Objective To observe the effect of instant moxibustion on the levels of prostaglandin E_2（PGE_2）,prostaglandin F2α（PGE_（2α）） and arginine vasopressin（AVP） in the uterine tissues of dismenorrhea rats with col...Objective To observe the effect of instant moxibustion on the levels of prostaglandin E_2（PGE_2）,prostaglandin F2α（PGE_（2α）） and arginine vasopressin（AVP） in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type and to explore its possible mechanism.Methods Female Wistar rats were randomly divided into blank group,model group,herble medicine group,pre-moxibustion group and instant moxibustion group,with 9 rats in each group.Cold-damp congealing and stagnation type primary dismenorrhea models were established by adopting（0±1）℃ ice waterextraction method combined with estradiol benzoate injection method.After modeling on the 8th day,in herble medicine group,Tongjingbao granules was given to the rats by intragastric administration.In pre-moxibustion group,mild moxibustion was carried out at ＂Shénquè＂（神阙 CV 8） and ＂Guānyuán＂（关元 CV 4） of the rats for 10 min at each acupoint.In instant moxibustion group,moxibustion as that in pre-moxibustion group was conducted for once after injection with oxytocin on the 11 th day.ELISA was adopted to detect the levels of PGE_2 and PGE_（2α） in the uterine tissues of rats,and radioimmunoassay was used for detection of AVP level in the uterine tissues of rats.Results Compared with the model group,the latent period of rats in herbal medicine group,premoxibustion group and instant moxibustion group obviously prolonged,the number of times of torsion reduced,and the total score of torsion decreased（P0.01）;compared with herbal medicine group,the latent period of rats in instant moxibustion group obviously prolonged,and the total score of torsion decreased（P0.05 or P0.01）;compared with pre-moxibustion group,the number of times of torsion of rats in instant moxibustion group reduced,and the total score of torsion decreased（P0.01）.Compared with blank group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in model group significantly increased（P0.01）,and the PGE_2 level significantly reduced（P0.01）;compared with model group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in herble medicine group,pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）,the PGE_2 level obviously increased（P0.01）,and the AVP level in the uterine tissues of rats in pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）;compared with herbal medicine group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group significantly reduced（P0.05 or P0.01）;compared with pre-moxibustion group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group obviously reduced（P0.05）,and the PGE_2 level obviously increased（P0.01）.Conclusion Both pre-moxibustion and instant moxibustion can obviously inhibit spasmodic uterine smooth muscle contraction of rats with dismenorrhea,regulate imbalanced levels of PGE_（2α） and PGE_2,reduce the AVP level,so as to improve the uterine hypoxia-ischemia,and play a role in alleviating pain.The efficacy of instant moxibustion was superior to that of pre-moxibustion.展开更多
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 s...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.展开更多
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...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.展开更多
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 vaso...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.展开更多
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...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.展开更多
The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discu...The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopul- monary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Iun N-terminal kinase and p38 expression were significantly decreased in the hippo- campus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Iun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation.展开更多
The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleu...The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.展开更多
Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception...Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.展开更多
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 ...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.展开更多
Autism spectrum disorder（ASD） is defined by impairments of social interaction and the presence of obsessive behaviors. The ＇＇twin＇＇ nonapeptides oxytocin（OXT） and arginine-vasopressin（AVP） are known to play ...Autism spectrum disorder（ASD） is defined by impairments of social interaction and the presence of obsessive behaviors. The ＇＇twin＇＇ nonapeptides oxytocin（OXT） and arginine-vasopressin（AVP） are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children.As expected, children with ASD had lower plasma OXT levels than gender-matched controls（P = 0.028）. No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication（Rho =-0.22,P = 0.076）, while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects（Rho =-0.231, P = 0.079）. Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children（P = 0.072）. In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.展开更多
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.How...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.展开更多
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...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）.展开更多
