Search

OBJECTIVE To describe a case of inappropriate antidiuretic hormone (ADH) secretion in a dog secondary to trauma. CASE SUMMARY A 14-year-old neutered female mixed breed dog presented for evaluation of bite wounds. The dog sustained multiple puncture wounds to the cervical area, stifle, and elbow. Treatment was initiated with isotonic crystalloid fluids, analgesia, broad-spectrum antimicrobials, and gastroprotectants. The dog developed hyponatremia with concurrent serum hypoosmolality and inappropriate urine hyperosmolality and urine sodium secretion, leading to a diagnosis of the syndrome of inappropriate ADH secretion. The hyponatremia improved, and the dog improved clinically and was discharged 3 days after admission. NEW OR UNIQUE INFORMATION PROVIDED This is the first case description of the syndrome of inappropriate ADH secretion in a dog suffering from trauma. Inappropriate ADH secretion is largely under-recognized in veterinary patients. Increased awareness of this syndrome can lead to initiation of appropriate treatment and improved outcomes.

We present a case of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with respiratory syncytial virus (RSV) infection. A retrospective analysis of all patients admitted to our hospital with RSV in the preceding 3-year period revealed hyponatraemia in 41 (28%) cases, of which 13 (8.9%) were moderate or severe. SIADH was explored and confirmed in five (3.4%) patients, raising this as an important, previously unrecognised, complication of RSV infection in adults. Physician awareness of SIADH as a potential complication of RSV will facilitate early diagnosis and treatment of this potentially fatal disorder.

BACKGROUND Several studies have demonstrated that non-osmotic antidiuretic hormone activity contributes to the development of hyponatremia in children with common febrile diseases. However the relationship between hyponatremia and body temperature has remained unclear. Therefore, we examined this relationship in children with common diseases. METHODS In this retrospective case study based on chart review, 1,973 children presenting with acute illnesses at Hirakata City Hospital between November 2008 and October 2009, and for whom blood test data were available, were enrolled. The median age of this cohort was 2.7 years and the mean serum sodium concentration was 136.4 mEq/L; 454 patients showed hyponatremia (

The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports.Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by3% was defined as hypervolemia and a decrease in body weight by3% was defined as hypovolemia.The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH.Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.

Hyponatraemia, a water-electrolyte disorder diagnosed in patients with subarachnoid haemorrhage (SAH), increases a risk of persistent vasospasm. In majority of cases, hyponatraemia results from inappropriate secretion of vasopressin (AVP). The effect of AVP-associated hyponatraemia on cerebral vasculature is unknown. The present study aimed to elucidate the role of AVP in the response of the middle cerebral artery (MCA) of the rat to hyponatraemia. Isolated, cannulated, and pressurized rat MCAs were perfused/superfused with physiological (Na+ = 144 mmol/L) buffer or low-sodium (Na+ = 121 mmol/L) buffer containing either AVP or angiotensin II (ANG II). ANG II was used to check if the effect of low plasma sodium concentration combined with AVP on the MCA tone is unique to vasopressin. At physiological Na+ concentration, vasopressin (1.4 × 10-11 mol/L) or angiotensin II (10-9 mol/L) resulted in relaxation of the MCA. Substitution of low-sodium for the normal sodium buffer with the same concentration of AVP, resulted in the constriction of the MCA. This effect was absent after removal of the endothelium, administration of vasopressin V1 receptor antagonist or concomitant inhibition of endothelin-1 receptors and synthesis of thromboxane A2. In contrast, no constriction of the MCA in low-sodium buffer was observed when AVP was replaced with ANG II. Our data suggest that presence of vasopressin and low sodium ion concentration results in the change of endothelium phenotype from pro-vasodilatory to pro-vasoconstrictory. This phenomenon may be an overlooked factor contributing to vasospasm in SAH patients with hyponatraemia caused by inappropriate antidiuretic hormone secretion (SIADH).

Aim Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. Methods Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (>= 2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] >= 90 mL/hour or nocturnal polyuria index [NPi] >= 0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. Results The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP >= 90 mL/hour and 1.96 (0.87-4.42) at NPi >= 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. Conclusions A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP >= 90 mL/hour, with similar odds ratios at NPi >= 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. Patient Summary Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

In a system already preconditioned by previous damage, as results of the cytokine release syndrome complicating the COVID‐19 disease, a small trigger may be sufficient to develop a SIADH complicating a GBS, even without a poor outcome.

Introduction Inappropriate antidiuretic hormone secretion syndrome can be a serious adverse event of cisplatin-based chemotherapy. Cisplatin had to be changed to other drugs or chemotherapy completely discontinued in earlier reported cases. Case presentation Three cycles of bleomycin, etoposide, and cisplatin chemotherapy were planned for a 40-year-old man with a diagnosis of lymph node recurrence of testicular cancer. On day 9, he suffered from vomiting and mental disturbance. Severe hyponatremia (110 mEq/L) with low plasma osmolality led to a diagnosis of a syndrome of inappropriate antidiuretic hormone secretion, and infusions of hypertonic saline and salt intake were prescribed. Second and third courses of bleomycin, etoposide, and cisplatin chemotherapy could then be given with careful electrolyte management. Conclusion Continuation of cisplatin administration with precise electrolyte adjustment can be a treatment option in regimens where cisplatin is essential for achieving optimal antitumor efficacy.

OBJECTIVE To review the pathophysiology, diagnostic approach, and treatment recommendations for hyponatremia in dogs and cats. ETIOLOGY Hyponatremia almost always results from an increase in total body water (TBW), and not from loss of sodium. Abnormalities in antidiuretic hormone (ADH) are commonly part of the etiology of hyponatremia. DIAGNOSIS Diagnosis of hyponatremia focuses on the cause of the increase of TBW. Assessment of the patient's volume status and measurement of urine sodium concentration are important factors. Measurement or calculated estimation of plasma osmolality can also guide the assessment of hyponatremia. THERAPY Too rapid correction of serum sodium can precipitate osmotic demyelination syndrome. As a general rule, serum sodium concentration should be raised ≤10 mmol/L over 24 hours, but rapid increases in serum sodium are indicated if neurologic abnormalities are evident. Serum sodium can be increased using hypertonic saline, with dosing based on the patient's calculated sodium deficit. Treatment of the underlying cause of water ingestion or retention is also required to fully resolve hyponatremia. PROGNOSIS Mortality rates are significantly higher in dogs and cats with hyponatremia compared to those with normal serum sodium concentrations, even in patients with mild hypontremia (

