Switching Habitual Small and Large Volume Drinkers

Dynamics of the Regulation of the Hypothalamo–Pituitary–Adrenal (HPA) Axis Determined Using a Nonsurgical Method for Collecting Pituitary Venous Blood from Horses

Carbamazepine, a drug used to treat manic-depressive illness, has been reported to possess antidiuretic properties, but its effects on arginine vasopressin (AVP) secretion are controversial. Consequently, we examined plasma AVP secretion during hypertonic (5%) saline infusion in seven manic-depressive patients while on placebo and after 3-5 weeks of carbamazepine treatment. We also measured carbamazepine's effects on basal levels of the hormone in cerebrospinal fluid. Carbamazepine significantly reduced the sensitivity of the plasma AVP response to osmotic stimulation without affecting the osmotic threshold for AVP secretion. Moreover, carbamazepine did not affect baseline weight, plasma osmolality, plasma sodium, urine output, plasma AVP, or cerebrospinal fluid AVP. Although the functional significance of these findings remain to be fully determined, the fact that carbamazepine significantly reduced AVP secretion without inducing diuresis supports previous suggestions that carbamazepine enhances renal responsivity to available AVP. In addition, since carbamazepine failed to affect the osmotic threshold, the reported cases of carbamazepine-induced inappropriate AVP secretion and water intoxication must be very uncommon and probably represent idiosyncratic responses.

Central serotonin (5-HT) and angiotensin (ANG II) stimulate arginine vasopressin (AVP), oxytocin (OT), and adrenocorticotropin (ACTH) secretion and increase blood pressure. Studies were conducted in conscious rats to determine whether neuroendocrine activation by 5-HT requires a brain angiotensinergic intermediate pathway. In the first study, ANG II formation was inhibited by the angiotensin-converting enzyme inhibitor enalapril before injection of the 5-HT releaser/uptake inhibitor d-fenfluramine. Fenfluramine (2 mg/kg ip) stimulated AVP, OT, corticosterone, and prolactin (PRL) secretion (P<0.01). Enalapril (60 mg/l in drinking water for 4 days and 10 mg/kg ip 2 h before the rats were killed) inhibited only the AVP response (P<0.01) to d-fenfluramine. In the second study, the effect of intracerebroventricular injection of the 5-HT2A/2C antagonist LY-53857 (10 microgram), or the ANG II AT1 antagonist DuP-753 (10 microgram), on intracerebroventricular 5-HT (10 microgram)-stimulated AVP, OT, ACTH, PRL, renin secretion, mean arterial pressure (MAP) and heart rate (HR) was tested. LY-53857 inhibited the AVP, OT, and ACTH responses to 5-HT (P<0.01), whereas DuP-753 inhibited only the AVP response (P<0.01). Intraventricular injection of 5-HT increased MAP and decreased HR. The MAP response was not affected by LY-53857 or DuP-753, and at no time did MAP decline below starting levels. The decreased HR was inhibited by LY-53857 but not by DuP-753. These results demonstrate that 5-HT-induced AVP secretion is mediated selectively via brain angiotensinergic mechanisms by way of the AT1 receptor.