Dysfunction of brain-derived arginine-vasopressin（AVP） systems may be involved in the etiology of autism spectrum disorder（ASD）. Certain regions such as the hypothalamus, amygdala, and hippocampus are known to con...Dysfunction of brain-derived arginine-vasopressin（AVP） systems may be involved in the etiology of autism spectrum disorder（ASD）. Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors.The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity（FC） of speci？c brain regions in autistic children compared with typically developing children（TDC） aged from 3 to5 years. The results showed：（1） children with ASD had a signi？cantly increased volume in the left amygdala and left hippocampus, and a signi？cantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level.（2） Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist.（3） The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD.（4） Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC.（5） The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale.These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.展开更多
BACKGROUND Arginine vasopressin is a neuropeptide produced in the hypothalamus and released by the posterior pituitary gland.In addition to maintaining plasma osmolarity,under hypovolemic or hypotensive conditions,it ...BACKGROUND Arginine vasopressin is a neuropeptide produced in the hypothalamus and released by the posterior pituitary gland.In addition to maintaining plasma osmolarity,under hypovolemic or hypotensive conditions,it helps maintain plasma volume through renal water reabsorption and increases systemic vascular tone.Its synthetic analogues are widely used in the intensive care unit as a continuous infusion,in addition to hospital floors as an intravenous or intranasal dose.A limited number of cases of hyponatremia in patients with septic or hemorrhagic shock have been reported previously with vasopressin.We report for the first time a normotensive patient who developed vasopressin-induced hyponatremia.CASE SUMMARY A 39-year-old man fell off a forklift and sustained an axial load injury to his cranium.He had no history of previous trauma.Examination was normal except for motor and sensory deficits.The Imagine test showed endplate fracture at C7 and acute traumatic disc at C7 with cortical degeneration.He underwent cervical discectomy and fusion,laminectomy,and posterior instrumented fusion.After intensive care unit admission post-surgery,he developed hyponatremia of 121-124 mEq/L post phenylephrine and vasopressin infusion to maintain blood pressure maintenance.He was evaluated for syndrome of inappropriate secretion of antidiuretic hormone,hypothyroid,adrenal-induced,or diuretic-induced hyponatremia.At the end of extensive evaluation for the underlying cause of hyponatremia,vasopressin was discontinued.He was also put on fluid restriction,given exogenous desmopressin,and a dextrose 5%in water infusion to prevent osmotic demyelination syndrome caused by sodium overcorrection which improved his sodium level to 135 mmol/L.CONCLUSION The presentation of vasopressin-induced hyponatremia is uncommon in normotensive patients,and the most difficult aspect of this condition is determining the underlying cause of hyponatremia.Our case illustrates that,considering the vast differential diagnosis of hyponatremia in hospitalized patients,both hospitalists and intensivists should be aware of this serious complication of vasopressin therapy.展开更多
A glycosylamino acid ＂cassette＂-based synthetic route has been developed for the preparation ofvasopressin analogues with glycosylation. This efficient protocol may be utilized in the synthesis of other novel cyclic...A glycosylamino acid ＂cassette＂-based synthetic route has been developed for the preparation ofvasopressin analogues with glycosylation. This efficient protocol may be utilized in the synthesis of other novel cyclic glycopeptide structures and derivatives.展开更多
Mongolian gerbils were used as delayed neuronal damage (DNDi animal models. At the end of 15Abstract:Mongolian gerbils were used as delayed neuronal damage (DND)animal models. At the end of 15 minute cerebral ischemi...Mongolian gerbils were used as delayed neuronal damage (DNDi animal models. At the end of 15Abstract:Mongolian gerbils were used as delayed neuronal damage (DND)animal models. At the end of 15 minute cerebral ischemia and at various reperfusion time ranging from 1 to 96 hours, the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassay. Furthermore, we also examined the effect of intracerebroventricular (ICV) injection of AVP, AVP antiserum on calcium, Na+, K+-ATPase activrty in the CA1 sector after ischemia and 96 hour reperfusion. The results showed that AVP contents of CA1 sector of hippocampus during 6 to 96 hour recirculation, and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased. After ICV inJection of AVP, the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased, and the Na+, K+- ATPase activity in CA1 sector was remarkably decreased as compared with that of control. While ICV injection of AVP antiserum, the water content and calcium in CA1 sector were significantly decreased as com pared with that of control. These suggested that AVP was involved in the pathophysiologic process of DND in hippocampus following cerebral ischemia and reperfusion. Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca ions over-load of neuron and inhibit the Na+, K+- ATPase activity , thereby to exacerbate the DND in hippocampus.展开更多
AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vaso...AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon.展开更多
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...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.展开更多
Hepatorenal syndrome (HRS) is a grave complication of end-stage liver disease and is associated with a very high mortality. This case report described a 42-year-old female with advanced alcohol-induced cirrhosis who d...Hepatorenal syndrome (HRS) is a grave complication of end-stage liver disease and is associated with a very high mortality. This case report described a 42-year-old female with advanced alcohol-induced cirrhosis who developed HRS that was initially treated with Midodrine and Octreotide but renal function continued to deteriorate. Vasopressin therapy was added and HRS was successfully reversed. There are few data available on the use of vasopressin for HRS and this case supports its use in treatment of HRS, particularly in countries where the more widely studied Terlipressin is unavailable. This case also demonstrates that a patient failing one medical therapy for HRS may respond to an alternative or adjunctive therapy. Therefore, this should be attempted to increase the patient’s chance of survival.展开更多
A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine...A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.展开更多
基金Supported by youth fund project fanded by Hebei Education Department:QN2015027scientific project funded by Administration of Traditional Chinese Medicine of Hebei Province:2015089
文摘Objective To observe the effect of instant moxibustion on the levels of prostaglandin E_2（PGE_2）,prostaglandin F2α（PGE_（2α）） and arginine vasopressin（AVP） in the uterine tissues of dismenorrhea rats with cold-damp congealing and stagnation type and to explore its possible mechanism.Methods Female Wistar rats were randomly divided into blank group,model group,herble medicine group,pre-moxibustion group and instant moxibustion group,with 9 rats in each group.Cold-damp congealing and stagnation type primary dismenorrhea models were established by adopting（0±1）℃ ice waterextraction method combined with estradiol benzoate injection method.After modeling on the 8th day,in herble medicine group,Tongjingbao granules was given to the rats by intragastric administration.In pre-moxibustion group,mild moxibustion was carried out at ＂Shénquè＂（神阙 CV 8） and ＂Guānyuán＂（关元 CV 4） of the rats for 10 min at each acupoint.In instant moxibustion group,moxibustion as that in pre-moxibustion group was conducted for once after injection with oxytocin on the 11 th day.ELISA was adopted to detect the levels of PGE_2 and PGE_（2α） in the uterine tissues of rats,and radioimmunoassay was used for detection of AVP level in the uterine tissues of rats.Results Compared with the model group,the latent period of rats in herbal medicine group,premoxibustion group and instant moxibustion group obviously prolonged,the number of times of torsion reduced,and the total score of torsion decreased（P0.01）;compared with herbal medicine group,the latent period of rats in instant moxibustion group obviously prolonged,and the total score of torsion decreased（P0.05 or P0.01）;compared with pre-moxibustion group,the number of times of torsion of rats in instant moxibustion group reduced,and the total score of torsion decreased（P0.01）.Compared with blank group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in model group significantly increased（P0.01）,and the PGE_2 level significantly reduced（P0.01）;compared with model group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in herble medicine group,pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）,the PGE_2 level obviously increased（P0.01）,and the AVP level in the uterine tissues of rats in pre-moxibustion group and instant moxibustion group obviously reduced（P0.05 or P0.01）;compared with herbal medicine group,the levels of PGE_（2α） and AVP and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group significantly reduced（P0.05 or P0.01）;compared with pre-moxibustion group,the PGE_（2α） level and the ratio of PGE_（2α） and PGE_2 in the uterine tissues of rats in instant moxibustion group obviously reduced（P0.05）,and the PGE_2 level obviously increased（P0.01）.Conclusion Both pre-moxibustion and instant moxibustion can obviously inhibit spasmodic uterine smooth muscle contraction of rats with dismenorrhea,regulate imbalanced levels of PGE_（2α） and PGE_2,reduce the AVP level,so as to improve the uterine hypoxia-ischemia,and play a role in alleviating pain.The efficacy of instant moxibustion was superior to that of pre-moxibustion.
基金Supported by National Natural Science Foundation of China:Effects of Different Frequencies of Electroacupuncture at"Baihui"(GV 20)and"Tinggong"(SI 19)on Endolymphatic Hydrops in Meniere's Disease and Underlying Mechanism(No.81704153)
文摘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.
文摘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.
文摘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.
基金the Postdoctoral Science Foundation of China,No. 20060390301the National Natural Science Foundation of China,No.30600341the Ph.D.Program Foundation of Ministry of Education of China,No.20050159011
文摘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.
