts were subjected to 20 min of no-flow ischemia, recoveries of mechanical function and cardiac efficiency were significantly impaired compared with glucose hearts. Glucose oxidation rates were significantly lower in glucose+palmitate hearts during reperfusion compared with glucose hearts, whereas glycolysis rates were unchanged. This resulted in an increase in H(+) production from uncoupled glucose metabolism, and a decreased rate of recovery of pH(i) in glucose+palmitate hearts during reperfusion compared with glucose-perfused hearts. Dichloroacetate (3 mmol/l) given at reperfusion to glucose+palmitate hearts resulted in a 3.2-fold increase in glucose oxidation, a 35% +/- 3% decrease in H(+) production from glucose metabolism, a 1.7-fold increase in cardiac efficiency and a 2.2-fold increase in the rate of pH(i) recovery during reperfusion. CONCLUSIONS: A high level of fatty acid delays the recovery of pH(i) during reperfusion of ischemic hearts because of an increased H(+) production from glycolysis uncoupled from glucose oxidation. Improving the coupling of glucose metabolism by stimulating glucose oxidation accelerates the recovery of pH(i) and improves both mechanical function and cardiac efficiency.     

Potential risk of mitomycin Cat high concentrations on peripheral nerve structure

Although the local application of mitomycin C may prevent epidural adhesion after laminectomy, mitomycin C can induce neurotoxicity in optic and acoustic nerves at high concentrations. To determine the safe concentration range for mitomycin C, cotton pads soaked with mitomycin C at different concentrations(0.1, 0.3, 0.5, and 0.7 mg/mL) were immediately applied for 5 minutes to the operation area of rats that had undergone laminectomy at L1. Rat sciatic nerves, instead of dorsal nerves, were used in this study. The results showed that mitomycin C at 0.1–0.5 mg/mL did not damage the structure and function of the sciatic nerve, while at 0.7 mg/mL, mitomycin C significantly reduced the thickness of the sciatic nerve myelin sheath compared with lower concentrations, though no functional change was found. These experimental findings indicate that the local application of mitomycin C at low concentrations is safe to prevent scar adhesion following laminectomy, but that mitomycin C at high concentrations( 0.7 mg/mL) has potential safety risks to peripheral nerve structures.     

Pharmacodynamics and pharmacokinetics of PLGA-based doxorubicin-loaded implants for tumor therapy

The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.     

Acupuncture anaesthesia in inguinal hernia repair

Background: The present study was undertaken to evaluate the efficacy of acupuncture anaesthesia in inguinal hernia repair. Methods: Twelve patients with non‐recurrent inguinal hernia had Lichtenstein mesh repair under acupuncture anaesthesia. Selected acupuncture loci were stimulated with fine needles connected to low frequency current. Supplementary local anaesthetic was given when required. Results: Four (33%) patients reported satisfactory analgesic effect throughout the operation without need for additional medication, eight (67%) patients experienced mild discomfort during the operation requiring 1?4 mL of 1% lignocaine injection. Blood pressure and heart rate were stable during the procedure. All patients were able to sit up and resume their diet immediately post­operatively. All but one patient were discharged on day one after the procedure, with no early or late complications reported. Most patients were satisfied with the analgesic effect of acupuncture anaesthesia. Conclusions: Acupuncture anaesthesia is a feasible anaesthetic option. It reduces the amount of local anaesthetic required, and thus the associated potential complications. It is effective in pain relief and inhibiting gastrointestinal upset. Postoperative recovery was rapid and complication free.     

中药五倍子对不同根面龋损提取非胶原蛋白后再矿化的影响

目的体外观察人工形成的牛牙根面龋提取非胶原蛋白前后,中药五倍子对人工龋再矿化的影响。方法体外37℃恒温箱中,两种脱矿溶液中用牛牙模拟人牙形成不同形态根面龋模型(酸蚀性病损和表层下脱矿)。每组随机选择两个样本用偏光显微镜(PLM)观察表面形态;用盐溶液提取根面龋暴露区的可溶性牙本质磷蛋白(S-DPP),在恒温箱中用五倍子多酚化合物(GCE)对提取非胶原蛋白前后的根面龋同时进行再矿化循环7d,用激光共聚焦扫描显微镜(LSCM)观察样本并分析平均荧光量。结果 PLM观察显示表层下脱矿形成了较完好的表层,而酸蚀性病损则无表层形成。LSCM分析结果显示在酸蚀性病损形态下提取S-DPP后GCE处理荧光强度明显下降(P<0.05),而在表层下脱矿形态下提取S-DPP前后GCE处理荧光强度无明显差异(P>0.05)。结论在酸蚀性病损条件下提取S-DDP后GCE可能有更高的再矿化效果。     