Central diabetes insipidus (CDI) is characterized by hypotonic polyuria due to impairment of AVP secretion from the posterior pituitary. In clinical practice, it needs to be distinguished from renal resistance to the antidiuretic effects of AVP (nephrogenic DI), and abnormalities of thirst appreciation (primary polydipsia). As nephrogenic diabetes insipidus is rare in adults, unless they are treated with lithium salts, the practical challenge is how to differentiate between CDI and clinical disorders of excess thirst. The differential diagnosis is usually straight forward, but the recommended gold standard test, the water deprivation test, is not without interpretative pitfalls. The addition of the measurement of plasma AVP concentrations improves diagnostic accuracy, but the radioimmunoassay for AVP is technically difficult, and is only available in a few specialized centres. More recently, the measurement of plasma copeptin concentrations has been claimed to provide a reliable alternative to measurement of plasma AVP, without the sampling handling challenges. In addition, the measurement of thirst ratings can help the differentiation between CDI and primary polydipsia. Once the diagnosis of CDI is biochemically certain, investigations to determine the cause of AVP deficiency are needed. In this review, we will outline the diagnostic approach to polyuria, revisit the caveats of the water deprivation test and review recent data on value of adding AVP/copeptin measurement. We will also discuss treatment strategies for CDI, with analysis of potential complications of treatment.

Background Gastric cancer ranks as a leading cause of cancer deaths worldwide. Information of prognostic factors related to gastric cancer are limited. Aim This study aimed to gather clinical data and prevalence of prognostic factors related to gastric adenocarcinoma in Thailand. Methods and results This retrospective cohort study was conducted at Thammasat University Hospital, Thailand between January 2010 and July 2018. Gastric adenocarcinoma patients were enrolled and followed up for at least 5 years. Total of 210 gastric tumor patients were enrolled. One hundred patients were diagnosed with gastric adenocarcinomas (57 men and 43 women, mean age = 61.1 years). The leading presenting symptoms were weight loss (65%), followed by dyspepsia (54%) and UGI bleeding. Common clinical manifestations were thrombocytosis (26%), followed by syndrome of inappropriate antidiuretic hormone (SIADH; 15%). Eosinophilia was present in early cancer (25.0% vs 6.5%, P = .123), while SIADH and thrombocytosis were more common in advanced stages (16.3% vs 0%, P = .602, and 28.3% vs 0%, P = .108, respectively). SIADH was significantly related to reduced 1‐year survival rate compared to normal serum sodium levels (21.4% vs 71.4%, OR 0.109, 95% CI 0.024‐0.497, P = .004). Five‐year survival rates were worse in patients with SIADH, but better in patients with eosinophilia compared to patients without these conditions (0% vs 27.8%, P = .058 and 20.0% vs 7.8%, P = .375, respectively). Conclusion Thrombocytosis and SIADH were common in gastric cancer. SIADH was significantly correlated with poor 1‐year survival. These clinical manifestations might be useful for predicting gastric cancer prognosis.

There is fast-emerging, cumulative clinical data on coronavirus disease 2019 (COVID-19) in kidney transplant recipients. Although respiratory tract symptoms are often the initial presentation among kidney transplant recipients who contract COVID-19, other clinical features which may indicate underlying SARS-CoV-2-related inflammation, such as gastrointestinal symptoms, are not uncommon. Hyponatremia can develop and may reflect underlying inflammation. Interferon-6 is an important pro-inflammatory cytokine involved in the pathogenesis of severe COVID-19 complications and may play a role in the inappropriately higher secretion of antidiuretic hormone leading to hyponatremia. This pathway is the so-called immuno-neuroendocrine interface. Hyponatremia in COVID-19 has been reported in a few case series of non-kidney transplant patients and only one reported kidney transplant recipient. However, the clinical course and prognostic value of hyponatremia in this population are not described in detail. We report a kidney transplant recipient who was infected with COVID-19 and exhibited severe hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia is one of the clinical presentations of COVID-19, although less common, and may occur more frequently in kidney transplant recipients. Thus, the possible underlying immuno-neuroendocrine relationship related to the inflammatory process of COVID-19 leading to hyponatremia and its prognostic value are reviewed.

This study aimed to determine the effect of dietary cation and anion difference (DCAD) on milk production and body fluid distribution in lactating dairy goats. Ten dairy goats were selected and divided into two groups, five animals each. Animals received either control DCAD (control, 22.81 mEq/100 g dry matter (DM)) or high DCAD (DCAD, 39.08 mEq/100 g DM). The results indicated that rectal temperature (Tr), respiration rate, milk yield and compositions did not differ between groups. But the percentage change of Tr from the DCAD group was lower than the control group between 09.00 and 13.00 hours. DM intake tended to increase in the DCAD group. Dairy goats in the DCAD group drank more water, but urinary excretion and plasma antidiuretic hormone concentration remained unchanged. Apparent water balance was higher from the DCAD group over 24 h. There was no effect of DCAD on plasma and blood volumes, but tended to increase in extracellular fluid and thereby increased total body water. The present results indicate that animals supplemented with high DCAD increase their total body water and apparent water balance. These results have contributed to the process of adaptation for evaporative cooling and would be useful in slowing down the elevation in Tr.

Hyponatremia is a common electrolyte disorder in cancer patients and has been associated with poor prognosis. A frequent cause of cancer‐related hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH). This study was a post hoc subgroup analysis of the SALT‐1 (Study of Ascending Levels of Tolvaptan in Hyponatremia) and SALT‐2 clinical trials. Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2‐receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once‐daily for 30 days. The initial tolvaptan dose (15 mg) was titrated over 4 days to 30 or 60 mg per day, as needed, according to serum sodium level and tolerability. Baseline serum sodium levels in the SIADH/cancer cohort of the SALT trials was 130 and 128 mEq/L for tolvaptan and placebo, respectively. Mean change from baseline in average daily serum sodium AUC for tolvaptan relative to placebo was 5.0 versus −0.3 mEq/L (P

Hyponatremia is often caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypersecretion of vasopressin from malignant tumors can be considered a cause of SIADH. Most of these ectopic productions of vasopressin are complications of small cell lung cancer. Cases concomitant with ovarian tumors are very rare, and a specific causative substance from the ovary is often unknown. A 16-year-old woman was diagnosed with an ovarian tumor. She developed hyponatremia that was resistant to medical treatment, but immediately improved after surgical resection of the tumor. Her diagnosis was SIADH caused by an ovarian tumor; however, her serum vasopressin level was normal. It is possible that a vasopressin-like substance causing SIADH was secreted by either nervous system tissue within an immature teratoma or small cell lung cancer. We should be cautious when SIADH is a complication of an ovarian tumor.