The possibility that metoclopramide (MCP) stimulates arginine vasopressin (AVP) secretion in man through a serotoninergic and/or a cholinergic muscarinic pathway was studied. Twenty normal male subjects were tested with MCP (10 mg in an i.v. bolus) alone or in the presence of the 5HT1 serotoninergic antagonist metergoline (10 mg/day p.o. in five divided doses for 4 days), the 5HT2 receptor blocker ketanserin (10 mg i.v. 5 min before MCP) (n = 10), the M1 and M2 muscarinic antagonist atropine (1.2 mg i.v. just before MCP administration) or the M1 muscarinic receptor blocker pirenzepine (40 mg i.v. 10 min before MCP) (n = 10). AVP doubled in response to MCP. the MCP-induced AVP rise did not change after metergoline, ketanserin or pirenzepine administration, whereas it was abolished by atropine. Additional experiments were performed in order to evaluate the effect of 1.2 mg atropine, given alone, on circulating AVP levels and whether the effect of atropine on the AVP response to MCP depends on the amount of the muscarinic antagonist (dose-response study). For these purposes, atropine was given alone to the same subjects previously tested with MCP plus atropine; furthermore, eight additional male subjects were tested with MCP plus atropine given in doses ranging from 0.8 to 1.4 mg. The results of these additional studies failed to show an effect of atropine alone on AVP secretion and demonstrated a dose-related inhibition of MCP-induced AVP rise by increasing atropine administration from 0.8 mg to 1.2 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the lung dose of a non-CFC salbutamol metered dose inhaler (MDI) formulation via three commonly used plastic spacer devices, of both large and small volume, compared with the MDI used on its own. Ten healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses of salbutamol from a non-CFC MDI (Airomir), as 12 sequential 100 microg puffs over 6 min, were delivered from the MDI alone and via two large volume spacer devices (Nebuhaler, Volumatic), and a small volume spacer (Aerochamber). All spacers were prewashed prior to each study day and mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min, with calculation of maximum (Cmax) and average (Cav) concentrations. This lung dose was assessed using the early lung absorption profile of salbutamol in the first 20 min after inhalation. Both of the large volume spacers, the Nebuhaler and the Volumatic, delivered significantly more salbutamol than the MDI alone. For Cav this amounted to a 2.07-fold difference (95% CI 1.48-2.90) between Nebuhaler vs MDI, and a 1.49-fold difference (95%CI 1.19-1.87) between Volumatic vs MDI. The Nebuhaler also produced greater deposition than either the Volumatic or the Aerochamber spacers; Nebuhaler vs Volumatic: 1.39-fold difference (95% CI 1.09-1.76), Nebuhaler vs Aerochamber: 1.63-fold difference (95% CI 1.20-2.21). There were no significant differences between the Aerochamber and the MDI alone. Using the early lung absorption profile, for administration of the same nominal dose, both of the large volume spacers (Nebuhaler and Volumatic) but not the small volume spacer (Aerochamber) delivered significantly more salbutamol than the MDI alone. The Nebuhaler also produced greater delivery than either the Volumatic or the Aerochamber spacer devices. Our results show that whilst lung delivery of non-CFC salbutamol MDI is improved by the use of a plastic spacer, there may be appreciable differences in performance, particularly between large and small volume devices.

In sheep, arginine vasopressin (AVP) appears to be a more potent ACTH-releasing factor than ovine corticotrophin-releasing hormone. In order to investigate the neuroendocrine regulation of AVP secretion we have developed a novel system for maintaining fetal ovine hypothalamic neurones in serum-free culture. Hypothalamic neurones derived from fetal sheep at day 70 gestation (term = 145 days) secreted AVP under basal conditions and in response to repeated potassium-induced depolarizations, for up to 35 days in vitro. AVP secretion was time- and calcium-dependent. AVP secreted from ovine hypothalamic cells co-eluted with synthetic AVP on a Sephadex chromatography column and diluted in parallel with AVP standard in the radioimmunoassay. The addition of cortisol (150 nM) to medium bathing ovine hypothalamic cells significantly inhibited basal, and potassium-induced AVP secretion without altering the AVP content of the cell cultures. Furthermore, the opioid peptide [D-Pro10]Dynorphin(1-11) which acts via the kappa opioid receptor, significantly inhibited basal and potassium-stimulated AVP secretion, an effect which was abolished when cells were cultured in the presence of cortisol. These data show that hypothalamic AVP is a site for negative feedback regulation within the ovine hypothalamic-pituitary-adrenal axis. Furthermore, these data suggest that the kappa opioid system inhibits AVP secretion from ovine hypothalamic neurones, a response which is modulated by glucocorticoids.

