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Biomedical subjects

C J Pfeiffer

Publications and source records attributed to C J Pfeiffer.

At least 73 records · Page 4Linked to original sources

Ultrastructure of the stomach of the small short-tailed shrew, Blarina brevicauda c.

The normal gastric ultrastructure has been characterized for the small short-tailed shrew, Blarina brevicauda c., which is a primitive eutherian and one of the smallest living mammals with extraordinarily high metabolic rate. In general the cell types present and cytologic character of gastric mucosal, submucosal, and muscularis cells were similar to that reported for other more advanced small mammalian species. Chief cells, endocrine cells, and lamina proprial elements were morphologically identical to their counterpart in rats, ferrets and other small carnivores. Distinctive cytologic features in this species of shrew included the scanty monolayer or small number of mucous granules in the simple columnar surface epithelial cells of the mucosa, and the thin elongated shape of their microvilli. Dense bodies were absent in the parietal cell mitochondria of the shrew, though usually abundant in other mammalian parietal cells. Our data indicate few morphologic specializations in the shrew stomach which can be correlated with their high rate of food assimilation and metabolic demands, though future studies of mucosal biochemistry and lower gut morphology may reveal such adaptations.

Animals↗

Pathogenesis of gastric ulceration produced by acetazolamide in rats.

The present experiment demonstrated that relatively high doses of acetazolamide (100 and 200 mg/kg s.c.) induced severe gastric hemorrhagic ulceration in rats. This ulceration was aggravated by oral administration of HC1, but was inhibited by NaHCO3. Further, the severity of ulceration was also decreased by pretreatment with methysergide, chlorpheniramine, or cimetidine. These protective effects were affirmed by an increase in serotonin and histamine released from the stomach after acetazolamide treatment. Acetazolamide injection also increased the protein level, but reduced the sialic acid content in the gastric secretion, indicating that the gastric mucosal barrier may have been damaged. Prostaglandin E2 content of the gastric mucosa was not affected by the drug; however, carbonic anhydrase activity was markedly reduced in a dose-dependent manner. Thus, it is suggested that the ulceration induced by acetazolamide is mainly due to the inhibition of carbonic anhydrase activity and mucus secretion. The increases in serotonin and histamine released may also have been contributing factors for gastric ulcer formation.

Acetazolamide↗

Study of the damaging effects of acetazolamide on gastric mucosa in rats.

The present study demonstrated that acetazolamide (100 and 200 mg/kg, s.c.) induced severe gastric hemorrhagic ulceration in rats. The ulceration was aggravated by oral administration of HCl, but was inhibited by NaHCO3. Furthermore, the severity of ulceration was also decreased by pretreatment with methysergide, chlorpheniramine, or cimetidine. These protective effects were accompanied by an increase in serotonin and histamine released from the stomach. Acetazolamide injection also increased the protein level but reduced the sialic acid content in the gastric secretion, indicating that the gastric mucosal barrier may have been damaged. Prostaglandin E2 content of the gastric mucosa was not affected by the drug; however, carbonic anhydrase activity was markedly reduced in a dose-dependent manner. Thus, it is suggested that the ulceration induced by acetazolamide is mainly due to the inhibition of carbonic anhydrase activity and mucus secretion. The increase in serotonin and histamine release also may have been the contributing factors for gastric ulcer formation.

Acetazolamide↗

Susceptibility of healed gastric ulcers to chemical carcinogenesis in rats and implications of cellular kinetic changes.

The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty-eight adenomatous hyperplasias and six-adenocarcinomas developed in the pyloric mucosae of rats, including five cases of adenomatous hyperplasia which developed in the periphery of the healed ulcer. In contrast, only one adenomatous lesion was found in the regenerated mucosa of the healed pyloric ulcer. No neoplasm was observed in the healed fundic ulcer area. The results demonstrated an increased incidence of neoplasms in the peripheral area of the healed pyloric ulcer and a decreased incidence of neoplasms in the regenerated mucosa within the healed pyloric ulcer scar, although these differences were not statistically significant in comparison with the intact pyloric mucosae of the MNNG-treated rats. Histoautoradiographs of the gastric mucosae demonstrated increased labeling indices in the healed ulcer periphery of the pyloric mucosa and decreased labeling indices in the regenerated mucosa within the healed pyloric ulcer scar of MNNG-treated rats, which might be related to the differential susceptibility of the two regions to gastric carcinogenesis. Intestinal metaplasia preferentially developed near the pyloroduodenal junction in MNNG-treated rats but was not localized in control rats. In the fundic ulcer scar area, an unusual squamous cell metaplasia was observed in one rat.

