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Biomedical subjects

E F Stange

Publications and source records attributed to E F Stange.

At least 145 records · Page 8Linked to original sources
PubMed1988

The role of enterocyte cholesterol metabolism in intestinal cell growth and differentiation.

Cholesterol is an essential constituent of all mammalian cell membranes, and its availability is therefore a prerequisite for cellular growth and other functions. To define further the role of cholesterol metabolism in the intestine both in vitro and in vivo, studies were performed. Several lines of evidence based on these studies suggest that the main purpose of local cholesterol synthesis in the gut is the support of rapid enterocyte proliferation: 1) growth was inhibited during pharmacologic suppression of cholesterol synthesis in intestinal organ or cell culture; 2) the endocrine regulation of intestinal growth was in most but not all instances accompanied by appropriate changes in cholesterol synthesis; 3) most of cholesterol synthesis and lipoprotein uptake was localized predominantly in the crypt and lower villus region; and 4) very little of the sterol synthesized by the intestinal mucosa was exported into lymph but seems rather to be incorporated into cell membranes.

Animals↗
PubMed1987

Prostaglandin synthesis along the gastrointestinal tract of the rabbit: differences in total synthesis and profile.

In the present study we systematically investigated the synthesis of prostaglandins in the mucosa and the muscle layer along the length of the rabbit gut. Homogenates of mucosa and muscle layer were incubated with (14C)-labelled arachidonic acid, and prostaglandin formation was determined using thin-layer chromatography. With respect to total prostaglandin synthesis the highest values in the mucosa were measured in fundus, antrum and colon, whereas the prostaglandin synthesis in the muscle layer was maximal in the small bowel, particularly the ileum. In the mucosa, the prostaglandins E2 and F2a predominated, and there were minor differences along the gastrointestinal tract. In the muscle layer of the stomach, high amounts of 6-keto prostaglandin F1a, the stable degradation product of prostacyclin were produced, while small and large bowel homogenates synthesized mostly F2a. Consistently the prostaglandins A2/B2 were a major product in most locations. In addition, PG E2 catabolism to 15-keto PG E2 and 13,14-dihydro-15-keto PG E2 in the absence of NAD was slow. No significant changes in total prostaglandin synthesis and prostaglandin profile were detected between 24 hrs fasted and normally fed rabbits at any part of the gastrointestinal tract.

Animals↗
PubMed1987

[Regulation of endogenous prostaglandin synthesis in the upper gastrointestinal tract].

Prostaglandins are involved in many physiological functions of the gastrointestinal tract, e.g. the secretion of acid, mucus and bicarbonate, the motility, the microcirculation and cytoprotection. The diverse prostaglandins as well as prostacyclin and thromboxane are synthesized by a complex enzymatic system, which is affected by a multitude of possibly regulatory influences. Such mechanisms are the availability of dietary essential fatty acids, the calcium, dependent activation of the phospholipase A2, the self-inactivation of the prostaglandin cyclooxygenase, the availability of cofactors, the catabolism of the prostanoids and others. A minireview concerning these potentially regulatory mechanisms in the upper gastrointestinal tract is presented.

Animals↗
PubMed1987

[Prostaglandin synthesis in stomach and duodenal mucosa of the human: effect of aspirin with and without antacid].

A decreased PG E2 content in gastric mucosa of humans receiving a longterm antirheumatic therapy has been reported to be partially reversed after a one week treatment with an antacid (Reimann et al., Fortschr Med 102 [1984], 25-26). Therefore the effect of an Aspirin treatment of healthy volunteers with or without an antacid on the prostaglandin synthesis in gastric or duodenal mucosa was investigated. 14C-labelled arachidonic acid was used as substrate during in vitro incubation of the mucosal homogenate for determination of the endogenous formation of prostaglandins. Aspirin suppressed the total prostaglandin synthesis to less than 10% of control after one week treatment. The addition of a high dose antacid did not influence this inhibition, and no significant effect on the prostaglandin profile was detectable. It is concluded that antacids do not influence the suppression of the endogenous prostaglandin synthesis by NOSAC's, however another effect, eg a prolonged stability of PG E2 in a less acidic environment is more likely.

Adult↗
PubMed1987

[Is there a hepatogenic ulcer? Prospective study of the incidence of peptic ulcer in portal hypertension].

During a 7 years study, the endoscopically determined prevalence and incidence of peptic gastroduodenal ulcer in 305 patients with portal hypertension (72% alcoholic cirrhosis, 21.3% non-alcoholic cirrhosis, 6.7% non-cirrhotic portal hypertension) were 4.3% and 3.9% per year, respectively. The yearly risk per patient of suffering from peptic ulcer was 7.4% if both, first and recurrent ulcers (total: 49) were considered. No association was disclosed of peptic ulcer with sex, age, etiology or severity of liver disease. Although an adequate control group was not yet available for comparison, the data do not support the previously postulated relationship between liver cirrhosis and peptic ulcer.