Hyponatremia is a common electrolyte disorder in children. It is generally defined as plasma sodium of less than 135 mmol/l. Sodium homeostasis is essential for maintaining intravascular volume and is tightly linked to water balance. Plasma water volume is regulated mainly by the secretion of an antidiuretic hormone (ADH) and by the thirst mechanism. ADH is synthesized in the hypothalamus and stored in the posterior hypophysis. It binds to V2 receptors in the distal nephron and induces translocation of aquaporin water channels in the plasma membrane to retain water. There are two main types of receptors involved in the control of the body water balance—osmoreceptors and baroreceptors. Osmoreceptors reside in hypothalamus and respond to changes of extracellular fluid (ECF) osmolality. Baroreceptors are mechanoreceptors that sense blood pressure in the vessel wall. Response reflexes from baroreceptors influence sympathetic outflow, vessel tonus, and cardiac output. An increase of 1% of plasma osmolality may cause an increase in ADH levels, while the threshold of volume receptors for ADH secretion is higher. However, significant hypotension is a more potent stimulus for ADH secretion than increased osmolality. The main cause of pediatric hyponatremia is an abundance of free water. This may occur in hypovolemic children with low ECF volume, normovolemic patients with inappropriately increased ADH secretion, and also in hypervolemic individuals with decreased effective circulating volume and appropriately increased ADH levels. Proper understanding of the pathophysiology of hyponatremic states is essential for establishing the correct diagnosis and appropriate therapy.

The effect of an acute fall in plasma cortisol on the secretion of CRH, arginine vasopressin (AVP), and ACTH was studied using our nonsurgical technique for collecting pituitary venous (PV) blood from horses. PV blood from six mares was collected continuously and divided into 30-sec segments for 0.5 h before and during a 3-h infusion of metyrapone, an 11-beta-hydroxylase inhibitor. During treatment, plasma cortisol fell (P < 0.01) to a mean nadir of 15% of pretreatment levels, and 11-deoxy-cortisol rose (P < 0.02). Three mares became mildly agitated during treatment. Mean PV concentrations of CRH (P < 0.025), AVP (P < 0.05), and ACTH (P < 0.005) were higher during the second hour of treatment than before. For AVP (P < 0.05) and ACTH (P < 0.01), the amount secreted in peaks detected by CLUSTER analysis increased during treatment, whereas peak frequency did not. Responses, particularly in CRH and AVP, tended to be amplified during agitation. Increases in CRH, AVP, and ACTH secretion commenced when cortisol had fallen to 50-59% of the initial value (P < 0.005 for each). By contrast, the cortisol concentration at this point varied 3-fold among mares. The ratio between PV concentrations of ACTH and CRH, which was used as an index of pituitary responsiveness to endogenous CRH, also rose (P < 0.005) as cortisol fell. The increase in this ratio preceded any significant change in CRH secretion and was maintained to the end of the experiment. We suggest that the initial response to falling cortisol in the horse is at the pituitary, via increased responsiveness to CRH. If cortisol continues to fall, AVP and then CRH secretion are stimulated. However, the magnitude of the hypothalamic response to hypocortisolemia may be augmented by concurrent stress. Last, the hypothalamo-pituitary-adrenal axis of the horse appears to monitor changes in plasma cortisol and not concentrations, at least in the short term.

Background: Familial central diabetes insipidus (DI) is rare and is characterised by polydipsia and polyuria with a variable age of onset. The evaluation of arginine vasopressin (AVP) secretion in these individuals has been reported infrequently and only in adulthood. Objective: To describe the clinical features, diagnosis and molecular investigation of children affected by familial central DI. Methods: Functional studies of AVP secretion were undertaken in children from two kindreds with familial central DI. The AVP-neurophysin II (AVP-NPII) gene was also sequenced in symptomatic individuals. Results: In affected individuals, the result of the water deprivation test may be inconclusive. However, the hypertonic saline test identified both the severe and partial forms of AVP deficiency. A novel mutation of the AVP-NPII gene was identified by direct gene sequencing in both families. Conclusions: This report highlights the progressive decline in AVP secretion with increasing age in this disorder and the usefulness of mutational analysis in these families. In symptomatic individuals, the hypertonic saline test may be a useful second-line investigation for functional studies of AVP secretion where molecular diagnostics are unavailable.

