Effect of moderate prolonged ethanol ingestion on intestinal disaccharidase activity and histology

A previous study has shown that long-term feeding of ethanol in high doses (36% of total calories) causes marked changes in intestinal mucosal disaccharidase activity as well as blunting of the intestinal villi. To determine whether similar damage occurs in response to a more moderate ethanol exposure, we pair fed rats a liquid diet that provided 15.5% of total calories from ethanol for 5 weeks. In the proximal segment of the intestine, we found that ethanol did not affect the total activities of maltase (8.0 +/- 2.4 U vs. control value of 6.7 +/- 1.8 U), sucrase (1.5 +/- 0.5 U vs. control of 1.2 +/- 0.3 U), or lactase (125 +/- 42 mU vs. control of 107 +/- 36 mU). Similarly, we found no differences from control values for the three disaccharidases in the middle or distal small bowel. The mucosal protein content of the experimental animals did not differ from values found in the control animals. In addition, no change in intestinal villus height or crypt depth was detected. The zinc content of hair and serum was not affected by the ethanol feeding. We conclude that prolonged ingestion of a moderate dose of ethanol does not damage the small intestinal disaccharidase enzymes, mucosal protein content, or intestinal architecture.     

Effect of ethanol ingestion on duodenal calcium transport.

Effects of chronic ethanol ingestion on duodenal calcium transport were investigated in rats ingesting 20 per cent ethanol. Calcium transport was inhibited by ethanol ingestion and the defect could not be reversed by vitamin D or 25-hydroxycholecalciferol administrationmethanol ingestion by vitamin D-deficient rats did not further suppress transport activity nor interfere with an increase in transport induced by vitamim D. Levels of intestinal calcium-binding activity were not suppressed. Brush-border alkaline phosphatase activity was suppressed by chronic ethanol ingestion as compared to ad libitum-fed control animals and administration of vitamin D to animals ingesting ethanol restored alkaline phosphatase activitymthe results suggest that ethanol interferes with calcium transport by a mechanism at least in part independent of the vitamin D pathway and that changes in alkaline phosphatase and calcium transport, although both affected by vitamin D, may represent independent metabolic consequences.     

Effect of ischemia on intestinal permeability of lipopolysaccharides

The enteral absorption of endotoxin (lipopolysaccharide, LPS) was studied in vitro and in vivo. The absorption of fluorescence (FITC) labelled LPS was investigated by uptake studies with rabbit jejunal brush-border membrane vesicles (BBMV), the human intestinal cell line Caco-2 and in rats. FITC-LPS from Salmonella typhimurium was taken up into BBMV in a dose-dependent manner. Uptake was neither pH- nor Na+-dependent, nor could it be inhibited by unlabelled LPS. 74.5% of vesicle-associated fluorescence was due to adhesion to the vesicular membranes, 25.5% was taken up into an osmotically-sensitive space. Transport of LPS across Caco-2 cell monolayers was dose-dependent. The permeation rate increased significantly under ischemic conditions, i.e. when the cells were incubated under oxygen-depleted conditions. However, no significant differences in transepithelial electrical resistances were observed between oxygen depleted and control cells. The release of lactate dehydrogenase was only marginally different from control cells, indicating cell integrity. In situ, after gut ischemia, a significantly increased uptake of fluorescent LPS was observed by fluorescence laser scanning microscopy. Conclusion LPS is taken up by the intestinal mucosa, predominantly by passive transcellular diffusion. Under ischemic conditions, the permeability of LPS is increased mainly by an enhanced paracellular permeability and epithelial destruction. The findings partly explain the clinically observed development of multiorgan system failure after temporary malperfusion of the gut during major vascular surgery or thromboembolism.     

Effect of chronic ethanol ingestion on alpha-mannosidase isoenzymes in rat liver

Identification of biochemical changes induced by ethanol ingestion would aid in the diagnosis and management of many alcohol-related problems in man. In this paper we identify a pH 5.5 alpha-mannosidase activity in the rat which is affected by chronic ethanol consumption. Chronic (16 wk) ingestion of alcohol (36% of calories) causes the activity of this alpha-mannosidase (thought to be the cytosolic alpha-mannosidase) in liver to decrease by 50%. We hypothesize that this deficiency of (pH 5.5) alpha-mannosidase activity may account for the reduced rate of secretion of glycoproteins by livers of alcohol-fed rats reported by other investigators (Volentine et al, Hepatology 1987;7:490-495).     

