arginine vasopressin (AVP). The aim of this study was to compare the incidence of hypotension within 24 hours based on whether NE or AVP was discontinued first in order to determine the optimal sequence for discontinuation of vasopressors.METHODS: A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Central Register. The primary end-point was incidence of hypotension within 24 hours after discontinuation of the first vasopressor.RESULTS: We identified five studies comprising 930 patients, of whom 631 (67.8%) discontinued NE first and 299 (32.2%) discontinued AVP first. In pooled estimates, a random-effect model showed that discontinuation of NE first was associated with a significant reduction of the incidence of hypotension compared to discontinuing AVP first (31.8% vs. 54.8%; risk ratios, 0.35; 95% confidence interval, 0.16 to 0.76; P = 0.008; I² = 90.7%). Although a substantial degree of heterogeneity existed among the trials, we could not identify the significant source of bias. In addition, there were no significant differences in intensive care unit (ICU) mortality, in-hospital mortality, 28-day mortality, or ICU length of stay between the groups.CONCLUSION: Discontinuing NE prior to AVP was associated with a lower incidence of hypotension in patients recovering from septic shock. However, our results should be interpreted with caution, due to the considerable between-study heterogeneity.]]>
Arginine Vasopressin ; Arginine ; Bias (Epidemiology) ; Consensus ; Hospital Mortality ; Humans ; Hypotension ; Incidence ; Intensive Care Units ; Length of Stay ; Mortality ; Norepinephrine ; Odds Ratio ; Population Characteristics ; Sepsis ; Shock, Septic ; Treatment Outcome ; Vasoconstrictor Agents

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.
Aquaporin 2 ; Arginine Vasopressin ; Body Water ; Cell Membrane ; Diabetes Insipidus, Nephrogenic ; Gene Expression Regulation ; Homeostasis ; Kidney ; Kidney Tubules, Collecting ; Osmolar Concentration ; Permeability ; Phenobarbital ; Receptors, Vasopressin ; Water

OBJECTIVE: To investigate the mechanism by which doublecortin promotes the recovery of cytoskeleton in arginine vasopressin (AVP) neurons in rats with electrical lesions of the pituitary stalk (PEL). METHODS: Thirty-two SD rats were randomized into PEL group with electrical lesions of the pituitary stalk through the floor of the skull base (=25) and sham operation group (=7), and the daily water consumption (DWC), daily urine volume (DUV) and urine specific gravity (USG) of the rats were recorded. Four rats on day 1 and 7 rats on each of days 3, 7 and 14 after PEL as well as the sham-operated rats were sacrificed for detection of the expressions of β-Tubulin (Tuj1), doublecortin and caspase- 3 in the AVP neurons of the supraoptic nucleus using immunofluorescence assay and Western blotting. RESULTS: After PEL, the rats exhibited a typical triphasic pattern of diabetes insipidus, with the postoperative days 1-2 as the phase one, days 3-5 as the phase two, and days 6-14 as the phase three. Immunofluorescent results indicated the repair of the AVP neurons evidenced by significantly increased doublecortin expressions in the AVP neurons following PEL; similarly, the expression of Tuj1 also increased progressively after PEL, reaching the peak level on day 7 after PEL. The apoptotic rates of the AVP neurons exhibited a reverse pattern of variation, peaking on postoperative day 3 followed by progressive reduction till day 14. Western blotting showed that the expressions of c-Jun and p-c-Jun were up-regulated significantly on day 3 ( < 0.05) and 7 ( < 0.01) after PEL, while an upregulated p-JNK expression was detected only on day 3 ( < 0.05), as was consistent with the time-courses of neuronal recovery and apoptosis after PEL. CONCLUSIONS JNK/c-Jun pathway is activated after PEL to induce apoptosis of AVP neurons in the acute phase and to promote the repair of neuronal cytoskeleton by up-regulation of doublecortin and Tuj1 expressions.
Animals ; Apoptosis ; Arginine Vasopressin ; pharmacology ; Cytoskeleton ; metabolism ; MAP Kinase Signaling System ; Neurons ; cytology ; Pituitary Gland ; cytology ; injuries ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Tubulin ; metabolism

PURPOSE: Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V4 Q5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V⁴Q⁵]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V⁴Q⁵]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. MATERIALS AND METHODS: Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V⁴Q⁵]dDAVP, both in vitro and in vivo. RESULTS: In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V⁴Q⁵]dDAVP (0.3 µg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V⁴Q⁵]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC₅₀ 1.08 µM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. CONCLUSION: The present preclinical study establishes for the first time the efficacy of [V⁴Q⁵]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.
Animals ; Arginine Vasopressin ; Capillaries ; Cell Line ; Colon ; Colorectal Neoplasms ; Complement System Proteins ; Drug Therapy ; Endothelial Cells ; Fluorouracil ; Humans ; In Vitro Techniques ; Liver ; Lung ; Membranes ; Mice ; Mice, Nude ; Models, Theoretical ; Neoplasm Metastasis ; Recurrence ; Robenidine ; Spleen ; Vasopressins

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.
Adolescent ; Adult ; Child ; Deamino Arginine Vasopressin ; Female ; Hemostatics ; Humans ; Male ; Middle Aged ; Young Adult ; von Willebrand Diseases ; von Willebrand Factor

