Estrogen synthesis in the brain—Role in synaptic plasticity and memory

Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200–1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus.Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1–10 nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2 h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.     

儿童新型冠状病毒感染诊断、治疗和预防专家共识(第二版)

自2019年12月新型冠状病毒感染暴发以来,我国政府采取了严格的防控措施,国内疫情已得到初步控制,但形势依然严峻,境外多个国家也相继出现疫情。根据世界卫生组织的报告:截至2020年3月5日,全球共报告95333例确诊病例(其中我国累计报告确诊病例80565例),85个国家有确诊病例报告,中国将面临输入性病例的传播风险,这为防治我国儿童的疾病疫情提出了新的挑战[1]。在这次疫情中,与成人病例相比,儿童病例相对较少、症状轻、预后较好。目前国内病例数据显示,18岁以下儿童占所有报告病例的2.4%,尚无死亡病例报告[2]。     

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n=5), an 84% Hx group (n=5) and an 84% Hx+PSS group (n=5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immuno-histochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.     

The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium

The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4 % vs. remote 86 ± 9 %, p < 0.05) were unchanged at 3 months (LAD 32 ± 3 %, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O₂ mg^?1 min^?1 at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.     

Biomedical Support Requirements in the Space Era

Chest radiographs made on 1,007 canine subjects at the University of Pennsylvania Veterinary Hospital between 1965 and 1968 were reviewed to determine whether a relationship between nonspecific chronic canine pulmonary disease and the urban environment could be demonstrated. Radiographs were graded for evidence of chronic pulmonary changes without prior knowledge of the animal’s age or residence. The environment was divided into urban and rural segments based upon the concentration of industrialization in the Philadelphia area and available atmospheric pollution data. No significant differences were noted in the urban-rural distribution of absent, moderate, and severe changes in younger dogs. In middle-aged and older dogs, however, significant differences appeared in the distribution of changes between environmental groups.     

Primary hypertrophic pyloric stenosis in the adult: a case report.

A 66-year-old male was admitted with a two-month history of vomiting and weight loss. Endoscopy showed a pyloric obstruction and the patient underwent subtotal gastrectomy with gastro- jejunostomy. The histopathological study of the specimen revealed primary hypertrophic pyloric stenosis without any evidence of duodenal peptic disease. In the adult, this is a rare cause of gastric outlet obstruction of unknown etiology. It is usually recognized by histopathological examination of the specimen after a gastric resection performed to treat gastric outlet obstruction syndrome. However, some endoscopic and radiological signs, such as the cervix sign, or elongation of the pyloric channel, may give clues about the presence of the disease preoperatively. In symptomatic cases, surgery is the preferred treatment modality.     

Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients

The aim of the present study was to investigate the relationships between insulin resistance and soluble E-selectin, body mass index (BMI), leptin, and serum lipid profile including triglycerides in nonobese Japanese type 2 diabetic patients. A total of 97 nonobese Japanese type 2 diabetic patients aged 43 to 84 years were examined. The duration of diabetes was 11.2 +/- 0.8 years. In conjunction with BMI and fasting concentrations of plasma glucose, serum lipids (triglycerides, total cholesterol, and high-density lipoprotein cholesterol) and serum insulin, soluble E-selectin, and leptin were also measured. The low-density lipoprotein (LDL) cholesterol level was calculated using the Friedewald formula. Insulin resistance was estimated by the homeostasis model assessment. The subjects were divided into 2 groups according to the value of insulin resistance estimated by the homeostasis model assessment. Values greater than 2.5 were indicative of the insulin-resistant state, and values less than 2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher levels of E-selectin, leptin, triglycerides, total and LDL cholesterol, and diastolic blood pressure as compared with the insulin-sensitive group. There was, however, no significant difference in age, sex, diabetes duration, BMI, systolic blood pressure, HbA1c, and high-density lipoprotein cholesterol between the 2 groups. Univariate regression analysis showed that insulin resistance was positively correlated to E-selectin (r = 0.305, P = .003), BMI (r = 0.283, P = .006), leptin (r = 0.296, P = .004), HbA1c (r = 0.241, P = .018), serum triglycerides (r = 0.385, P < .001), serum total (r = 0.240, P = .019) and LDL cholesterol (r = 0.254, P = .013) levels, and systolic (r = 0.247, P = .024) and diastolic (r = 0.305, P = .006) blood pressure. Multiple regression analyses showed that insulin resistance was independently predicted by serum E-selectin (F = 18.4), serum leptin (F = 14.0) and serum triglycerides (F = 20.0) levels, which explained 45.0% of the variability of insulin resistance. From these results, it can be concluded that in conjunction with serum triglycerides and serum leptin, serum E-selectin is another important independent factor associated with insulin resistance in nonobese Japanese type 2 diabetic patients.