Effect of zinc supplementation on intestinal permeability in experimental colitis

Increased small-intestine permeability has been documented in experimental colitis in the rat. Zinc supplementation improves mucosal repair in patients with diarrhea, as well as paracellular permeability in malnourished guinea pigs. In this study, we sought to evaluate the effect of zinc supplementation on small-and large-intestine tight junctions in rats with acute colitis. Rats were given zinc at a dosage of 2 or 30 mg/kg body wt or glucose by gavage starting 3 days before colitis was induced through the intrarectal administration of dinitro-benzene-sulfonic acid and for 7 days thereafter. We evaluated small-intestine permeability by the number of tight junctions showing extravasation of lanthanum under electron microscopy. Low-dose zinc affected none of the examined parameters of colitis severity. Rats given high-dose zinc showed colitis of similar macroscopic and biochemical severity. However, zinc-treated rats weighed more than unsupplemented ones. The number of perfused tight-junction complexes was significantly higher in animals with colitis than in controls and in the rats with colitis given high-dose zinc. Zinc may regulate tight-junction permeability, with possible implications for healing processes in inflammatory bowel diseases.     

Effects of ethanol ingestion on blood pressure reactivity

We examined the acute effects of ethanol consumption on circulatory responses to the cold pressor test, to handgrip exercise and to intravenous infusion of methoxamine in eight normal male subjects. Ethanol consumption reduced systolic blood pressure responses to the cold pressor test and to handgrip exercise and depressed both systolic and diastolic blood pressure responses to infusion of methoxamine. The depressant effects of ethanol on blood pressure responses to methoxamine were considerably greater than the effects on the cold pressor test and handgrip exercise. Catecholamine concentrations during the cold pressor test and handgrip exercise were not significantly different with or without prior ethanol consumption. Alcohol has been shown to have an acute hypotensive action with all the stimuli.     

大黄对大鼠肠粘膜及肠血管通透性的影响

目的：研究大黄对肠粘膜及肠血管通透性的影响。方法：选用低血容量性休克和内毒素性休克大鼠动物模型，以荧光标记白蛋白和小肠湿／干重比值检测内毒素性休克肠血管通透性，以血浆内毒素含量来衡量肠粘膜通透性。结果：内毒素能引起小肠组织明显水肿，其湿／干重比值显著增高，同时明显提高肠血管壁对荧光标记白蛋白的通透性；而大黄能减轻肠壁水肿和湿／干重比值（内毒素组为３．７５±０．６８，大黄组为１．６６±０．３３，Ｐ＜０．０１），降低肠血管通透性〔小肠组织荧光标记白蛋白含量：内毒素组为（１．２５４±０．１１７）μｍｏｌ／ｇ，大黄组为（０．９００±０．０７１）μｍｏｌ／ｇ，Ｐ＜０．０１〕。低血容量性休克能破坏肠粘膜屏障，提高肠粘膜对内毒素的通透性，而大黄可明显降低低血容量性休克大鼠肠粘膜通透性，抑制肠道内毒素的吸收〔血浆内毒素含量：休克组为（０．５５７±０．０６９）ＥＵ／ｍｌ，大黄组为（０．３４５±０．０５５）ＥＵ／ｍｌ，Ｐ＜０．０１〕。结论：大黄能保护肠粘膜屏障，抑制肠道内毒素吸收，降低肠粘膜及肠毛细血管通透性。     

