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
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 hippocamp展开更多
The arginine-vasopressin(AVP)hormone plays a pivotal role in regulating various physiological processes,such as hormone secretion,cardiovascular modulation,and social behavior.Recent studies have highlighted the V1a r...The arginine-vasopressin(AVP)hormone plays a pivotal role in regulating various physiological processes,such as hormone secretion,cardiovascular modulation,and social behavior.Recent studies have highlighted the V1a receptor as a promising therapeutic target.In-depth insights into V1a receptor-related pathologies,attained through in vivo imaging and quantification in both peripheral organs and the central nervous system(CNS),could significantly advance the development of effective V1a inhibitors.To address this need,we develop a novel V1a-targeted positron emission tomography(PET)ligand,[^(18)F]V1A-2303([^(18)F]8),which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor.Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies,autoradiography,biodistribution assessments.Furthermore,[^(18)F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity,whole-body distribution,and kinetic properties.Our research indicated[^(18)F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs,and as a foundational element for the development of next-generation,brain-penetrant ligands specifically designed for the CNS.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
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
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 hippocamp
基金the National Natural Science Foundation of China(Nos.82071974,82102107,and 82371998)the Science and Technology Program of Guangzhou,China(Nos.202206010106 and 2023A04J1921)the Guangdong Science and Technology Planning Project,China(2022A0505050042).
文摘The arginine-vasopressin(AVP)hormone plays a pivotal role in regulating various physiological processes,such as hormone secretion,cardiovascular modulation,and social behavior.Recent studies have highlighted the V1a receptor as a promising therapeutic target.In-depth insights into V1a receptor-related pathologies,attained through in vivo imaging and quantification in both peripheral organs and the central nervous system(CNS),could significantly advance the development of effective V1a inhibitors.To address this need,we develop a novel V1a-targeted positron emission tomography(PET)ligand,[^(18)F]V1A-2303([^(18)F]8),which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor.Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies,autoradiography,biodistribution assessments.Furthermore,[^(18)F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity,whole-body distribution,and kinetic properties.Our research indicated[^(18)F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs,and as a foundational element for the development of next-generation,brain-penetrant ligands specifically designed for the CNS.
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.
