cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Clinical Study in Nocturnal Enuretic Children

PURPOSE: Nocturnal Enuresis, an involuntary discharge of urine after bladder control, is frequent in children. It brings patients and family many psychogenic problems. So we investigated its clinical characteristics and drug effects. METHODS: The study subjects enrolled were 36 children with nocturnal enuresis. We evaluated family history, accompanying urinary symptoms and clinical characteristics through questionnaries. We evaluated the effect of imipramine and desmopressin in 26 children among the 36 cases. RESULTS: The ratio of boys to girls was 1.6 to 1. The age range in 15 cases(41.7%) was 4-5 years, in 14 cases(38.9%) 6-7 years, in 4 cases(11.1%) 8-9 years, and in 3 cases(9.3%) it was above 10 years. Twenty four(67%) were primary enuresis and 12(33%) were secondary enuresis. In eighteen cases(50%), these was a family history of enuresis. Seven of these cases had a parental enuresis history. The accompanying urinary symptoms were urgency(47.2%), frequency (38.9%), and dysuria(13.9%). The responses to imipramine were as follows : an excellent response in 2 cases(20%), a good response in 4(40%), a transient response in 2(20%), and no response in 2(20%). The responses to desmopressin were as follows : an excellent response in 7(43.8%), a good response in 4(25%), a transient response in 3(18.7%), and no response in 2(12.5%). CONCLUSION: Enuresis is more frequent in boys and primary type. Half of 36 enuresis children had a family history of enuresis. We recommend continuous drug medication to control nocturnal enuresis along with encouragement.

Clinical Study in Nocturnal Enuretic Children

PURPOSE: Nocturnal Enuresis, an involuntary discharge of urine after bladder control, is frequent in children. It brings patients and family many psychogenic problems. So we investigated its clinical characteristics and drug effects. METHODS: The study subjects enrolled were 36 children with nocturnal enuresis. We evaluated family history, accompanying urinary symptoms and clinical characteristics through questionnaries. We evaluated the effect of imipramine and desmopressin in 26 children among the 36 cases. RESULTS: The ratio of boys to girls was 1.6 to 1. The age range in 15 cases(41.7%) was 4-5 years, in 14 cases(38.9%) 6-7 years, in 4 cases(11.1%) 8-9 years, and in 3 cases(9.3%) it was above 10 years. Twenty four(67%) were primary enuresis and 12(33%) were secondary enuresis. In eighteen cases(50%), these was a family history of enuresis. Seven of these cases had a parental enuresis history. The accompanying urinary symptoms were urgency(47.2%), frequency (38.9%), and dysuria(13.9%). The responses to imipramine were as follows : an excellent response in 2 cases(20%), a good response in 4(40%), a transient response in 2(20%), and no response in 2(20%). The responses to desmopressin were as follows : an excellent response in 7(43.8%), a good response in 4(25%), a transient response in 3(18.7%), and no response in 2(12.5%). CONCLUSION: Enuresis is more frequent in boys and primary type. Half of 36 enuresis children had a family history of enuresis. We recommend continuous drug medication to control nocturnal enuresis along with encouragement.

The Effect of Desmopressin Acetate on Coagulation in Rabbits Subjected to Severe Hemorrhagic Shock / 대한마취과학회지

BACKGROUND: Desmopressin acetate (DDAVP) may improve hemostasis in congenital or acquired disorders of coagulation and reduce operative blood loss in patients undergoing surgical procedures. The effects of DDAVP on coagulation in hemorrhagic shock were studied in rabbits subjected to severe hemorrhage. METHODS: 20 rabbits were bled to shock and infused lactated Ringer's solution simultaneously so that the mean arterial pressure were maintained above 50 mmHg. Animals were randomly received DDAVP 0.3 ug/kg (group Dl), 3 ug/kg (group D10) or saline (group S) over 15 minutes. Bleeding time and factor VIII coagulant activity (FVIII:C) were measured before, after shock and 45 minutes after DDAVP or saline infusion. RESULTS: After shock, bleeding time was not changed but FVIII:C was decreased significantly in all groups. After saline or DDAVP infusion, bleeding time was not changed in group S and group Dl, whereas shortened in group D10 from 107.5+/-11.3 second to 87.5+/-17.5 second (P<0.05). After saline or DDAVP infusion, FVIII:C was decreased in group S and group Dl (P<0.05), but not changed in group D10. CONCLUSIONS: Infusion of DDAVP 3 ug/kg shortens bleeding time and causes an increase of FVIII:C than other groups in rabbits resuscitated from hemorrhagic shock.

Curative Effect of Desmopressin Acetate Combined with Bladder Training Therapy on Primary Nocturnal Enuresis in Children / 实用儿科临床杂志

Objective To observe the curative effect and recurrence rate of desmopressin acetate(DDAVP) combined with bladder training therapy on primary nocturnal enuresis(PNE) in chlidren.Methods One hundred children with PNE were randomly divided into control group and observation group(50 cases in each group).Children in control group were treated with simple DDAVP,and patients in observation group were treated with bladder training while DDAVP was using.The course of treatment were 3 months.The therapeutic effect between the 2 groups when the treatment was finished was compared and then followed up all the cases for 3 months to compare the near-term and long-term recurrence rate between the 2 groups.SPSS 13.0 software was used to analyze the data.Results The total effective rate in control group was 72.9%,and the near-term recurrence rate and the long-term recurrence rate were 22.9% and 54.3%,respectively.The total effective rate in observation group was 91.3%,and the near-term recurrence rate and the long-term recurrence rate were 11.9% and 28.6%,respectively.The total effective rate was significantly higher in observation group than that in control group(Z=-1.972,P=0.049).The near-term recurrence rate in 2 groups had no significant difference(?2=1.632,P=0.201).The long-term recurrence rate was extremely lower in observation group than that in control group(?2=5.249,P=0.022).Conclusions There is significant curative effect that DDAVP combined with bladder training therapy on PNE in children,and it can lower the long-term recurrence rate.