Deamination of vasopressin (AVP) enhances its antidiuretic activity. Moreover, introduction of D-Arg8 instead of its L enantiomer in deamino-vasopressin (dAVP) results in an extremely potent and selective antidiuretic agonist - desmopressin (dDAVP). In this study we describe the synthesis, pharmacological properties and structures of these two potent antidiuretic agonists, and their inverso analogs. The structures of the peptides are studied in micellar and liposomic models of cell membrane using CD spectroscopy. Additionally, three-dimensional structures in mixed anionic-zwitterionic micelles are obtained using NMR spectroscopy supported by molecular dynamics simulations. Our conformational studies have shown that desmopressin in a membrane mimicking environment adopts one of the characteristic for vasopressin-like peptides β-turn - in position 3,4. Furthermore, dDAVP shows the tendency to create a β-turn in the Cys6-Gly9 C-tail, considered to be important for the antidiuretic activity, and also some tendency to adopt a 5,6 β-turn. In desmopressin, in contrast to the native vasopressin, deamino-vasopressin and [D-Arg8]-vasopressin (DAVP), the Arg8 side chain, crucial for the pressor and antidiuretic activities, is very well exposed for interaction with the receptor, whereas Gly9, crucial for the pressor and uterotonic activities, is situated together with the C-terminal amide group very close to the tocin ring. The arrangements of the Gln4 and Asn5 side chains, being crucial for OT activity, also differ in desmopressin as compared to those of AVP, dAVP and DAVP. These differences in arrangement of the important for activities side chains are likely to explain extremely potent and selective antidiuretic activities of desmopressin. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 245-259, 2016.

AIM: Using fluid restriction to treat syndrome of inappropriate antidiuretic hormone secretion (SIADH) in infants is potentially hazardous, as fluid and caloric intake are connected. Antagonists for the type 2 vasopressin receptor have demonstrated efficacy in adult patients with SIADH, but evidence in children is lacking. We reviewed our experience from two cases in the UK. METHODS: This was a retrospective review of the clinical data on two patients diagnosed with SIADH in infancy and treated with tolvaptan, an oral vasopressin receptor antagonist. RESULTS: Persistent hyponatraemia was noted in both patients in the first month of life and eventually led to SIADH diagnoses. Initial salt supplementation in one patient resulted in severe hypertension, treated with four anti-hypertensive drugs. Tolvaptan was commenced at two and four months of age, respectively, and was associated with normalisation of plasma sodium values and blood pressure without the need for anti-hypertensive treatment. There was transient hypernatraemia in one patient, which was normalised with a dose reduction. Tolvaptan was administered by crushing the tablet and mixing it with water. CONCLUSION: Tolvaptan provided effective treatment for SIADH in both infants and could be administered orally.

The syndrome of inappropriate antidiuretic hormone (SIADH) is reported as the most common cause of hyponatraemia. This retrospective cross-sectional study evaluated the diagnosis of SIADH in 110 hospitalised patients in an Australian tertiary hospital with reference to recently published clinical guidelines. Investigation of SIADH was incomplete in all but 20% of cases. Adrenal insufficiency and hypothyroidism were not excluded in a significant number of cases.

The syndrome of inappropriate antidiuretic hormone (SIADH) consists of a number of key features, namely hyponatraemia, inappropriate urinary concentration and clinical euvolaemia or hypervolaemia. It is caused by inappropriate secretion of the antidiuretic hormone (ADH), which activates the vasopressin type 2 receptor (AVPR2) in the principal cells of the collecting duct of the kidney and leads to increased reabsorption of water through aquaporin 2 channels. Common causes of SIADH in children include trauma, asphyxia, pain, stress, certain drugs and recent neurosurgery (1).

Desmopressin is frequently used in patients with bleeding disorders because of its prohaemostatic effects. In recent years desmopressin use increased due to reported high incidence of inhibitors in mild haemophilia after clotting factor infusion and the rising costs of clotting factor concentrates. The safety and frequency of side effects have hardly been assessed in well-designed studies.We therefore prospectively evaluated side effects of desmopressin in a large unselected cohort of bleeding disorder patients, who received a desmopressin test dose.Blood was drawn prior to, one, three, six and 24 h after desmopressin. Primary outcome was change in serum sodium, haematocrit, serum- and urine osmolality, body weight and vital signs. Self-reported side effects were evaluated as secondary outcome.In total, 108 patients were included, median age 30 years, the majority of whom had von Willebrand disease type 1 (76%). A significant change in water balance parameters was observed. Four patients (4%) had hyponatraemia (≤135 mmol L(-1) ) after 24 h but no severe hyponatraemia occurred (≤125 mmol L(-1) ). After infusion, 41 (38%) patients were hypotensive (≤90 mmHg SBP and/or ≤60 mmHg DBP) and 10 (9%) presented with tachycardia (100 min(-1) ). However, none of these effects sustained at 24 h. Infusion was discontinued in one patient because of tachycardia, nausea and malaise. Self-reported side effects included: headache, fatigue, flush and dizziness.Observed side effects correspond with the known antidiuretic and vasomotor effects of desmopressin. Changes in parameters were temporary and not clinically relevant. In conclusion, our study supports desmopressin use as a safe treatment option in patients with various bleeding disorders.