文摘The American Heart Association and the European Resuscitation Council recently recommend- ed that vasopressin can be used for cardiopulmonary resuscitation, instead of epinephrine. However, the guidelines do not discuss the effects of vasopressin during cerebral resuscitation. In this study, we intraperitoneally injected epinephrine and/or vasopressin during cardiopul- monary resuscitation in a rat model of asphyxial cardiac arrest. The results demonstrated that, compared with epinephrine alone, the pathological damage to nerve cells was lessened, and the levels of c-Iun N-terminal kinase and p38 expression were significantly decreased in the hippo- campus after treatment with vasopressin alone or the vasopressin and epinephrine combination. No significant difference in resuscitation effects was detected between vasopressin alone and the vasopressin and epinephrine combination. These results suggest that vasopressin alone or the vasopressin and epinephrine combination suppress the activation of mitogen-activated protein kinase and c-Iun N-terminal kinase signaling pathways and reduce neuronal apoptosis during cardiopulmonary resuscitation.
基金supported by grants from the National Natural Science Foundation of China (31271215, 81770423, 81973945, and 81673766)the Health Vocational and Technical Education Research Program of Jiangsu Province, China (J201506)。
文摘The present study was designed to investigate the mechanisms by which P2X7 receptors(P2X7Rs)mediate the activation of vasopressinergic neurons thereby increasing sympathetic hyperactivity in the paraventricular nucleus(PVN) of the hypothalamus of rats with acute myocardial ischemia(AMI). The left anterior descending branch of the coronary artery was ligated to induce AMI in rats. The rats were pretreated with BBG(brilliant blue G, a P2X7R antagonist), nelivaptan(a vasopressin V1b receptor antagonist), or diphenyleneiodonium(DPI) [an nicotinamide adenine dinucleotide phosphate(NADPH)oxidase inhibitor]. Hemodynamic parameters of the heart were monitored. Myocardial injury and cardiomyocyte apoptosis were assessed. In the PVN of AMI rats, P2X7R mediated microglial activation, while reactive oxygen species(ROS) and NADPH oxidase 2(NOX2) were higher than in the sham group. Intraperitoneal injection of BBG effectively reduced ROS production and vasopressin expression in the PVN of AMI rats. Moreover, both BBG and DPI pretreatment effectively reduced sympathetic hyperactivity and ameliorated AMI injury, as represented by reduced inflammation and apoptosis of cardiomyocytes.Furthermore, microinjection of nelivaptan into the PVN improved cardiac function and reduced the norepinephrine(AE) levels in AMI rats. Collectively, the results suggest that, within the PVN of AMI rats, P2X7R upregulation mediates microglial activation and the overproduction of ROS, which in turn activates vasopressinergic neuron V1b receptors and sympathetic hyperactivity, hence aggravating myocardial injury in the AMI setting.
文摘Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.
文摘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.
基金supported by grants from the Research Special Fund for Public Welfare Industry of Health of China (201302002-11)the National Natural Science Foundation of China (81271507)
文摘Autism spectrum disorder（ASD） is defined by impairments of social interaction and the presence of obsessive behaviors. The ＇＇twin＇＇ nonapeptides oxytocin（OXT） and arginine-vasopressin（AVP） are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children.As expected, children with ASD had lower plasma OXT levels than gender-matched controls（P = 0.028）. No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication（Rho =-0.22,P = 0.076）, while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects（Rho =-0.231, P = 0.079）. Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children（P = 0.072）. In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.
基金the National Natural Science Foundation of China,No.30470608,30500171
文摘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.
基金supported by a fund from University of Ulm-Peking University Health Science Center Joint Center for Neuroscience(BMU20160563)
文摘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）.
基金support provided by the Department of Radiology,Peking University Third Hospital and the Brainnetome Center,Institute of Automation,Chines Academy of Sciences are highly appreciatedsupported by the UULM-PUHSC Joint Center for Neuroscience Fund(BMU20160563)
文摘Dysfunction of brain-derived arginine-vasopressin（AVP） systems may be involved in the etiology of autism spectrum disorder（ASD）. Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors.The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity（FC） of speci？c brain regions in autistic children compared with typically developing children（TDC） aged from 3 to5 years. The results showed：（1） children with ASD had a signi？cantly increased volume in the left amygdala and left hippocampus, and a signi？cantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level.（2） Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist.（3） The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD.（4） Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC.（5） The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale.These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.
