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Biomedical subjects

M Donowitz

Publications and source records attributed to M Donowitz.

At least 163 records · Page 9Linked to original sources
PubMed1980

Effect of serotonin on active electrolyte transport in rabbit ileum, gallbladder, and colon.

The effect of serotonin on active electrolyte transport was evaluated in vitro in epithelial sheets of rabbit ileum, gallbladder, and colon under short-circuited conditions. Serotonin added to the serosal surface of rabbit ileum caused a dose-dependent short-lived increase in short-circuit current and a more prolonged equal effect on net Na and Cl fluxes. The latter consisted primarily of inhibition of mucosal-to-serosal fluxes of both Na and Cl. In addition serosal serotonin decreased ileal Na influx from the mucosal solution into the epithelium, suggesting an effect on Na absorption. Serotonin did not alter all aspects of ileal absorptive function and did not affect glucose-dependent Na absorption. Consistent with serotonin acting by inhibiting NaCl absorption in the ileum, serotonin induced equal inhibition of net Na and Cl absorption in rabbit gallbladder (which has a linked Na and Cl absorptive process) but had no effect on rabbit colon (which lacks a linked Na and Cl absorptive process). In addition, adenosine 3',5'-cyclic monophosphate and serotonin both appeared to alter the same ileal NaCl absorptive process, since following stimulation of ileal secretion with the maximum concentration of theophylline, addition of serotonin did not cause any further effects.

Animals↗
PubMed1980

Calcium dependence of serotonin-induced changes in rabbit ileal electrolyte transport.

These studies describe the calcium dependence of the serotonin-induced changes in active electrolyte transport in rabbit ileum in vitro. In the presence of a standard calcium concentration (1.2 mM) in the serosal bathing fluid, serosal serotonin caused a transient increase in short-circuit current and a prolonged decrease in net Na and Cl fluxes. Removing calcium from the serosal (no calcium plus 1 mM EGTA) but not the mucosal bathing fluid inhibited the serotoin-induced increase in ileal short-circuit current, and also completely blocked the serotonin effects on net Na and net Cl fluxes. This inhibition was rapidly reversed by readding calcium. Removing serosal calcium did not inhibit all active electrolyte transport processes, as the effect of a maximum concentration of theophylline (10 mM) was not altered. Similarly, d,l-verapamil, a calcium channel blocker, inhibited the serotonin-induced changes in short-circuit current and in net Na and net Cl fluxes, but did not alter the theophylline effects. In contrast, d-verapamil, a stereoisomer which does not block calcium channels, did not inhibit the serotonin-induced changes. The calcium dependence of these serotonin effects was associated with increased uptake of 45Ca into rabbit ileum, including increaed 45Ca uptake from the serosal surface. Serotonin also increased the rate of 45Ca efflux from rabbit ileum into a calcium-free solution, compatible with serotonin increasing the ileal plasma membrane permeability to calcium. It is postulated that serotonin affects active intestinal electrolyte transport by a mechanism dependent on serosal but not mucosal calcium that involves an increase in the intestinal plasma membrane permeability to calcium, and perhaps an increase in intracellular calcium.

Animals↗
PubMed1980

Trifluoperazine reversal of secretory diarrhea in pancreatic cholera.

Diarrhea in a patient with pancreatic cholera syndrome caused by a vasoactive intestinal polypeptide producing pancreatic islet-cell carcinoma responded rapidly and dramatically to the phenothiazine trifluoperazine. Treatment with intravenous somatostatin decreased the plasma vasoactive intestinal polypeptide level without changing the diarrhea. The chemotherapeutic agent chlorozotocin, the 2-chloroethyl analogue of streptozocin, caused a decrease in plasma vasoactive intestinal polypeptide but caused significant renal toxicity with proteinuria.

Adenoma, Islet Cell↗
PubMed1979

Mild chronic watery diarrhea-hypokalemia syndrome associated with pancreatic islet cell hyperplasia. Elevated plasma and tissue levels of gastric inhibitory polypeptide and successful management with nicotinic acid.

A 46 year old woman is described who had a 13 half year history of watery diarrhea associated with hypokalemia and hypochlorhydria. The diarrhea was secretory as measured by triple lumen tube perfusion and was associated with an increased concentration of fasting plasma immunoreactive gastric inhibitory polypeptide (GIP) of 750 pg/ml which was stimulated to 4,000 pg/ml after a standard meal. The diarrhea decreased after partial pancreatectomy. Diffuse pancreatic islet cell hyperplasia was present and, although GIP was unmeasureable in the pancreas of normal subjects, it was at least 83 ng/g wet weight in this patient. Postoperatively, the patient's diarrhea responded dramatically to the oral administration of nicotinic acid.