To study the effect of tolvaptan on non-acute, non-hypovolemic hyponatremia in inappropriate secretion of antidiuretic hormone (SIADH) syndrome in Chinese patients. Hyponatremic SIADH patients received placebo (N = 18) or tolvaptan (N = 19) at an initial dose of 15 mg/day with further titration to 30 mg/day and 60 mg/day based on serum sodium concentrations. Randomized, double-blind, placebo-controlled trial. Primary endpoint was the change of the serum sodium from baseline to days 4 and 7. Analysis of covariance (ANCOVA) was used for statistical analysis. At day 4, average daily changes in serum sodium levels from baseline was 1.9 ± 2.9 mmol/L (1.9 ± 2.9 mEq/L) in the placebo group and 8.1 ± 3.6 mmol/L (8.1 ± 3.6 mEq/L) in the tolvaptan group; at day 7, the values were 2.5 ± 3.9 mmol/L (2.5 ± 3.9 mEq/L) and 8.6 ± 3.9 mmol/L (8.6 ± 3.9 mmEq/L) for the placebo and tolvaptan groups (ANCOVA, P

Key Clinical Message Diabetes insipidus (DI) arises from impaired function of antidiuretic hormone, characterized by hypovolemia, hypernatremia, polyuria, and polydipsia. This case is a reminder of the rare but challenging obstacle that undiagnosed DI poses in fasting surgical patients, requiring prompt recognition and vigilant management of marked homeostatic imbalances.

Objective Various studies have shown that a number of infectious disease causes syndrome of inappropriate antidiuretic hormone (SIADH). However, the relationship between infectious disease and SIADH is not yet fully known. In this prospective study, we aimed to assess the presence of SIADH in patients with brucellosis. Patients and methods Thirty-five patients with acute brucellosis were retrospectively reviewed. The diagnosis of brucellosis was performed using the Wright test in connection with blood culture. SIADH was defined by euvolemic hyponatremia (serum sodium level lower than 135 mEq/l) with increased urinary sodium excretion (urinary sodium higher than 40 mmol/l). Results Of the 35 patients, 19 (54%) had SIADH; 20 (57%) also had hypouricemia (uric acid level lower than 4 mg/dl). Additionally, all of the studied patients had a high mean urinary sodium excretion rate (mean 132 mmol/l; range 40–224). Most importantly, the hyponatremic patients were more likely to have a lower albumin level (P < 0.01). Conclusions SIADH is a major complication of brucellosis. The presence of SIADH could be a diagnostic tool for diagnosing brucellosis. Further larger randomized studies may confirm these findings.

Strategies to manage nocturia include lifestyle modifications and treatment with alpha-blockers, antimuscarinic therapies, and antidiuretics. The concept of achieving success should not be limited to reduction of nighttime voids; it should ideally include proof of improvement of conditions generally associated with nocturia, such as falls, quality of life, and overall health. Few studies have looked specifically at parameters other than nocturnal voids, such as sleep latency, first undisturbed sleep period (FUSP), and total sleep time, including their clinical relevance to patient well-being. Lifestyle modifications, such as voiding before bedtime, limiting caffeine and alcohol, and adjusting medication timing, may be initially effective in mild cases of nocturia. Statistically significant reductions in voiding have been reported with antimuscarinic agents and alpha-blockers as initial therapy, but these reductions generally are not clinically relevant. The antidiuretic therapy desmopressin acetate, a selective vasopressin receptor 2 agonist, is effective in adults with nocturia associated with nocturnal polyuria; however, hyponatremia can occur. The newest formulation-desmopressin orally disintegrating sublingual tablet (ODST)--has greater bioavailability; thus, lower doses can be used, potentially reducing hyponatremia risk. A phase 3 study demonstrated statistically significant reductions in nocturnal voids for desmopressin ODST 50 and 100 µg versus placebo (-1.18 and -1.43 vs. -0.86; P = 0.02 and P < 0.0001, respectively) in patients with nocturia. Treatment was well-tolerated, and low-dose desmopressin ODST was associated with statistically significant increases in duration of FUSP. Development of a validated composite endpoint may help clinicians identify and compare strategies for treating nocturia.

Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion, sex, and advanced age affect urine formation and may contribute to nocturia. Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting duct. Changes in AVP concentration have the greatest relative effects on urine volume when AVP levels are low; therefore small changes can have a large effect on renal water excretion. AVP is the major regulator of water excretion by the kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of several studies show that patients with nocturia had no significant variation in plasma AVP, whereas patients without nocturia had significant diurnal variation in plasma AVP. The V2 receptor gene is located on the X chromosome, which has important sex-specific consequences. For example, mutations in the V2 gene can cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes in water metabolism are associated with overall body composition, kidney, and brain. Older people generally experience decreased extracellular fluid and plasma volume, which leads to increased adverse consequences from net body water gain or loss. Renal function declines with age, and the ability to concentrate urine and conserve sodium is reduced in the elderly. Thirst perception is also decreased in the elderly, who, compared with younger people, tend to hypersecrete AVP in response to higher plasma osmolality, possibly resulting in hyponatremia. These aspects of renal physiology should be considered when antidiuretic drugs are prescribed for the treatment of nocturia. Neurourol. Urodynam. 33:S6–S9, 2014. © 2014 Wiley Periodicals, Inc.

Acute intermittent porphyria (AIP) is an autosomal dominant metabolic disorder caused by deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase (approved gene symbol HMBS), also known as porphobilinogen deaminase (PBGD). AIP is characterised by intermittent attacks of abdominal pain, vomiting, and neurological complaints. The highly variable symptomatic presentation of AIP causes confusion with other diseases and results in a high misdiagnosis rate (68% in China) and delayed effective treatments. Based on biochemical and genetic analysis of two Chinese families, a new and a previously reported HMBS mutation were identified in patients with AIP and syndrome of inappropriate antidiuretic hormone (SIADH). The novel HMBS mutation is the 655G>C point mutation (A219P). In addition, the 973C>T point mutation (R325X), which had been previously reported in two Danish families, was identified.

Bleeding disorders, including haemophilia, von Willebrand disease, and platelet function abnormalities pose a substantial, ongoing management challenge. Patients with these disorders not only require treatment during bleeding events but also need effective management strategies to prepare for events ranging from minor dental procedures to major surgery and childbirth. Moreover, women with bleeding disorders often require ongoing treatment to prevent menorrhagia during childbearing years. Desmopressin (DDAVP), a synthetic derivative of the antidiuretic hormone l-arginine vasopressin, has become a well-established tool for the management of patients with bleeding disorders in a variety of clinical settings. However, despite the widespread use of DDAVP, the available clinical evidence on its efficacy and safety in these settings is limited, and there has not been a recent comprehensive review of its role in the clinical management of patients with bleeding disorders. As such, this article provides a review of the mechanism of action and pharmacokinetic properties of DDAVP, followed by a concise summary of the available evidence for its use in the treatment and prevention of bleeding.

