Arginine vasopressin as a target in the treatment of acute heart failure

Congestive heart failure(CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1 a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis(free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

Aquaporin-4 in the formation of cerebral edema following severe burns What role do arginine vasopressin levels play?

BACKGROUND： Aquaporin-4 （AQP-4）, which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE： To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin （AVP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS： Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS： A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points： 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES： Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS： Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema （r= 0.870, 0.848, P 〈 0.01）. CONCLUSION： AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.

ARGININE VASOPRESSIN GENE EXPRESSION IN SUPRAOPTIC NUCLEUS AND PARAVENTRICULAR NUCLEUS OF HYPOTHALAMOUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION

Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON) and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioimmunoassay(RIA), immunocytochemistry(ⅡC), situ hybridization and computed image pattern analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periventricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During different periods of cerebral ischemia (30～120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Conclusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON, PVN. Under the specific condition of cerebral ischemia and reperfusion, the activity and contents of central AVP increased abnormally is one of the important factors which causes ischemia brain damage.

Congenital nephrogenic diabetes insipidus arginine vasopressin receptor 2 gene mutation at new site:A case report

BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.

非对称性二甲基精氨酸在不明原因复发性流产患者绒毛及外周血的表达及其意义

目的 探讨不明原因复发性流产(URSA)患者绒毛及外周血非对称性二甲基精氨酸(ADMA)表达及其临床价值。方法 选取URSA患者168例,采用计算机产生随机数法将就诊患者以3∶1的比例分为训练集126例(URSA组)和测试集42例,另选取同期于我院进行终止妊娠的126例孕妇作为对照,对比训练集及对照组临床资料及外周血和绒毛组织ADMA表达,通过拟合曲线和阈值效应分析患者血清URSA表达与URSA发生的关系,采用多因素Logistics回归模型分析发生URSA的独立危险因素,构建列线图模型。结果 与对照组比较,URSA组患者IL-6、IL-117、Th17、Th17/Treg及血浆、绒毛组织ADMA表达显著增加,孕酮、IL-10、TGF-β及Treg显著降低(P<0.05)。IL-6、IL-17、Th17、Th17/Treg及血浆ADMA、绒毛组织ADMA是发生URSA的独立危险因素,而IL-10、TGF-β及Treg是发生URSA的保护因素(P<0.05)。当血浆ADMA≥1.43μmol/L时,血浆ADMA每增加0.6μmol/L,孕妇发生VRSA的风险增加17%,差异具有统计学意义(OR=0.115,95%CI:0.102~0.133,P<0.05);当绒毛ADMA≥1.92μmol/L时,绒毛ADMA每增加0.6μmol/L,孕妇发生URSA的风险增加14%,差异具有统计学意义(OR=1.192,95%CI:1.085~1.302,P<0.05)。依据独立影响因素构建的列线图预测模型具有较高的区分度、准确性和临床适用性。结论 ADMA在URSA患者血浆及绒毛组织中的表达增加,是URSA发生的独立危险因素,对URSA的发生具有一定的预测价值。

Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Expression of hippocampal corticosteroid receptors,as well as corticotrophin-releasing hormone and vasopressin in the hypothalamic paraventricular nucleus,in fornix transected rats

BACKGROUND： The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE： To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor （MR） and glucocorticoid receptor （GR） in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS： Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone （CRH） and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS： A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups （n = 45）. Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES： Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS： Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed （P 〈 0.05-0.01）. CONCLUSION： Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.

Vasopressin in vasoplegic shock:A systematic review

BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.

精氨酸加压素兴奋视前区正中核谷氨酸能神经元及其机制

目的研究精氨酸加压素(AVP)对小鼠视前区正中核谷氨酸能(MnPO^(Vglut2))神经元放电活动的影响及其机制。方法采用Vglut2-tdTomato雄性小鼠制作脑片,通过荧光显微镜找到表达红色荧光蛋白的MnPO^(Vglut2)神经元,应用全细胞膜片钳技术观察AVP对MnPO^(Vglut2)神经元放电频率的影响;或观察突触传递阻断剂(STBs)对AVP引起的MnPO^(Vglut2)神经元放电频率改变的影响;或观察AVP的V1a受体拮抗剂对AVP引起的MnPO^(Vglut2)神经元放电频率改变的影响。结果与灌流人工脑脊液(ACSF)时比较,灌流ACSF+AVP时,MnPO^(Vglut2)神经元的平均放电频率明显升高(P<0.01),表明AVP可兴奋MnPO^(Vglut2)神经元。与灌流ACSF+STBs时比较,灌流ACSF+STBs+AVP时,MnPO^(Vglut2)神经元的平均放电频率仍明显升高(P<0.001);此外,与灌流ACSF+AVP时比较,灌流ACSF+STBs+AVP时,AVP引起的MnPO^(Vglut2)神经元的放电频率增加幅度无明显改变(P>0.05),提示AVP通过突触后的机制直接兴奋MnPO^(Vglut2)神经元。与灌流ACSF+STBs+AVP时比较,灌流ACSF+STBs+AVP+V1a受体拮抗剂时,AVP引起的MnPO^(Vglut2)神经元的放电频率增加幅度明显下降(P<0.01),提示AVP通过V1a受体直接兴奋MnPO^(Vglut2)神经元。结论AVP可通过突触后的机制经V1a受体直接兴奋MnPO^(Vglut2)神经元。该研究揭示了AVP作用的MnPO神经元的分子标记。

