Flt3L对COPD大鼠铜绿假单胞菌肺炎的防治研究

目的 建立铜绿假单胞菌(PA)肺部感染大鼠慢性阻塞性肺疾病(COPD)模型,研究Flt3L(Fms-like tyrosine kinase-3 ligand )对其炎症反应的防治作用.方法 将50只健康雄性清洁级Wistar大鼠随机分为对照组(NS组)、PA感染对照组(NPA组)、COPD大鼠组(COPD组)、COPD大鼠PA感染组(CPA组)和COPD大鼠PA感染Flt3L处理组(Flt3L组),每组动物各10只.用烟雾暴露法复制大鼠COPD模型,气管内滴入PA溶液复制肺部PA感染模型.COPD组、CPA组、Flt3L组大鼠分别在第1～60天以烟雾暴露法复制COPD模型,Flt3L组于第61～65天连续给予Flt3L(20g/kg)腹腔注射,每天1次,连续5d,第66天同时建立NPA组、CPA组和Flt3L组模型.24h后计算大鼠死亡率,对支气管肺泡灌洗液(BALF)、肺组织进行细菌学、细胞学、病理学等研究.无菌操作下取出大鼠脏器进行细菌培养、菌落计数及细菌鉴定.结果 Flt3L组大鼠存活率(87.5%)显著高于CPA组(50.0%)(P<0.01),Flt3L组大鼠支气管肺泡灌洗液中淋巴细胞数[(0.41～0.05)×109/L]与CPA组[(0.24～0.04)×109/L]比较显著增加(P<0.01),光镜下观察比较发现Flt3L组大鼠肺组织炎症反应较CPA组明显减轻,脏器细菌培养阳性率CPA组(37.5%)显著高于Flt3L组(12.5%)(P<0.01).结论 Flt3L能够增强COPD大鼠对PA肺部感染的抗病力.     

Serum heparan sulfate levels are elevated in endotoxemia

Background

Increased vascular permeability is a characteristic feature of sepsis which, in the past, has been ascribed exclusively to a malfunction of endothelial cells. However, recently it has become evident that the endothelial glycocalyx is of considerable importance concerning various aspects of vascular physiology, e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential components is characteristically traceable in blood, in case the endothelial glycocalyx is damaged or destroyed.

Methods

In 15 pigs we investigated whether the administration of endotoxin from gram-negative bacteria (Escherichia coli) results in increased serum levels of heparan sulfate, signalizing a shedding of the glycocalyx. In addition, markers of inflammation (white blood cell count, platelet count, tumour necrosis factor-α and interleukin-6) were evaluated over an observation period of 6 hours.

Results

Serum heparan sulfate concentrations significantly increased over time in the endotoxin group and were significantly elevated in comparison to the control group 6 hours after administration of endotoxin (p < 0.001). In the endotoxin group all markers of inflammation significantly changed during the time course.

Conclusions

The administration of bacterial endotoxin induced a significant rise in degradation products of the endothelial glycocalyx.     

Are there any limits to assisted conception possibilities? Pregnancy and birth following oocyte donation and intracytoplasmic injection of spermatozoa obtained by percutaneous epididymal aspiration

Intracytoplasmic injection of donor oocytes with spermatozoa recovered by percutaneous epididymal aspiration resulted in pregnancy and the birth of a healthy male infant.      

Effects of hyperoxic ventilation on hemodilution-induced changes in anesthetized dogs