Animals↗

Trophic effects of cholecystokinin octapeptide on the pancreas of the Syrian hamster.

Repeated subcutaneous injections of cholecystokinin octapeptide (CCK-OP) to Syrian golden hamsters for 10 days elicited a marked trophic effect on the pancreas, characterized by increased pancreatic weight and increased RNA/DNA ratios with an enhanced content of amylase in the pancreas in treated hamsters. These responses were observed after relatively small doses (100--300 ng CCK-OP x day-1 . 100 g body weight-1) of the hormone over a 10-day period. Although there was a small increase in total pancreatic DNA there was no definite evidence of hyperplasia in response to CCK-OP. DNA synthesis, as measured by histoautoradiography of tritiated thymidine labelled tissues, was increased in pancreatic acinar and islet cells, but not in ductal cells. This investigation, therefore, demonstrates a trophic action of CCK on the pancreas of the hamster similar to that reported for the rat and this may have relevance in studies of carcinogenesis since the hamster is an established species for studying pancreatic cancer.

Amylases↗

Experimental studies on the pathophysiology of peptic ulcer disease.

The pathophysiology of clinical peptic ulcer, which is diverse for duodenal, chronic gastric or stress ulcer in humans, has been only partially elucidated by experimental animal studies. A central role of vascular disturbance and acid back diffusion for human stress and animal stress ulcers is evident, whereas a complex and variable set of functional disorders may relate to duodenal ulcer, though the role of acid is paramount. Mucosal resistance factors are of major importance in all types of ulcer and are of particular interest in chronic gastric ulcer. The importance of selecting, for anti-ulcer drug testing, appropriate ulcer models is emphasized, and more extensive use of chronic experimental ulcer healing rate changes, mucus glycoprotein analysis, and cytoprotective changes is recommended. Novel compounds such as pirenzepine, which act on some muscarinic receptors, will help elucidate ulcer pathophysiology as well as provide medical therapy, particularly since all postganglionic vagal transmitter substances in gastric or duodenal mucosae have not yet been identified.

Animals↗

Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1- and H2-blocking agents.

Histamine is known to induce gastric ulcers in guinea pigs after intraperitoneal administration and duodenal ulcers after repeated intramuscular administrations. This study was undertaken to clarify further the differential role of H1 and H2 receptor sites in respect to gastric and duodenal ulcer in the guinea pig. Groups of guinea pigs were treated with histamine, intraperitoneal (1.81 mg/kg intraperitoneal) or intramuscular (0.09 mg/kg intramuscular X 8 doses); the selective H2 agonist dimaprit (0.09-0.18 mg/kg X 8 doses intramuscular or 1.81-3.62 mg/kg intraperitoneal); NaCl, 154 mM (control); and the selective H1 and H2 antagonists, diphenhydramine (125 mg/kg X 2 doses, intramuscular) or cimetidine (50 mg/kg X 3 doses, intramuscular). Gastric and duodenal lesions were evaluated and residual gastric contents were analyzed. The selective induction of gastric or duodenal ulceration by histamine was confirmed, and the H2 agonist, dimaprit, has been shown to be ulcerogenic to the guinea pig duodenum by intraperitoneal or intramuscular administration. Diphenhydramine produced considerably more protection against histamine-induced gastric ulceration (62% decrease in incidence), while cimetidine was particularly effective in the prevention of histamine-induced duodenal ulcer (64% decrease in incidence). A differential role of histamine in the pathogenesis of gastric as opposed to duodenal ulcer is suggested by the present findings.

Animals↗

Endoscopic diagnosis of intestinal metaplasia in Canada and Japan.

