Syphacia muris: Water permeability of eggs and its effect on hatching

As a result of a previous study, it appeared that hatching of eggs of Syphacia muris is activated by the application of heat (37 °C) or cysteine or trypsin but that these are not the essential stimuli. In the present study it has been established that exposure of eggs prior to hatching for several hours to 37 °C or cysteine or trypsin, or for 3 days to 22 °C, accelerated hatching. Pretreatment with 37 °C or cysteine or trypsin also increased permeability of the eggshell to water; however, it did not induce the operculum to open. The operculum opened only if the eggs, after pretreatment, were immersed in water. The larvae could leave the opened eggs only in water and not in any other medium such as paraffin oil. These data made it possible to distinguish between three stages in the hatching process. During Stage 1, the eggshell becomes permeable to water. This can be induced by dissolving the proteins of the eggshell in a trypsin solution or by stimulating the larvae with temperature or cysteine. The permeability of the eggshell is essential to successful hatching. In Stage 2, which occurs only in the presence of water, the larvae dissolve the chitinous seal between the operculum and the eggshell. In Stage 3 the larvae probably increase their size by water absorption and leave the eggs. In the discussion it has been proposed that all nematodes, both those hatching in the intestine and the species hatching in the open, could well have an identical hatching mechanism to the one observed in Syphacia muris.     

Effect of in vitro zinc supplementation on HSPs expression and Interleukin 10 production in heat treated peripheral blood mononuclear cells of transition Sahiwal and Karan Fries cows

The changing climatic scenario with apprehended rise in global temperature is likely to affect the livestock adversely vis-à-vis production and reproduction. This has prompted more focus in addressing the unfavorable effects of thermal stress in livestock system. Presuming that the trace element zinc is indispensible for cellular antioxidant system and immune function, the present study was designed to investigate the effect of zinc treatment on heat stress alleviation and immune modulation in peripheral blood mononuclear cells (PBMC) of indigenous and crossbred transition cows. Twelve cows, six each of Sahiwal and Karan Fries (KF) in their second parity with confirmed pregnancy were selected for the experiment. The blood samples were collected at −21, 0 and +21 days in relation to expected date of calving. The experiment was carried out in vitro after isolating PBMC from whole blood. The 48 h cultured PBMC were subjected to assorted levels of exposures viz. 37 °C, 42 °C to impose heat stress and 42 °C+zinc to alleviate heat stress and modulate immunity. The PBMC viability was 86%, 69% and 78%, respectively. The mRNA expression of heat shock proteins (HSP 40, 70 and 90α) and Interleukin-10 (IL-10) production varied between the two breeds vis-à-vis days and levels of exposure. The mRNA expression of HSP40 and HSP70 was significantly (P<0.05) higher in Karan Fries than the Sahiwal cows. Both the breeds showed maximum expression of HSP on the day of parturition, more so in KF than Sahiwal. There was a significant (P<0.05) difference in the HSP mRNA expression at different levels of exposure. Zinc treatment to heat stressed PBMC caused a significant (P<0.05) down regulation of HSP. For immune status, anti-inflammatory cytokine, IL-10 in the culture supernatant was accessed. The IL-10 was significantly (P<0.05) higher in Karan Fries (168.18±14.09 pg/ml) than the Sahiwal cows (147.24±11.82 pg/ml). The IL-10 concentration was highest on the day of calving. Zinc treatment reduced the IL-10 concentration. From the study, it could be concluded that the zinc supplementation in heat stressed PBMC can ameliorate thermal stress and modulate immune response which can act as a model for reducing heat stress during the periparturient period in tropical livestock.     

The expression of Candida albicans enolase is not heat shock inducible

Abstract An isoprotein of enolase from the yeast Saccharomyces cerevisiae was reported to be a heat shock protein. The possible role of the C. albicans enolase as a heat shock protein was therefore investigated. The de novo synthesis of C. albicans enolase protein and mRNA did not increase during heat stress, but remained constitutively expressed. Amino acid similarity to the heat shock proteins suggests that although the C. albicans enolase is not a classical heat shock protein, it may be a memberof a group of constitutively expressed, structurally related proteins, the heat shock cognate proteins.     

Anticoagulation for the Acute Management of Ischemic Stroke

Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others.     

State-dependency of host-seeking in Rhodnius prolixus: The post-ecdysis time

The source of blood of most haematophagous insects plays at the same time the double role of host and potential predator. Feeding behaviour should be triggered only when necessary and should be completed as quickly as possible. From an epidemiological point of view, this modulation has an impact on the feeding frequency of disease vectors and, as a consequence, on the transmission of parasites. At present, not many data are available on the influence of the physiological state on the motivation to feed, and mostly limited to a few mosquito species. We analyzed the host-seeking behaviour of Rhodnius prolixus as a function of the time elapsed since the ecdysis, by testing the response of larvae to a blood source, and long- (CO₂) and short-range (heat) orientation cues associated to their vertebrate hosts. Our experiments demonstrated that during the first days following the ecdysis insects do not respond to any stimuli. The ability to follow chemical and physical cues increases either gradually (heat) or step-wise (CO₂) with post-ecdysis time. A few insects started to feed on day 2, but only at day 7 following the ecdysis 50% of them took a blood meal, to reach the highest motivation to feed on day 10. The reasons for the “maturation period” in feeding behaviour of R. prolixus are discussed.     