补阳还五汤治疗大鼠气虚血瘀型脑缺血的代谢组学研究

目的:探讨补阳还五汤对气虚血瘀型脑缺血大鼠生物代谢途径的影响。方法:将30只大鼠随机分为假手术组、模型组和补阳还五汤组(3.49 g/kg)。模型组和补阳还五汤组采用荧光微球诱导多发性脑梗死合并睡眠剥夺,建立气虚血瘀型脑缺血动物模型,并分别给予蒸馏水或补阳还五汤灌胃。假手术组给予蒸馏水灌胃,不睡眠剥夺和微球注射。记录各组大鼠的体质量。实验结束后,处死大鼠,采血分析。酶联免疫吸附试验法检测大鼠血清中血栓素B 2(TXB 2)和6-酮基-前列环素1α(6-keto-PGF 1α)水平。采用液质联用的代谢组学方法检测血清样品。结果:与假手术组比较,模型组大鼠平均体质量明显降低,TXB 2/6-keto-PGF 1α比值升高(均P<0.05);与模型组比较,补阳还五汤组大鼠平均体质量升高,药物干预可降低TXB 2/6-keto-PGF 1α比值(P<0.05)。代谢组学结果显示,假手术组与模型组比较,差异有统计学意义(P<0.05),补阳还五汤组部分逆转模型组的变化,指标向假手术组回调的趋势明显。结论:模型大鼠体内的生物代谢途径受到明显干扰,补阳还五汤可以对异常生物代谢途径进行明显的调整,其调整的代谢途径包括:精氨酸的生物合成、精氨酸和脯氨酸代谢、谷胱甘肽代谢、赖氨酸的生物合成。

Blood pressure and atherosclerosis

930082 Clinical administration of atrial natri-uretic factor in reno-vascular hypertension.ZHANG Weiguo(张卫国),et al.Cardiovasc In-stit & Fuwai Hosp,CAMS,Beijing.Chin Cir J1992;7(5):450-452.In order to evaluate the effects of atrial natri-uretic factor(ANF)on patients with reno-vas-cular hypertension,α-hANF(0.025μg/kg/min×60min)was administered to 7 patients byi.v.drip..The renin-angiotensin-aldosteronesystem,plasma catecholamine and arginine va-sopressin were suppressed with diuresis and na-triuresis and lowering of blood pressure.

肝硬化腹水低钠血症与精氨酸加压素关系和V2受体拮抗剂应用的争议问题

肝硬化腹水患者限钠、利尿治疗中忽视补充丢失NaCl常导致低钠血症及精氨酸加压素(arginine vasopressin,AVP)合成与分泌增加和水潴留,有人强调给予AVP-V2受体拮抗剂(托伐普坦)治疗,但存在较多争议:(1)AVP升高及水潴留是否与低钠血症有关;(2)补充因应用利尿剂丢失NaCl是否能抑制AVP合成与释放;(3)高渗NaCl纠正低钠血症效果是否优于托伐普坦;(4)应用托伐普坦时如何规避等渗性血容量不足潜在风险因素;(5)从源头防止低钠血症是否能抑制AVP分泌等,本文就上述问题提出商榷。

Copeptin作为代谢性疾病生物标志物的研究进展

精氨酸加压素是一种由下丘脑合成以应对血浆渗透压增加和血容量减少的激素,它可以与精氨酸加压素受体结合影响糖脂代谢。最近有研究表明,Copeptin是一个稳定、敏感且暂未发现有生物活性的精氨酸加压素替代标志物,与精氨酸加压素以等摩尔量释放入血,其循环水平升高与糖尿病、糖尿病并发症、肥胖、胰岛素抵抗、高血压、高脂血症、非酒精性脂肪性肝病等代谢性疾病密切相关。积极探索Copeptin与代谢性疾病中的关系有助于疾病的早期诊断。

