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Biomedical subjects

E Kivilaakso

Publications and source records attributed to E Kivilaakso.

At least 127 records · Page 7Linked to original sources
PubMed1984

HCO3- secretion and surface pH gradient in rat duodenum exposed to luminal acid.

A pH gradient is maintained at the surface of rat duodenum exposed to luminal acid. The alkalinity and thickness of this gradient are dependent on the rate of surface epithelial HCO3- secretion (transport into the lumen). Acidification of the luminal solution stimulates HCO3- secretion and enhances the alkalinity at the mucosal surface by a mechanism dependent on endogenous prostaglandin synthesis. This stimulated HCO3- secretion is quantitatively sufficient to maintain neutrality at the epithelial surface of the mucosa even in the presence of as high luminal acidity as pH 2.0, which is the maximal 'physiologic' acidity within human duodenal bulb. Exogenous prostaglandin E2 increases HCO3- secretion as well as the dimensions of the pH gradient, which may, in part, account for its cytoprotective actions in gastroduodenal mucosa. The findings suggest that epithelial HCO3- secretion in the duodenal mucosa has a protective function by forming an unstirred alkaline layer at the mucosal surface which impedes the diffusion of luminal acid into the mucosa.

Acetazolamide↗
PubMed1983

Morphological alterations in experimental esophagitis. Light microscopic and scanning and transmission electron microscopic study.

The morphology of esophagitis, both in the presence and absence of acid, was studied by light microscopy and transmission and scanning electron microscopy. For this purpose the rabbit esophagus was isolated in situ and perfused with agents known to cause esophageal mucosal damage (HCl, pepsin, taurocholate, and deoxycholate). In addition, changes in the permeability of the plasma membrane of the esophageal epithelial cells were assessed by staining the esophageal epithelium with trypan blue and antinuclear antibodies. The results indicate that HCl alone causes relatively few changes in the esophageal epithelium. However, when combined with pepsin or taurocholate, severe ulcerative changes were caused within an hour. Deoxycholate, which is formed in the upper gastrointestinal tract under nonacidic conditions, also causes severe damage. Further, it was shown that the esophagitis caused by pepsin and bile salts are clearly morphologically different. Bile salts affect primarily the cell membrane and intracellular organelles, while pepsin seems to affect the intercellular substance causing the epithelial cells to be shed. In contrast, the presence or absence of acid per se does not seem to influence the nature of the epithelial damage, since the lesions caused by the two bile salts (deoxycholate vs taurocholate + HCl) were morphologically similar.

Animals↗
PubMed1983

Early detection of acute fulminant pancreatitis by contrast-enhanced computed tomography.

Twenty-eight consecutive patients with a first attack of acute alcohol-induced pancreatitis were examined by computed tomography (CT). After a survey scan of the abdomen a rapid contrast bolus (400 mg I/kg) was given intravenously, and the contrast enhancement of the pancreatic parenchyma was measured from a consecutive series of pancreatic scans. Nine patients with a fulminant course of the disease were operated on, and haemorrhagic necrotizing pancreatitis was found in eight. In all of these the contrast enhancement was decreased or absent. Patients recovering by conservative treatment showed normal or increased enhancement. The contrast enhancement seems to constitute a useful criterion for the early differentiation of acute fulminant pancreatitis from less severe forms of the disease.

Acute Disease↗
PubMed1983

Contribution of ambient HCO3- to mucosal protection and intracellular pH in isolated amphibian gastric mucosa.

The relationship between mucosal protection by ambient HCO3- and its impact on intracellular pH was studied in isolated frog gastric mucosa. Closed sacs of gastric mucosa, containing exogenous HCl and pepsin, readily ulcerated when incubated in Ringer solution devoid of HCO3-, but were effectively protected against ulceration when ambient HCO3- was present. This protection was abolished by blocking anion exchange in cell membrane by 4-acetamido-4'-isothiocyanostillbene-2,2'-disulfonic acid or by inhibiting mucosal carbonic anhydrase by azetazolamide. Intracellular pH, measured by the 14C-labeled 5,5-dimethylxazolidine-2,4-dione method, was significantly higher when open sheets of mucosas were incubated in a medium containing HCO3- than when they were incubated in a medium devoid of HCO3- at the same external pH. Furthermore, a positive pH gradient across the cell membrane (intracellular pH was greater than extracellular pH) was generated only if HCO3- was present in the incubation medium. 4-Acetamido-4'-isothiocyano-stillbene-2,2'-disulfonic acid completely abolished these effects of ambient HCO3- on intracellular pH, suggesting that ambient HCO3- contributes to intracellular pH by acting as an intracellular base. In contrast, acetazolamide had no significant influence on these effects, suggesting that carbonic anhydrase acts in the protective mechanism distally to the entry of HCO3- into the cell. The data indicate that ambient HCO3- significantly contributes to intracellular pH in the gastric mucosa, a feature that may enhance the ability of the mucosa to withstand intraluminal acid.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

Demonstration of a pH gradient at the luminal surface of rat duodenum in vivo and its dependence on mucosal alkaline secretion.

