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, ...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.展开更多
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 observe the effects of moxibustion therapy on the improvements of clinical symptom scale score and neuropeptide substance in vascular dementia （VD） and investigate a mechanism of moxibustion for VD. Met...Objective To observe the effects of moxibustion therapy on the improvements of clinical symptom scale score and neuropeptide substance in vascular dementia （VD） and investigate a mechanism of moxibustion for VD. Methods Eighty-seven cases of VD were divided randomly into a moxibustion group （43 cases） and a medication group （44 cases）. In moxibustion group, the isolated moxibustion with Typhonium Rhizome was applied to Baihui （百会 GV 20）, and suspended moxibustion was used on Shenting （神庭 GV 24） and Dazhui （大椎 GV 14）. In medication group, Piracetam tablet was taken orally. After 4-session treatment, the scores in Hasegawa＇s Dementia Scale （HDS）, Mini Mental Status Examination （MMSE） and Activity of Daily Living Scale （ADL） as well as the content of active substances, somatostatin （SS） and arginine vasopressin （AVP） in cerebral spinal fluid relevant with learning and memory were compared with those before treatment. Results The total effective rate was 81.4% （35/43） in moxibustion group, which was superior to 63.6% （28/44） in medication group （P〈0.01）. The scores in HDS, MMSE and ADL after treatment were all improved as compared with those before treatment in two groups （P〈0.05, P〈0.01）. The improvements of the scores in MMSE and ADL in moxibustion group were superior to those in medication group （both P〈0.05）. After treatment, SS and AVP content in cerebral spinal fluid increased remarkably as compared with those before treatment in two groups （both P〈0.01）, and SS and AVP levels after treatment in moxibustion group were improved significantly as compared with those in medication group （P〈0.05, P〈0.01）. Conclusion Moxibustion therapy is superior to oral administration of Piracetam tablet no matter in the improvement of symptom scores or in the regulation of neuropeptide substances relevant with learning and memory, which deserves to be promoted in application.展开更多
Objective To investigate the effect of acupuncture treatment on silencing the expression of Oonnexin 43 （Cx43）, and to study the analgesic mechanism of acupuncture treatment for primary dysmenorrhea （PD） in rats. ...Objective To investigate the effect of acupuncture treatment on silencing the expression of Oonnexin 43 （Cx43）, and to study the analgesic mechanism of acupuncture treatment for primary dysmenorrhea （PD） in rats. Methods We used estrostilben to develop the model of primary dysmenorrhea in rat, and RNA interference technology to silence the expression of Cx43 in acupoints. Fifty female rats were randomly divided into five groups （n = 10 in each group） ： normal, model, acupuncture, acupuncture ＋ interference and acupuncture＋ interference control group, pSilencer-Cx43-shRNA and pSilencer-Oon-shRNA were injected locally into the acupoints in interference group and interference-control group, respectively. The incidence rate of writhe reaction over the period of 30 min was evaluated. The expression of the oxytocin receptor （OTR） and vasopressin receptor（VasR） in rat myometrium with Semiquantitative RT-POR and immunohistochemistry. Results （1）The mRNA and protein level of Cx43 in acupoints in interference group were significantly lower those of in the acupuncture group （P〈0.05）. There was no significant difference between acupuncture and interference-control group. （2） Acupuncture could significantly prolong the latency period of writhing body and decrease the number of writhing body as compared with that of model group and interference group. （3）The level of OTR and VasR mRNA and protein in the model group were significantly higher （P〈0.05） as compared to normal group. The results in acupuncture group and interference-control group were similar to the normal group. The results in interference group were similar to the model group. Conclusions Acupuncture may be useful in the treatment of the model of primary dysmenorrhea in the rats. Local injection of Cx43 shRNA expression vetor could silence the expression of Cx43 in acupoint and markedly influence acupuncture effect, demonstrating Cx43 is involved in acupuncture effect.展开更多
TO THE EDITORWe read with interest the article entitled ＂Bleeding gastric varices： Results of endoscopic injection with cyanoacrylate at King Chulalongkorn Memorial Hospital＂ by Noophun et al. They performed n-buty...TO THE EDITORWe read with interest the article entitled ＂Bleeding gastric varices： Results of endoscopic injection with cyanoacrylate at King Chulalongkorn Memorial Hospital＂ by Noophun et al. They performed n-butyl-2-cyanoacrylate （CA） injection therapy for bleeding gastric varices in twentyfour patients, and hemostasis was achieved in seventeen （71%） patients. They concluded that CA injection therapy was effective and safe for bleeding gastric varices. However, we disagreed with the author＇s conclusion.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
The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents ...The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.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
AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis(UC).METHODS: The rats were anesthetized with 10% chloral hydr...AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis(UC).METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus(p VN), and the effect of the nucleus tractus solitarius(NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the p VN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin(IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the p VN in rats were detected by Western blot. Malondialdehyde(MDA) content and superoxide dismutase(SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulationof the p VN on rats with UC were eliminated after chemical damage to the p VN. After glutamate receptor antagonist kynurenic acid was injected into the p VN, the protective effects of the chemical stimulation of the p VN were eliminated in rats with UC. After AVpVl receptor antagonist([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of p VN on UC was also eliminated. After chemical stimulation of the p VN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic p VN provides a protective effect against UC injury in rats. Hypothalamic p VN, NTS and vagus nerve play key roles in this process.展开更多
Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been express...Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods(e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.展开更多
Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support t...Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin(AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2(vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phasetwo studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.展开更多
Objective: The objective of this study was to investigate the effects of EA on EH and the regulation of AQP2 and AQP7 protein expression in rats.Methods: Twenty-four rats were allocated randomly to four groups of blan...Objective: The objective of this study was to investigate the effects of EA on EH and the regulation of AQP2 and AQP7 protein expression in rats.Methods: Twenty-four rats were allocated randomly to four groups of blank group, EH group,EH+tolvaptan group and EH + EA group(n = 6 per group). EH rat model was established by intraperitoneally injection of arginine vasopressin(AVP). EA was administered at acupoints "Baihui(百会 GV 20)"and "Tinggong(听宫 SI 19)". Rats in the EH + tolvaptan group and EH+ EA group were treated with tolvaptan and EA, respectively, after EH establishment. Hematoxylin-eosin staining was used to measure the cochlear hydrops degree, and then the ratio of scala media(SM) area to SM + scala vestibuli(SV) area(R value) was calculated. Immunohistochemical method was used to observe AQP2/AQP7 protein expression in the rat cochlear lateral wall after treatment.Results: ①There was no endolymphatic hydrops in the blank group. Reissner' s membrane was extended markedly and bulged into SV in cochleae of the EH group and endolymphatic hydrops was noted. Statistical analysis revealed that R value in the EH group showed a significant increase compared with that in the blank group(0.42 ± 0.02 vs. 0.31 ± 0.05, P=0.000). The distension of Reissner's membrane was less obvious in the EH + tolvaptan group and EH + EA group when compared with the EH group. R value in the EH + tolvaptan group and the EH + EA group was significantly less than that in EH group(0.32±0.04 vs. 0.42 ± 0.02, =0.001;0.35 ± 0.05 vs. 0.42 ± 0.02, P=0.012). The degree of the hydrops in the EH + EA group was not different from that in the EH + tolvaptan group(0.35 ± 0.05 vs. 0.32 ±0.04,P= 1.000). ②The AQP2 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group(12.74 ± 5.18 vs. 5.92 ± 1.52, P = 0.014). The AQP2 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group(6.52 ± 2.73 vs. 12.74 ± 5.18. P = 0.029;6.95 ± 3.10 vs. 12.74 ± 5.18, P = 0.047).The AQP2 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group(6.95 ± 3.10 vs. 6.52 ± 2.73, P= 1.000).③The AQP7 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group(30.32 ± 6.39 vs 16.64 ± 3.21, P=0.000). The AQP7 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group(18.32 ± 2.45 vs.30.32 ± 6.39, P= 0.001;19.54 ± 4.61 vs. 30.32 ± 6.39, P= 0.003). The AQP7 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group(19.54 ±4.61 vs. 18.32 ± 2.45, P= 1.000).Conclusions: These results indicate that repeated EA stimulation exerted the same effects as tolvaptan application on AQPs levels and subsequent aquaretic effects. And dehydrating effect of EA on the inner ear might be associated with its down-regulation of both AQP2 and AQP7 protein expression, thereby provide a potential molecular mechanism involved in the treatment of Meniere's disease by EA.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 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
Sepsis is among the most common reason for admission to intensive care units throughout the world. In the US and most Western nations sepsis is largely a disease of the elderly. Management of elderly patients with sev...Sepsis is among the most common reason for admission to intensive care units throughout the world. In the US and most Western nations sepsis is largely a disease of the elderly. Management of elderly patients with severe sepsis is challenging. Early recognition of this syndrome, together with the early administration of appropriate antibiotics and cautious fluid resuscitation is the cornerstone of therapy. Echocardiography together with non-invasive or invasive hemodynamic monitoring is recommended in patients who have responded poorly to fluids or have significant underlying cardiac disease. This paper reviews the hemodynamic changes that characterize sepsis, particularly as they apply to elderly patients and provides recommendations for the management of these patients.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
Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the in...Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.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
基金supported by the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515011371 (to JP),2021A1515110290 (to YO),2020A1515110564 (to XW)2023A 1 515010150 (to MZ)+2 种基金Science and Technology Planning Project of Guangzhou,No.202102020977 (to ZF)the National Natural Science Foundation of China,Nos.82201516 (to YO) and 81900709 (to ZF)President Foundation of Nanfang Hospital,Southern Medical University,Nos.2019C001 (to MZ),2019C016 (to XW), 2021C045 (to YO)。
文摘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.
