RISK pathway is involved in oxytocin postconditioning in isolated rat heart

The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal transduction cascade in the cardioprotective mechanism of ischemic postconditioning. In the present study, we examined the cardioprotective role of oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt and ERK1/2).Animals were randomly divided into 6 groups. The hearts were subjected under 30 minutes (min) ischemia and 100 min reperfusion. OT was perfused 15 min at the early phase of reperfusion. RISK pathway inhibitors (Wortmannin; an Akt inhibitor, PD98059; an ERK1/2 inhibitor) and Atosiban (an OT receptor antagonist) were applied either alone 10 min before the onset of the ischemia or in the combination with OT during early reperfusion phase. Myocardial infarct size, hemodynamic factors, ventricular arrhythmia, coronary flow and cardiac biochemical marker were measured at the end of reperfusion.OT postconditioning (OTpost), significantly decreased the infarct size, arrhythmia score, incidence of ventricular fibrillation, Lactate dehydrogenase and it increased coronary flow. The cardioprotective effect of OTpos was abrogated by PI3K/Akt, ERK1/2 inhibitors and Atosiban.Our data have shown that OTpost can activate RISK pathway mostly via the PI3K/Akt and ERK1/2 signaling cascades during the early phase of reperfusion.     

垂体后叶素及缩宫素止血在腹腔镜肌壁间子宫肌瘤剔除术中应用的比较观察

目的:对比分析采用垂体后叶素及缩宫素止血在腹腔镜子宫肌瘤剔除术中临床疗效。方法:将我院接受治疗的76例患者按照手术止血方法,分为垂体后叶素止血组(A组)与缩宫素止血组(B组),观察两组患者各自手术治疗后的时间、术中出血量、术后血红蛋白水平的变化以及治疗前后血压的变化情况。结果:两组患者手术治疗均成功完成,A组患者在手术时间、术中出血量、术后血红蛋白下降差值等方面,均显著优于B组患者(P0.05);A组患者用药15 min后收缩压水平与B组差异显著(P0.05),而30min与45 min后,二者差异不显著(P0.05)。两组患者用药前,HR和SPO2水平对比差异不显著(P0.05)。两组患者用药后HR与用药前对比,差异均显著(均P0.05)。而SPO2在两组内以及两组间对比,差异均不显著(P0.05)。A组患者用药5 min和10 min、30 min后HR分别与B组对比,差异均具有显著性(均P0.05)。结论:临床上进行腹腔镜手术治疗子宫肌瘤疾病过程中,采用垂体后叶素对患者进行止血,能有效减少手术治疗时间、降低手术出血量水平,手术止血效果整体优于缩宫素止血,产生的临床效果显著,值得临床上进一步推广应用。     

Oxytocin promotes heat stress tolerance via insulin signals in Caenorhabditis elegans

ABSTRACT

Oxytocin, has various physiological functions that have been well studied and many that remain unknown. Here, we aimed to determine new physiological functions of oxytocin using Caenorhabditis elegans. Oxytocin treatment promoted the restoration of movement after heat stress and enhanced the viability under heat stress. However, oxytocin had no effect on the life span and only little effect on the oxidative stress tolerance. In contrast, oxytocin treatment didn’t promote the restoration of movement or enhance the viability of deficient mutants of ntr-1/2, which is the gene encoding the oxytocin receptor. In addition, for mutants of daf-16, daf-2, tax-4, and some insulin-like peptides, the heat stress tolerance effect by oxytocin was canceled. Furthermore, oxytocin increased the expression levels of the DAF-16 target genes. Our results suggest that oxytocin treatment promoted the heat stress tolerance of C. elegans via the insulin/IGF-1 signaling pathway.     

The effects of methyl palmitate,a putative regulator from perivascular fat,on the contractility of pregnant human myometrium

Aims

Methyl palmitate is thought to cause relaxation in vascular smooth muscle by opening voltage-activated potassium channels. We have tested the hypothesis that methyl palmitate, a putative regulator from perivascular fat, is an inhibitor of the contractility of human pregnant myometrium and that its effects might partially explain the higher incidence of dysfunctional labor in obese women compared to those with normal body mass indices.

Main methods

Strips of myometrium obtained with informed consent from women undergoing elective cesarean section at term were mounted in organ baths. Strips stimulated with oxytocin (1 nM) or KCl (30 mM) were exposed to cumulatively increasing concentrations of methyl palmitate up to 10 μM. Similar strips were exposed to cumulative addition of the potassium channel blockers 4-aminopyridine and tetraethylammonium. The contractility of the strips was monitored and analyzed using conventional methods.

Key findings

Methyl palmitate failed to inhibit oxytocin- or KCl-induced contractions over the concentration range tested. In fact, it exerted a slight excitatory effect in the presence of KCl, though not in the presence of oxytocin. The contractility of naïve strips was unaltered by exposure to 1 μM methyl palmitate. Both 4-aminopyridine and tetraethylammonium produced concentration-dependent contractions of human pregnant myometrium providing pharmacological evidence for the presence of voltage-activated potassium channels in this preparation.

