Trichinella spiralis: Generation in the presence of rat serum of factors chemotactic for rat cells

Chemotaxis of rat peritoneal cells, of which the eosinophil was the predominant migratory cell type, toward incubates of Trichinella spiralis was studied using a modified Boyden chamber. Excysted muscle larvae, preadults, and adults were incubated in a buffered medium for 20 hr at 37 C. Worms were incubated alone or with serum or spleen cells, or both, from immune and nonimmune rats. Incubates of worm stages alone possessed no chemotactic activity as compared with incubation medium as a negative control and zymosan-activated serum as a positive control. Both normal and immune sera tested alone stimulated cell migration to the same degree. Incubates of spleen cells from either normal or immunized hosts did not show chemotactic activity. Chemotaxis caused by normal and immune sera were not altered by incubation with homologous spleen cells. Addition of larva, preadults, and adult worms to sera, however, enhanced chemotactic activity over sera alone. Chemotaxis caused by larvae plus immune sera was significantly greater than that stimulated by larvae plus normal sera. This difference decreased when preadults were substituted for larvae and was not observed when adult worms were used. Reversal of the chemical gradients showed that active cell migration caused by various incubates was due to Chemotaxis.     

Fasciola hepatica: IgG and IgA levels in the serum and bile of infected cattle

Bile and serum samples were collected from calves with an implanted cannula throughout a 20-week period of infection with Fasciola hepatica. Using indirect fluorescent antibody labelling and plastic-embedded sections of juvenile and adult flukes as antigens, estimates were made of the relative concentrations of IgG and IgA specific for fluke tegumental and gut antigens in the samples of serum and bile. In serum, antibodies against juvenile (t1) tegument and gut antigens reached peak concentrations 4–6 weeks postinfection and declined slowly thereafter as flukes became established in the bile ducts. IgG against adult tegument (t2) antigens appeared in the serum 6 weeks after infection, but no IgA against t2 was detected. In the bile, both IgG and IgA titres against t1 and gut antigens rose to peak values at 4–6 weeks after infection, but there was no activity against t2 antigen. The Ig levels in bile were considerably lower than in serum. Much more IgA relative to IgG occurred in bile as compared to serum (IgG/IgA ratio in serum was 16–32, in bile 1–2) suggesting a role for IgA in defence at mucosal surfaces. Comparison of the antibody profiles in bile and serum suggested that IgG in the bile was derived from circulating IgG whereas IgA may have been preferentially concentrated in the bile.     

Entamoeba histolytica: cytopathogenicity of intact amebae and cell-free extracts; isolation and characterization of an intracellular toxin.

Toxicity assays on cell-free extracts of virulent and nonvirulent strains of Entamoeba histolytica were carried out in microtiter plates. These extracts had a cytopathogenic effect (CPE) on monolayers of baby hamster kidney cells. CPE was inhibited by normal human serum, fetal calf serum, and other sera, probably due to their IgG component. Using gel chromatography the toxic material, a protein, was found in a fraction with molecular weight between 35,000 and 45,000. This fraction contained a strong glycoprotein antigen. CPE caused by this toxin differs in several ways from the earlier described “contact lysis” caused by intact amebae. The possible significance of these two modes of toxicity of Entamoeba histolytica for the pathogenesis of amebiasis is discussed.     

A calcitonin-like action of prostaglandin E1

The pharmacological effects of PGE₁ (6 and 9 days, 21,250 μg/kg per day subcutaneously) upon the growth and the bone resorption of mammals were studied using the proximal tibia and upper incisor of immature rats along with lead acetate as a time marker, and upon the serum calcium and inorganic phosphorus levels. The following results were obtained. 1. PGE₁ hardly affected the body weight or the weight of organs of the rats but apparently inhibited the longitudinal growth of proximal tibia in a dose related manner. 2. PGE₁ clearly inhibited not only the longitudinal growth (incisor growth) but also the appositional growth (dentin formation) of incisal dentin. 3. The grade of the inhibitory effect on the growth was in the order of bone growth >dentin formation >incisor growth. 4. The occurrence of osteoporosis due to a low calcium diet was inhibited by the simultaneous administration of PGE₁, the mechanism being considered to be mainly due to the inhibitory effect on the bone resorption. 5. PGE₁ lowered the level of serum calcium and the lowering effect was not observed in the thyro-parathyroidectomized rat. From the facts that the above effects were exactly the same as those of calcitonin (1), the possibility that the subcutaneous injection of PGE₁ may induce a calcitonin-like action, a part of which may dependent on the calcinonin secretion is suggested.     

Serum metabonomics study of pregnant women with gestational diabetes mellitus based on LC-MS

ObjectiveThrough metabolomics method, the objective of the paper is to differentially screen serum metabolites of GDM patients and healthy pregnant women, to explore potential biomarkers of GDM and analyze related pathways, and to explain the potential mechanism and biological significance of GDM.MethodsThe serum samples from 30 GDM patients and 30 healthy pregnant women were selected to conduct non-targeted metabolomics study by liquid chromatography-mass spectrometry. The differential metabolites between the two groups were searched and the metabolic pathway was analyzed by KEGG database.ResultsMultivariate statistical analysis found that serum metabolism in GDM patients was different significantly from healthy pregnant women, 36 differential metabolites and corresponding metabolic pathways were identified in serum, which involved several metabolic ways like, fatty acid metabolism, butyric acid metabolism, bile secretion, and amino acid metabolism.ConclusionThe discovery of these biomarkers provided a new theoretical basis and experimental basis for further study of the early diagnosis and pathogenesis of GDM. At the same time, LC-MS-based serum metabolomics methods also showed great application values in disease diagnosis and mechanism research.     

Should biochemical markers of bone turnover be considered standard practice for safety pharmacology?

