Induction of Experimental Antiphospholipid Antibody Syndrome in PL/J Mice Following Immunization With β2GPI

PROBLEM: Immunization with β₂-glycoprotein I (β₂GPI) induces antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we reported early onset of autoimmunity in MRL/++ mice following immunization with β₂GPI. There is a close association between aPL with thrombosis, recurrent fetal loss, and intrauterine growth retardation. In this study we evaluated the effect of β₂GPI-induced aPL on pregnancy outcomes in an inbred strain of mice (PL/J). METHOD: Three groups of seven-week-old female PL/J mice (12 per group) were studied. Group A was immunized with β₂GPI and group B with ovalbumin; group C was not immunized. After two booster injections, the mice were tested for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical densities (OD) were 1.72±0.6 and 0.699±0.25 for group A, 0.091 ±0.040 and 0.230±0.47 for group B, and 0.0435±0.003 and 0.119±0.026 for group C (comparing group A with groups B and C combined, P<0.001). ANA titers rose in groups A and B by age, but they were significantly higher at 14 weeks in group A. The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P<0.001). The platelet counts were not significantly different among the three groups. The litter size was significantly smaller in group A, as evidenced by the numbers of viable fetuses among the mice that became pregnant in each group: 0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in group A had complete resorption, seven pregnant mice in group B showed focal (partial) resorption areas, and only one mouse in group C had complete resorption of the embryos, as shown by histopathological studies, although the fecundity rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic role for β₂GPI-induced aPL in the development of experimental models of APS in PL/J mice.     

Renewal of the membrane complex of Schistosoma mansoni is closely associated with lipid metabolism

Metabolic pathways leading to lipid biosynthesis in four different developmental stages of Schistosoma mansoni were explored and quantified by incubation in the presence of labeled precursors in a chemically defined medium. At the schistosomulum stage and in male, female, or paired worms, glycerol and oleate incorporation into neutral lipids, mainly in the form of triacylglycerols, was greater than into phospholipids, whereas in 11-and 15-day-old worms, synthesis mainly led to phospholipids. Incorporation into phospholipids was recovered largely in phosphatidylcholine, and distribution into other phospholipids depended on the developmental stage. Incorporation of choline and ethanolamine into their respective phospholipids represented up to 15% of the parasitic phospholipid content. The formation of phosphatidylcholine by phosphatidylethanolamine methylation occurred mainly in the immature parasitic stages. Inositol incorporation was also measurable, whereas [14C]serine incorporation was low or undetectable. Addition of 1-palmitoyl-2-[14C]oleyl phosphatidylcholine revealed a very high uptake of this phospholipid by the immature stages but further metabolism was not detectable. In contrast, adult S. mansoni were completely unable to take up or absorb this exogenous phospholipid. The most striking aspect of this study was the relatively high metabolic activity in 11-day-old worms and the lower but sustained activity on day 15 and at the schistosomulum stage. By comparison, biosynthetic activity in adult S. mansoni, on which research studies have been focused until now, was very low. We also discuss the participation of lipid metabolism in the constant renewal of the membrane complex which is essential to parasitism by S. mansoni.     

Anti‐alanyl tRNA positive antisynthase syndrome with Kaposi sarcoma

We report a rare case of antisynthase syndrome (ASS) complicated with Kaposi sarcoma, analyze its clinical characteristics, and review the literature on the topic. An 80‐year‐old male patient developed fever, cough, and shortness of breath. Lung high‐resolution computed tomography showed nonspecific interstitial pneumonia in both lungs, and myositis antibody examination showed strongly positive anti‐alanyl tRNA synthase (PL‐12) antibodies. Based on these findings, the patient was diagnosed with ASS. After full‐dose glucocorticoid treatment, the symptoms of fever and cough were relieved, but skin thickening and pigmentation in both feet were observed. We confirmed Kaposi sarcoma through skin pathology and immunohistochemical examination of the bottom of the patient's feet, and the patient was transferred to a cancer hospital for radiotherapy. ASS presents with some skin changes that might lead to misdiagnosis. ASS complicated with Kaposi sarcoma is rare, and to our knowledge, this is the first case reported in China.     