精氨酸加压素在睡眠-觉醒及焦虑、抑郁情绪调控中的作用

精氨酸加压素(argininevasopressin,AVP),又称抗利尿激素,是由下丘脑视上核或室旁核分泌的高度保守的神经肽,具有复杂的生理功能。本文对AVP的生理学特性进行了简单概述,阐述AVP可能通过下丘脑泌素能系统和去甲肾上腺素能系统参与睡眠-觉醒调控,并通过促进视交叉上核神经元细胞间耦合来维持昼夜节律稳态;并描述了AVP在焦虑和抑郁情绪调控的可能作用。

Effect of electroacupuncture on arginine vasopressin-induced endolymphatic hydrops

OBJECTIVE: To investigate the influence of electroacupuncture(EA) on experimentally induced endolymphatic hydrops(EH) in guinea pigs, and elucidate the association between the dehydrating effect of EA and changes in stria vascularis ultrastructure and expression of vasopressin type 2 receptor(V2R), cyclic adenosine monophosphate(cAMP),and aquaporin 2(AQP2) in the endolymphatic sac(ES).METHODS: The EH model was established by intraperitoneal injection of arginine vasopressin(AVP).As a treatment, EA was delivered to Baihui(GV 20)and Tinggong(SI 19) acupoints, once daily for 10 consecutive days. For histomorphological studies,degree of cochlear hydrops was evaluated by hematoxylin-eosin staining, and the ratio of scala media(SM) area to SM + scala vestibuli area was calculated. In mechanical studies, ultrastructural changes in stria vascularis tissue were examined by transmission electron microscopy. In addition, cAMP levels and mRNA expression levels of V2 R and AQP2 in the ES were compared among groups.RESULTS: EA treatment significantly reduced cochlear hydrops compared with hydropic guinea pigs(P = 0.015). Furthermore, EA attenuated ultrastructural changes in the stria vascularis tissue following EH, significantly upregulated the expression of V2 R(P = 0.016), and attenuated AVP-induced upregulation of both cAMP(P = 0.038) and AQP2 expression(P = 0.017) in the ES.CONCLUSION: Collectively, the results of the present study suggest that the dehydrating effect of EA is associated with improvement of stria vascularis ultrastructure and V2 R-cAMP-AQP2 signaling pathway regulation in the ES.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Endolymphatic Hydrops

Objective: To investigate the effects of electroacupuncture(EA) on endolymphatic hydrops(EH) and the regulation of arginine vasopressin(AVP)-aquaporin-2(AQP2) pathway in guinea pigs. Methods: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui(GV 20) and Tinggong(SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin(HE) staining, and then the ratio of scala media(SM) area to SM + scala vestibuli(SV) area(R value) was calculated. In mechanical studies, a comparison of plasma AVP(p-AVP) concentrations, cyclic adenosine monophosphate(cAMP) levels, vasopressin type 2 receptor(V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. Results: EA significantly reduced cochlear hydrops in guinea pigs(P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations(P=0.006), cochlear c AMP levels(P=0.003) and AQP2 mRNA expression(P=0.016), and up-regulated the expression of V2R mRNA(P=0.004) in the cochlea. Conclusion: The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

Early changes of endothelin,nitric oxide and arginine-vasopressin in patients with acute cerebral injury

Objective: To investigate the early changes and clinical significance of plasma endothelin (ET), nitric oxide (NO) and arginine vasopressin (AVP) in patients with acute moderate or severe cerebral injury. Methods: The early (at 24 hours after injury) plasma concentrations of ET, NO and AVP were measured with radioimmunoassay and Green technique in 48 cases of acute moderate (GCS≤8 in 27cases ) or severe (GCS>8 in 21 cases) cerebral injury (Group A), in 42 cases of non cerebral injury (Group B) and in 38 normal individuals (Group C), respectively. Results: The early plasma concentrations of ET ( 109.73 ng/L±12.61 ng/L ), NO ( 92.82 μmol/L± 18.21 μmol/L ) and AVP ( 49.78 ng/L±14.29 ng/L ) in Group A were higher than those in Group B ( 67.90 ng/L ±11.33 ng/L , 52.66 μmol/L±12.82 μmol/L and 29.93 ng/L±12.11 ng/L , respectively, P<0.01 ) and Group C ( 50.65 ng/L±17.12 ng/L , 36.12 μmol/L ±12.16 μmol/L and 5.18 ng/L ± 4.18 ng/L , respectively, P<0.001 ). The amounts of ET, NO and AVP in patients with severe cerebral injury were 116.18 ng/L± 18.12 ng/L , 108.19 μmol/L±13.28 μmol/L and 58.13 ng/L±16.78 ng/L , respectively, which were significantly higher than that of the patients with moderate cerebral injury ( 92.33 ng/L±16.32 ng/L , 76.38 μmol/L ±12.71 μmol/L and 36.18 ng/L±12.13 ng/L respectively, P<0.01 ). The early levels of ET, NO and AVP in Group A were negatively related to the GCS scales. The amounts of ET, NO and AVP were 126.23 ng/L± 15.23 ng/L , 118.18 μmol/L±10.12 μmol/L and 63.49 ng/L±14.36 ng/L respectively in patients with subdural hematoma, which were significantly higher than those in patients with epidural hematoma ( 81.13 ng/L ±12.37 ng/L , 68.02 μmol/L±13.18 μmol/L and 45.63 ng/L±12.41 ng/L respectively, P<0.01 ). The plasma concentrations of ET, NO and AVP in stable duration (at 336 hours after injury) in Group A and Group B were similar to those in Group C. Conclusions: ET, NO and AVP were related to the pathophysiological process that occurs in the early stage of acute cerebral injury and the values of ET, NO and AVP correlate positively with the clinical manifestations. The changes of plasma ET, NO and AVP can be regarded as important indices to assess the severity of acute cerebral injury.