The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path Initiative in 2004 to modernize drug development and safety pharmacology. Bone is that largest tissue by weight, and is continuously remodelled. Changes in bone turnover lead to complications such as osteoporosis and fracture, that is associated with an increased mortality. Recent findings have identified bone as a possible endocrine organ and the availability of valid biochemical bone markers suggests that assessing bone turnover should also play an important role in general safety pharmacology.     

Supplemental vitamin D increases serum cytokines in those with initially low 25-hydroxyvitamin D: A randomized,double blind,placebo-controlled study

The purpose of this study was to determine if vitamin D status before supplementation influences the cytokine response after supplemental vitamin D. Forty-six reportedly healthy adults (mean(SD); age, 32(7) y; body mass index (BMI), 25.3(4.5) kg/m²; serum 25-hydroxyvitamin D (25(OH)D), 34.8(12.2) ng/mL) were randomly assigned (double blind) to one of three groups: (1) placebo (n = 15), or supplemental vitamin D (cholecalciferol) at (2) 4000 (n = 14) or (3) 8000 IU (n = 17). Supplements were taken daily for 35 days. Fasting blood samples were obtained before (Baseline, Bsl) and 35-days after (35-d) supplementation. Serum 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), cytokines, and intact parathyroid hormone with calcium were measured in each blood sample. Supplemental vitamin D increased serum 25(OH)D (4000 IU, ≈29%; 8000 IU, ≈57%) and 1,25(OH)D (4000 IU, ≈12%; 8000 IU, ≈38%) without altering intact parathyroid hormone or calcium. The vitamin D metabolite increases in the supplemental vitamin D groups (n = 31) were dependent on initial levels as serum 25(OH)D (r = −0.63, p < 0.05) and 1,25(OH)D (r = −0.45, p < 0.05) at Bsl correlated with their increases after supplementation. Supplemental vitamin D increased interferon (IFN)-γ and interleukin (IL)-10 in subjects that were vitamin D insufficient (serum 25(OH)D < 29 ng/mL) compared to sufficient (serum 25(OH)D ⩾ 30 ng/mL) at Bsl. We conclude that supplemental vitamin D increase a pro- and anti-inflammatory cytokine in those with initially low serum 25(OH)D.     

Plasma netrin-1 is a diagnostic biomarker of human cancers

Context:?The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues.

Objectives:?To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods:?A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results:?Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion:?Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.     

不同病情急性缺血性脑卒中患者血清过氧化还原蛋白1、钙调蛋白、触珠蛋白水平与预后的关系分析

摘要 目的：探讨不同病情急性缺血性脑卒中（AIS）患者血清过氧化还原蛋白1(PRDX1)、钙调蛋白(CAM)、触珠蛋白(HPT)水平与预后的关系。方法：收集2018年4月~2019年4月期间本院收治的127例AIS患者为研究对象,根据患者的病情分为轻度组(39例)、中度组(48例)、重度组(40例),根据患者的改良Rankin 量表( mRS)评分将患者分为预后良好组(73例)和预后不良组(54例),另选同期在我院进行健康检查的健康受试者50例为对照组。对比所有受试者PRDX1、CAM、HPT水平。对比不同预后患者的一般资料、PRDX1、CAM、HPT水平。分析PRDX1、CAM、HPT与NIHSS评分、mRS评分的关系。以多因素Logistic回归分析AIS患者预后的影响因素。结果：轻度组、中度组、中度组的PRDX1、CAM、HPT水平均高于对照组,且随着患者的病情加重,PRDX1、CAM、HPT水平依次升高,差异均有统计学意义(P<0.05)。预后不良组患者的年龄、PRDX1、CAM、HPT均高于预后良好组(P<0.05)。经Pearson检验,AIS患者的PRDX1、CAM、HPT与NIHSS、mRS评分均呈正相关(P<0.05)。经多因素Logistic回归分析可得,年龄较高、PRDX1水平升高、CAM水平升高、HPT水平升高是AIS患者预后不良的危险因素(P<0.05)。结论：AIS患者的PRDX1、CAM、HPT水平异常升高,且与其病情及预后呈现明显的相关性,年龄、PRDX1、CAM、HPT是患者预后的影响因素,对于病情的评估、预后的判断有一定的临床指导价值。     

不同病理分期肺腺癌患者血清代谢组学研究

肺癌是当今世界最常见的恶性肿瘤之一,其新发率和死亡率多年来都居于各类癌症之首,其中85%的肺癌都是非小细胞癌,而腺癌又是最常见的非小细胞癌。肺癌的高隐匿性是造成其高死亡率的最主要原因,因此为肺癌的早期诊断和病理分期寻求高效可靠的方法是十分必要的。代谢组学揭示了小分子代谢物的一系列变化,反映了生命活动的最终状态,因此也能直接反映疾病不同发展阶段的病理生理变化。本研究利用核磁共振氢谱(1H-NMR),对在我院就诊的27例不同病理分期的肺腺癌患者和13例健康志愿者进行了血清代谢物分析,运用正交偏最小二乘判别分析(OPLS-DA)对1H-NMR数据进行建模,单变量统计分析对模型进行评价。结果表明肺腺癌患者组的血清中有14种代谢物出现明显差异,其中丙酮酸、丙氨酸、NAC1、乳酸、GPC和甘氨酸比起对照组来有显著上升,而葡萄糖、谷氨酰胺、亮氨酸、异亮氨酸、缬氨酸、丙酮、乙酰乙酸和苏氨酸则显著下降。而在不同分期肺腺癌患者间进行比较后发现,异亮氨酸、乙酰乙酸、NAC1和乳酸的变化与肺腺癌的发展有相关性,可能是肺腺癌早期诊断和分期的潜在生物标志物。