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
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
Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with...Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.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
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.
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.
文摘Women with nocturia are more sensitive to desmopressin, a synthetic arginine vasopressin (AVP) analogue, with significant antidiuretic responses to desmopressin orally disintegrating tablet (ODT) 25 μg, compared with men who require 58 μg to achieve similar responses. In children the current desmopressin dose recommendation to treat primary nocturnal enuresis (PNE) is the same for boys and girls. This post hoc analysis of data from a randomised, doubleblind single-dose study of 84 children with PNE aged 6 - 12 years explored gender differences in sensitivity to desmopressin in children. Following water loading to suppress endogenous AVP, placebo or desmopres-sin 30, 60, 120, 240, 360 or 480 μg was administered when urinary production reached >0.13 mL/min/kg. The endpoints of urinary osmolality and duration of urinary-concentrating action (DOA) (above three thresholds: 125, 200 and 400 mOsm/kg) were analysed to compare efficacy in boys and girls, in each treatment group. The DOA and urinary osmolality were similar in both genders in the desmopressin 120 - 480 μg groups. Boys receiving desmopressin ODT 30 - 60 μg tended to increased urinary osmolality and experienced 1 - 2 hours longer DOA than girls. The same pattern of higher values in boys compared with girls was seen for all measures of urinary osmolality. Conclusion: In a limited sample of pre-pubertal children the antidiuretic response to desmopressin was largely similar between genders, in contrast to findings in adults.
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.
