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Ultrastructural studies of the rat submandibular gland in streptozotocin induced diabetes mellitus.

Increased fluid intake (polydipsia) is one of the classic symptoms of diabetes mellitus. Xerostomia (dry mouth) and resultant thirst are other symptoms of the disease and bear a close relationship to polydipsia. The xerostomia in individuals with diabetes is primarily due to decreased saliva flow which appears to be associated with degenerative changes in the salivary glands. This study examines the response of the rat submandibular gland to streptozotocin induced diabetes mellitus. Adult male rats were given a single I.V. dose of streptozotocin (65 mg/kg body weight) in citrate buffer (pH 4.5). Salivary glands were examined by light and electron microscopy at 4, 8 and 24 h and 3, 7, 14 and 21 days posttreatment. The changes in the acinar cells were characterized by an accumulation of secretory material within the cytoplasm. This secretory protein accumulation was followed by degenerative changes in the acinar cells which frequently resulted in cell death and replacement of secretory cells by connective tissue elements. The loss of secretory volume and potential changes in secretory kinetics are discussed with regard to the xerostomia, thirst and polydipsia exhibited by individuals with diabetes mellitus.

Animals↗

Ethanol dependence as a determinant of fluid preference.

Rats made dependent on ethanol by a schedule-induced polydipsia procedure preferred 5% ethanol to an increasing concentration of dextrose solution to a greater extent than animals on a non-dependent, non-polydipsic procedure which allowed an equivalent opportunity to drink ethanol, confirming a previous study. Two corresponding groups of animals drinking isotonic (0.9%) NaCl rather than 5% ethanol behaved similarly to the latter group, changing to a dextrose preference at a lower dextrose concentration than the ethanol polydipsic group. Therefore, neither the intermittent food regimen (polydipsia-generating procedure) in itself, nor a history of isotonic saline polydipsia biased fluid preference against dextrose solution choices. The enhanced preference for ethanol over dextrose solutions shown by the ethanol polydipsic group can be attributed to physical dependence rather than regiment produced artifacts.

Animals↗

Schedule-induced cocaine drinking: choice between cocaine and vehicle.

Rats were exposed to daily 3-hr schedule-induced polydipsia sessions (fixed-time 1-min food-pellet delivery) with two drinking fluids available: cocaine solution and water. Fluid position was alternated daily. Polydipsia occurred mostly from a preferred-side spout (position preference) until cocaine solution concentration was increased to between 0.52 and 1.04 mg/ml and animals drank mostly water. Within a lower concentration range (0.28-0.6 mg/ml) maximum session cocaine intakes ranged from 54.3 to 120.1 mg/kg. Postsession serum cocaine levels were about 200 ng/ml. At individually chosen cocaine solution concentrations, the addition of saccharin to the solution did not increase cocaine intake, but a compound solution (saccharin plus glucose) did. With progressive dilution of the compound vehicle, an almost complete preference for cocaine solution was maintained. But with a return to water as the vehicle, animals reverted to a position preference after a few sessions, although one maintained a clear cocaine preference. Schedule-induced polydipsia produced chronic, oral self-administration of cocaine resulting in pharmacologically significant intakes and serum levels.

Animals↗

Increased urine volume in chronic schizophrenic patients.

Polydipsia and polyuria have a long association with schizophrenia. To assess the prevalence of polydipsia and polyuria in schizophrenia, urine volume was examined in medication-free chronic schizophrenic patients, normal controls, and nonschizophrenic patients. Mean urine volume was significantly higher in the schizophrenic patients (2319 +/- SD 2052 ml/24 hours) than in the other two groups (1054 +/- SD 471 ml/24 hours for nonschizophrenic patients and 1265 +/- SD 613 ml/24 hours for normals). Seven of 35 patients with schizophrenia but 0/7 nonschizophrenics had urine volumes greater than any normal control. Polyuria was associated with a good premorbid history and a positive neuroleptic response. Among polyuric patients, those with hyponatremia may represent a different, distinct subgroup. Neuroleptic treatment was associated with a further, significant increase in urine volume. Hence, polydipsia and polyuria appear to be relatively common in schizophrenia.

Adult↗

Ethanol polydipsic choice: effects of alternative fluid polydipsic history.

