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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.
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PMID:Gastroschisis increases small bowel nitric oxide synthase activity. 886 30

Five experiments were conducted to investigate the production of nitric oxide (NO) and superoxide anion (O2-) during infections of chickens with the coccidial parasite, Eimeria maxima, in order to assess the importance of these free radical species in the pathogenesis of the infections. Nitric oxide production was estimated by analyzing NO2(-)+NO3-, stable metabolites of NO, in the plasma and intestinal mucosa. The potential for O2- production was estimated from activities of beta-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in mucosal homogenates. Levels of NO2(-)+NO3- reached maximum values at about 6 d postinoculation, a time when mucosal damage was high and oocysts were being shed. The activity of NADPH oxidase in infected mucosa was also increased. Thus, at that time, there was a potential for oxidative destruction of mucosal tissue from these free radicals and their reaction products. Levels of NO2(-)+NO3- did not increase in a stepwise manner with increasing infective dose, suggesting that production of NO may be regulated post-transcriptionally by other factors elaborated by the immune response to infection, or may be controlled by substrate limitations. A comparison of two E. maxima strains indicated that the virulence of a strain was not directly related to NO production. Increased production of O2- due to increased NADPH oxidase activity during infection may cause a reduction in levels of carotenoid pigments that is unrelated to malabsorption.
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PMID:Production of free radical species during Eimeria maxima infections in chickens. 918 13

As part of a program to study the pathological effects of coccidia infections on growth, we have examined the relationship of plasma L-arginine (ARG) levels to infective doses of Eimeria acervulina and infection-associated changes in weight gain, plasma carotenoids, and plasma NO2- + NO3-. Chickens consuming a starter ration containing 1.68% ARG were infected with a range of doses of E. acervulina. At 6 d postinoculation (PI), weight gains were significantly reduced by infections with 5 x 10(5) and 1 x 10(6) oocysts per chick (OPC). Gross lesion scores of chickens infected with 5 x 10(4) through 1 x 10(6) OPC were significantly greater than scores of chicks infected with 1 x 10(3) OPC. Compared with levels from uninfected controls, plasma NO2- + NO3- concentrations were significantly increased by infection with 5 x 10(5) and 1 x 10(6) OPC, plasma concentrations of ARG were significantly decreased by infection with 5 x 10(4) through 1 x 10(6) OPC, and plasma carotenoids were significantly decreased by all infection doses. Plasma arginine was significantly correlated with plasma carotenoids (P > 0.0187), but not with infection dose or weight gain; plasma NO2- + NO3- was positively correlated (P > 0.0043) with infection dose and negatively correlated (P > 0.0158) with weight gain. Regression analysis of the measured variables indicated that the strongest relationship existed between plasma ARG and carotenoids. This finding suggests that in this infection model, reduction in plasma ARG is most likely associated with nutrient malabsorption that accompanies infection and is likely not significantly impacted by synthesis of nitric oxide that is associated with the immune response.
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PMID:Effect of Eimeria acervulina infections on plasma L-arginine. 1105 46

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.
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PMID:Small bowel review: normal physiology part 1. 1176 47

The pathomechanism of neuropathies associated with diabetes and chronic liver diseases are poorly understood. Both metabolic and vascular factors are involved in the pathogenesis of diabetic neuropathy. It seems likely, that microangiopathy on the one hand and changes of various metabolic pathways due to hyperglycaemia on the other hand are much more related to each other than it was suggested previously. Nitric oxide may be the link between the metabolic and vascular hypotheses of diabetic neuropathy. Both reduced endoneurinal blood flow and increased oxidative stress leads to reduced nitric oxide synthetase activity. There are widespread inter-relationships between the most relevant metabolic changes included polyol pathway hyperactivity, reduced myoinosit concentration, advanced glycation end products formation, increased oxidative stress and lipid peroxidation. Changes of hemorheological conditions and primary hemostasis leeds to hyperviscosity just as to increased activity of the coagulation system. Among patients with chronic alcoholic liver diseases the direct toxic effect of alcohol is of particular relevance, however, malabsorption, impairment of axoplasmatic transport, changes of intermedier metabolism as well as thiamine and pyridoxine deficiency are of importance as well. The role of decreased insulin sensitivity and various degrees of glucose intolerance related to chronic liver diseases are still underestimated. Impairment of proteoglycan metabolism as well as increased oxydative stress are thought to be important factors in the pathogenesis of both diabetic and hepatic neuropathies. Glucose autooxidation and enhanced lipid peroxidation contribute to increased oxidative stress in patients with diabetes and chronic liver diseases as well. Vitamin E deficiency, autoimmun processes, circulating immune complexes, cryoglobulinemia, just as changes of vascular responsiveness associated with nitric oxide activity plays a role in the development of neural damage of hepatic origin. Most likely, similarly to diabetes mellitus, vascular changes contribute to the development of neuropathy in patients with chronic liver diseases.
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PMID:[The pathogenesis of diabetic and hepatic neuropathies]. 1177 53