PURPOSE: To characterize the course of treatment for nonmonosymptomatic enuresis with overactive bladder (OAB) in a real clinical setting. METHODS: Data from 111 OAB patients with moderate to severe enuresis were analyzed. The baseline analysis included a questionnaire, voiding diary, uroflowmetry with postvoid residual urine measurement, and plain abdominal radiography of the kidneys, ureters, and bladder (KUB). Following standard urotherapy for 1 month, anticholinergic medication was administered with or without laxatives. Desmopressin was added if there was a partial response to OAB. Patients were followed every 3 months to evaluate the status of OAB and enuresis. Multivariate analysis was performed to identify predictors associated with the lack of complete response (CR) in enuresis at 12 months. RESULTS: Following 12 months of treatment, 64% and 88% of patients experienced at least partial response in enuresis and OAB, respectively. Urgency improved more quickly than enuresis, supporting the need to address daytime symptoms before enuresis. Seventy-nine patients (71%) had fecal impaction on KUB and/or subjective constipation. The combination of anticholinergics with either laxatives or desmopressin fared better than anticholinergics alone. Daytime incontinence and anticholinergics-only treatment were associated with a lack of CR during 12 months of treatment. CONCLUSIONS: The data confirmed the validity of addressing OAB before treating enuresis. The results of this study also highlight the need to address fecal impaction. Patients should be counseled about the need for a prolonged course of treatment before starting treatment. Anticholinergics should be accompanied with either desmopressin or laxatives for better control of enuresis.
Cholinergic Antagonists ; Constipation ; Deamino Arginine Vasopressin ; Enuresis* ; Fecal Impaction ; Humans ; Kidney ; Laxatives ; Multivariate Analysis ; Radiography, Abdominal ; Ureter ; Urinary Bladder ; Urinary Bladder, Overactive*

Nocturia causes lack of sleep and excessive daytime somnolence, reducing overall well-being, vitality, productivity, and mental health. Nocturia is significantly associated with testosterone deficiency, lower urinary tract symptoms (LUTS), and sleep disorders. The development of LUTS is commonly associated with testosterone deficiency in elderly men, and recent studies have suggested that testosterone has an ameliorative effect on nocturia. In hypogonadal men with nocturia, a negative feedback cycle can arise, in which testosterone deficiency leads to the development of nocturia, and nocturia contributes to the decline in testosterone levels. Therefore, patients with nocturia should receive appropriate treatment in order to improve their quality of life. Nocturia is generally treated by restricting nighttime water intake, as well as by the administration of medications, such as alpha-1 blockers, anticholinergic drugs, and desmopressin. Testosterone replacement therapy (TRT) is used worldwide as a treatment for many hypogonadal conditions. TRT represents an alternative treatment option for nocturia in hypogonadal men. However, limited information is currently available regarding the effects of TRT on nocturia in hypogonadal men, and further studies are required to reach more definitive conclusions.
Aged ; Deamino Arginine Vasopressin ; Drinking ; Efficiency ; Humans ; Hypogonadism ; Lower Urinary Tract Symptoms ; Male ; Mental Health ; Nocturia* ; Quality of Life ; Sleep Wake Disorders ; Testosterone*

Nocturnal enuresis is a common problem of children during sleeping at preschool or school age. It may affect negatively the psychosocial development of children. Children with enuresis may have lower self-esteem and lower quality of life. There are three main factors of the pathophysiology of enuresis: high nocturnal urine production, nocturnal low bladder capacity or increased detrusor muscle activity, and arousal disorder. As pharmacological therapy for nocturnal enuresis, several medications including desmopressin, anticholinergics, imipramine have been used for a long time. As first-line therapy, desmopressin combined with anticholinergics has good response in primary monosymptomatic nocturnal enuresis. Because imipramine has serious and lethal cardiotoxic effect with overdosage, imipramine should be prescribed after EKG to rule out the conduction problem of heart.
Arousal ; Child ; Cholinergic Antagonists ; Deamino Arginine Vasopressin ; Electrocardiography ; Enuresis ; Heart ; Humans ; Imipramine ; Nocturnal Enuresis* ; Quality of Life ; Urinary Bladder

Behavioral therapy refers to a broad range of treatment modalities that regulate the child's behavior to induce a therapeutic effect on nocturnal enuresis. Simple behavioral therapies include fluid restriction, lifting, waking, introducing reward systems, and bladder training. Simple behavioral therapy is significantly less effective than an enuresis alarm or desmopressin. If a child needs treatment, an enuresis alarm or desmopressin should not be delayed. Enuresis alarms are an effective form of treatment, although they require active involvement of the health care provider to reduce the likelihood of dropout and to motivate the child and parents.
Behavior Therapy ; Child ; Deamino Arginine Vasopressin ; Enuresis* ; Health Personnel ; Humans ; Lifting ; Nocturnal Enuresis ; Parents ; Reward ; Urinary Bladder

A 17-year-old girl presented with polyuria (7 L/day) and polydipsia for one year. Initial urine osmolality was 113mOsm/kg H₂O. Following 6 h of fluid restriction, serum plasma osmolality reached 300mOsm/kg H₂O, whereas urine osmolality was 108mOsm/kg H₂O. Urine osmolality was increased by 427% from 108 to 557mOsm/kg after vasopressin challenge. The patient was diagnosed with central diabetes insipidus, possibly derived from the atypical occupation of a Rathke's cleft cyst at the pituitary stalk following magnetic resonance imaging with enhancement. She was discharged with desmopressin nasal spray (10 µg); urine output was maintained at 2-3 L/day, and urine osmolality was >300 mOsm/kg. Additional pituitary image studies and evaluation of hypopituitarism should be included in the differential diagnosis of patients with central diabetes insipidus.
Adolescent* ; Deamino Arginine Vasopressin ; Diabetes Insipidus, Neurogenic* ; Diagnosis, Differential ; Female* ; Humans ; Hypopituitarism ; Magnetic Resonance Imaging ; Occupations ; Osmolar Concentration ; Pituitary Gland ; Plasma ; Polydipsia ; Polyuria* ; Vasopressins