Effects of ethanol ingestion on maternal and fetal glucose homeostasis

Carbohydrate metabolism has been studied in the offspring of rats fed liquid diet containing ethanol during gestation (EF group). Weight-matched control dams were given liquid diet either by the pair-fed technique (PF group) or ad libitum (AF group). EF and PF dams showed reduced food consumption and attenuated gain in body weight during the gestation period compared with the AF group. Blood glucose, liver glycogen, and plasma insulin levels were significantly reduced in EF and PF dams. Ethanol ingestion resulted in a significant decrease in litter survival and fetal body weight. At term, EF pups on average showed a 30% decrease in blood glucose levels and 40% decrease in plasma insulin levels compared with AF pups. One hour after birth, EF pups exhibited a marked increase in blood sugar level compared with either control group; subsequently, there was a marked decrease in blood glucose levels in EF pups. Liver glycogen stores were significantly reduced in term EF fetuses and were mobilized more rapidly in EF neonates than in either control group. Fetal hyperinsulinemia disappeared shortly after delivery in control pups, as expected; however, in EF pups, the fall in plasma insulin level was gradual. Fetal and neonatal plasma glucagon levels were not altered by ethanol exposure in utero. Blood glucose levels remained significantly low at 2 days of age in EF pups, but reached near control values at 4 days of age. Plasma insulin and glucagon were nearly equal in EF and control pups at 2 and 4 days of age. These results show aberrations in blood glucose, plasma insulin, and liver glycogen levels in offspring exposed to ethanol in utero.     

Vasoactive intestinal polypeptide response to ethanol in dogs

Only one report has described the ethanol-induced release of vasoactive intestinal polypeptide (VIP), and its mechanism of action is unknown. We studied changes in mesenteric immunoreactive VIP (IR-VIP) concentrations following the intrajejunal administration of 100 ml of normal saline, 5% and 10% ethanol, and hypertonic saline which was isoosmolar to 10% ethanol (1,670 mOsm/liter) in dogs. Administration of 5% and 10% ethanol resulted in significant and dose-dependent increases in mesenteric IR-VIP. Mesenteric IR-VIP changes and incremental integrated responses to 10% ethanol and to hypertonic saline were the same. We concluded that ethanol-induced VIP release in dogs is mainly due to ethanol's hyperosmolarity.     

Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin

In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently described cytoplasmic organelle, the vesiculo-vacuolar organelle or VVO (VVOs are grapelike clusters of interconnected, uncoated vesicles and vacuoles). However, equivalent VVOs are also present in the cytoplasm of normal venules that do not leak substantial amounts of plasma protein. To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation. To test this hypothesis, VPF was injected intradermally in normal animals after intravenous injection of a soluble macromolecular tracer, ferritin, whose extravasation could be followed by electron microscopy. VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels. Ultrathin (14-nm) serial electron microscopic sections and computer-aided three-dimensional reconstructions better defined VVO structure. VVOs occupied 16-18% of endothelial cytoplasm in normal venules. Individual VVOs were clusters of numerous (median, 124) interconnected vesicles and vacuoles that formed complex pathways across venular endothelium with multiple openings to both luminal and abluminal surfaces. Like VPF, histamine and serotonin also stimulated ferritin extravasation across venules by way of VVOs. Together, these data establish VVOs as the major pathway by which soluble plasma proteins exit venules in response to several mediators that increase venular hyperpermeability. These same mediators also increased the extravasation of colloidal carbon, but this large particulate nonphysiological tracer exited venules primarily through endothelial gaps.     

Effects of acute ethanol ingestion and burn injury on serum immunoglobulin

Previous studies have found that acute ethanol ingestion before burn injury caused further impairment of mitogenic response of B lymphocytes compared with burn injury alone. The principal role of B lymphocytes is immunoglobulin production. This study was designed to determine the effect of acute ethanol ingestion on circulating immunoglobulin levels before injury. Serum concentrations of IgG, IgM, and IgA in rats were measured with the use of radial immunodiffusion plates at 4 days after a 30% burn injury in animals that had received a single ingestion of 3.0 ml ethanol per kilogram of body weight. The immunoglobulin levels were compared with appropriate controls. A 30% burn injury produced significant decreases in serum IgG and IgA levels but not in IgM levels, whereas acute ethanol ingestion only decreased IgA levels. Acute ethanol ingestion before injury did not induce any further significant decrease than did burn injury alone.     

