Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention

Background：Several studies have demonstrated that primary percutaneous coronary intervention （PCI） can result in reperfusion injury.This study aims to investigate the effectiveness of liposomal prostaglandin E l （Lipo-PGE1,Alprostadil,Beijing Tide Pharmaceutical Co.,Ltd.） for enhancing microcirculation in reperfusion injury.In addition,this study determined the optimal administration method for acute ST elevation myocardial infarction （STEMI） patients undergoing primary PCI.Methods：Totally,68 patients with STEMI were randomly assigned to two groups：intravenous administration ofLipo-PGE 1 （Group A）,and no Lipo-PGE1 administration （Group B）.The corrected thrombolysis in myocardial infarction （TIMI） frame count （cTFC） and myocardial blush grade （MBG） were calculated.Patients were followed up for 6 months.Major adverse cardiac events （MACE） were also measured.Results：There was no significant difference in the baseline characteristics between the two groups.The cTFC parameter in Group A was significantly lower than Group B （18.06 ± 2.06 vs.25.31 ± 2.59,P ＜ 0.01）.The ratio of final MBG grade-3 was significantly higher （P ＜ 0.05） in Group A （87.9％） relative to Group B （65.7％）.There was no significant difference between the two groups in final TIMI-3 flow and no-reflow.Patients were followed up for 6 months,and the occurrence of MACE in Group A was significantly lower than that in Group B （6.1％ vs.25.9％ respectively,P ＜ 0.05）.Conclusions：Myocardial microcirculation of reperfusion injury in patients with STEMI,after primary PCI,can be improved by administering Lipo-PGE1.

Comparison of the Concentrations of Lidocaine in Different Body Fluids/Tissues after Subarachnoid Space and Intravenous Administration of a Lethal Dose of Lidocaine

The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine.Totally 18 dogs were used in the experiment.Six dogs were given subarachnoid anesthesia,another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride.As soon as its vital signs disappeared,each dog was dissected and the specimen,such as brain,cerebrospinal fluid(CSF)in lateral ventricle,CSF in subarachnoid space,spinal cord(cervical spinal cord,thoracic spinal cord,lumbar spinal cord,and waist spinal cord),heart,lung,liver,spleen,kidney,bile,urine,heart blood,peripheral blood,muscle in injection location,and muscle in no injection location,were collected for analysis of lidocaine immediately.Analysis was performed with gas chromatography‑mass spectrometry(GC‑MS).From the maximum to the minimum,the order of lidocaine concentration detected in the subarachnoid space‑administered dogs was as follows:CSF in subarachnoid space,waist spinal cord,thoracic spinal cord,CSF in lateral ventricle,lumbar spinal cord,cervical spinal cord,lung,kidney,muscle in injection location,heart,brain,spleen,heart blood,liver,peripheral blood,bile,muscle in no injection location,and urine.The order of lidocaine concentration detected in the intravenously administered dogs was as followed:Kidney,heart,lung,spleen,brain,liver,peripheral blood,bile,heart blood,cervical spinal cord,thoracic spinal cord,muscle in injection location,lumbar spinal cord,muscle in no injection location,CSF in subarachnoid space,urine,and CSF in lateral ventricle.The maximum concentration of lidocaine was detected in the subarachnoid space CSF of subarachnoid space‑administered dead dogs,while in intravenously injected dead dogs,the maximum concentration of lidocaine was detected in the kidney.Our study provides some useful data for the forensic identification of epidural anesthesia accidents to decide the way the lidocaine enters the body.

Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

Intranasal insulin neuroprotection in ischemic stroke

Acute ischemic stroke（AIS）is a leading cause of death and long-term disability in the USA and worldwide.Significant advances in the last two decades have resulted in the introduction of intravenous tissue plasminogen activator and more recently catheter based endovascular interventions in selected patients（Berkhemer et al.,2015;Goyal et al.,2015）.

A Novel Thermosensitive In-situ Gel of Gabexate Mesilate for Treatment of Traumatic Pancreatitis:An Experimental Study

Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate（GMTI） was developed,and the optimum formulation of GMTI containing 20.6%（w/w） P-407 and 5.79%（w/w） P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin（HE） staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase（AMS）,C-reactive protein（CRP） and trypsinogen activation peptide（TAP）,and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively（P〈0.05 vs. P-407）,and completely inhibited at 10.0 and 20.0 mg/m L（P〈0.01 vs. P-407）. After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group（P〈0.01）,and significantly decreased in GM group as compared with TP group（P〈0.01）,and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group（P〈0.05）,and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared with TP group（P〈0.01）. HE staining results demonstrated that pancreas cells were uniformly distributed in control group,and they were loosely arranged,partially dissolved,with deeply stained nuclei in TP group. Expectedly,after gradient GMTI treatment,pancreas cells were gradually restored to tight distribution,with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes,and alleviate the severity of trauma-induced pancreatitis,and had a potential drug developing and clinic application value.