Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic sclerosis is an extremely variable disease in its manifestations and consequently, treatment needs to be individualized depending on the specific problems that each patient has. Limited scleroderma patients have a prolonged duration of Raynaud's phenomenon and puffy fingers before they develop any skin thickening, digital ulcers or gastrointestinal symptoms. They are likely to present with all the classic manifestations of scleroderma. Diffuse scleroderma patients have a much more acute systemic onset with marked whole hand swelling and may initially have only subtle skin thickening. A good understanding of the differences between the natural history of limited and diffuse scleroderma will enable the physician to treat present problems and anticipate future ones more effectively. One should determine which major subset and organ systems are involved before deciding on the appropriate therapy. Advances in organ-specific therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton pump inhibitors in esophageal reflux, intravenous iloprost and endothelin receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal crisis, have decreased morbidity and mortality in patients with scleroderma. Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in progress. Further clinical experience in wound healing, gastrointestinal malabsorption and physical therapy for loss of motion has helped patients to have a more comfortable life. In recent years, a significant number of controlled clinical trials have been performed and there has been improved understanding of the best way to perform studies and of which patients are most likely to respond to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and cyclosporine have all been studied in controlled trials with variable outcomes. Although an overall remittive therapy has not yet been determined, new, potentially useful agents are being investigated.
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PMID:Treatment of systemic sclerosis. 1172 50

In two trials, broiler chickens, processed similarly to those placed in commercial operation, were fed, from 1 d of age, a range (13 to 200 ppm) of DL-alpha-tocopheryl acetate (VE-AC) levels, and the effects on the pathology of Eimeria maxima infections were assessed at 6 d postinoculation (PI). In Trial 1, dietary levels of VE-AC had little significant effect on variables characterizing pathology except for the number of oocysts shed, which was significantly increased in chicks treated with higher VE-AC levels. The infection was judged to be mild based on moderate lesion scores (2.2+/-0.2), lack of significant effects on weight gain (7+/-1.6% decrease), moderate reduction in plasma carotenoids (21+/-2%) and small increases in plasma NO2-+NO3- (141+/-12%). In uninfected and infected chickens, plasma alpha-tocopherol (AT) increased with dietary levels of VE-AC; however, E. maxima infection caused a fairly constant decrease in AT of 35.3+/-3.2% across these levels. Plasma gamma-tocopherol (GT) levels were unaffected by dietary VE-AC or E. maxima infection. In Trial 2, pathology, again, was relatively unaffected by dietary VE-AC level. The infection was judged to be severe based on lesion scores (3.5+/-0.1), reduction in weight gain (30.7+/-3%), plasma carotenoids (72.4+/-1.5%), uric acid (16.3+/-3.4), albumin (37.8+/-2.8%), large increases (261+/-8%) in plasma NO2-+NO3-, and high numbers of oocysts shed per chick (4.12+/-0.4 x 10(7)). Plasma AT again increased with increasing dietary VE-AC levels in uninfected and infected chicks, but the mean decrease across VE-AC levels caused by E. maxima infection was 73.14+/-3.3%. GT levels were erratic and unrelated to dietary VEAC or infection. Thus, in processed broiler chickens, high dietary VE-AC did not prevent or lessen the pathology caused by mild or severe infections with E. maxima. The main effect of E. maxima infection appeared to be reduction in plasma AT levels. We postulate that this reduction may be due to malabsorption of AT, which results from physical damage to the absorptive mucosa, reduction in esterases required to hydrolyze the VE-AC, and a generalized lipid malabsorption, preventing movement of the free AT to circulating blood and infected tissues.
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PMID:Interaction of dietary vitamin E with Eimeria maxima infections in chickens. 1188 98