Two groups of rats drinking either 5% ethanol or 0.9% NaCl solution under a fixed-time 1-min schedule of food pellet delivery became polydipsic during daily 3-hr sessions. When both fluids were made available to animals during sessions, strong side preferences typically developed so that neither fluid was preferred in spite of the fact that one group had a mild-to-moderate physical dependence on ethanol. The group that drank 0.9% NaCl solution initially failed to acquire a strong 5% ethanol polydipsia when this became the sole available fluid, and special procedures were required to induce an ethanol polydipsia comparable to that of the other group. Hence, a history of 0.9% NaCl solution polydipsia interfered with the institution of chronic, ethanol overdrinking in this group. Equal ethanol intakes were maintained in the groups when a compound solution consisting of 5% ethanol plus 0.9% NaCl solution was available along with a 5% ethanol choice. Whenever a 0.9% NaCl solution was presented in competition with either 5% ethanol or the compound 5% ethanol plus 0.9% NaCl solution, ethanol intake was reduced. Implications for the prevention and amelioration of human ethanol overdrinking are discussed.

Alcohol Drinking↗

Chronic alcohol dependence and water-electrolyte status.

Altered water-electrolyte status resulting from chronic alcohol dependence has been reported, although the nature of any such derangement is controversial. To illuminate this problem, four groups of rats were exposed chronically to schedule-induced polydipsia conditions with a single fluid available: 5% ethanol, 0.9% NaCl solution of 5% ethanol, 0.9% NaCl solution, or distilled water. An ad lib control group was also used. The water-electrolyte status of these groups was evaluated in two ways. First, the diuretic response to hydrochlorothiazide doses (8-12 mg/kg) was measured after 3.5 months of chronic polydipsia. Second, after approximately two additional months of polydipsia, extracellular fluid volume, as well as plasma volume and electrolytes were measured. Both alcohol-intake groups drank approximately 11.5 g ethanol/kg/day over the course of the experiment. Urinary volume response to the diuretic agent did not reveal that chronic ethanol led to either water retention or dehydration, even when extra NaCl intake was imposed chronically (NaCl-EtoH group). Animals that were overdrinking either water or the 0.9% NaCl solution had extracellular fluid volumes that were greater than the NaCl-EtOH-polydipsic group, but they were not significantly larger than ad lib controls. There were no significant differences with respect to serum electrolyte concentration measures among the groups. In conclusion, animals that drank ethanol chronically in a pattern known to produce physical dependence revealed no altered water-electrolyte status when evaluated by acute responses to a diuretic agent, a chronically-imposed extra NaCl load, or body fluid compartment and electrolyte concentration measures.

Alcohol Drinking↗

Congenital phimosis in a cat.

An 8-week-old domestic shorthair cat was presented with a history of pollakiuria and polydipsia. No abnormalities were detected during the clinical examination other than the penis could not be extruded from the prepuce. Urine culture demonstrated a growth of E. coli, which was treated with a prolonged course of amoxycillin. The polydipsia resolved and the pollakiuria improved but did not completely abate after antibiotic treatment and the cat had occasional bouts of haematuria. Because of the history of pollakiuria and polydipsia and the ongoing, occasional bouts of haematuria, the cat underwent surgical correction of the congenital phimosis. A small wedge of the dorsal prepuce was removed and the ipsilateral edges of the prepuce were apposed using a simple interrupted pattern. The procedure was quick, easy to perform and led to a resolution of the occasional bouts of haematuria and pollakiuria.

Animals↗

Enhanced effects of central angiotensin II on cardiovascular and drinking responses in inbred polydipsic (STR/N) mice.

STR/N, an inbred strain of mice, is known to exhibit extreme polydipsia and polyuria. The objective of this study was to investigate the possible reasons for polydipsia. First, comparisons were made between STR/N mice and control mice from the Institute of Cancer Research (ICR) concerning daily drinking, urinary excretion, and basal cardiovascular function. Then, since angiotensin II (ANG II) is a potent stimulus for drinking behavior, we investigated the effects of intracerebroventricular (i.c.v.) administration of ANG II on cardiovascular and water intake responses. Daily water intake, food intake, urinary volume, and urinary electrolytes (Na and K) excretion were larger in STR/N mice than in ICR mice, and the basal blood pressure was significantly lower in STR/N mice than in ICR mice. The i.c.v. administration of ANG II (10 pmol/per mouse) resulted in increased mean arterial blood pressure (MAP) and water intake in both STR/N and ICR mice, but the changes in MAP were significantly larger in STR/N mice than in ICR mice. These results suggest that polydipsia in STR/N mice is at least partially attributable to high sensitivity of central ANG II receptors and low MAP.