Effect of total starvation and very low calorie diets on intestinal permeability in man

1. The effect of total starvation for 4-5 days on the intestinal uptake and urinary excretion of markers from an orally administered mixture of mannitol (5g), [14C]mannitol (0.5 microCi), lactulose (10 g) and 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA) (30 microCi), was assessed in five lean (group 1) and four obese (group 2) subjects. The effect of a very low calorie diet for 1 week and of a subsequent 5 day period of total starvation on intestinal permeability was assessed in a similar way in another group of obese subjects (group 3). Transit time from mouth to caecum of the fastest component of the oral mixture was assessed by the appearance of hydrogen in breath (all subjects), and the configuration of the transit spectrum through various segments of the gastrointestinal tract, was assessed by a radionuclide scan method (group 2 subjects only). The effect of starvation on plasma/renal clearance of these markers in subjects of group 2 was assessed with the use of a bolus intravenous injection of a mixture of mannitol (2 g). [14C]mannitol (10 microCi), lactulose (0.1 g) and 51Cr-EDTA (5 microCi). 2. The uptake and urinary excretion of orally administered mannitol was decreased by total starvation. The mean decrease was 47% in the lean subjects (P less than 0.025), 33% in group 2 obese subjects (P less than 0.05) and 41% in group 3 obese subjects P greater than 0.05). In contrast, starvation produced no significant change in either the excretion of 51Cr-EDTA or lactulose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats

Bacterial translocation and ileal and cecal injury have been shown to occur 24 h after limited periods of hemorrhagic shock. The present studies were performed to determine the temporal sequence of mucosal injury, permeability, and bacterial translocation after hemorrhagic shock. The results indicated that bacterial translocation and mucosal injury have occurred by 2 h after a 30-min episode of shock (mean arterial pressure 30 mm Hg). Although the histologic extent of the intestinal mucosal injury was less at 2 h postshock than at 24 h postshock, at both times intestinal barrier function was lost as measured by permeability to horseradish peroxidase. Since the role of translocating bacteria in potentiating the loss of intestinal barrier function after shock is unclear, the second goal was to determine whether the extent of shock-induced mucosal injury and permeability could be reduced or abrogated by antibiotic decontamination of the gut. The extent of shock-induced mucosal injury and intestinal permeability was similar between rats with a normal gut flora (greater than 10(6) bacteria/g cecum) and antibiotic-decontaminated rats (less than 10(3) bacteria/g cecum) 2 h postshock, although the incidences of bacterial translocation were 67% and 0, respectively. Thus, shock-induced mucosal permeability and injury appear not to be directly related to the presence of translocating bacteria.     

Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient

We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/microg total RNA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly throughout this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. These results suggested that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation.     

Effects of ethanol on the permeability of frog skin.

Ethanol (3%) decreases the potential difference and short-circuit current across the isolated frog skin in chloride Ringer's solution. Unidirectional fluxes of Na and Cl indicate that the drop in short-circuit current is due to an inhibition of the sodium influx. However, ethanol had no effect on the electrical parameters or sodium fluxes, when the frog skin was bathed in chloride-free solutions on both sides or the outside alone. The ethanol response is anion-dependent. In addition, chloride-free media in the inside bathing solution reduced the short-circuit current, indicating a sodium transport pathway which is dependent on chloride and confirming previous data in the literature. Other anions such as sulfate and nitrate could not substitute for chloride. The vasopressin-induced natriferic response and the ethanol effect were found to work independently of each other and different pathways of action are suggested for these agents. The intracellular sodium content of the isolated frog skin epithelium increased and potassium decreased in the presence of the Na-K adenosine triphosphatase inhibitor, ouabain, whereas ethanol or amiloride had no effect. The oxygen consumption of the isolated frog skin was unaffected by up to 10% ethanol. A general metabolic action is probably thus not mediating the response. Urea, in iso-osmotic concentrations to the ethanol, did not mimic its effect. Tritiated water fluxes (in the absence of an osmotic gradient) were reduced by 30% in the presence of 3% ethanol. It is suggested that ethanol may impede the flow of water across frog skin by a physicochemical interaction with membrane pores and the water molecules. The permeability coefficient (Ktrans) for ethanol was found to be 10 times smaller than the Ktrans for water.