Pulmonary arterial hypertension is common in patients with SSc. Fig. 1 shows the diagnostic and therapeutic approach to PAH in SSc. Doppler echocardiography may suggest the diagnosis, but RHC is necessary to confirm PAH and to measure vasoreactivity. Therapy is directed at the underlying connective tissue disease. Vasoreactive patients often benefit from therapy with high-dose calcium-channel [figure: see text] blockers, but most patients are not vasoreactive. Intravenous epoprostenol and oral endothelin-1 receptor antagonists improve hemodynamic measurements and symptoms in SSc-associated PAH. The therapy of right ventricular failure is focused on vasodilators, inotropes, and diuretics with careful attention to avoiding systemic hypotension. The scleroderma pulmonary-renal syndrome and the scleroderma renal crisis are distinct syndromes with different clinical presentations, histopathologic manifestations, treatments, and outcomes. The scleroderma pulmonary renal syndrome is an autoimmune vasculitis of kidney and lung associated with normal blood pressure. Treatment is supportive, and prognosis is dismal. In contrast, scleroderma renal crisis is associated with systemic hypertension, onion skinning of afferent arterioles, and response to ACE inhibition and renal replacement therapy. Pericardial effusions are common but only occasionally lead to tamponade. Esophageal dysmotility is often associated with aspiration, leading to pulmonary fibrosis, pneumonia, or ARDS. Diffuse bowel involvement may result in pseudo-obstruction, bacterial overgrowth, or malabsorption. Prokinetic agents, antibiotics, and parenteral nutrition may be required.
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PMID:Life-threatening complications of systemic sclerosis. 1241 43

Vitamin E and carotenoids are known to act as antioxidants both in vitro and in vivo. In this review we present a series of studies in healthy subjects and in patients who exhibit either acute or chronic oxidative stress. In the EU-Commission funded VITAGE project we investigated the status and effects of vitamin E and carotenoids on oxidative stress in 300 healthy volunteers. Depletion studies limiting dietary vitamin E or carotenoid intake to approximately 25% of the dietary reference intakes and subsequent repletion by supplementation with either large doses of vitamin E or intermediate doses of carotenoids showed significant changes in ex vivo LDL oxidizability, total plasma peroxide concentrations and urinary 8-oxo-7,8-dihydro-2(')-deoxyguanosine excretion. Patients on chronic hemodialysis present with oxidative stress in the presence of normal vitamin E but impaired vitamin C status and, due to anemia, need to be treated with parenteral iron. We studied the effects of a single oral dose of vitamin E taken 6 h prior to intravenous infusion of 100 mg iron, which exceeded the iron-binding capacity of transferrin. Vitamin E significantly reduced and in combination with a single dose of vitamin C completely abrogated acute oxidative stress induced by the iron load. Patients with cystic fibrosis are exposed to chronic oxidative stress due to an overproduction of reactive oxygen species as a result of neutrophil-dominated lung inflammation and impaired antioxidant status. Biochemical vitamin E and carotenoid deficiencies could be fully corrected even in the presence of fat malabsorption using intermediate doses of either RRR alpha-tocopherol or all-rac alpha-tocopheryl acetate and water-miscible all-trans beta-carotene. Long-term supplementation reduced ex vivo LDL oxidizability, in vivo lipid peroxidation and lung inflammation.
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PMID:Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies. 1458 10

Nenatal necrotizing enterocolitis (NEC) is a disease mainly affects premature infants. It is well known that prematurity, enteral formula feeding, and bacterial colonization are three major risk factors for NEC. Acetic acid, propionic acid and butyric acid are short chain fatty acids (SCFAs), which are produced mainly in the colon by bacterial fermentation of undigested carbohydrates. Although luminal production of modest quantities of SCFAs is essential for normal colonic mucosal function, excessive production/accumulation of SCFAs may arise in premature infants due to increased luminal carbohydrates malabsorption and poor gastrointestinal motility, and may have deleterious effects on mucosal integrity. Therefore, it is proposed that too much luminal short chain fatty acids cause neonatal NEC.
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PMID:Too much short chain fatty acids cause neonatal necrotizing enterocolitis. 1496 41