Angiotensin II↗

The induction of parturition in the bitch using sodium cloprostenol.

The objectives of this studies were to determine a continuous low-dose treatment regimen for the administration of sodium cloprostenol to the bitch that did not cause polydipsia, and whether this treatment would induce normal and timed parturition in bitches during late pregnancy. Non-pregnant greyhound bitches (n=18) received sodium cloprostenol subcutaneously, via a miniosmotic pump, at dose rates of 0.875 to 4.5 microg/kg/24 h, for 7 days (Days 0 to 7). Daily water intake was measured from Day -2 to Day 9. Polydipsia was observed in bitches treated with the higher dose rates but not in bitches treated with the lowest dose rate of 0.875 microg/kg/24 h. In the second experiment, pregnant greyhound bitches received sodium cloprostenol at dose rates of 1 (n=4), 2 (n=1) and 3 microg/kg/24 h (n=1), on Day 57 of pregnancy. Polydipsia was observed in bitches treated at the higher dose rates of 2 and 3 microg/kg/24 h, but not in the bitches treated at the lower dose rate of 1 microg/kg/24 h. These treatments resulted in the successful induction of parturition. Parturition was associated with a decrease in plasma progesterone concentrations, a reduction in body temperature, and an increase in plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2alpha. The first puppy was born 37.7 +/- 2.9 h after the start of treatment (range 28 to 46 h). The duration of whelping was approximately 15.7 +/- 2.2 h (range 10 to 24 h). The litter size was 9.2 +/- 0.8 pups (range 6 to 12 pups), and the puppy survival rate was 6.0 +/- 0.8 per litter (range 4 to 9 pups). This study demonstrated that the administration of sodium cloprostenol in continuous low dose for 24 h is an effective treatment for the induction of parturition in bitches during late pregnancy. This treatment resulted in the birth of healthy pups, with minimal or no side effects to the bitch.

Animals↗

Disordered control of thirst in hypothalamic-pituitary sarcoidosis.

We evaluated water metabolism in 11 patients with hypothalamic-pituitary sarcoidosis. Seven patients had abnormal water metabolism: one had partial antidiuretic hormone (ADH) deficiency, one had severe ADH deficiency, one had severe ADH deficiency and deficient thirst, one had only deficient thirst, and three had excessive thirst. In four of the five with thirst disturbances, there was loss of congruence of osmotic thresholds for thirst and ADH release. Five of our patients presented with polyuria and polydipsia, but only two had true diabetes insipidus, whereas three had organic primary polydipsia with adequate endogenous ADH. That disordered thirst resulting in polydipsia was more common than true diabetes insipidus is at odds with previously held views on the prevalence of ADH deficiency in this condition.

Adolescent↗

A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria.

The diagnoses provided by a standard indirect test of vasopressin function were compared with those obtained by radioimmunoassay of plasma vasopressin in 24 patients with nonglucosuric polyuria. All seven cases of severe neurogenic diabetes insipidus diagnosed by the indirect tests were confirmed by the vasopressin assay. However, two of six patients with partial neurogenic diabetes insipidus by indirect criteria had normal vasopressin secretion by the direct assay; one was found to have primary polydipsia, and the other nephrogenic diabetes insipidus. Moreover, three of 10 patients diagnosed as having primary polydipsia by the indirect test had clear evidence of partial vasopressin deficiency by the direct assay. The inability of the indirect test to distinguish accurately between partial neurogenic diabetes insipidus and primary polydipsia may be explained by increased sensitivity to low concentrations of vasopressin in the former disorder and a reduction of maximal concentrating ability in both. We conclude that the incorporation of a vasopressin assay improves accuracy in the differential diagnosis of polyuria.

Adolescent↗

Aggravation of subclinical diabetes insipidus during pregnancy.

BACKGROUND: Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. METHODS: We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. RESULTS: One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration. CONCLUSIONS: Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.

Adult↗

Dietary self-selection patterns of rats with mild diabetes.

Rats were allowed a free selection of a diet from among separate sources of protein, fat and carbohydrate or were fed a composite diet formulated to approximate the nutrient composition of a commonly used nonpurified diet. Immediately after streptozotocin injections, diabetic rats displayed polyuria, polydipsia and glycosuria as well as elevated fasting plasma glucose levels and glucose intolerance indicative of mild diabetes. Diabetic rats allowed a free choice tended to consume more protein and consumed significantly less carbohydrate than nondiabetics. This pattern of nutrient choice was associated with a reduction of diabetic signs including reduced polyuria, polydipsia and glycosuria. Diabetic rats permitted to choose their diets were not hyperphagic and maintained a slow but steady rate of body weight gain, accompanied by a sparing of body fat stores. In contrast, diabetic rats consuming the composite diet experienced no improvement in diabetic status; these rats displayed a deterioration of fasting plasma glucose, severe polydipsia, polyuria and glycosuria as well as hyperphagia and wasting of fat stores. These data demonstrate that when mildly diabetic rats are given the opportunity to select their own diets, they choose a diet that leads to improvement of their diabetic status.