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 Projects of Natural Science Foundation of Anhui Province: 30430070
文摘Objective To observe the effects of moxibustion therapy on the improvements of clinical symptom scale score and neuropeptide substance in vascular dementia （VD） and investigate a mechanism of moxibustion for VD. Methods Eighty-seven cases of VD were divided randomly into a moxibustion group （43 cases） and a medication group （44 cases）. In moxibustion group, the isolated moxibustion with Typhonium Rhizome was applied to Baihui （百会 GV 20）, and suspended moxibustion was used on Shenting （神庭 GV 24） and Dazhui （大椎 GV 14）. In medication group, Piracetam tablet was taken orally. After 4-session treatment, the scores in Hasegawa＇s Dementia Scale （HDS）, Mini Mental Status Examination （MMSE） and Activity of Daily Living Scale （ADL） as well as the content of active substances, somatostatin （SS） and arginine vasopressin （AVP） in cerebral spinal fluid relevant with learning and memory were compared with those before treatment. Results The total effective rate was 81.4% （35/43） in moxibustion group, which was superior to 63.6% （28/44） in medication group （P〈0.01）. The scores in HDS, MMSE and ADL after treatment were all improved as compared with those before treatment in two groups （P〈0.05, P〈0.01）. The improvements of the scores in MMSE and ADL in moxibustion group were superior to those in medication group （both P〈0.05）. After treatment, SS and AVP content in cerebral spinal fluid increased remarkably as compared with those before treatment in two groups （both P〈0.01）, and SS and AVP levels after treatment in moxibustion group were improved significantly as compared with those in medication group （P〈0.05, P〈0.01）. Conclusion Moxibustion therapy is superior to oral administration of Piracetam tablet no matter in the improvement of symptom scores or in the regulation of neuropeptide substances relevant with learning and memory, which deserves to be promoted in application.
基金National Basic Research Program of China(973 program, No:2006CB504502)Chinese National Foundation of Natural Sciences .(No.90209009)
文摘Objective To investigate the effect of acupuncture treatment on silencing the expression of Oonnexin 43 （Cx43）, and to study the analgesic mechanism of acupuncture treatment for primary dysmenorrhea （PD） in rats. Methods We used estrostilben to develop the model of primary dysmenorrhea in rat, and RNA interference technology to silence the expression of Cx43 in acupoints. Fifty female rats were randomly divided into five groups （n = 10 in each group） ： normal, model, acupuncture, acupuncture ＋ interference and acupuncture＋ interference control group, pSilencer-Cx43-shRNA and pSilencer-Oon-shRNA were injected locally into the acupoints in interference group and interference-control group, respectively. The incidence rate of writhe reaction over the period of 30 min was evaluated. The expression of the oxytocin receptor （OTR） and vasopressin receptor（VasR） in rat myometrium with Semiquantitative RT-POR and immunohistochemistry. Results （1）The mRNA and protein level of Cx43 in acupoints in interference group were significantly lower those of in the acupuncture group （P〈0.05）. There was no significant difference between acupuncture and interference-control group. （2） Acupuncture could significantly prolong the latency period of writhing body and decrease the number of writhing body as compared with that of model group and interference group. （3）The level of OTR and VasR mRNA and protein in the model group were significantly higher （P〈0.05） as compared to normal group. The results in acupuncture group and interference-control group were similar to the normal group. The results in interference group were similar to the model group. Conclusions Acupuncture may be useful in the treatment of the model of primary dysmenorrhea in the rats. Local injection of Cx43 shRNA expression vetor could silence the expression of Cx43 in acupoint and markedly influence acupuncture effect, demonstrating Cx43 is involved in acupuncture effect.