The relationship between surface epithelial alkaline secretion and pH at the mucosal cell surface was studied in the duodenum of anesthetized rats. Alkaline secretion was measured by direct titration in situ using perfused segments of duodenum just distal to the Brunner gland area and devoid of pancreatic and biliary HCO3-. Mucosal surface pH was measured by advancing a pH-sensitive antimony microelectrode from the luminal solution to the mucosal cell surface during continuous recording of pH. Acidification of the luminal solution markedly stimulated epithelial alkaline secretion: a change of luminal pH from 7.60 to 5.00 by approximately 100%, and from pH 7.60 to 2.00 by approximately 600%. Maximal pH in the immediate vicinity of the (luminal) cell surface remained at or slightly above neutrality during exposure to both luminal acidities. Prostaglandins (E2, 16,16-dimethyl E2, and F2 alpha, 3-140 microM luminally) increased the rate of alkaline secretion, surface alkalinity, and thickness of the pH gradient. Acetazolamide (40-80 mg/kg, i.v.) was a much more potent inhibitor of prostaglandin or acid-stimulated secretion than of basal alkaline secretion and decreased surface pH in acid-exposed duodenum. Aspirin (30 mg/kg, i.v.) had no effect on basal alkaline secretion (titrated at luminal pH 7.60) but significantly inhibited secretion at luminal pH 2.00, resulting in a decrease of surface pH. These data suggest that endogenous prostaglandins may be involved in mediating the alkaline response to luminal acid. Furthermore, because it is quantitatively sufficient to maintain neutral pH at the mucosal cell surface at luminal acidities normally encountered within the duodenal bulb, epithelial alkaline secretion presumably has an important role in duodenal protection against acid.

Acetazolamide↗
PubMed1983

Role of bile salts and trypsin in the pathogenesis of experimental alkaline esophagitis.

The pathogenesis of alkaline reflux esophagitis was investigated in an experimental model by assessing individually the influence of different bile salt moieties and trypsin on esophageal mucosa. An isolated segment of rabbit esophagus was perfused at pH 7 with a solution containing the test agent under study, and the severity of mucosal damage was assessed by using as indicators of mucosal integrity transmucosal potential difference, net flux of Na+, and mucosal permeability to two neutral molecules of different sizes, 3H-H2O and 14C-erythritol. The data indicate that the secondary dihydroxy bile salt, deoxycholate, in its deconjugated form was highly injurious to esophageal mucosa; it was the only test agent that caused gross mucosal lesions during the experiment. The respective conjugated bile salt moiety, taurodeoxycholate, had a weaker effect. Also the primary dihydroxy bile salt, chenodeoxycholate, in its deconjugated form caused moderate damage to the mucosa, whereas its conjugated form, taurochenodeoxycholate, had no effect. The effect of the other three bile salts tested--cholate, taurocholate, and taurolithocholate--was negligible. Trypsin also adversely affected the mucosa, but its effect was weaker than that of deoxycholate. The results suggest that the deconjugated bile salts deoxycholate and chenodeoxycholate (which are formed following bacterial colonization of the upper gastrointestinal tract in the absence of gastric acid), the conjugated bile salt taurodeoxycholate, and the proteolytic enzyme trypsin may have significant roles in the pathogenesis of alkaline reflux esophagitis.

Alkalies↗
PubMed1982

Bile acid composition and esophagitis after total gastrectomy.

Ten patients who had undergone total or subtotal gastrectomy for carcinoma 1 to 8 years earlier were evaluated in terms of subjective symptoms, endoscopy and the presence of bile in esophagojejunal aspirates obtained by direct aspiration during endoscopy. The concentrations of individual bile acids were determined by means of gas chromatography. Six of the patients had macroscopic esophagitis and all of them also had bile in their aspirate. The remaining four patients with normal esophageal mucosa did not have positive specimens. Neither did the total bile acid concentration nor any of the individual bile acids, regardless of whether they were free or conjugated, correlate with the severity of symptoms or the degree of endoscopic esophagitis. Esophagitis healed in all three patients who underwent conversion of loop esophagojejunostomy to a long Roux-Y reconstruction.