Achlorhydria↗
PubMed1979

Effects of radiation on the human gastrointestinal tract.

Radiation therapy directed at the abdomen may damage the digestive tract, the type and extent of injury depending on the dose of the radiation and the radiation sensitivity of the gut. Characteristic early changes are manifest in the mucosa of the gut: for later ulceration, changes in the collagen tissues and particularly in the vascular channels occur. This paper describes and characterizes injuries to the esophagus, stomach, small intestine and colon. It emphasizes the importance of recognizing radiation-induced damage to the gut which may occur early or late after radiation.

Adult↗
PubMed1979

Significance of abnormal rabbit ileal histology in the pathogenesis of diarrhea.

In spite of several macroscopic criteria for predicting the presence of histological abnormalities in rabbit ileum, microscopic ileal abnormalities still can escape detection. The effect of histologically abnormal rabbit ileum was evaluated on basal intestinal absorption, on basal absorption, on basal adenylate cyclase activity, and on cholera toxin-induced secretion and cholera toxin-induced stimulation of adenylate cyclase activity. Compared to histologically normal rabbit ileum, the presence of histological abnormalities was associated with decreased basal intestinal water, Na, Cl, and glucose absorption, absent glucose-dependent water absorption, and elevated basal adenylate cyclase activities. However, histologically abnormal rabbit ileum responded to inoculation of purified cholera toxin with stimulation of intestinal water secretion and adenylate cyclase activity similar to that in histologically normal ileum. These data have implications concerning the design of experiments that attempt to study the pathogenesis of diarrheal diseases by correlating changes in ileal transport with changes in ileal mucosal adenylate cyclase activity. In spite of abnormal ileal histology, studies of intestinal secretory states which attempt to define the role of adenylate cyclase in secretory processes can be performed provided animals are used as their own controls. However, when groups of animals are compared, the presence of an histologically abnormal ileum can cause changes in basal and intestinal secretagogue-stimulated ileal water and electrolyte transport and in basal and intestinal secretagogue-stimulated mucosal adenylate cyclase activity which can lead to erroneous conclusions if the presence of the abnormal ileal histology is not considered.

Adenylyl Cyclases↗
PubMed1979

Effect of altered intestinal water transport on rabbit ileal blood flow.

A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow.

Animals↗
PubMed1977

Effect of serotonin treatment on intestinal transport in the rabbit.

The hormone serotonin (5-hydroxytryptamine) has been implicated as the cause of the diarrhea seen in many patients with the carcinoid syndrome. To determine whether serotonin is an intestinal secretagogue, the effect of serotonin on intestinal water and electrolyte transport was evaluated in the rabbit. Two weeks of daily subcutaneous injection of serotonin suspended in oil resulted in a blood serotonin level elevated to twice that of controls. Intestinal transport was studied in vivo by a perfusion technique. Serotonin treatment resulted in ileal secretion and decreased mid-jejunal absorption of water and electrolytes but did not effect water absorption in the proximal jejunum or colon. Intestinal absorption of D-glucose and the amino acid L-tryptophan and glucose-dependent water and electrolyte absorption were normal in serotonin-treated animals. Serotonin-induced ileal secretion was reversed by methysergide, a peripheral antagonist of serotonin action. No alterations in intestinal histology or permeability occurred in serotonin-treated animals. Serotonin-induced intestinal secretion was not associated with alterations in the activities of intestinal mucosal adenylate cyclase, cyclic nucleotide phosphodiesterase, or Na-K-ATPase.

Animals↗
PubMed1977

Colo-rectal biopsy in inflammatory bowel disease.