Vasopressin and nonmammalian hormone vasotocin are known to increase the water permeability of mammalian collecting ducts, frog skin and the urinary bladder. Neurohypophysial nonapeptides have also been shown to interfere with the regulation of renal ion transport. The subject of this study was a search for vasopressin and vasotocin analogues with selective effects on renal water, sodium and potassium excretion. During this study, we synthesised the following peptides: 13 vasotocin analogues modified at positions 4 (Thr or Arg), 7 (Gly or Leu) and 8 (D-Arg, Lys or Glu); 4 vasopressin analogues modified at positions 4 and 8; and 9 peptides shortened or extended at the C-terminal or with substitutions for Gly-NH2. Most of these peptides had mercaptopropionic acid (Mpa) instead of Cys in position 1. The effects of these nonapeptides on renal water, sodium and potassium transport were evaluated in in vivo experiments using Wistar rats. Some nonapeptides possessed antidiuretic, natriuretic and kaliuretic activities ([Mpa(1)]-arginine vasotocin, [Mpa(1), homoArg(8)]-vasotocin, [Mpa(1), Thr(4)]-arginine vasotocin and [Mpa(1), Arg(4)]-arginine vasopressin). Substitutions at positions 4 and 8 increased the selectivity of peptide actions. The antidiuretic [D-Arg(8)]-vasotocin analogues had no effects on sodium excretion. [Mpa(1), Arg(4)]-arginine vasotocin was antidiuretic and kaliuretic but not natriuretic. [Mpa(1), Glu(8)]-oxytocin had weak natriuretic activity without any effects on water and potassium transport. In accordance with the data obtained, synthesised vasotocin analogues could be good candidates for pharmaceuticals selectively regulating renal sodium and potassium transport, which is of clinical importance.

What's known on the subject? and What does the study add? Antichollnergic agents are anticipated to diminish storage symptoms, as well as nocturia. Nevertheless, the effect of this treatment on polyuria related to nocturia is not clear. By subgroup analysis of the data set from a phase III clinical trial of antimuscarinic agent for OAB patients in Japan, imidafenacin was found to improve nocturia with a reduction in nocturnal polyuria. This study adds the effects and underlying mechanism of antimuscarinic agents decreasing urine production through inhibition of C-fibre in the bladder of water-leaded rats. Objective To evaluate the effects and underlying mechanisms of antimuscarinic agents used to decrease in urine production in water-loaded rats. Subjects and Methods Urine production was measured using a cystostomy catheter in female Sprague–Dawley rats every 2 h. The effect of the antimuscarinic agents atropine, tolterodine and imidafenacin on urine production was investigated under water-loaded conditions, which were induced by i.p. injection of 15 mL saline. Blood samples were collected to determine the levels of antidiuretic hormone (ADH), aldosterone (ALD), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) before, and 2 and 8 h after, antimuscarinic agent administration. To induce desensitization of C-fibre afferent nerves, resiniferatoxin (RTX)was injected s.c. or intravesically 2 days before experiments. Results Urine production increased and reached its maximum 2 h after 15 mL saline injection. Imidafenacin and tolterodine decreased urine production in water-loaded rats, but ADH, ALD, ANP and BNP levels were not different between imidafenacin-treated and vehicle-treated rats. The inhibitory effect on urine production was not found in RTX-treated rats. Atropine did not reduce urine production. Conclusion These results suggest that antimuscarinic agents decrease urine volume through C-fibres in the bladder; thus, antimuscarinics with inhibitory effects on C-fibres could be beneficial for nocturia with nocturnal polyuria.

In this study, we present the synthesis and pharmacological properties of new analogues of arginine vasopressin modified in the N-terminal part of the molecule with proline derivatives: indoline-2-carboxylic acid (Ica) and (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid. All the peptides were tested for pressor, antidiuretic and in vitro uterotonic activities. We also determined their binding affinity to the human oxytocin receptor. The Ica(2) substitution resulted in two moderately potent and selective antioxytocic agents: [Mpa(1), Ica(2), D-Arg(8)]VP and [Mpa(1),Ica(2),Val(4),D-Arg(8)]VP (pA(2) = 7.09 and 7.50, respectively). On the other hand, peptides modified with (2S,4R)-4-(naphthalene-2-ylmethyl)pyrrolidine-2-carboxylic acid, apart from their moderate antioxytocic activity, turned out to be weak antagonists of the pressor response to arginine vasopressin. The results of this study provide useful information about the structure-activity relationship of arginine vasopressin analogues and can help to design compounds with desired biological properties.

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo-SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus-6-associated post-transplantation acute limbic encephalitis (HHV-6 PALE) after allo-SCT. A 45-year-old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus-mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of serum sodium levels in high-risk patients for HHV-6 PALE is necessary for immediate diagnosis and treatment initiation.

Context Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), resulting from activating mutations in the arginine vasopressin receptor type 2 (AVPR2), is a rare cause of hyponatraemia. However, its true prevalence may be underestimated and it should be considered in the investigation of unexplained hyponatraemia, with implications for management and targeted gene testing. Objective We describe a structured approach to the investigation of hyponatraemia in a young patient, which allowed a diagnosis of NSIAD to be made. We review current knowledge of NSIAD and use a structural modelling approach to further our understanding of the potential mechanisms by which the causative mutation leads to a constitutively active AVPR2. Design Clinical and biochemical investigation of hyponatraemia; a formal water load test with measurement of arginine vasopressin levels (AVP); sequencing of AVPR2; and computed structural modelling of the wild-type and constitutively activated mutant receptors. Results A 38-year-old man presented with intermittent confusion and nausea associated with hyponatraemia and a biochemical picture consistent with syndrome of inappropriate antidiuretic hormone (SIADH). Adrenocortical and thyroid function and an acute intermittent porphyria screen were normal. Cross-sectional imaging of the head, chest and abdomen did not identify an underlying cause and so we proceeded to a water load test. This demonstrated a marked inability to excrete a free water load (just 15% of a 20 ml/kg oral load by 240 min postingestion), with the onset of hyponatraemia (Na(+) 125 mmol/l, urine osmolality 808 mOsm/kg). However, AVP levels were low throughout the test (0·4-0·9 pmol/l), consistent with a diagnosis of NSIAD. AVPR2 sequencing revealed a previously described hemizygous activating mutation (p.Arg137Cys). Through structural modelling of AVPR2, we suggest that disruption of a hydrogen bond between residues Thr269 and Arg137 may promote stabilization of the receptor in its active conformation. Since diagnosis, the patient has adhered to modest fluid restriction and remained well, with no further episodes of hyponatraemia. Conclusion NSIAD should be considered in young patients with unexplained hyponatraemia. A water load test with AVP measurement is a potentially informative investigation, while AVPR2 sequencing provides a definitive molecular genetic diagnosis and a rationale for long-term fluid restriction.