Adult↗
PubMed1982

Gastric blood flow, tissue gas tension and microvascular changes during hemorrhage-induced stress ulceration in the pig.

Various features of blood supply to the gastric mucosa were studied in the piglet stomach during stress ulceration induced by hemorrhagic shock. Gastric blood flow, as measured by the radioactive microsphere technique, significantly decreased during shock, but no major change occurred in the gastric function of total cardiac output. There was no difference in the magnitude of the decrease of mucosal blood flow between the nonulcerating antral mucosa and the more readily ulcerating corpus or fundic mucosa. At the same time, a significant decrease in tissue partial pressure of oxygen and increase in tissue partial pressure of carbon dioxide occurred, but again no difference was observed between the antrum and the corpus. Microangiographic studies demonstrated a clearly diminished filling of the arterial and capillary bed of the gastric mucosa during shock, suggesting intense vasoconstriction, thrombosis of the mucosal blood vessels, or both. These changes were more prominent in the corpus portion of the stomach than in the antrum. At the site of mucosal lesions, the filling defects persisted even after the shock, suggesting permanent thrombosis of the blood vessels.

Angiography↗
PubMed1982

Decreased prevalence of gallstones in gastric cancer.

The prevalence of gallstones and the frequency of previously performed cholecystectomy were examined in 498 autopsy subjects who had gastric cancer and their age- and sex-matched control subjects. The frequency of gallstones not treated by operation and previous cholecystectomy was significantly (p less than 0.01) lower in those with gastric cancer than in the matched-control subjects. It is not possible to determine on the basis of this study what the possible factors that cause this phenomenon are.

Adult↗
PubMed1982

Inhibition of gastric mucosal carbonic anhydrase by taurocholic acid and other ulcerogenic agents.

Carbonic anhydrase, an enzyme catalyzing hydration of CO2 and vice versa, is exceptionally abundant in the gastric mucosa, including the surface epithelial cells where it seems to have a protective function. The present study evaluated various ulcerogenic agents in terms of their ability to influence the activity of carbonic anhydrase in the gastric mucosa. Taurocholic acid, acetylsalicylic acid, and ethanol all significantly inhibited carbonic anhydrase derived from gastric mucosa of the rat in in vitro conditions, and this inhibition occurred in concentrations that are likely to be present within the stomach. In contrast, lysolecithin and urea had no effect on carbonic anhydrase activity. In in vivo situations, intragastric taurocholic acid (20 mM) likewise significantly inhibited the activity of carbonic anhydrase in the gastric mucosa. The inhibition was stronger in the presence of luminal acid (hydrochloric acid, 100 mM) than in the absence of it. In contrast, intragastric acetylsalicylic acid (20 mM) or ethanol (20 percent vol/vol) had no effect. Yet, intravenous acetylsalicylic acid (20 mg/kg body weight) did have a slight but significant inhibitory action. The results indicate that taurocholic acid is able to inhibit gastric mucosal carbonic anhydrase, a feature which may contribute to its ulcerogenic action. Even though acetylsalicylic acid and ethanol likewise inhibit gastric carbonic anhydrase in vitro conditions, their action in in vivo situations remains questionable.

Animals↗
PubMed1982

Serum phospholipase A2 and pulmonary changes in acute fulminant pancreatitis.

Twenty-three patients with acute fulminant pancreatitis were studied. The diagnosis was confirmed at laparotomy in every case. Blood samples for the assay of phospholipase A2 were collected for 14 days, and the pulmonary status of the patients was followed by monitoring the blood gases and the inspired oxygen fraction and studying a derived variable, the alveolar to arterial oxygen tension difference--the arterial oxygen tension ratio (A--aDo2/PaO2). The serum phospholipase A2 activities correlated with the changes in pulmonary function and with the outcome of the disease. Eight patients succumbed and they showed higher phospholipase A2 activities and A--aDo2/PaO2 ratios than the five patients who survived after major complications and the ten patients who survived without major complications. The results suggest that in acute fulminant pancreatitis serum phospholipase A2 activity correlates with the severity of the pulmonary changes. Furthermore, it seems to reflect the prognosis.

Acute Disease↗
PubMed1982

Antacids and bile salts.

Antacids, especially aluminium hydroxide, adsorb bile salts and lysolecithin with an affinity and capacity comparable to that of cholestyramine, a property which is likely to contribute to the beneficial effect of antacids in peptic ulceration. Dihydroxy bile salts are bound more strongly than trihydroxy bile salts and glycine conjugates more strongly than taurine conjugates, but ambient pH does not seem to have any effect on the binding. The bile salt-binding property of aluminium hydroxide may be of therapeutic value in the management of bile salt-induced diarrhoea, but its usefulness in the management of bile-reflux gastritis still remains questionable.