Animals↗

Involvement of the endogenous opioid system in the drinking behavior of schizophrenic patients displaying self-induced water intoxication: a double-blind controlled study with naloxone.

Previously we found significant suppression of polydipsia in a schizophrenic patient with PIP syndrome (psychosis, intermittent hyponatremia, and polydipsia). Suppression was obtained with a small dose of naloxone injected once every 2 weeks in long-term repeated studies. We attempted to confirm the effect of naloxone on PIP syndrome by using a double-blind controlled study. The body weights of eight schizophrenic inpatients with PIP syndrome were checked five times daily, and the maximum weight gain during 1 day was chosen as an index of their polydipsia. Naloxone (0.6 mg in three divided doses) or placebo (saline) injection was given once every 2 weeks three times. Assignment to either the naloxone or placebo series was done randomly in a double-blind, crossover design. Naloxone decreased the maximum weight gain per day significantly in five cases. However, naloxone also increased weight gain significantly in three cases. There was no correlation of the weight-increasing effect of naloxone with the duration and intensity of excessive drinking. Our findings showed that the endogenous opioid system might be related to compulsive drinking behavior in the PIP syndrome and that opioid antagonists such as naloxone or naltrexone could be useful in the therapy of PIP syndrome.

Adult↗

Renal dysplasia in boxers and Finnish harriers.

Puppies from two litters of dogs were found to have severe polyuria and polydipsia. Four of the dogs were investigated by means of clinical examination, haematological and biochemical analysis, and urinalysis. A modified water deprivation response test was also performed in two of the dogs. Renal changes on postmortem examination in three of the dogs were found to be consistent with renal dysplasia. A possible explanation for the finding of hyposthenuria and the extreme polyuria and polydipsia in association with renal dysplasia may be lack of response to antidiuretic hormone owing to anomalous maturation of the renal tubules. Six other puppies from the two litters of dogs did not show any clinical signs of polyuria and polydipsia, although postmortem examination in one of them also revealed renal dysplasia. The clinical features of renal dysplasia may therefore vary greatly between individuals.

Animals↗

Trauma-induced central diabetes insipidus in a cat.

A 1-year-old neutered male domestic shorthair cat presented with a 4-week history of polydipsia that began immediately after an 8 metre fall. Trauma-induced central diabetes insipidus was suspected on the basis of the identification of hyposthenuria, normal haematology and serum biochemistry profile and unremarkable abdominal ultrasound examination. Failure to concentrate urine with water deprivation followed by production of hypersthenuric urine with administration of the synthetic antidiuretic hormone, Deamino-8-D-arginine vasopressin (DDAVP), confirmed the diagnosis of central diabetes insipidus. Treatment via conjunctival administration of DDAVP failed to attenuate the polydipsia, however, resolution of polydipsia was achieved with subcutaneous administration of DDAVP and the cat remains eudipsic with twice daily subcutaneous DDAVP administration 17 months after diagnosis.

Accidental Falls↗

Genetic analysis of the nephrogenic diabetes insipidus defect in SWV mice.

Females of the SWV mouse strain had an age-dependent nephrogenic diabetes insipidus. The distribution of water intakes in the F1, F2 and backcross to each parental strain indicated that at least the polydipsia was determined by a few major dominant genes; rather than by a polygenic system. The Smirnof and chi square analyses revealed more than one major gene was involved. A hypothesis was presented that there are two dominant genes (one fully dominant and one codominant) which may be linked. The expression of these major genes was influenced multiplicatively by environmental factors and the water intakes approached a continuous distribution. The defect was sex influenced: SWV males had only a very mild urine concentrating defect but the reciprocal crosses showed no X-linkage. The kidney weight of the SWV females correlated significantly (P less than 0.05) with the polydipsia in the F1, BC SWV and F2 progeny and the use of both traits provided a qualitative measure for classification. The polydipsia and enlarged kidneys probably represent pleiotropy.

Animals↗