In this paper, we investigated the structure-activity relationship of two vasopressin analogues, [Cpa(1),(L-1-Nal)(2) ]AVP (I) and [Cpa(1),(D-Nal)(2) ]AVP (II) by NMR spectroscopy and molecular modeling. Both peptides exhibit antioxytocic and antipressor potency. Inversion of configuration of the residue at position 2 converted a weak antidiuretic agonist (peptide I) into a highly potent antidiuretic antagonist (peptide II). For this reason, the purpose of our study was to explain the causes of different interactions of the analogues with V(2) receptors. The results have shown that both analogues display the tendency to adopt β-turns in the 1-4 and 2-5 fragments, which is characteristic of OT and V(1a) receptors antagonists. In addition, the [Cpa(1),(L-1-Nal)(2) ]AVP (I) shows the propensity to assume β-turn at position 7,8, which is believed to enhance antidiuretic activity, although not being crucial for its appearance. Moreover, the C-terminal amide group seems to be crucial for signal transduction. Its high accessibility in [Cpa(1),(L-1-Nal)(2) ]AVP (I) in contrast to [Cpa(1),(D-1-Nal)(2) ]AVP (II), probably results in V(2) receptor activation.

Summary Central diabetes insipidus (DI) was diagnosed in a 20-year-old American Quarter Horse gelding that was concomitantly affected with pituitary pars intermedia dysfunction (PPID). The diagnosis of DI was supported by a positive response to administered desmopressin acetate. Diagnosis of PPID was supported by physical appearance and elevated plasma adrenocorticotropic hormone concentration following domperidone administration. The horse's physical condition improved following treatment with pergolide but long-term treatment with desmopressin was not undertaken and severe polyuria and polydipsia persisted. Desmopressin acetate appears to be useful for the diagnosis of DI in mature horses concomitantly affected with PPID.

Hyponatremia is the main complication of inappropriate antidiuretic hormone secretion (SIADH), sometimes fatal. Treatment strategy depends on the cause and the severity of the hyponatremia. Recent studies have shown the efficacy of urea in treating acute hyponatremia secondary to SIADH, by inducing an osmotic water drive. We describe an infant with chronic hyponatremia secondary to SIADH in which the long-term oral treatment with urea was successful and well tolerated. The aim of this paper is to highlight the potential benefits of urea treatment in case of chronic hyponatremia secondary to SIADH.

OBJECTIVE • To evaluate the statistical and clinical efficacy of the pharmacological treatments of nocturia using non-antidiuretic agents. PATIENTS AND METHODS • A literature review of treatments of nocturia specifically addressing the impact of alpha blockers, 5-alpha reductase inhibitors (5ARI) and antimuscarinics on reduction in nocturnal voids. RESULTS • Despite commonly reported statistically significant results, nocturia has shown a poor clinical response to traditional therapies for benign prostatic hyperplasia including alpha blockers and 5ARI. • Similarly, nocturia has shown a poor clinical response to traditional therapies for overactive bladder including antimuscarinics. CONCLUSIONS • Statistical success has been achieved in some groups with a variety of alpha blockers and antimuscarinic agents, but the clinical significance of these changes is doubtful. • It is likely that other types of therapy will need to be employed in order to achieve a clinically significant reduction in nocturia.

Intravenous infusion of angiotensin II ([Asn¹ Val⁵]-Ang II) at 10⁻⁹ mol min⁻¹ kg⁻¹ body mass produced a significant antidiuresis in river lamprey Lampetra fluviatilis, captured during upstream migration and maintained in fresh water. Although the renin-angiotensin hormonal system (RAS) is now recognized in jawless fishes, until this study, the role of homologous Ang II in L. fluviatilis kidney function had not been examined. This study provides the first evidence for an antidiuretic action of Ang II in cyclostomes and, in evolutionary terms, suggests a renal function for the RAS in early vertebrates.

Hyponatremia is independently associated with adverse outcomes in patients with congestive heart failure (CHF). The primary cause of hyponatremia in CHF is the inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). The binding of AVP to V(2) receptors in the renal collecting duct promotes water retention, a process that can lead to dilutional hyponatremia as well as increased ventricular preload. Conventional treatment of hyponatremia in CHF is largely based on water restriction, which is neither effective nor well-tolerated. V(2)- and dual V(1a)/V(2)-receptor antagonists offer physiologically based treatment for dilutional hyponatremia. Clinical trials in patients with hyponatremia including those with CHF using both selective and nonselective vasopressin antagonists have demonstrated the effectiveness and safety of these agents in correcting this common electrolyte abnormality.

Arginine vasopressin (AVP or antidiuretic hormone) is one of the key hormones in the human body responsible for a variety of cardiovascular and renal functions. It has so far escaped introduction into the routine clinical laboratory due to technical difficulties and preanalytical errors. Copeptin, the C-terminal part of the AVP precursor peptide, was found to be a stable and sensitive surrogate marker for AVP release. Copeptin behaves in a similar manner to mature AVP in the circulation, with respect to osmotic stimuli and hypotension. During the past years, copeptin measurement has been shown to be of interest in a variety of clinical indications, including cardiovascular diseases such as heart failure, myocardial infarction, and stroke. This review summarizes the recent progress on the diagnostic use of copeptin in cardiovascular and renal diseases and discusses the potential use of copeptin measurement in the context of therapeutic interventions with vasopressin receptor antagonists.

