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Biomedical subjects

L B Katz

Publications and source records attributed to L B Katz.

At least 37 records · Page 2Linked to original sources
PubMed1987

Altered susceptibility of arthritic rats to the gastric lesion-inducing effects of aspirin or ethanol and the antilesion effect of rioprostil.

It is well known that nonsteroidal antiinflammatory agents produce gastric mucosal lesions in both laboratory animals and man. However, the effect of an arthritic condition on their susceptibility to ulcerogenic agents and on the efficacy of antiulcer agents is less definitive. As a model to explore these questions, the effect of oral administration of aspirin or ethanol on gastric lesion formation was examined in rats with or without established adjuvant-induced polyarthritis. In addition, the antilesion efficacy of rioprostil, a primary alcohol prostaglandin E1 analog, was evaluated in both groups of rats. The results demonstrated that arthritic rats were more sensitive to the lesion-inducing effect of aspirin, but were more resistant to the lesion-inducing effect of ethanol when compared to normal rats. An increase in endogenous gastric prostaglandin production in arthritic rats may account for their relative resistance to ethanol. Aspirin inhibited the prostaglandin synthetic capacity of the stomach in both normal and arthritic rats, which may be responsible for eliminating the relative resistance of arthritic rats to gastric irritation. Rioprostil effectively prevented aspirin or ethanol-induced lesion formation in both arthritic and nonarthritic rats, but its potency against either irritant was decreased in arthritic rats.

Animals↗
PubMed1987

Use of a five-day test to predict the long-term effects of gastric antisecretory agents on serum gastrin in rats.

It has been hypothesized that prolonged achlorhydria causes compensatory elevation of serum gastrin, and that there is an association in rats between sustained hypergastrinemia, hyperplasia of gastric enterochromaffin-like cells, and subsequent formation of gastric carcinoids in 2-year carcinogenicity studies. The present study examined whether daily administration of gastric antisecretory drugs in rats for 4 days could cause hypergastrinemia associated with inhibition of acid output. Rats were dosed orally for 4 days with the histamine H2-receptor antagonist ranitidine or the H+,K+-sensitive ATPase inhibitor omeprazole, and examined on day 5 for effects on gastric acid secretion and serum gastrin. Omeprazole (138 mg/kg/day significantly inhibited gastric acid secretion and increased serum gastrin levels. Large, single daily doses of ranitidine (1000-2000 mg/kg/day) had no effect on 24-hr acid or gastrin secretion; however, ranitidine did inhibit next-day acid secretion with associated increases in serum gastrin when administered in three divided doses. These results with ranitidine support the hypothesis that a sustained gastric antisecretory action will cause a compensatory hypergastrinemia, regardless of the antisecretory agent used. The ability to detect increased serum gastrin levels associated with inhibition of acid secretion, after administration of antisecretory agents for only 4 days, suggest that this short 5-day test may be useful for determining the potential of antisecretory agents to cause hypergastrinemia due to 24-hr inhibition of acid secretion and may be predictive of long-term hyperplastic changes.

Animals↗
PubMed1987

Effects of ORF 17583, other histamine H2-receptor antagonists and omeprazole on gastric acid secretory states in rats and dogs.

ORF 17583, a histamine H2-receptor antagonist, inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 4.9 mg/kg intraduodenal; 3.4 mg/kg p.o.; and 0.21 mg/kg i.p.) and in total gastric fistula or Heidenhain pouch dogs stimulated by betazole (ED50 = 0.12 mg/kg p.o. and 0.08 mg/kg i.v.), histamine, tetragastrin, bethanechol, 2-deoxy-D-glucose or a meal (ED50 values ranged from 0.11-0.26 mg/kg p.o.). The nonspecific inhibition of gastric acid by ORF 17583 supports the existence of interdependence between histamine and the gastrin and cholinergic receptors on the parietal cell surface. Antisecretory potency of ORF 17583 after intraduodenal administration in pylorus-ligated rats was 6.4 times greater than cimetidine, 1.8 times greater than ranitidine, equal to that of omeprazole and 8 times less than that of famotidine. Oral antisecretory potency of ORF 17583 in gastric fistula dogs was 31 times greater than cimetidine, 3.7 times greater than ranitidine and equal to that of omeprazole and famotidine. Studies using equieffective antisecretory doses of ORF 17583 and ranitidine in dogs suggested that ORF 17583 has a short duration of antisecretory activity similar to that of ranitidine.

Animals↗
PubMed1987

Selective gastric antilesion properties of rioprostil, a prostaglandin E1 analog, in rats and dogs.

