piperidines and Dehydration

Topics: Clinical Trials as Topic; Dehydration; Diarrhea, Infantile; Double-Blind Method; Feces; Humans; Infant; Loperamide; Male; Piperidines; Vomiting

The development of enhanced recovery after surgery (ERAS) protocols for patients undergoing radical cystectomy (RC) represents a significant advance in perioperative care.. To evaluate gastrointestinal (GI) complications following RC and urinary diversion (UD) using our institutional ERAS protocol.. We identified 377 consecutive cases of open RC and UD for which our ERAS protocol was used from May 2012 to December 2015. Exclusion criteria were consent refusal; non-bladder primary disease; palliative, salvage, or additional surgery; and prolonged postoperative intubation. A matched cohort of 144 patients for whom a traditional postoperative protocol (pre-ERAS) was used between 2003 and 2012 was selected for comparison.. A total of 292 ERAS patients with median age of 70 yr were included in the study, 65% of whom received an orthotopic neobladder. The median time to first flatus and bowel movement was 2 d. The median length of stay was 4 d. GI complications occurred in 45 patients (15.4%) during the first 30 d following RC, 93% of which were of minor grade. The most common GI complication was postoperative ileus (POI) in 34 cases (11.6%). Some 22 patients (7.5%) required a nasogastric tube, and parenteral nutrition was required in three patients. The rate of 30-d GI complications was significantly lower in the ERAS cohort than in the control group (13% vs 27%; p=0.003), as was the rate of POI (7% vs 23%; p<0.001). This effect was independent of other variables (hazard ratio 0.38, 95% confidence interval 0.18-0.82; p=0.01).. Our institutional ERAS protocol for RC is associated with significantly improved perioperative GI recovery and lower rates of GI complications. This protocol can be tested in multi-institutional studies to reduce GI morbidity associated with RC.. In this study, we showed that an enhanced recovery protocol for patients undergoing radical cystectomy for bladder cancer was associated with a significantly shorter length of hospital stay and lower rates of gastrointestinal complications, especially postoperative ileus.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Transitional Cell; Case-Control Studies; Clinical Protocols; Cystectomy; Dehydration; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Ileus; Intubation, Gastrointestinal; Length of Stay; Male; Middle Aged; Parenteral Nutrition; Perioperative Care; Piperidines; Postoperative Complications; Proportional Hazards Models; Urinary Bladder Neoplasms; Urinary Diversion; Urinary Tract Infections

A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.

Topics: Cyclization; Dehydration; Ketones; Molecular Structure; Phosphites; Piperidines; Stereoisomerism

Histamine H3 receptors (H3Rs) are presynaptic receptors that negatively regulate the release of histamine. The present study examined the physiological role of H3Rs in drinking behavior. In water-replete rats, intracerebroventricular (i.c.v.) administration of R-alpha-methylhistamine (RalphaMeHA), an H3R agonist, elicited drinking behavior. In contrast, i.c.v. administration of thioperamide, an H3R inverse agonist, significantly attenuated the drinking behavior elicited by either overnight dehydration or i.c.v. administration of angiotensin-II (AT-II). Inhibition of histamine release with alpha-fluoromethylhistidine, an inhibitor of histidine decarboxylase, did not elicit drinking behavior. Moreover, the inhibitory effects of thioperamide on drinking behavior in water-depleted rats were not mimicked by i.c.v. administration of histamine. These results suggest that the predominant effects of H3Rs on drinking behavior are not mediated by the modulation of histamine release. In H3R-deficient (H3RKO) mice, drinking behavior induced by overnight dehydration or i.c.v. administration of AT-II was significantly impaired compared to wild type mice. Collectively, these observations suggest that brain H3Rs play a pivotal role in drinking behavior in response to dehydration and AT-II, and these effects may be largely independent of the modulation of histaminergic tone.

Topics: Angiotensin II; Animals; Behavior, Animal; Dehydration; Drinking Behavior; Male; Methylhistamines; Mice; Mice, Knockout; Piperidines; Rats; Receptors, Histamine H3; Time Factors

Ninety, seven- to 10-day-old calves were allocated to three groups of 30 and treated daily for seven days with either 100 microg/kg halofuginone hydrobromide or 2.5 mg/kg decoquinate orally or left untreated as controls. The levels of diarrhoea and dehydration were monitored daily for 28 days from the first day of treatment (day 0) and samples of faeces were collected on days 0, 7, 14, 21 and 28, to quantify the excretion of Cryptosporidium parvum oocysts. The calves were weighed on days 3 and 28. The treatments had no effect on the levels of diarrhoea or dehydration, the proportions of diarrhoeic calves or the proportions of calves shedding oocysts. However, unlike decoquinate, halofuginone significantly reduced the excretion of oocysts on day 7 (P<0.0001), and decoquinate increased the average daily weight gain of the calves (P=0.049).