The term inflammatory bowel disease (IBD) is viewed as all-inclusive, covering the full panoply of intestinal disorders in which inflammatory changes are a prominent feature, including those of infectious, toxic, and intrinsic origin as well as the idiopathic entities ulcerative colitis and Crohn's disease. This chapter describes and discusses those aspects of colo-rectal biopsy in IBD which can help pathologists make optimal interpretations. The areas covered are: 1) methods used to prepare biopsy specimens for study, 2) normal histologic findings and common artefacts, 3) basic pathologic changes occurring in IBD, 4) a general approach to differential diagnosis in IBD, and 5) discussion of the various individual forms of IBD. The importance of full and reliable information exchange between the endoscopist and pathologist is stressed. Special attention is given to features in biopsy specimens which help in differentiating between ulcerative colitis and Crohn's disease. Other entities discussed are bacterial dysenteries; gonococcal proctitis; tuberculosis; Whipple's disease; amebiasis; balantidiasis; schistosomiasis; cryptosporidiosis; lymphopathia venereum; cytomegalovirus infection; histoplasmosis; antibiotic colitis; IBD due to cytotoxic drugs (5-FU), heavy metals, and foodstuffs; irradiation colitis; ischemic colitis; solitary ulcer syndrome; diverticulitis; and colitis secondary to obstruction. The term pseudomembranous enterocolitis is also considered.

Biopsy↗
PubMed1976

Effect of enterotoxins of Vibrio cholerae, Escherichia coli, and Shigella dysenteriae type 1 on fluid and electrolyte transport in the colon.

Experiments were designed to determine whether the enterotoxins of Vibrio cholerae, Escherichia coli, and Shigella dysenteriae type 1 alter the movement of fluid and electrolytes in the rat cecum. Net secretion of water and sodium were observed after incubation of 1.67 X10(-5) mug of purified cholera toxin (choleragen)/ml for 18 hr or of 50 mug/ml for 3 hr. The effect of choleragen on cecal transport of water and electrolytes was related to the dose. In addition, choleragen increased cecal mucosal content of adenosine 3':5'-cyclic phosphate but did not alter the histology of the cecum. The results demonstrate that the colon responds to choleragen in a manner similar to that of other tissues. In contrast, the enterotoxins of both E. coli and S. dysenteriae type 1 failed to affect cecal transport of water and electrolytes. These observations may explain several phenomena associated with the diarrhea produced by bacterial enterotoxins.

Animals↗
PubMed1976

Prevention and reversal of cholera enterotoxin-induced intestinal secretion by methylprednisolone induction of Na+-K+-ATPase.

The relationship of the mucosal enzyme systems Na+-K+-activated adenosine triphophatase (Na-K-ATPase) and adenylate cyclase and their associated intestinal transport processes was studied in the rat ileum. Two ileal loops were constructed in each anesthetized rat; one loop was inoculated with saline, the other loop with choleragen. Net transport of water and electrolytes was measured in vivo after which enzyme activity was measured in the mucosa of the perfused loops. All doses of choleragen between 5 and 150 mug decreased water movement as early as 3 1/2 h after inoculation. A linear relationship between the dose of choleragen and the level of net water and electrolyte secretion was observed when choleragen doses between 5 and 150 mug were incubated in ileal loops for 4 h. Adenylate cyclase activity was always increased in secreting intestinal loops, whereas Na-K-ATPase was unaffected by choleragen. In animals pretreated with methylprednisolone acetate, 3 mg/100 g per day for 3 days before loop inoculation, saline loops had enhanced mucosal Na-K-ATPase activity had increased net water and electrolyte absorption; choleragen-exposed loops had increased adenylate cyclase and Na-K-ATPase activities, and net absorption of water and electrolytes 4 h after inoculation. These effects of methylprednisolone acetate were still present 19 1/2 h after inoculation. When a single injection of methylprednisolone acetate was given 3 1/2 h after choleragen inoculation, both adenylate cyclase and Na-K-ATPase were activated, and net intestinal absorption of water and electrolytes was observed 19 1/2 h after inoculation. These results suggest that methylprednisolone can prevent and reverse the secretory effects of choleragen by selectively stimulating a coexisting absorptive process.

Adenosine Triphosphatases↗
PubMed1975

Jejunal fluid and electrolyte secretion in carcinoid syndrome.

To evaluate the pathogenesis of the diarrhea of carcinoid syndrome, triple-lumen jejunal-perfusion studies were performed in three patients with carcinoid syndrome and diarrhea and eleven control subjects. In contrast to the net absorption observed in the control subjects during perfusion with an isotonic mannitol-saline solution, net secretion occurred in two of the three carcinoid-syndrome patients. Glucose absorption and glucose-stimulated fluid absorption were normal in the carcinoid-syndrome patients. Methysergide controlled the diarrhea and in one patient net absorption was observed during methysergide therapy. These studies suggest that intestinal secretion may be one of the pathogenetic factors responsible for the diarrhea of carcinoid syndrome and provide additional evidence of the importance of intestinal electrolyte secretion in the genesis of many diarrheal states.

Aged↗