This paper characterizes the ability of rioprostil, a synthetic primary alcohol prostaglandin E1 analog, to inhibit gastric acid secretion and prevent experimentally induced gastric lesions in rats and dogs, and determines the selectivity (the separation in potency) for these effects. In 4-hr pylorus ligated rats, rioprostil inhibited gastric acid output when administered i.v., s.c., p.o. or intraduodenally, with ED50 values of 0.9, 1.8, 2.9 and 3.7 mg/kg, respectively. Rioprostil suppressed meal-stimulated acid output in Heidenhain pouch dogs and inhibited gastric acid output stimulated by tetragastrin, 2-deoxy-D-glucose, betazole or bethanechol in gastric fistula dogs with ED50 values of 7, 10, 16 and 17 micrograms/kg p.o., respectively. These values in dogs were not significantly different from each other, suggesting that the mechanism of the antisecretory effect of rioprostil is similar regardless of the secretagogue used. Rioprostil prevented ethanol induced gastric lesions in rats (ED50 = 1.5 micrograms/kg p.o.; 12.0 micrograms/kg s.c.) after a 30-min pretreatment. The 8-fold difference in potency between the p.o. and s.c. routes may reflect a local component in the antilesion mechanism of rioprostil. In dogs, rioprostil inhibited aspirin-induced gastric lesions with a p.o. ED50 of 1.6 micrograms/kg. Maximum antilesion activity in dogs for cimetidine or ranitidine was less than 50%, whereas rioprostil inhibited lesion formation by 100% without the appearance of side effects. Oral antilesion selectivity of rioprostil in rats (antisecretory ED50/antilesion ED50) was nearly 2000-fold using the optimum pretreatment time (30 min), and was 12-fold when the pretreatment time (4 hr) was the same as the duration of the antisecretory assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Antiulcer effect of rioprostil, a prostaglandin E1 analog, in combination with antacid.

Rioprostil, a primary alcohol prostaglandin E1 analog, is currently undergoing clinical evaluation for use in the treatment of peptic ulcer disease. Since antacids are often used in conjunction with other antiulcer agents, studies were conducted to determine if concomitantly administered antacid modifies the antiulcer activity of rioprostil. This investigation showed that concomitant administration of antacid (0.25-1.0 ml Maalox) does not inhibit the ability of rioprostil (0.125-4.0 micrograms/kg, p.o.) to prevent ethanol-induced gastric lesions in rats. The antiulcer effect of the drug combination was additive, suggesting that each compound acts independently to prevent gastric bleeding. These results in animals suggest that clinically the use of antacid will not compromise the efficacy of rioprostil and that the combination may be a useful mode of therapy for the treatment of peptic ulcer disease.

Alprostadil↗
PubMed1986

Pharmacology of ORF 17578, a new histamine H2-receptor antagonist: comparison with cimetidine and ranitidine.

This paper describes the pharmacology of ORF 17578, a new histamine H2-receptor antagonist, in comparison to the standard H2-blockers cimetidine and ranitidine. ORF 17578 inhibited betazole-stimulated gastric acid output in gastric fistula dogs and gastric acid secretion in pylorus-ligated rats. When administered enterally (p.o. or i.d.) ORF 17578 (ED50 = 0.21 mg/kg in dogs and 2.5 mg/kg in rats) was 10 to 11 times more potent than cimetidine and 1.8 to 2.1 time more potent than ranitidine in dogs and rats. In both species, duration of p.o. antisecretory activity was longer than with ranitidine. When administered parenterally ORF 17578 (ED50 = 0.15 mg/kg i.v. in dogs and 1.1 mg/kg i.p. in rats) was more potent than cimetidine and ranitidine in rats and similar in potency to ranitidine in dogs. Comparison of parenteral to enteral potencies suggests that ORF 17578 was well absorbed from the gastrointestinal tract of both species with a bioavailability profile similar to that of ranitidine. In rabbit isolated parietal cells (pA2 = 7.53) and guinea-pig isolated atria (pA2 = 7.26), ORF 17578 competitively antagonized the effects of histamine with a potency greater than cimetidine and similar to ranitidine. Results from several additional test systems indicated that ORF 17578 was specific for the histamine H2-receptor and did not exhibit the additional pharmacology often associated with cimetidine.

Animals↗
PubMed1986

Pharmacological comparison of ORF 17910, a potent, long-acting histamine H2-receptor antagonist, to cimetidine and ranitidine.