BACKGROUND Blood loss is an important issue for patients with rheumatoid arthritis undergoing hip surgery. We hypothesised that intraoperative desmopressin treatment would result in a reduction in blood loss in rheumatoid patients undergoing total hip arthroplasty. METHODS Seventy-five patients scheduled for elective total hip arthroplasty were randomised to three groups to receive 0.4 microg/kg desmopressin (D 0.4), 0.2 microg/kg desmopressin (D 0.2) or placebo intraoperatively in a double-blind fashion. Blood transfusions were based on calculated safe allowable blood loss and haemoglobin measurements (trigger 90 g/l, 5.59 mmol/l). The primary endpoint was the total blood loss measured till the end of the fourth post-operative day. Secondary endpoints included red cell transfusion requirements and haemoglobin. RESULTS Total blood loss during the study period was not significantly different between the groups (D 0.4 1829 +/- 1068; D 0.2 2240 +/- 843 and placebo 2254 +/- 1040 ml; P= 0.50). The total amount of red cell transfusions was fewer in group D 0.4 (3.6 +/- 1.6 U) when compared with D 0.2 (4.4 +/- 1.7 U; P=0.009) and placebo (4.5 +/- 2.0 U; P= 0.011) groups. Haemoglobin concentration was lower in the placebo group in the first (5.42 +/- 1.16 vs. 5.98 +/- 0.47 mmol/l; P=0.033) and the second (6.28 +/- 0.66 vs. 6.69 +/- 0.47 mmol/l; P=0.033) post-operative mornings compared with group D 0.4. CONCLUSION Despite a lack of difference in the primary outcome, total blood loss, intraoperative administration of 0.4 microg/kg desmopressin resulted in fewer total red cell transfusion requirements in rheumatoid patients undergoing total hip arthroplasty when compared with 0.2 microg/kg treatment and placebo.

Summary Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 C. The other samples were incubated for 30 min and measured at 32 C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Background Hyponatremia is a common metabolic disorder in cancer patients. However, little information is available for patients receiving chemotherapy or stem cell transplantation (SCT). We analyzed the frequency, characteristics, and various causes of hyponatremia including routine use of hypotonic fluids in children following chemotherapy or SCT. Procedure We reviewed the clinical and laboratory data of 63 children who received chemotherapy or SCT at the Department of Pediatrics, Hanyang University Medical Center from July 2005 to July 2008. Results All 63 patients at admission received routine parenteral fluids of 0.25% or 0.45% NaCl and 82 episodes of hyponatremia were observed in 40 (63.5%) patients. Of these 82 episodes, 50 episodes of hyponatremia developed in 29 children following chemotherapy and 32 episodes in 16 children following SCT. Seventy-six out of 82 episodes (92.7%) of hyponatremia developed in 37 patients receiving hypotonic fluids with NaCl concentrations between 30 and 150 mEq/L. The frequency of SIADH in the SCT setting was more frequent (14/21, 66.6%) than in the chemotherapy setting (18/58, 31.0%) (P = 0.02), even though the leading cause of hyponatremia was SIADH in both settings. Conclusions SIADH is a leading cause of hyponatremia in children following chemotherapy or SCT, and more frequent in SCT settings than in chemotherapy settings. Furthermore, the routine use of hypotonic fluids which could aggravate the development of hyponatremia for these patients should be avoided and then switched to isotonic fluids. Pediatr Blood Cancer 2010;54:734–737. © 2010 Wiley-Liss, Inc.

Aim The chronic fatigue syndrome is associated with alterations in the hypothalamus-pituitary-adrenal axis and cardiovascular autonomic nervous activity, suggesting a central dysregulation. This study explored differences among adolescent chronic fatigue syndrome patients and healthy controls regarding antidiuretic hormone, the renin-angiotensin-aldosterone-system, sex hormones and cardiac peptides. Methods We included a consecutive sample of 67 adolescents aged 12-18 years with chronic fatigue syndrome diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 55 healthy control subjects of equal gender and age distribution. Hormones were assayed with standard laboratory methods. Results Among patients, plasma antidiuretic hormone was significantly decreased and serum osmolality and plasma renin activity were significantly increased (p Conclusion Chronic fatigue syndrome in adolescents is associated with alterations in hormonal systems controlling osmolality and blood volume, possibly supporting a theory of central dysregulation.

Continuing our efforts to obtain potent and selective analogues of AVP we synthesized and pharmacologically evaluated ten new compounds modified at position 2 with α-2-indanylglycine or its D-enantiomer (Igl or D-Igl, respectively). All the peptides were tested for pressor, antidiuretic, and in vitro uterotonic activities. We also determined the binding affinity of these compounds to human OT receptor. The Igl2 substitution resulted in a significant change of the pharmacological profile of the peptides. The new analogues were moderate or potent OT antagonists (pA2 values ranging from 7.19 to 7.98) and practically did not interact with V1a and V2 receptors. It is worth emphasizing that these new peptides were exceptionally selective. On the other hand, the D-Igl2 substituted counterparts turned out to be weak antagonists of the pressor response to AVP and displayed no antidiuretic activity. Some of the results were unexpected, e.g. dual activity in the rat uterotonic test in vitro: the D-Igl peptides showed a strong antioxytocic potency (pA2 values ranging from 7.70 to 8.20) at low concentrations and full agonism at high concentrations. The results provided useful information about the SAR of AVP analogues. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.

The aim of the present study was to elucidate the mechanism by which ketone bodies increase antidiuretic hormone (ADH) secretion. Four male Holstein calves (5 weeks of age) were utilized. Four levels of butyrate (0 g, 11 g, 22 g and 44 g) were administrated intra-ruminally in a 4 x 4 Latin square design and cerebrospinal fluid (CSF, six-position lumbar puncture), blood plasma and urine were collected. The concentration of total plasma and CSF protein was 5.5-5.6 g/dL and 27.5-28.3 mg/dL, respectively. CSF concentrations of a specific ketone body, 3-hydroxybutyric acid, were significantly higher in the 22 g and 44 g butyrate groups than in the control group. CSF concentrations of ADH in the 11 g and 44 g butyrate groups were significantly higher than in the control group. Plasma concentration of 3-hydroxybutyric acid was increased by intraruminal administration of butyrate within 15 min in a dose-dependent manner, and it was higher in the 22 g and 44 g butyrate group than in the control group from 15 min to 4 h. With the exception of the 11 g butyrate group, plasma concentrations of ADH also increased in response to butyrate treatment, and it was higher in the 44 g butyrate group than in the 22 g butyrate group from 15 min to 1.5 h. The duration of the elevated plasma concentrations of ADH was shorter than that of the plasma concentration of 3-hydroxybutyric acid. The relationship between the plasma concentrations of ADH and 3-hydroxybutyric acid was statistically significant but the correlation between the two concentrations was not high. Butyrate treatment elevated the plasma concentration of ADH and also resulted in reduced urine volume and increased urine osmolality. Haematocrit (Ht) values, and the osmolality of CSF and plasma were not different among the groups. Our results suggested that the increased ADH secretion observed in suckling calves fed dry feeds was caused by butyrate-derived ketone body that crossed the blood-brain barrier rapidly.