We carried out comparative studies on chronic atrophic gastritis with accompanying intestinal metaplasia using the methylene blue dye spraying, endoscopic technique on 167 Japanese and 77 Canadian outpatients free of gross stomach disease. In both population samples (Kyoto, Japan and St. John's, Newfoundland) with increasing subject age, the fundic-pyloric (F-P) border shifted cephalad indicating atrophy of the fundic mucosal glands. Japanese subjects, however, showed greater variation in location of the F-P border. The reduction in fundic gland area with aging was followed by intestinal metaplasia, the incidence and severity of which was greater in Japanese than in Canadian outpatients. From these data we conclude that a difference in the gastric mucosa in these two countries may be related to the pathogenesis of gastric cancer.

Adult↗

Experimental analysis of hydrogen ion diffusion in gastrointestinal mucus glycoprotein.

Experiments were undertaken to test the hypothesis that mucus glycoproteins retard the diffusion of hydrogen ions, a possible protective action of gastric mucus. Mucus and mucus glycoproteins (visible mucus, crude mucin, mucus glycoprotein fractions) were evaluated in two devices designed for this test, a linear diffusion chamber and a hydrogen ion flux chamber. The linear diffusion chamber assessed ion diffusion from a point source through mucus glycoproteins to a H+ detector. A mathematical model of diffusion, based on Fick's law, was adapted to characterize diffusion in this chamber. The H+ flux chamber assessed H+ flux rates across a steep concentration gradient through controlled amounts of mucus glycoprotein. With the exception of human sulfomucin, tested only at dilute concentrations and only in the flux chamber, both procedures indicated that mucosubstances retarded, in a dose-related manner, diffusion of hydrogen ions. Experiments on buffering by crude porcine gastric mucin did not demonstrate significant buffering under physiological conditions. Thus, the present experimental data, the principles of which should be extrapolative to the mucous barrier at the biological level, suggest that mucus glycoproteins can in fact inhibit the diffusion of hydrogen ions.

Animals↗

Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc.

The effects of graded doses of zinc sulfate pretreatment on reserpine-induced gastric ulceration and on lysosomal fragility both in vivo and in vitro, were studied in rats. Reserpine treatment (5 mg/kg, i.p., 18 h before sacrifice) induced marked gastric glandular ulceration and elicited the release of free beta-glucuronidase from lysosomes in the gastric mucosa. A similar effect on release of this enzyme from isolated rat hepatic lysosomes was observed after in vitro incubation with reserpine. Zinc sulfate (22, 44 or 88 mg/kg, i.p., 30 h before reserpinization, or 10(-3) M in vitro) inhibited the reserpine-induced response, and zinc sulfate alone (10(-11)--10(-3) M) also stabilized lysosomal membrane permeability to beta-glucuronidase. No direct effect of zinc or reserpine on purified beta-glucuronidase activity was observed. In conclusion, it is postulated that the stabilizing effect of zinc on lysosomal membranes, as manifest by reduced release of beta-glucuronidase from isolated lysosomes, is one of the protective mechanisms of zinc against reserpine-induced ulceration.

Animals↗

Studies of zinc and histamine on lysosomal fragility: possible role in stress ulceration.

A combined in vivo and in vitro study was undertaken with rats to test the hypothesis that zinc would protect against cold water immersion--restraint gastric ulcers, and that this phenomenon was mediated in part by stabilization of lysosomal membranes. This postulate was confirmed by observed activity changes in released beta-glucuronidase in mucosal tissue, as well as by dose-response in vitro data on isolated hepatic lysosomes exposed to zinc. Histamine, a known ulcer-enhancing agent, induced the opposite effect and increased the lysosomal release of this marker acid hydrolase.

Animals↗

Inhibition by zinc of hepatic lysosomal release of beta-glucuronidase induced by phorbol-12-myristate-13-acetate (PMA).

The tumor promoter, phorbol-12-myristate-13-acetate (PMA), elicited a significant increase in lysosomal membrane permeability, as measured by release of free beta-glucurnidase, in guinea pig and hamster isolated hepatic lysosomes in vitro. This response was antagonized by zinc sulfate; zinc compounds having previously been shown to inhibit tumor growth at multiple sites in several species. Since phorbol ester tumor promotion is likely associated in part with actions on cellular membrane systems, its inhibition by zinc may relate to the membrane stabilizing activity of zinc compounds.