Acute diabetes insipidus-like symptoms have been reported as a complication after hypophysectomy in dogs. These symptoms are believed to be the consequence of deficiency of arginine vasopressin (AVP) secretion. The symptoms spontaneously resolve within 2 weeks, but the mechanism is unclear. In the present study, AVP secretion related to increases in Na+ concentration and serum osmotic pressure was measured, and immunohistochemical analysis in the paraventricular and supraoptic nuclei was performed after hypophysectomy in normal dog. In the hypertonic saline test, the plasma AVP concentration slightly increased in hypophysectomized dogs, although the increase was markedly smaller than that in normal dogs. An immunohistochemical study of the hypothalamus nucleus revealed that, AVP-positive cells tended to decrease after hypophysectomy. It suggests that excision of the posterior lobe by surgery injured the axon of magnocellular neuron in the hypothalamus. A decrease in the function and the number of AVP-producing and -secreting magnocellular neurons after hypophysectomy, suggests that the clinical improvement of postoperative diabetes insipidus-like symptoms may not be related to the recovery of AVP secretion.

Experiments were conducted to test the effect of overcrowding on egg production rates in the copepod Centropages typiciis. Fertility was not significantly reduced by the presence of other conspecifics when the volume of water was the same for females incubated alone or in the presence of other females and males. There was no evidence of chemical cues affecting egg production when females were kept in large (1 female in 100 ml sea water [SW] or small (1 female in 25 ml SW) volumes of water, with or without partitions, and in the presence or absence of food or males. Also, spawning rate was not reduced when females were incubated in flow-through experimental chambers which allowed diffusion of pheromones between females incubated alone or in high densities (100 ind. in 50 ml SW). Only when females were placed at unnaturally high densities (1 female ml) was egg production significantly reduced, probably due to physical disturbance and increased number of collisions rather than chemical communication among individuals. The results show that chemical cues do not affect spawning behaviour when population densities are close to field conditions. By contrast, overcrowding induced by swarming or aggregation may potentially limit reproductive success due to reduced feeding, and production and cannibalism of eggs.

Gastric emptying of liquids in the fasted dog

The aim of this study was to evaluate the influence of diluent, stored volume and the cryodiluent medium supplementation with sulfated polysaccharides (SP) extracted from Nile tilapia skin on P. brevis vitrified sperm. Six pools were diluted in 5% Glucose or Powder Coconut Water (ACP-104), supplemented or not with 0.5 mg/mL of SP, and submitted to vitrification. Subsequently, they were stored in cryotubes in two volumes (60 μL and 420 μL). After 15 days, the samples were devitrified and evaluated for kinetics, membrane integrity and sperm DNA integrity. ACP-104 proved to be the best diluent for P. brevis sperm vitrification. Membrane and DNA integrity rates were higher (P < 0.05) when stored in smaller and larger volume, respectively. Additionally, the best rates (P < 0.05) of these same parameters were obtained with supplemented medium. There was interaction (P < 0.05) between diluent and stored volume, with ACP-104 exceeding 5% Glucose for motility in both volumes, while for average path speed (VAP) and membrane integrity the same happened in the larger volume. 5% Glucose had higher VAP and membrane integrity when stored in smaller volume. There was a triple interaction (P < 0.05) for DNA integrity, and better results were obtained when semen was vitrified in ACP-104 and stored in the larger volume, regardless of supplementation, which influenced only the 5% Glucose medium in the smaller volume. It was concluded that ACP-104, supplemented with SP and stored in larger volume make up the best treatment for P. brevis sperm vitrification.

Water volume influences antibiotic resistomes and microbiomes during fish corpse decomposition

The study of the dynamics of two small volumes of water with negative buoyancy (patches of salt water), imitated a sinking of dense water into an underlying water, was carried out. These volumes usually appear in the process of surface water cooling during seasonal convection in the coastal zone of the sea. The main tools of investigation were laboratory and numerical experiments. The main stages of motion of patches were identified: sinking, contact, and spreading along a bottom slope. The process of interaction of the water patches during their movement up the bottom slope was detailed in laboratory experiments. Patches of salt water retained unmixed long time, that confirm the laminar character of the appearing flows. Distributions of tracers obtained in the calculations was analyzed with the aim to identify the characteristic stages of the flow of patches up the slope. Three stages were suggested: initial contact, diving, wrapping and breaking. For the first time dense water flow up the slope, which occur as a result of sinking of small volumes of salt water, was described. The results allow us to notice the intensification of mixing of water dense than underlying waters in the process of surface water cooling in coastal zone of the sea.