Adsorption↗
PubMed1982

Role of luminal H+ in the pathogenesis of experimental esophagitis.

The pathogenesis of acidic reflux esophagitis was investigated in an experimental model with special emphasis on the role of lumen-to-mucus diffusion of H+ in the pathogenetic mechanism. Esophageal damage was produced by perfusing an isolated segment of rabbit esophagus in situ with three injurious endogenous secretions of the upper gastrointestinal tract (taurocholate, 10 mM; pepsin, 2500 U/ml; lysolecithin, 2 mg/ml) with and without acid (HCl, 10 to 150 mM). The severity of mucosal damage was assessed using as indicators of mucosal integrity transmucosal potential difference, net flux of Na+, and mucosal permeability to two neutral molecules of different sizes--3H-H2O and 14C-erythritol. The data indicate that although the presence of luminal acid is needed for mucosal damage to develop, there is no relationship between the severity of the damage and the magnitude of the lumen-to-mucosa diffusion of H+. Even markedly increased diffusion of H+ alone, induced by an unphysiological high concentration of luminal acid (300 mM HCl), had only a minor influence on mucosal integrity, whereas all three test agents were able to cause severe mucosal damage in association with much lower rates of H+ diffusion. Furthermore, the severity of the mucosal damage caused by an individual test agent was not dependent on the HCl; concentration used (and hence on the magnitude of lumen-to-mucosa diffusion of H+). The data suggest that esophageal mucosal damage caused by taurocholate, pepsin, or lysolecithin in the presence of luminal acid is due to the direct action of the agent itself rather than to excessive accumulation of luminal H+ into the mucosal tissue.

Animals↗
PubMed1982

Splenectomy for myelofibrosis.

In 30 consecutive splenectomies for myelofibrosis (MF) with cytopenia(s) and/or massive splenomegaly the operative mortality was 6.7% (2 patients). Postoperative complications were observed in 11 (37%) patients. When surgery was undertaken within one year of the diagnosis of MF the postoperative morbidity rate was 13% (2/16), but significantly (p less than 0.01) higher at 64% (9/14) in patients operated on later. A similar significant difference was observed in the amount of intraoperative blood loss. Of the patients undergoing splenectomy for anaemia and/or thrombocytopenia, 79% gained definite benefit from the operation for 2 to 70 months (median 10 months). It is concluded that, although splenectomy probably does not prolong the life of patients with MF, it gives considerable symptomatic relief in cases with massive splenomegaly, and can improve the patient's haematological status and reduce blood transfusion requirements. To avoid the increased risks of postoperative complications surgery is best undertaken as soon as cytopenia is present.

Aged↗
PubMed1981

Experimental ulceration of rabbit antral mucosa.

The mechanism of acute ulceration and the nature of mucosal protective mechanisms were investigated in rabbit antrum, which is more resistant to injury than fundus of the same species, with particular reference to the relationship between H+ back diffusion, tissue acidification, and occurrence of ulceration. Exposure of antral pouches to increasing luminal [H+] during short-term hemorrhagic shock caused progressive acidification of the mucosa as measured by a microelectrode in the lamina propria, but ulceration of the mucosa did not occur unless an unphysiologically high [H+] (225 mM) was used. Addition of exogenous pepsin to a luminal [H+] of 80 mM increased the rate of H+ back diffusion and the degree of mucosal acidification, but ulcerations did not develop, suggesting that endogenous pepsin does not account for the ulceration of fundic mucosa under the same experimental situation. In contrast, addition of sodium taurocholate (5 mM) to the same luminal [H+] (80 mM) produced ulcerations and increased the rate of H+ back diffusion. Systemic administration of acetazolamide, an inhibitor of carbonic anhydrase, enhanced the development of ulceration without increasing the rate of back diffusion or the degree of tissue acidification. The results suggest that rabbit antral mucosa is protected from excessive acidification and ulceration by its relative impermeability to H+. When the rate of H+ back diffusion is artificially augmented to a level encountered in the fundus in an ulcerogenic situation, profound acidification with ulcerogenic situation, profound acidification with ulceration also occurs in the antral mucosa. The data also suggest that carbonic anhydrase, an enzyme abundantly present in gastric mucosa, may have a protective function in the mucosa, possibly by contributing to the regulation of intracellular pH and/or to the maintenance of mucosal HCO3- secretion.

Acetazolamide↗