Dehydration increases vasopressin (antidiuretic hormone) secretion from the posterior pituitary gland to reduce water loss in the urine. Vasopressin secretion is determined by action potential firing in vasopressin neurones, which can exhibit continuous, phasic (alternating periods of activity and silence), or irregular activity. Autocrine κ-opioid inhibition contributes to the generation of activity patterning of vasopressin neurones under basal conditions and so we used in vivo extracellular single unit recording to test the hypothesis that changes in autocrine κ-opioid inhibition drive changes in activity patterning of vasopressin neurones during dehydration. Dehydration increased the firing rate of rat vasopressin neurones displaying continuous activity (from 7.1 ± 0.5 to 9.0 ± 0.6 spikes s−1) and phasic activity (from 4.2 ± 0.7 to 7.8 ± 0.9 spikes s−1), but not those displaying irregular activity. The dehydration-induced increase in phasic activity was via an increase in intraburst firing rate. The selective κ-opioid receptor antagonist nor-binaltorphimine increased the firing rate of phasic neurones in non-dehydrated rats (from 3.4 ± 0.8 to 5.3 ± 0.6 spikes s−1) and dehydrated rats (from 6.4 ± 0.5 to 9.1 ± 1.2 spikes s−1), indicating that κ-opioid feedback inhibition of phasic bursts is maintained during dehydration. In a separate series of experiments, prodynorphin mRNA expression was increased in vasopressin neurones of hyperosmotic rats, compared to hypo-osmotic rats. Hence, it appears that dynorphin expression in vasopressin neurones undergoes dynamic changes in proportion to the required secretion of vasopressin so that, even under stimulated conditions, autocrine feedback inhibition of vasopressin neurones prevents over-excitation.

The roles of two antidiuretic hormone analogues, namely arginine vasotocin (AVT) and lysine vasopressin (LVP), in solute transport across the ventral abdominal skin of frogs (Rana hexadactyla) were studied using voltage-clamp methods on intact and nystatin-permeabilized preparations. Arginine vasotocin (40 nm), the amphibian analogue of antidiuretic hormone, did not have any effect on the skin of Rana hexadactyla. However, LVP, the porcine antidiuretic hormone, increased the transepithelial potential difference (TEPD) and short-circuit current (SCC) significantly, without affecting the slope conductance. Lysine vasopressin had no action subsequent to addition of amiloride (100 microm) on the apical side or ouabain (10 microm) on the basolateral side. Lysine vasopressin increased slope conductance in the nystatin-permeablized skin while decreasing TEPD. Such a change was not seen in chloride-free solutions. To elucidate the mechanism of action of LVP on intact skin, experiments were done with forskolin and a V(2) receptor blocker. The effects of forskolin (10 microm) were different from those of LVP in that forskolin significantly increased SCC and conductance of the intact skin, while decreasing TEPD. The forskolin-induced increase in conductance was not abolished by amiloride. Use of the V(2) receptor blocker inhibited the effects of LVP. We conclude that AVT does not have an action on the skin of Rana hexadactyla. Lysine vasopressin enhances transepithelial sodium transport by increasing sodium-potassium pump activity, while not affecting the epithelial sodium channel conductance. Lysine vasopressin also enhances an inward-directed conductance on the basolateral membrane, probably a chloride conductance. The action of LVP on the intact frog skin is through the V(2) receptors; however, downstream signalling does not seem to be mediated by cAMP. Analysis of the electrophysiological model of frog skin with LVP allows us additionally to conclude that modulation of channel activity and not carrier-mediated transport affects slope conductance.

Background and Methods Unusual water intake and drinking behaviour has occasionally been observed in individuals with Prader–Willi syndrome (PWS). The aim of this study is to explore whether this observation is a part of the PWS phenotype and what the consequences may be. The parents of 51 individuals with PWS (age range 2–40 years) were asked by questionnaire to answer on past and present water intake, drinking behaviour, fluid preferences and medical treatment in their PWS-affected and unaffected children. Questionnaires with information on 47 PWS individuals and 17 without PWS were returned for analysis. The questionnaire information was complemented with information from the individual's medical records. Siblings to PWS individuals made up the control group. The study was approved by the regional medical research ethics committee. Results During infancy, 36 (76%) individuals with PWS disliked water without any flavouring and had an extremely small daily intake of water. Seven individuals (15%) increased the daily water intake to unusually high amounts. In 45 the clinical PWS diagnosis was confirmed by molecular (genetic) testing: nine of them with a confirmed PWS diagnosis had a deletion of chromosome 15q11-13, in nine individuals no deletion was identified. The majority of individuals who increased their water consumption to extreme values belonged to the non-deletion group. Two in the non-deletion group developed hyponatraemia while receiving psychiatric medication. Conclusions Infants with PWS seem to be predisposed to unusual drinking behaviour. They dislike and have an unusually small intake of pure water without flavouring, and most of them continue this even after infancy. Some individuals, especially those without deletion, increase their fluid intake and also accept pure water. They have an increased risk of developing water retention and severe hyponatraemia if exposed to medication known to cause side effects like the syndrome of inappropriate antidiuretic hormone secretion. Perhaps this behaviour is just secondary to overeating; perhaps it is a result of a dysfunction of the hypothalamic nuclei engaged in antidiuretic hormone production.

Eight patients with previously untreated hereditary, hypothalamic diabetes insipidus have been investigated. Infusion of hypertonic saline produced no significant antidiuresis in any of seven patients tested. In two, however, urine osmolality increased to values exceeding plasma osmolality. During water deprivation (818 h) urine osmolality increased in all patients, but only in three were values exceeding plasma osmolality reached. Administration of a new, long-acting analogue of vasopressin, 1-deamino-8-D-arginine vasopressin (DDAVP), effectively decreased urine volumes and increased urine osmolality in all the patients. The peptide was used for long-term treatment in seven cases. The results are discussed in relation to the pathogenesis of the disease.