文摘TO THE EDITORWe read with interest the article entitled ＂Bleeding gastric varices： Results of endoscopic injection with cyanoacrylate at King Chulalongkorn Memorial Hospital＂ by Noophun et al. They performed n-butyl-2-cyanoacrylate （CA） injection therapy for bleeding gastric varices in twentyfour patients, and hemostasis was achieved in seventeen （71%） patients. They concluded that CA injection therapy was effective and safe for bleeding gastric varices. However, we disagreed with the author＇s conclusion.
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.
文摘The present review analyses the mechanisms relating heart failure and hyponatremia,describes the association of hyponatremia with the progress of disease and morbidity/mortality in heart failure patients and presents treatment options focusing on the role of arginine vasopressin(AVP)-receptor antagonists.Hyponatremia is the most common electrolyte disorder in the clinical setting and in hospitalized patients.Patients with hyponatremia may have neurologic symptoms since low sodium concentration produces brain edema,but the rapid correction of hyponatremia is also associated with major neurologic complications.Patients with heart failure often develop hyponatremia owing to the activation of many neurohormonal systems leading to decrease of sodium levels.A large number of clinical studies have associated hyponatremia with increased morbidity and mortality in patients hospitalized for heart failure or outpatients with chronic heart failure.Treatment options for hyponatremia in heart failure,such as water restriction or the use of hypertonic saline with loop diuretics,have limited efficacy.AVP-receptor antagonists increase sodium levels effectively and their use seems promising in patients with hyponatremia.However,the effects of AVP-receptor antagonists on hard outcomes in patients with heart failure and hyponatremia have not been thoroughly examined.
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AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis(UC).METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus(p VN), and the effect of the nucleus tractus solitarius(NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the p VN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin(IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the p VN in rats were detected by Western blot. Malondialdehyde(MDA) content and superoxide dismutase(SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulationof the p VN on rats with UC were eliminated after chemical damage to the p VN. After glutamate receptor antagonist kynurenic acid was injected into the p VN, the protective effects of the chemical stimulation of the p VN were eliminated in rats with UC. After AVpVl receptor antagonist([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of p VN on UC was also eliminated. After chemical stimulation of the p VN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic p VN provides a protective effect against UC injury in rats. Hypothalamic p VN, NTS and vagus nerve play key roles in this process.
文摘Splanchnic circulation is the primary mechanism thatregulates volumes of circulating blood and systemic blood pressure in patients with cirrhosis accompanied by portal hypertension. Recently, interest has been expressed in modulating splanchnic circulation in patients with liver cirrhosis, because this capability might produce beneficial effects in cirrhotic patients undergoing a liver transplant. Pharmacologic modulation of splanchnic circulation by use of vasoconstrictors might minimize venous congestion, replenish central blood flow, and thus optimize management of blood volume during a liver transplant operation. Moreover, splanchnic modulation minimizes any high portal blood flow that may occur following liver resection and the subsequent liver transplant. This effect is significant, because high portal flow impairs liver regeneration, and thus adversely affects the postoperative recovery of a transplant patient. An increase in portal blood flow can be minimized by either surgical methods(e.g., splenic artery ligation, splenectomy or portocaval shunting) or administration of splanchnic vasoconstrictor drugs such as Vasopressin or terlipressin. Finally, modulation of splanchnic circulation can help maintain perioperative renal function. Splanchnic vasoconstrictors such as terlipressin may help protect against acute kidney injury in patients undergoing liver transplantation by reducing portal pressure and the severity of a hyperdynamic state. These effects are especially important in patients who receive a too small for size graft. Terlipressin selectively stimulates V1 receptors, and thus causes arteriolar vasoconstriction in the splanchnic region, with a consequent shift of blood from splanchnic to systemic circulation. As a result, terlipressin enhances renal perfusion by increasing both effective blood volume and mean arterial pressure.