Evidences of endocytosis via caveolae following blood–brain barrier breakdown by Phoneutria nigriventer spider venom

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood–brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.     

Reproductive actions of prolactin mediated through short and long receptor isoforms

Prolactin (PRL) is a polypeptide hormone with a wide range of physiological functions, and is critical for female reproduction. PRL exerts its action by binding to membrane bound receptor isoforms broadly classified as the long form and the short form receptors. Both receptor isoforms are highly expressed in the ovary as well as in the uterus. Although signaling through the long form is believed to be more predominant, it remains unclear whether activation of this isoform alone is sufficient to support reproductive functions or whether both types of receptor are required. The generation of transgenic mice selectively expressing either the short or the long form of PRL receptor has provided insight into the differential signaling mechanisms and physiological functions of these receptors. This review describes the essential finding that both long and short receptor isoforms are crucial for ovarian functions and female fertility, and highlights novel mechanisms of action for these receptors.     

Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels

The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150–499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.     

血细胞计数影响因素分析

本文分析血细胞计数的影响因素,发现血细胞检测结果受环境温度、放置时间、采血方式等因素的影响,检验人员在采血和检测过程中应尽可能排除各种影响因素,为临床提供真实可靠的检验结果。     

羟基红花黄色素A磷脂复合物的制备及理化性质研究

目的:确定羟基红花黄色素A与大豆磷脂形成复合物的最佳工艺,并对其理化性质进行研究.方法:以羟基红花黄色素A与大豆磷脂的复合率为评估标准,采用单因素考察进行系统研究,对所制得的复合物进行UV、DSC、IR等分析,并考察其在正辛醇中的溶解性能.结果:该制备方法的复合率达98.7%,研究表明羟基红花黄色素A磷脂复合物是以非共价键结合;羟基红花黄色素A磷脂复合物明显改善羟基红花黄色素A在正辛醇中的溶解性能.结论:羟基红花黄色素A磷脂复合物的形成受反应溶剂和反应物料比例的影响较大;复合物的脂溶性有较大提高.     

建立闭路式强化优先注视法检测系统的初探

目的建立由电脑控制的闭路式强化优先注视法视力检测系统(Closed-circuitOperantPreferentialLookingSystem,COPL),并探讨其临床的实用性。方法装置:本系统由刺激显示部分和眼动监视部分组成。刺激显示部分含动画图像强化幼儿注视条栅的行为,眼动监视部分可观察到幼儿的注视行为。测试过程由电脑控制。对象:随机选择符合录入标准的幼儿79人(男42人,女37人)作为研究对象,年龄12～40月,平均23.81±8.38月,按年龄分为7组。结果可测性:完成视力检查的幼儿66人,男35人,女31人,总可测性为83.54%,男可测性为83.33%,女可测性为83.78%。测试时间:统计完成视力检查的幼儿的平均测试时间329.70±86.60秒。视力情况(以折合5分记录表示):(1)视力与性别的关系:采用独立样本t检验比较男女视力,差异无显著性(=0.41)。(2)各年龄组的平均视力:12～16月组4.47±0.12,17～20月组4.58±0.17,P21～24月组4.60±0.21,25～28月组4.79±0.19,29～32月组4.81±0.16,33～36月组4.88±0.18,37～40月组5.0±0.00。(3)视力与年龄的关系:12～40月幼儿的视力发育与年龄呈高度正相关(相关系数r=0.76,P=0.00),进一步推出视力(Y)与月龄(X)之间的回归直线为:Y=0.0208X+4.1872。(4)重复性:20名幼儿完成两次视力检查,且两次皆由一位检查者操作