Adolescent↗
PubMed1986

Influence of triamcinolone and somatostatin on morphometric parameters of cultured intestinal mucosa.

Mucosal biopsies from rabbit ileum were organ cultured for 24 h. The influence of triamcinolone and somatostatin on villus height and diameter as well as crypt depth and the number of mitoses was measured at various times during 24 h of culture as indices of cell proliferation and tissue maintenance. It could be shown that triamcinolone reduced cell proliferation slightly but preserved mucosal structure in organ culture. Somatostatin inhibited crypt cell proliferation, without any effect on other morphological parameters.

Animals↗
PubMed1986

Effect of pentagastrin, secretin and cholecystokinin on growth and differentiation in organ cultured rabbit small intestine.

The effect of pentagastrin, secretin and cholecystokinin on biochemical parameters of mucosal growth and differentiation was studied in organ cultured rabbit jejunum and ileum. Pentagastrin at 0.05-5.0 microgram/ml did not affect DNA content of the biopsy, but led to a significant decrease of sucrase and alkaline phosphatase activity in the ileum. Secretin prompted a significant decrease of DNA and protein in the ileum at a level of 10(-7) and 10(-5) M, but had no effect in the jejunum. Of the brush border enzymes, sucrase and alkaline phosphatase were suppressed in both parts of the intestine both with respect to specific activity and total biopsy content. Cholecystokinin, like pentagastrin, did not influence DNA or protein content, but reduced sucrase, maltase and alkaline phosphatase activity. HMG-CoA reductase, the key enzyme of cholesterol synthesis, was not significantly affected by any of the three hormones tested. When brush border enzymes or DNA from desquamated cells were measured in the post-culture medium, no consistent effect of any gastrointestinal hormone was apparent. The present study demonstrates a direct "antitrophic" effect of secretin in cultured mucosa. Pentagastrin and cholecystokinin did not influence mucosal DNA content in vitro but apparently inhibited villus cell differentiation.

Animals↗
PubMed1986

Bile acids regulate hepatic low density lipoprotein receptor activity in the hamster by altering cholesterol flux across the liver.

The effect of different bile acids on receptor-dependent and receptor-independent low density lipoprotein (LDL) uptake in the liver and intestine was investigated. When fed at the 0.1% level for three weeks, cholic acid and chenodeoxycholic acid suppressed hepatic cholesterol synthesis in the rat by 80% and 50%, respectively, while ursodeoxycholic acid had no effect. In contrast, hepatic cholesteryl ester levels, rates of hepatic LDL transport, and concentrations of plasma LDL-cholesterol were not affected by bile acid feeding in this species. Cholic acid and chenodeoxycholic acid also suppressed hepatic cholesterol synthesis in the hamster. However, since basal rates of hepatic cholesterol synthesis in this species, as in man, are very low, the absolute reduction in hepatic synthesis could not compensate for the change in hepatic sterol balance induced by bile acid feeding. Hence, in the hamster the feeding of cholic acid and chenodeoxycholic acid increased hepatic cholesteryl ester levels 660% and 39%, respectively, reduced hepatic receptor-dependent LDL uptake by 50% and 32%, respectively, and elevated plasma LDL-cholesterol levels by 160% and 50%, respectively. Ursodeoxycholic acid feeding did not alter any of these processes, and none of the bile acids changed the rate of hepatic receptor-independent LDL transport. In the intestine, none of the bile acids altered rates of cholesterol synthesis or LDL uptake. When cholic acids, chenodeoxycholic acid, or ursodeoxycholic acid was infused continuously for 8 hr in supranormal amounts into control hamsters or rats or into animals pretreated with cholestyramine, there were no changes in LDL transport or any other parameter of hepatic cholesterol metabolism. Thus, these studies indicated that cholic acid and chenodeoxycholic acid have no acute, direct effect on rates of receptor-dependent LDL transport or cholesterol synthesis but do alter these processes indirectly by inducing changes in cholesterol balance across the liver. Ursodeoxycholic acid, in contrast, does not affect these processes either directly or indirectly and so causes no change in plasma LDL levels.

Animals↗
PubMed1986

Prostaglandins are not involved in the differentiation or growth of cultured small intestinal cells.

Prostaglandins have been reported to exert trophic effects on gastrointestinal tissues. To determine whether there is a direct interaction with enterocytes, prostaglandins PGE2, PGF2 alpha, PGA2, PGB2 and the stable PGE2 derivative suleprost as well as the prostacyclin derivative nileprost were tested in rabbit ileal mucosa under organ culture conditions. At concentrations between 10(-9) and 10(-5) M, none of the prostaglandins significantly affected biopsy DNA or protein content, or the activity of the brush border enzymes alkaline phosphatase, lactase, sucrase or maltase. The inhibition of endogenous prostaglandin synthesis with indomethacin also failed to alter these parameters. Moreover, the growth rate of a rat duodenal crypt cell line was unaffected when cultured in the presence of PGE2, PGF2 alpha or indomethacin. Thus, there was no evidence for a direct effect of exogenous or endogenous prostaglandins or their deficiency on the differentiation or growth in cultured small intestinal cells.