Changes of arginine vasopressin in elderly patients with acute traumatic cerebral injury

Objective: To investigate the changes and clinical significance of arginine vasopressin (AVP) in elderly patients with acute traumatic cerebral injury. Methods: With radioimmunoassay, the plasma levels of AVP were measured in 32 elderly patients with acute traumatic cerebral injury, 30 traumatic patients without cerebral injury and 30 healthy elderly volunteers, respectively. Results: The plasma level of AVP in patients with acute traumatic cerebral injury in the early stage ( 48.30 ng/L±8.28 ng/L ) was much higher than that of the traumatic patients without cerebral injury ( 25.56 ng/L±4.64 ng/L , P< 0.01 ), which was much higher than that of the healthy volunteers ( 5.06 ng/L±4.12 ng/L , P< 0.01 ). The level of AVP in the patients with acute traumatic cerebral injury was negatively related with GCS scores. Conclusions: AVP may play an important role in the pathophysiological process in patients with acute traumatic cerebral injury in the early stage. The severer the cerebral injury is, the higher the level of AVP is, which indicates that the level of AVP may be one of the severity indices of traumatic cerebral injury in elderly patients.

Early changes of arginine vasopressin and angiotensin II in patients with acute cerebral injury

Objective: To study the changes and clinical significance of arginine vasopressin (AVP) and angiotensin II (AT II) in patients with acute moderate and severe cerebral injury. Methods: The early plasma concentration was checked by radioimmunoassay in 47 cases of acute moderate and severe cerebral injury, 30 cases of non cerebral injury and 30 healthy volunteers. Results: The early plasma concentrations of AVP ( 50.23 ng/L± 15.31 ng/L) and AT II ( 248.18 ng/L± 82.47 ng/L) in cerebral injury group were higher than those in non cerebral injury group (AVP for 30.91 ng/L± 11.48 ng/L and AT II for 120.67 ng/L± 42.49 ng/L, P< 0.01 ). The early plasma concentrations of AVP and AT II in cerebral injury group were also obviously higher than those of the volunteers (AVP for 5.16 ng/L± 4.23 ng/L and AT II for 43.11 ng/L± 16.39 ng/L, P< 0.001 ). At the same time, the early plasma level of AVP ( 58.90 ng/L± 18.12 ng/L) and AT II ( 292.13 ng/L± 101.17 ng/L) was higher in severe cerebral injured patients than moderate cerebral injured ones (AVP for 36.68 ng/L± 12.16 ng/L and AT II for 201.42 ng/L± 66.10 ng/L, P< 0.01 ). The early level of AVP and AT II was negatively related to the GCS scales in acute cerebral injury. The early plasma concentrations of AVP ( 45.98 ng/L± 13.48 ng/L) and AT II ( 263.28 ng/L± 80.23 ng/L) were lower in epidural hematoma group than those of subdural hematoma and cerebral injury group (AVP for 64.12 ng/L± 15.56 ng/L and AT II for 319.82 ng/L± 108.11 ng/L, P< 0.01 ). Conclusions: AVP and AT II may play an important role in pathophysiologic process in the secondary cerebral injury. The more severe the cerebral injury is, the higher the early level of AVP and AT II will be. The early plasma level of AVP and AT II may be one of the severity indexes of cerebral injury.

Genes Related to Oxytocin and Arginine-Vasopressin Pathways:Associations with Autism Spectrum Disorders

Autism spectrum disorder（ASD） is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication de？cits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood,several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin（OXT） and arginine-vasopressin（AVP）, as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a（AVPR1a）, OXT receptor（OXTR）, theoxytocinase/vasopressinase（LNPEP）, and ADP-ribosyl cyclase（CD38）.