Topics: Animals; Cattle; Cattle Diseases; Coccidiostats; Cryptosporidiosis; Cryptosporidium parvum; Decoquinate; Dehydration; Diarrhea; Feces; Female; Male; Parasite Egg Count; Piperidines; Quinazolinones; Random Allocation; Treatment Outcome; Weight Gain

The pharmacologic profile of YM471 ((Z)-4'-[4,4-difluoro-5-[2-(4-dimethylaminopiperidino)-2-oxoethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl]-2-phenylbenzanilide monohydrochloride), a novel potent vasopressin V(1A) and V(2) receptor antagonist, was investigated using several in vitro and in vivo techniques. YM471 showed high affinity for rat vasopressin V(1A) and V(2) receptors, exhibiting K(i) values of 0.16 and 0.77 nM, respectively. In contrast, YM471 exhibited much lower affinity for rat vasopressin V(1B) and oxytocin receptors, with K(i) values of 10.5 microM and 31.0 nM, respectively. In conscious rats, oral administration of YM471 (0.1-3.0 mg/kg) produced dose-dependent inhibition of the pressor response caused by exogenous vasopressin and increased urine excretion and decreased urine osmolality; this effect lasted more than 8 h. In all biological assays used, YM471 exhibited no agonistic activity. These results demonstrate that YM471 exerts potent and long-lasting antagonistic activity on both vasopressin V(1A) and V(2) receptors, and that this compound may be a useful tool for clarifying the physiologic and pathophysiologic roles of vasopressin and the therapeutic usefulness of the vasopressin receptor antagonist.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Azepines; Decerebrate State; Dehydration; Diuresis; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Male; Osmolar Concentration; Piperidines; Radioligand Assay; Rats; Rats, Wistar; Vasopressins

The intrarenal localization and role of the V1a vasopressin receptor in body fluid homeostasis are unclear. We investigated the intranephron localization of V1a receptor mRNA and protein using reverse transcription (RT)-competitive polymerase chain reaction (PCR) and immunohistochemistry with a specific polyclonal antibody. To determine whether the V1a receptor is involved in the regulation of acid-base balance, we also examined the effects of acute and chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA was expressed most abundantly in the cortical collecting ducts (CCD) and decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs was low. The immunohistochemical study revealed the presence of the V1a receptor in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased V1a mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA expression in the CD but decreased V2 receptor mRNA expression. Western blot analysis revealed up-regulation of the V1a receptor protein in chronic metabolic acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low-pH (or or low-HCO3-) medium increased the levels of V1a receptor mRNA but decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA expression compared with incubation with AVP alone. These data suggest that V1a receptors are present primarily in the principal and intercalated cells in the CD and that these receptors are involved in the regulation of water and acid-base balance.

Topics: Acidosis; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Bicarbonates; Dehydration; Down-Regulation; Homeostasis; Immunohistochemistry; Male; Nephrons; Piperidines; Polymerase Chain Reaction; Quinolones; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; RNA, Messenger; Up-Regulation; Vacuolar Proton-Translocating ATPases

The present study was performed to evaluate the role of central vasopressin in cardiovascular regulation. First, a novel vasopressin V1 antagonist (OPC21268) was injected intracerebroventricularly in conscious rats. In water-deprived animals, the mean arterial blood pressure (MABP) and heart rate were significantly decreased compared with euhydrated control rats. There was, however, no significant difference in the concentration of vasopressin in the perfusate of cerebrospinal fluid between groups. Second, vasopressin was intracerebroventricularly injected in male and female homozygous Brattleboro rats. The increase in MABP was greater in males than in females. These results suggest that central vasopressin is involved in blood pressure regulation in pathophysiological states.

Topics: Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Dehydration; Female; Heart Rate; Injections, Intraventricular; Male; Piperidines; Quinolones; Rats; Rats, Brattleboro; Sex Factors; Vasopressins

Topics: Biopsy; Body Temperature; Body Weight; Brain Diseases; Calcium; Child; Child, Preschool; Chlorides; Creatine; Dehydration; Diabetes Insipidus; Diagnosis, Differential; Diet; Diuresis; Feeding and Eating Disorders; Female; Humans; Hydrochlorothiazide; Hypothalamus; Infant; Kidney; Male; Mineralocorticoid Receptor Antagonists; Obesity; Osmolar Concentration; Osmosis; Piperidines; Potassium; Sodium; Urography; Vasopressins