Significance

Our findings do not support the hypothesis that methyl palmitate is an inhibitor of human pregnant myometrial contractility. Alternate hypotheses must be pursued to explain the higher incidence of dysfunctional labor in obese women.     

The pattern of cervical penetration and the effect of topical treatment with prostaglandin and/or FSH and oxytocin on the depth of cervical penetration in the ewe during the peri-ovulatory period

Artificial insemination in sheep has two major limiting factors: the poor quality of frozen-thawed ram semen and the convoluted anatomy of the sheep cervix that does not allow transcervical passage of an inseminating catheter. It has been demonstrated that in the ewe during estrus, there is a degree of cervical relaxation mediated by ovarian and possibly gonadotrohic hormones, and we set out to investigate factors that might enhance cervical relaxation. Five experiments were conducted on ewes of different breeds to determine: 1) the pattern of cervical penetration during the periovulatory period in ewes of several breeds (Welsh Mountain, Île-de-France, Vendéenne, Romanov and Sarda); 2) the effect of the “ram effect” a socio-sexual stimulus, on cervical penetration; and 3) the effects of the intracervical administration of follicle-stimulating hormone (FSH), oxytocin and a prostaglandin E agonist (misoprostol) on the depth of cervical penetration during the periovulatory period. The results showed that during the periovulatory period in all breeds examined, there was increased penetration of the cervical canal (P < 0.05) by an inseminating catheter. Cervical penetration increased to a maximum 54 h after the removal of progestagen sponges and then gradually declined. Furthermore, the depth of cervical penetration but not its pattern, was affected (P < 0.05) by the breed of ewe. The maximum depth of cervical penetration was lower (P < 0.05) in the Vendéenne breed compared to the Île-de-France and Romanov breeds, which did not differ from one another. In the presence of rams, the depth of cervical penetration was increased at 48 and 54 h after removal of sponges (P < 0.05) and reduced at 72 h (P < 0.05). The local administration of hormones FSH, misoprostol (a PGE agonist) and oxytocin alone and in various combinations did not have any significant effect on the depth of cervical penetration during the periovulatory period. In conclusion, the natural relaxation of the cervix observed in ewes of several breeds occurs at a time during estrus, 54 h after the removal of progestagen sponges, which is the most suitable for artificial insemination. The effect was enhanced by the presence of a ram but not by the local intracervical administration of FSH, misoprostol and oxytocin even though oxytocin and PGE₂ are involved in cervical function. The time of maximum cervical penetration in the preovulatory period (54 h) coincides with high LH and estradiol concentrations suggesting they might be responsible for the relaxation of the cervix probably through an oxytocin-PGE mediated pathway.     

Oxytocin alleviates hepatic ischemia-reperfusion injury in rats

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.     

催产素及其受体与哺乳动物的生殖

催产素（OT）是一种9肽激素,主要由哺乳动物下丘脑产生,以神经内分泌,旁分泌或自分泌形成,在哺乳动物生殖过程中发挥重要作用,催产素受体（OTR）是与G－蛋白相耦联的膜蛋白,通过激活磷脂酶C发挥其生理作用,OT在交配,分娩,哺池时由神经垂体（垂体后叶）脉冲式释放,促进子宫平滑肌和乳腺肌上皮细胞收缩,利用精子运行,胎儿娩出和射出乳汁,OT在中枢神经系统中参与调节母性行为,在性腺中促进某些物种的黄体形成,OT与PGF2a共同作用使有蹄动物黄体退化,以上过程都依赖于OT和OTR基因的时空特异性表达,多种激素参与它们的表达调控,但OT的生理作用有时也可被其它途径所替代。     

Coexpression of Glucagon-Like Peptide-1 (GLP-1) Receptor, Vasopressin, and Oxytocin mRNAs in Neurons of the Rat Hypothalamic Supraoptic and Paraventricular Nuclei

Abstract : This study was designed to gain better insight into the relationship between glucagon-like peptide-1 (GLP-1) (7-36) amide and vasopressin (AVP) and oxytocin (OX). In situ hybridization histochemistry revealed colocalization of the mRNAs for GLP-1 receptor, AVP, and OX in neurons of the hypothalamic supraoptic and paraventricular nuclei. To determine whether GLP-1(7-36)amide alters AVP and/or OX release, both in vivo and in vitro experimental study designs were used. In vivo, intravenous administration of 1 μg of GLP-1(7-36)amide into the jugular vein significantly decreased plasma AVP and OX concentrations. In vitro incubation of the neurohypophysis with either 0.1 or 1 μg of GLP-1(7-36)amide did not modify the release of AVP. However, addition of 1 μg of GLP-1(7-36)amide to the incubation medium increased slightly the secretion of OX. The coexpression of GLP-1 receptor and AVP mRNAs in hypothalamic supraoptic and paraventricular nuclei gives further support to the already reported central effects of GLP-1(7-36)amide on AVP. Our findings also suggest a dual secretory response of AVP and OX to the effect of GLP-1(7-36)amide, which most likely is related to the amount and/or the route of peptide administration.