Animals↗
PubMed1986

Prostaglandin biosynthesis in gastroduodenal mucosa: methodological difficulties and their implications.

A deficiency of locally synthesized prostaglandins has been suggested to underly gastric and duodenal ulcer disease and to mediate the mucosal lesions induced by non-steroidal anti-inflammatory drugs. The exact definition of their role is hampered by various methodological problems. First, the mucosal content of prostaglandins is affected by mechanical manipulation and homogenization and does not correspond to the rate of synthesis. Secondly, the assay of this rate in mass terms is also susceptible to these artefacts, and a steady state of prostaglandin secretion in vitro is usually not achieved. Thirdly, if prostaglandin synthesis is measured in vitro by the incorporation of labelled arachidonic acid, the possibly rate-limiting role of substrate supply is not taken into account. Thus, it is likely that a part of the disagreement in the field stems from the problems in measuring the true rates of prostaglandin synthesis in vivo.

Animals↗
PubMed1985

Fenofibrate treatment inhibits HMG-CoA reductase activity in mononuclear cells from hyperlipoproteinemic patients.

The effect of fenofibrate treatment on serum cholesterol levels was studied in relation to the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in mononuclear cells from patients with hyperlipoproteinemia type IIa and IIb. When patients who had received fenofibrate (300 mg/day) for at least 8 weeks were given placebo during a subsequent 2-months period, both serum cholesterol concentration and mononuclear cell HMGR increased significantly in both types IIa and IIb. After reinstitution of fenofibrate treatment both parameters gradually declined and returned close to the initial level after another 28 weeks. It is concluded that a part of the lipid-lowering action of fenofibrate may be due to an inhibition of cholesterol synthesis.

Adult↗
PubMed1985

[Mucosa dimensions and cell proliferation in intestinal organ cultures with and without inhibition of cholesterol synthesis].

The changes in the structure and proliferative activity of rabbit ileal mucosa have been studied with morphometric and stathmokinetic techniques during 24 h organ culture. Under control conditions the villus base diameter and villus height decreased by 34 and 53%, respectively, whereas the number of villi per mm2 remained constant. The reduction of crypt depth was less pronounced than the loss in villus height, leading to a decrease in the villus height to crypt depth ratio from 3.4 to 2.3. The likely reason for this culture induced hypoplasia was a significant drop in mitotic activity as early as 2 h after starting the culture. Inhibition of HMG-CoA reductase, the key enzyme of cholesterogenesis, lead to a further reduction in mucosal dimensions and a near complete suppression of crypt cell regeneration. These data imply that despite the well-known preservation of differentiated function mucosal cell renewal during organ culture is impaired.

Animals↗
PubMed1985

The origin of cholesterol in the mesenteric lymph of the rat.

These studies were performed to quantitate the amounts of newly synthesized cholesterol secreted in the mesenteric lymph of the rat and to define the origin of this cholesterol. In control animals receiving no dietary fat, the amount of newly synthesized sterol entering the lymph increased linearly with respect to time over 24 hr. When a continuous intravenous infusion of chylomicrons was given or when the animals were prefed a diet containing 2.0% cholesterol to inhibit hepatic, but not intestinal or peripheral, cholesterol synthesis, the secretion of newly synthesized sterol in lymph was markedly suppressed, suggesting that the liver was its ultimate site of origin. When the animals were subjected to either blockade of intestinal cholesterol absorption or biliary diversion, there was a decrease in both the newly synthesized and total mass of cholesterol in lymph by approximately 60%, indicating that the majority was normally derived from the absorption of luminal (primarily biliary) sterol. In the absence of dietary cholesterol, the remainder was probably derived from plasma lipoproteins that were filtered through the intestinal capillaries into the lymph. In contrast, when lymph was collected during active fat absorption, the intestine was found to secrete sterol newly synthesized by the epithelium. Such newly synthesized cholesterol was found predominantly in the unesterified fraction and accounted for approximately 27% of the total sterol found in lymph at the end of the experiment. From these studies it was concluded that in the absence of fat absorption, sterol synthesized in the intestinal mucosa was incorporated predominantly into cell membranes and did not enter intestinal lymph to any significant degree. However, during fat absorption, a fraction of this newly synthesized sterol pool was incorporated into lipoproteins and so was delivered through the intestinal lymph to the body pools of cholesterol.

Animals↗