文摘Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin(AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V2(vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phasetwo studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.
基金Supported by the National Natural Science Foundation of China:81704153
文摘Objective: The objective of this study was to investigate the effects of EA on EH and the regulation of AQP2 and AQP7 protein expression in rats.Methods: Twenty-four rats were allocated randomly to four groups of blank group, EH group,EH+tolvaptan group and EH + EA group(n = 6 per group). EH rat model was established by intraperitoneally injection of arginine vasopressin(AVP). EA was administered at acupoints "Baihui(百会 GV 20)"and "Tinggong(听宫 SI 19)". Rats in the EH + tolvaptan group and EH+ EA group were treated with tolvaptan and EA, respectively, after EH establishment. Hematoxylin-eosin staining was used to measure the cochlear hydrops degree, and then the ratio of scala media(SM) area to SM + scala vestibuli(SV) area(R value) was calculated. Immunohistochemical method was used to observe AQP2/AQP7 protein expression in the rat cochlear lateral wall after treatment.Results: ①There was no endolymphatic hydrops in the blank group. Reissner' s membrane was extended markedly and bulged into SV in cochleae of the EH group and endolymphatic hydrops was noted. Statistical analysis revealed that R value in the EH group showed a significant increase compared with that in the blank group(0.42 ± 0.02 vs. 0.31 ± 0.05, P=0.000). The distension of Reissner's membrane was less obvious in the EH + tolvaptan group and EH + EA group when compared with the EH group. R value in the EH + tolvaptan group and the EH + EA group was significantly less than that in EH group(0.32±0.04 vs. 0.42 ± 0.02, =0.001;0.35 ± 0.05 vs. 0.42 ± 0.02, P=0.012). The degree of the hydrops in the EH + EA group was not different from that in the EH + tolvaptan group(0.35 ± 0.05 vs. 0.32 ±0.04,P= 1.000). ②The AQP2 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group(12.74 ± 5.18 vs. 5.92 ± 1.52, P = 0.014). The AQP2 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group(6.52 ± 2.73 vs. 12.74 ± 5.18. P = 0.029;6.95 ± 3.10 vs. 12.74 ± 5.18, P = 0.047).The AQP2 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group(6.95 ± 3.10 vs. 6.52 ± 2.73, P= 1.000).③The AQP7 protein expression in the rat cochlear lateral wall of EH group was significantly increased when compared with the blank group(30.32 ± 6.39 vs 16.64 ± 3.21, P=0.000). The AQP7 protein expression in the rat cochlear lateral wall of EH + tolvaptan group and EH + EA group were all lower than that of the EH group(18.32 ± 2.45 vs.30.32 ± 6.39, P= 0.001;19.54 ± 4.61 vs. 30.32 ± 6.39, P= 0.003). The AQP7 protein expression in the rat cochlear lateral wall of EH + EA group was not different from that in the EH + tolvaptan group(19.54 ±4.61 vs. 18.32 ± 2.45, P= 1.000).Conclusions: These results indicate that repeated EA stimulation exerted the same effects as tolvaptan application on AQPs levels and subsequent aquaretic effects. And dehydrating effect of EA on the inner ear might be associated with its down-regulation of both AQP2 and AQP7 protein expression, thereby provide a potential molecular mechanism involved in the treatment of Meniere's disease by EA.
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.
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Sepsis is among the most common reason for admission to intensive care units throughout the world. In the US and most Western nations sepsis is largely a disease of the elderly. Management of elderly patients with severe sepsis is challenging. Early recognition of this syndrome, together with the early administration of appropriate antibiotics and cautious fluid resuscitation is the cornerstone of therapy. Echocardiography together with non-invasive or invasive hemodynamic monitoring is recommended in patients who have responded poorly to fluids or have significant underlying cardiac disease. This paper reviews the hemodynamic changes that characterize sepsis, particularly as they apply to elderly patients and provides recommendations for the management of these patients.
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 United States National Institute of Neurological Disorders and Stroke,No.R01 NS076975-03a predoctoral fellowship from the United States National Institute of Aging,Training in the Neurobiology of Aging,No.T31 AG020494a predoctoral fellowship from the University of North Texas Health Science Center’s Physician Scientist Program
文摘Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.
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.