Animals↗

Modulating effect by zinc on hepatic lysosomal fragility induced by surface-active agents.

In vitro studies on rat hepatic lysosomal stability, as assessed by release of beta-glucuronidase, were undertaken to demonstrate the comparative influence of surface-active agents which act by various mechanisms. Bile acids, short chain alcohols, acetylsalicylic acid, and Triton X-100 were studied, as well as their interaction with zinc. The detergents and alcohols enhanced release of this acid hydrolase in a dose dependent fashion, but acetylsalicylic acid did not. Zinc antagonized these effects in a non-specific manner. It is postulated that zinc stabilized lysosomes by direct action on the lysosomal membrane, such as by surface protein interactions, but the precise mechanism remains unknown.

Alcohols↗

Spontaneous regressive epitheliomas in the Japanese newt, Cynops pyrrhogaster.

Spontaneous tumors in urodele amphibians have been considered uncommon, and this resistance has sometimes been associated with the natural regenerative capacity of tissues in such species. This report describes spontaneous, nonpigmented, benign epitheliomas which were found in 44 of 1586 (2.8%) adult newts, Cynops pyrrhogaster, captured in central Japan. Both sexes were affected equally, usually with single tumors occurring at any epidermal site. Under laboratory conditions, these large tumors rapidly regressed or disappeared. Lesions were histologically noninvasive, hyperplastic epidermal reactions accompanied by loss of basal, subdermal melanocytes. Ultrastructurally, enlargement of intercellular spaces between tumor cells, increased pigment granules and membrane-bound cytoplasmic aggregates within the spaces, swollen rough endoplasmic reticula, degenerating pigment granules, and altered corneal cells were noted. Virus-like particles were observed in one tumor cell. Prelminary attempts failed to demonstrate transmissibility of the tumor, and no new cases arose under laboratory conditions. The cause of these tumors in the Japanese newt remains unknown, and it is suggested that if a viral agent is involved then other environmental cofactors (diet, temperature, or water constituents) are required for its expression.

Animals↗

Experimental production of diffuse colitis in rats.

Diffuse, topical application of dilute acetic acid to the serosal surface of rat colon, or standardized intraluminal (per rectum) instillation induced a reproducible, diffuse colitis in a dose-response manner. These lesions were reproduced with 100% reliability and were evaluated up to 60 days when healing occurred. Histopathological features of this chemically induced colitis were diffuse ulceration of the distal colon, occurrence of pseudopolyp-like structures, alterations in crypt depth and mucus secretion, and a transmural, nonspecific inflammatory response.

Acetates↗

Seabirds--a possible environmental factor in gastric cancer in Newfoundland.

Because of the high incidence of gastric cancer in fishermen, in seabird catchers, and in regions generally associated with a temperate or cool marine environment, the association of seabirds with gastric cancer risk was investigated regionally in Newfoundland. Cartographic plotting and correlation analyses of 23 individual or combined regions of Newfoundland with respect to M, F or M + F mortality rates showed a close similarity between high risk areas and large seabird aggregations which were in the southeast region of the island. Coastal fish processing plants were also prevalent focal points in this region between fishermen and seabird populations, suggesting that a chemical or viral carcinogen should be sought within this triad of fishermen, seabirds, and fish plants.

Animals↗

Novel telemetric system for extraluminal measurement of gastrointestinal motility.

A frequency-modulated, telemetric system with a transducer sensitive to variation in distance between two points was developed and used to measure in vivo small intestinal motor function in unanesthetized dogs. The construction of the system and one application of it to the study of gastrointestinal motility is described. Data were recorded after fasting, 1 h after feeding a standardized meat meal, and after intravenous injections of pentagastrin. A significant increase in motility was seen after pentagastrin injections and feeding as compared to the motility pattern seen in a fasting animal, and the telemetric system was proven adequate for in vivo measurement of motility of the gastrointestinal tract.

Animals↗