Melatonin against acute ischaemic stroke dependently via suppressing both inflammatory and oxidative stress downstream signallings

This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4^?/?) (n = 6 per each TLR4^?/? group) mice were categorized into sham control (SC^B6), SC^TLR4?/?, IS^B6, IS^TLR4?/?, IS^B6 + Mel (i.p. daily administration) and IS^TLR4?/? + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK‐α/p‐NF‐κB/nuclear‐NF‐κB/nuclear‐IRF‐3&7/IL‐1β/IL‐6/TNF‐α/IFN‐γ) and oxidative stress (NOX‐1/NOX‐2/ASK1/p‐MKK4&7/p‐JNK/p‐c‐JUN) downstream pathways as well as mitochondrial‐damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group IS^B6, lowest in groups SC^B6 and SC^TLR4?/?, lower in group IS^TLR4?/? + Mel than in groups IS^TLR4?/? and IS^B6 + Mel and lower in group IS^B6 + Mel than in group IS^TLR4?/? (all P < .0001). The brain infarct volume, brain infarct area and the number of inflammatory cells in brain (CD14/F4‐88) and in circulation (MPO+//Ly6C+/CD11b+//Ly6G+/CD11b+) exhibited an identical pattern, whereas the neurological function displayed an opposite pattern of inflammatory protein expression among the six groups (all P < .0001). In conclusion, TLR inflammatory and oxidative stress signallings played crucial roles for brain damage and impaired neurological function after IS that were significantly reversed by Mel therapy.     

VEGF signalling enhances lesion burden in KRIT1 deficient mice

The exact molecular mechanisms underlying CCM pathogenesis remain a complicated and controversial topic. Our previous work illustrated an important VEGF signalling loop in KRIT1 depleted endothelial cells. As VEGF is a major mediator of many vascular pathologies, we asked whether the increased VEGF signalling downstream of KRIT1 depletion was involved in CCM formation. Using an inducible KRIT1 endothelial‐specific knockout mouse that models CCM, we show that VEGFR2 activation plays a role in CCM pathogenesis in mice. Inhibition of VEGFR2 using a specific inhibitor, SU5416, significantly decreased the number of lesions formed and slightly lowered the average lesion size. Notably, VEGFR2 inhibition also decreased the appearance of lesion haemorrhage as denoted by the presence of free iron in adjacent tissues. The presence of free iron correlated with increased microvessel permeability in both skeletal muscle and brain, which was completely reversed by SU5416 treatment. Finally, we show that VEGFR2 activation is a common downstream consequence of KRIT1, CCM2 and CCM3 loss of function, though the mechanism by which VEGFR2 activation occurs likely varies. Thus, our study clearly shows that VEGFR2 activation downstream of KRIT1 depletion enhances the severity of CCM formation in mice, and suggests that targeting VEGF signalling may be a potential future therapy for CCM.     

Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities

A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by ¹H‐NMR, ¹³C‐NMR, FT‐IR and HR‐ESI‐MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti‐ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate‐induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone, (4‐bromophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, (4‐chlorophenyl)(1‐{2‐[(naphthalen‐2‐yl)oxy]ethyl}piperidin‐4‐yl)methanone, (4‐chlorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone and {1‐[2‐(4‐bromophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, (4‐fluorophenyl){1‐[2‐(naphthalen‐2‐yloxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti‐ischemic stroke agents. Basic structure–activity relationships are also presented.     

加味星蒌承气汤对急性缺血性脑卒中患者神经功能及血脂、血液流变学的影响

目的:探讨加味星蒌承气汤对急性缺血性脑卒中患者神经功能及血脂、血液流变学的影响。方法:选取2017年8月～2019年6月期间我院收治的急性缺血性脑卒中患者96例,将入选患者根据随机数字表法分为对照组(n=48)和研究组(n=48),对照组患者予以常规西医治疗,研究组患者在对照组基础上联合加味星蒌承气汤治疗,对比两组患者疗效、神经功能及血脂、血液流变学情况,记录两组患者治疗期间不良反应情况。结果:研究组治疗8 d后的临床总有效率为91.67%(44/48),显著高于对照组患者的72.92%(35/48)(P0.05)。两组治疗8 d后加拿大神经功能评分量表(CNS)、美国国立卫生研究所卒中量表(NIHSS)评分均下降(P0.05),且研究组低于对照组(P0.05)。两组治疗8 d后总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、全血黏度高切、全血黏度低切、血浆黏度、纤维蛋白原均下降(P0.05),且研究组低于对照组(P0.05);高密度脂蛋白胆固醇(HDL-C)升高(P0.05),且研究组高于对照组(P0.05)。两组不良反应发生率比较无明显差异(P0.05)。结论:急性缺血性脑卒中患者采用加味星蒌承气汤治疗,疗效显著,可有效改善患者神经功能及血脂、血液流变学,且安全性较好。