文摘BACKGROUND Arginine vasopressin is a neuropeptide produced in the hypothalamus and released by the posterior pituitary gland.In addition to maintaining plasma osmolarity,under hypovolemic or hypotensive conditions,it helps maintain plasma volume through renal water reabsorption and increases systemic vascular tone.Its synthetic analogues are widely used in the intensive care unit as a continuous infusion,in addition to hospital floors as an intravenous or intranasal dose.A limited number of cases of hyponatremia in patients with septic or hemorrhagic shock have been reported previously with vasopressin.We report for the first time a normotensive patient who developed vasopressin-induced hyponatremia.CASE SUMMARY A 39-year-old man fell off a forklift and sustained an axial load injury to his cranium.He had no history of previous trauma.Examination was normal except for motor and sensory deficits.The Imagine test showed endplate fracture at C7 and acute traumatic disc at C7 with cortical degeneration.He underwent cervical discectomy and fusion,laminectomy,and posterior instrumented fusion.After intensive care unit admission post-surgery,he developed hyponatremia of 121-124 mEq/L post phenylephrine and vasopressin infusion to maintain blood pressure maintenance.He was evaluated for syndrome of inappropriate secretion of antidiuretic hormone,hypothyroid,adrenal-induced,or diuretic-induced hyponatremia.At the end of extensive evaluation for the underlying cause of hyponatremia,vasopressin was discontinued.He was also put on fluid restriction,given exogenous desmopressin,and a dextrose 5%in water infusion to prevent osmotic demyelination syndrome caused by sodium overcorrection which improved his sodium level to 135 mmol/L.CONCLUSION The presentation of vasopressin-induced hyponatremia is uncommon in normotensive patients,and the most difficult aspect of this condition is determining the underlying cause of hyponatremia.Our case illustrates that,considering the vast differential diagnosis of hyponatremia in hospitalized patients,both hospitalists and intensivists should be aware of this serious complication of vasopressin therapy.
基金Peking University Health Science Center(BMU20130354),State Key Laboratory of Natural and Biomimetic Drugs,and the National Recruitment Program of Global Youth Experts(1000 Plan)
文摘A glycosylamino acid ＂cassette＂-based synthetic route has been developed for the preparation ofvasopressin analogues with glycosylation. This efficient protocol may be utilized in the synthesis of other novel cyclic glycopeptide structures and derivatives.
文摘Mongolian gerbils were used as delayed neuronal damage (DNDi animal models. At the end of 15Abstract:Mongolian gerbils were used as delayed neuronal damage (DND)animal models. At the end of 15 minute cerebral ischemia and at various reperfusion time ranging from 1 to 96 hours, the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassay. Furthermore, we also examined the effect of intracerebroventricular (ICV) injection of AVP, AVP antiserum on calcium, Na+, K+-ATPase activrty in the CA1 sector after ischemia and 96 hour reperfusion. The results showed that AVP contents of CA1 sector of hippocampus during 6 to 96 hour recirculation, and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased. After ICV inJection of AVP, the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased, and the Na+, K+- ATPase activity in CA1 sector was remarkably decreased as compared with that of control. While ICV injection of AVP antiserum, the water content and calcium in CA1 sector were significantly decreased as com pared with that of control. These suggested that AVP was involved in the pathophysiologic process of DND in hippocampus following cerebral ischemia and reperfusion. Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca ions over-load of neuron and inhibit the Na+, K+- ATPase activity , thereby to exacerbate the DND in hippocampus.
基金Supported by National Natural Science Foundation of China,No.31271290 and No.31000514Scientific Research Key Program of Beijing Municipal Commission of Education No.KZ201310025020+1 种基金Beijing Postdoctoral Research FoundationBeijing Natural Science Foundation No.7142025
文摘AIM: To investigate whether Na<sup>+</sup>-K<sup>+</sup>-2Cl<sup>-</sup> cotransporter (NKCC2) is expressed in the mouse distal colonic epithelia and whether it is regulated by vasopressin in the colon.
文摘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.
文摘Hepatorenal syndrome (HRS) is a grave complication of end-stage liver disease and is associated with a very high mortality. This case report described a 42-year-old female with advanced alcohol-induced cirrhosis who developed HRS that was initially treated with Midodrine and Octreotide but renal function continued to deteriorate. Vasopressin therapy was added and HRS was successfully reversed. There are few data available on the use of vasopressin for HRS and this case supports its use in treatment of HRS, particularly in countries where the more widely studied Terlipressin is unavailable. This case also demonstrates that a patient failing one medical therapy for HRS may respond to an alternative or adjunctive therapy. Therefore, this should be attempted to increase the patient’s chance of survival.
基金supported by National Major Scientific and Technological Special Project for "Significant New Drugs Development"(Nos.2011ZX09401-009 and 2013ZX09102014)
文摘A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.