BACKGROUND: In subjects who have undergone acute preoperative normovolemic hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate return of autologous blood collected during ANH. Simply increasing blood oxygen content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might compensate for the acute anemia, allow further ANH, and delay onset of autologous blood return. STUDY DESIGN AND METHODS: This study 1) evaluated the effects of HV (FIO2 1.0) upon ANH to a hemoglobin (Hb) concentration of 7 g per dL in anesthetized dogs ventilated with room air and 2) compared the effects of subsequent profound ANH (Hb, 3 g/dL) with and without an intravenous perfluorocarbon emulsion (perflubron 60% wt/vol) versus those of autologous red cell transfusion. The results of the entire study are presented in two parts. Organ tissue oxygenation was assessed in skeletal muscle and liver, and systemic oxygenation status was evaluated. Myocardial contractility was deduced from left ventricular pressure-volume relationship. Seven of 22 dogs underwent further hemodilution while breathing 100-percent O2, for a determination of the Hb concentration at which HV-induced effects were abolished. RESULTS: HV completely reversed the ANH-induced increase in cardiac index (4.6 +/− 0.7 vs. 3.8 +/− 0.9 L/min/m2 before and during HV; p < 0.05) and partially reversed the decrease in systemic vascular resistance (1784 +/− 329 vs. 2087 +/− 524 dyn × cm-5 × sec × m-2; p < 0.05). Despite unchanged global O2 delivery, organ tissue oxygenation improved during HV (mixed venous partial pressure of O2: 40 +/− 3 vs. 59 +/− 7 torr; coronary venous pressure of O2: 30 +/− 4 vs. 43 +/− 6 torr; p < 0.05; liver surface: 31 +/− 11 vs. 39 +/− 13 torr; skeletal muscle surface: 30 +/− 14 vs. 41 +/− 22 torr; p < 0.05). This improvement was due to an increased contribution of physically dissolved O2 in plasma to O2 delivery (3.2 +/− 0.2% before HV vs. 14.6 +/− 1% during HV; p < 0.05) and O2 consumption (whole body: 6 +/− 1% vs. 47 +/− 8%, p < 0.05; myocardium: 4.3 +/− 0.9% vs. 31 +/− 6%, p < 0.05). The beneficial effects of HV were lost after an additional volume-compensated exchange of 19 percent of blood volume (Hb, 5.6 g/dL). CONCLUSION: In anesthetized dogs ventilated with room air and hemodiluted to a Hb of 7 g per dL, simple oxygen therapy by HV (FIO2 1.0) rapidly improves tissue oxygenation and permits extended hemodilution to Hb of 5.8 g per dL until the HV-induced effects are lost.     

Utility of percutaneous epididymal sperm aspiration in situations of unexpected obstructive azoospermia

Surgical sperm retrieval through percutaneous epididymal aspiration was used to manage effectively unexpected obstructive azoospermia on the day of oocyte retrieval.      

DIURNAL EFFECTS OF FLUOXETINE AND NALOXONE ON THE HUMAN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

1. Central serotonergic pathways are hypothesized to be involved in the stimulation of hypothalamic adrenocorticotropic hormone (ACTH) secretagogue release by both circadian- and stress-induced mechanisms. We aimed to investigate this hypothesis by measuring the effect of the highly specific serotonin re-uptake inhibitor fluoxetine (FX) on ACTH and Cortisol release in the morning and in the afternoon in humans, both by itself and in combination with the opioid antagonist naloxone (Nal). Naloxone causes ACTH release in humans by removing an endogenous inhibitory opioid tone on central noradrenergic pathways stimulatory to hypothalamic corticotropin-releasing hormone (CRH) secretion. Serotonergic agents may act directly or indirectly through these central noradrenergic pathways and, if so, would be expected to be additive to or synergistic with Nal in causing ACTH and Cortisol release. 2. Oral FX (40 mg) was given at approximately 07.00 or 11.00 h, either alone or with intravenous Nal 3 h later, to normal human volunteers. Plasma ACTH and Cortisol levels were measured for 5 h after FX dosing. 3. Fluoxetine produced a small but non-significant increase in Nal-stiimilated ACTH and Cortisol release in both morning and afternoon studies. Naloxone alone did not cause different ACTH and Cortisol responses in the morning and afternoon. 4. These results suggest that serotonergic pathways are not major regulators of the hypothalamic-pituitary-adrenal axis in humans or that FX has counteracting acute inhibitory effects on the axis, such as inhibition of hypothalamic arginine vasopressin secretion, which has been demonstrated in chronic animal studies.