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.
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PMID:Regulation mechanisms of intestinal secretion: implications in nutrient absorption. 1198 1

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.
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PMID:Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction. 1203 96

Zinc has been recognized as an antioxidant with potential for chronic and acute effects. Oxidative damage produced by free radicals, including nitric oxide (NO), is responsible for certain types of intestinal malabsorption syndromes and diarrhea. Under physiologic or mildly stimulatory conditions for NO synthesis, the small intestine characteristically is in a proabsorptive state; however, an excessive production of NO triggers formation of cyclic nucleotides, which cause secretion and malabsorption. In this study, we hypothesized that low-molecular-weight, soluble zinc chelates could modulate the effects of induced NO excess on the small intestine. In vitro experiments demonstrated that zinc-citrate or zinc-histidine at > or =0.66 mM, as well as a known NO scavenger, 2-[carboxyphenyl]-4,4,4,4-tetramethylimidazoline-1-oxyl-3-oxide, at 2 microM, were effective at removing chemically generated NO. In vivo jejunal perfusions, conducted in healthy rats under anesthesia, showed that c-PTIO reduced the proabsorptive effects produced by 1 mM L-arginine, the precursor of NO. In a standard oral rehydration solution, 1 mM zinc-citrate partially reversed the antiabsorptive effects on potassium caused by an excess of NO generated from 20 mM L-arginine but did not alter sodium or water absorption. The data are consistent with the view that soluble zinc compounds incorporated into an oral rehydration solution may deserve further attention as a means to scavenge NO with fluids used for the treatment of chronic or acute diarrhea, especially in malnourished children who are often zinc deficient.
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PMID:Zinc as a potential enteroprotector in oral rehydration solutions: its role in nitric oxide metabolism. 1259 91

The analysis of exhaled breath is a potentially useful method for application in veterinary diagnostics. Breath samples can be easily collected from animals by means of a face mask or collection chamber with minimal disturbance to the animal. After the administration of a 13C-labelled compound the recovery of 13C in breath can be used to investigate gastrointestinal and digestive functions. Exhaled hydrogen can be used to assess orocaecal transit time and malabsorption, and exhaled nitric oxide, carbon monoxide and pentane can be used to assess oxidative stress and inflammation. The analysis of compounds dissolved in the aqueous phase of breath (the exhaled breath condensate) can be used to assess airway inflammation. This review summarises the current status of breath analysis in veterinary medicine, and analyses its potential for assessing animal health and disease.
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PMID:Current and future uses of breath analysis as a diagnostic tool. 1507 25

Cardiovascular (CV) complications, associated with space flight (SF), are caused by microgravity, hypokinesia and radiation, particularly beyond earth orbit, with all three conducive to oxidative stress. Except for emergencies, pharmaceuticals appear to be contraindicated, because of unpredictable side effects from malabsorption (M) and potential hepatic and renal impairment. Magnesium (Mg) depletion and elevations of cytokines (interleukin 6) occur during SF, conducive to self-sustaining vascular inflammation mechanisms. There are potential endothelial injuries (EI) and reduced Cyclic GMP (a second messenger of nitric oxide: NO) and elevated urinary excretion of C-peptide (insulin resistance: IR). Recent findings that show reductions in vascular endothelial growth factor (VEGF) suggest that this may result from SF-related thrombocytopenia since platelets (P) are the major source of VEGF, and that NO might play a role. Both VEGF and Mg are vital for angiogenesis, endothelial function and reendothelialization. Insulin is necessary for VEGF expression. To prevent SF-related CV complications in the presence of IR and M and with the potential for renal insufficiency, closely monitored subcutaneous (SC) Mg should be provided. The dosage can be monitored by sublingual intracellular Mg assays. Needed is development of a SC Mg reservoir device, which can be replenished before extra-vehicular activities (EVA) and which must be reliable despite vigorous movements during EVA, that can last up to 8 hours. This could also be protective against decompression sickness and EVA-related 100% oxygen requirements before and during this activity, both of which predispost to EI.
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PMID:The case for a subcutaneous magnesium product and delivery device for space missions. 1546 57


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