This paper describes the pharmacology of ORF 17910, a specific, long-acting histamine H2-receptor antagonist. ORF 17910 (ED50 = 0.26 mg/kg) is 26 and 2.7 times more potent p.o. than cimetidine and ranitidine, respectively, at inhibiting acid output in betazole-stimulated total gastric fistula dogs. When given i.v., ORF 17910 (ED50 = 0.06 mg/kg) is 3.6 times more potent than ranitidine. Qualitatively similar antisecretory potency differences are seen in rats (ED50 = 3.7 mg/kg intraduodenal). ORF 17910 retains 43 and 37% of its antisecretory potency 16 hr after dosing in dogs and rats, respectively, suggesting a long duration of action, whereas ranitidine is either inactive (rats) or loses 97% of its potency (dogs) at this time. When the parenteral and enteral (p.o. or intraduodenal) potencies of ORF 17910 and ranitidine are compared, ORF 17910 appears less bioavailable than ranitidine, although this difference is greater in the rat than in the dog and diminishes with time. In rabbit isolated parietal cell (pA2 = 7.96) and guinea pig isolated atria preparations (pA2 = 7.51), ORF 17910 is more potent than both cimetidine and ranitidine at inhibiting the effects of histamine. At high concentrations, the inhibitory effect of ORF 17910 in atria can not be overcome completely, a property which may contribute to its long duration of action in vivo. In several additional test systems, ORF 17910 does not exhibit any biologically significant pharmacology and appears to be specific for the histamine H2-receptor.

Androgen Antagonists↗
PubMed1986

Pharmacological profile of etintidine, a new histamine H2-receptor antagonist.

Etintidine is a potent competitive antagonist of histamine H2-receptors. It is 4.6 and 2.2 times more potent than cimetidine in the isolated guinea pig atrium (pA2 = 7.18) and the isolated rabbit parietal cell (pA2 = 6.51), respectively. Etintidine is 2.0 (ED50 = 1.8 mg/kg, i.g.) times more potent than cimetidine at inhibiting betazole-stimulated total acid output in the chronic gastric fistula dog. In the 4 hr pylorus-ligated rat etintidine is a potent inhibitor of total acid output (ED50 = 22 mg/kg, i.d.), total pepsin output, and is well absorbed from the gastrointestinal tract. Additional pharmacological and biochemical studies indicate that etintidine displays minimal competition with appropriate ligands for the alpha 1, alpha 2, cholinergic and neuroleptic receptors in vitro, and has minimal effects on the immunological, autonomic and central nervous systems at doses much higher than antisecretory doses. While high doses of both cimetidine and etintidine increase serum prolactin levels in rats, the effect of etintidine is less than that of cimetidine. Similarly, the prolongation of hexobarbital-induced sleep time in rats is less than with cimetidine. These data indicate that etintidine may be potentially useful and safe in the treatment of peptic ulcer disease and may offer some advantages over cimetidine in terms of less potential for side effects.

Animals↗
PubMed1986

Preoperative localization and intraoperative glucose monitoring in the management of patients with pancreatic insulinoma.

Whipples triad of hypoglycemic episodes associated with fasting blood sugar levels of less than 50 milligrams per 100 milliliters with relief of the symptoms by the administration of glucose intravenously leads to the clinical diagnosis of insulinoma. This diagnosis can be confirmed in a laboratory by the biochemical measurement of an inappropriate insulin elevation in response to fasting or the infusion of calcium or tolbutamide. Since more than 90 per cent of the tumors are benign, the potential for operative cure is high. Unfortunately, because of multicentricity (12 to 13 per cent) and the frequent small size of the tumor, some series report 15 to 30 per cent of inadequate or failed operations. Preoperative localization, in most centers, has depended upon sonography (positive in one of six patients in our series), computerized tomographic scanning (positive in one of five patients), celiac axis angiography (positive in six of 15 patients) and transportal venous sampling for insulin levels (positive in 11 of 13 patients in our series). We found that the combination of arteriography and transportal sampling has been the most accurate means of precise preoperative localization. In conjunction with preoperative localization, we have used intraoperative monitoring of glucose levels as a guide to the completeness of resection of insulin producing tumors. Sustained elevation of blood glucose levels has confirmed the adequacy of surgical intervention. Failure of the blood sugar level to increase had led to the successful search for additional tumors not identified preoperatively or to further resection. The combination of arteriography, transportal sampling and monitoring of glucose levels has led to the cure of 15 patients operated upon at the Mount Sinai Hospital from 1977 to 1984.

Adenoma, Islet Cell↗
PubMed1986

Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and arthritic rats.

Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.

Animals↗
PubMed1985

Colonic variceal hemorrhage: diagnosis and management.

Lower gastrointestinal bleeding colonic varices is infrequent. We report a patient in whom the diagnosis was made by angiography and in whom portosystemic shunt has been helpful. We believe that the treatment of choice for colonic varices is portosystemic shunt, as attempts at resection, judged by the reports in the literature, have usually resulted in death.