补阳还五汤中不同黄芪剂量对促进大鼠难愈性创面愈合作用的观察

目的：观察不同黄芪剂量补阳还五汤治疗大鼠难愈性创面的疗效,探讨作用机制。方法：108只雄性SD大鼠背部制造全层皮肤缺损开放性创面,肌肉注射醋酸氢化可的松建立难愈性创面模型,随机分为模型组,含黄芪15g、30g、60g、120g的补阳还五汤组,观察各组大鼠创面愈合情况,通过免疫组化和图像分析等技术,观察各组大鼠创面肉芽组织中血管内皮生长因子（VEGF）表达情况和微血管计数（MVC）。结果：模型组与开放性创面模型（对照）组比较,创面愈合率低,愈合时间延长（P〈0.01,P〈0.05）;不同黄芪剂量补阳还五汤各组与模型组比较,创面愈合率显著提高,愈合时间明显缩短（P〈0.01,P〈0.05）;黄芪剂量在方剂中增至30g时,疗效好。模型组VEGF表达和MVC明显低于对照组（P〈0.01）;不同黄芪剂量补阳还五汤各组与模型组比较,VEGF表达、MVC均较显著升高（P〈0.01,P〈0.05）,且与黄芪剂量呈正相关。结论：不同黄芪剂量补阳还五汤均可明显促进难愈性创面愈合,其作用机制可能与上调VEGF表达、诱导新生血管有关,方中黄芪宜增至30g为宜。     

Pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: a meta-analysis of randomized controlled trials

Background

The best reconstruction method for the pancreatic remnant after pancreaticoduodenectomy remains debatable. We aimed to investigate the perioperative outcomes of 2 popular reconstruction methods: pancreaticogastrostomy and pancreaticojejunostomy.

Data Sources

Randomized controlled trials comparing pancreaticogastrostomy versus pancreaticojejunostomy were identified from literature databases (MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Library).The meta-analysis included 8 studies: 607 patients who underwent pancreaticogastrostomy and 604 who underwent pancreaticojejunostomy. Postoperative pancreatic fistula and intra-abdominal fluid collection rates were significantly lower after pancreaticogastrostomy compared with pancreaticojejunostomy. No statistically significant differences were found in the incidence of delayed gastric emptying, biliary fistula, hemorrhage, reoperation, wound infection, overall morbidity, mortality, and length of hospital stay.

Conclusions

Our meta-analysis suggests that pancreaticogastrostomy not only reduces the rate of postoperative pancreatic fistula but also decreases its severity. Pancreaticogastrostomy is associated with a lower rate of intra-abdominal fluid collection. Our results suggest that pancreaticogastrostomy should be the preferred reconstruction method.     

Blockade of indirect recognition mediated by CD4+ T cells leads to prolonged cardiac xenograft survival

Abstract:  The T-cell response to xenografts is induced by direct and indirect recognition of xenoantigens. Although the importance of indirect recognition is well established in vitro, the contribution of this pathway to xenograft rejection in vivo remains to be fully elucidated. We herein investigated the direct contribution of indirect recognition to cardiac xenograft rejection in the rat-to-mouse (PVG.R8-to-C57BL/10) concordant model. Rat xenoantigens invoked a vigorous proliferative response in mouse T cells harvested from naïve or graft recipients at rejection. Indirect recognition predominated the response, as antibodies against mouse class II I-A^b, CD80, or CD86 molecules significantly (45 to 60%) blocked the proliferative response. Importantly, the blockade of indirect recognition in vivo by treating the graft recipients with a monoclonal antibody (mAb) against class II I-A^b molecule on days 0, 1, and 3 post-transplantation resulted in significant ( P  < 0.009) prolongation of cardiac xenograft survival (Mean Survival Time (MST) >94 ± 55 days vs. 7 ± 0.8 days for controls). In contrast, treatment of recipients with a mAb against mouse class I H-2K^b/D^b molecules did not significantly affect graft rejection (MST = 8 ± 1 days). These results demonstrate that indirect recognition mediated by CD4⁺ T cells plays a critical role in the rejection of cardiac grafts in the rat-to-mouse xenogeneic model.