Colon↗
PubMed1984

Characterization of the enhanced paw edema response to carrageenan and dextran in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

Rats pretreated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 10 micrograms/kg) are supersensitive to the edemagenic effects of carrageenan and dextran as indicated by the increased potency of these irritants in TCDD-treated animals compared to controls. This effect of TCDD was characterized using indomethacin, dexamethasone and a combination of cyproheptadine and pyrilamine as inhibitors of edema formation. Because TCDD increases the potency of carrageenan and dextran, it was necessary to select appropriate doses of the edemagenic irritants in order to evaluate the effect of edema inhibitors properly. At low and moderate irritant doses, TCDD-treated and control rats exhibited similar responses to inhibitory agents, suggesting that the mechanisms by which carrageenan and dextran produce edema involve the same mediators in control and TCDD-treated animals. The effect of TCDD on edema induced by bradykinin, histamine, prostaglandin E2 and serotonin, substances which are postulated endogenous mediators of carrageenan-, dextran- and/or compound 48/80-induced edemas, was also examined. Inasmuch as TCDD increased the edemagenic potency of bradykinin and histamine, but not that of prostaglandin E2 or serotonin, it was concluded that TCDD enhances carrageenan-, dextran- and compound 48/80-induced edema formation by augmenting the edemagenic activities of bradykinin and histamine. It is postulated that the mechanism of enhancement may involve TCDD-induced potentiation of the ability of bradykinin and histamine to stimulate phospholipase activity in vascular endothelial cells.

Animals↗
PubMed1983

Enhancement of carrageenan and dextran-induced edemas by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

Paw edema formation after the subplantar injection of carrageenan was enhanced in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The enhanced carrageenan response could be detected as early as 4.5 hr after TCDD; however, the magnitude of enhancement was greatest when rats were challenged with carrageenan 5 days after TCDD. In the latter case, the ED50 of TCDD in enhancing the carrageenan response was 6 micrograms/kg. TCDD also enhanced dextran-induced paw edema, which follows a time course different from that of carrageenan-induced edema and is produced by a different mechanism. The enhancement of carrageenan and dextran paw edemas was due to an increase in the edema-producing potency of the irritants and not to a change in their maximum effect. The ability of other 3-methylcholanthene-type inducers to enhance carrageenan-induced paw edema and the inability of phenobarbital-type inducers to cause the response suggest that the TCDD binding protein might be involved in edema enhancement. TCDD also enhanced carrageenan-induced pleural edema; however, the number and type of leukocytes recovered in the pleural exudate was not affected. TCDD did not alter granuloma formation produced by the subcutaneous implantation of cotton pellets, indicating that enhancement by TCDD was peculiar to edema formation and not to inflammation in general. It is suggested that TCDD may enhance carrageenan and dextran edemas by increasing the availability of mediators involved in each type of edema formation and/or by increasing the responsiveness of the vasculature to mediators.

Animals↗
PubMed1983

Hydrothorax as a late complication of central venous indwelling catheters.

Two cases of delayed onset hydrothorax following central venous catheterization are reported. Both involved left internal jugular vein percutaneous insertion sites, and chest roentgenograms of both demonstrated that the catheter tips were juxtaposed against the superior vena cava wall. Although both catheters functioned well for several days, we believe that this left neck site allowed for catheter tip motion, resulting in delayed perforation of the vessel. To avoid this complication we recommend that central venous catheters be checked routinely for position, with the catheter tip being parallel to the vessel wall. The left neck approach should be avoided if possible because of anatomic and mobility problems. These cases emphasize the fact that hydrothorax can occur long after successful catheter insertion, and they demonstrate the need to have continued suspicion of the possibility of this occurrence.

Aged↗
PubMed1982

Tissue carcinoembryonic antigen, dysplasia, and disease duration in colonic inflammatory bowel disease.

Tissue carcinoembryonic antigen (CEA) was studied in five groups of patients: eight ulcerative colitis patients with mild or no dysplasia, five ulcerative colitis patients with severe dysplasia, seven Crohn's disease patients with nondiseased colon, nine Crohn's disease patients with diseased colon, and 18 colorectal cancer patients from the noncancerous colon resection margins. CEA levels were significantly lower in the normal colon Crohn's group than all other groups (p less than 0.05). CEA levels were significantly higher in the severe dysplasia ulcerative colitis group than all other groups (p less than 0.05). The Crohn's disease patients with diseased colon, the ulcerative colitis patients with mild or no dysplasia, and the colorectal cancer group with noncancerous colon all had similar intermediate CEA levels.

Carcinoembryonic Antigen↗