Biochemicals in the upper-gut aspirate in 31 patients with malabsorption syndrome (MAS) with and without small intestinal bacterial overgrowth (SIBO), and 10 disease-free controls were analyzed using high-resolution (1)H-NMR spectroscopy, and were correlated with the degree of SIBO and severity of MAS. Compared to controls, the patients had higher quantities (micromol/L: median [range]) of total bile acids/cholesterol (2000 [0-12000] vs. 300 [0-600]), lactate (700 [0-5200] vs. nil [0-30]), acetate (200 [0-6500] vs. 20 [0-200]), and formate (80 [0-900] vs. nil [0-50]) (P < 0.01, Mann-Whitney U-test). However, amino acids and glucose were comparable in both. Quantities (micromol/L: median [range]) of acetate (1330 [220-6500] vs. 100 [0-1430]), lactate (1430 [670-3300] vs. 300 [0-5200]), formate (360 [0-600] vs. 25 [0-800]), and unconjugated bile acids (500 [40-600] vs. 10 [0-300]) were higher in MAS patients with SIBO than those without SIBO (P < 0.01, Mann-Whitney U-test, for all). In patients with MAS the quantity of acetate positively correlated with the degree of SIBO, and unconjugated bile acids correlated with the degree of steatorrhoea (Spearman's rank correlation coefficient, two-tailed, P < 0.05: 0.46 and 0.52, respectively). This study demonstrates the bacterial production of metabolites and deconjugation of bile acids in patients with MAS.
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PMID:Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy. 1697 11

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. We present here the first characterization of fecal extracts obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resolution 1H NMR spectroscopy and multivariate pattern recognition techniques. The fecal extracts of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms.
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PMID:Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. 1726 11

Impaired functioning of the gastrointestinal system may also contribute to malnutrition and cardiac cachexia (CC) in patients with chronic heart failure (CHF). Targets for future interventions include the deranged hormonal systems involved in energy balance as well as malabsorption from the gut and dietary supplementation. Other targets are the inhibition of proteasome-dependent protein degradation and the direct inhibition of pro-inflammatory pathways. The beneficial effects of ACE inhibitors, aldesterone inhibitors and beta-blockers in preventing or delaying the collagen deposition in the small intestine wall need to be elucidated. We strongly believe that by improving our understanding of the role of the gut in CC will lead to the development of novel therapeutic strategies in the near future.
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PMID:The small intestine: a critical linkage in pathophysiology of cardiac cachexia. 2111 52

The mechanism underlying the motor fluctuations that develop after long-term L-dopa therapy is not fully known. It has been speculated that malabsorption of L-dopa from the small intestine occurs. It was reported that gastric retention in Parkinson's disease (PD) patients with motor fluctuations is increased as compared with that in PD without fluctuations. Because L-dopa therapy may worsen the symptoms of delayed gastric emptying (GE), it was not clear whether the delayed GE of PD patients with motor fluctuation was affected by L-dopa therapy. We assessed GE in PD patients with and without motor fluctuations. We investigated GE in 40 patients with PD under long-term L-dopa therapy, 20 fluctuators with "delayed-on" and "noon" phenomena, 20 nonfluctuators, and 20 healthy volunteers. GE was examined by the 13C-acetate breath test ((13)CABT) [the half emptying time (HET), the peak time of the (13)C-%-dose-excess curve (T(max))], with expirations collected for 4 h after a test meal and analyzed for (13)CO(2) using an infrared (IR) spectrophotometer. The T(max) of GE as assessed using the (13)C-ABT was significantly delayed in all PD patients as compared with controls (P = 0.002). The HET was significantly delayed in all PD patients as compared with controls (P < 0.001). The T(max) and HET were not significantly delayed in PD patients with motor fluctuations as compared with PD patients without motor fluctuations. These results demonstrated that GE is commonly delayed in PD patients with long-term L-dopa therapy. Delayed GE does not differ between PD patients with and without motor fluctuations. This finding demonstrated that the motor fluctuation in PD may not be influenced by GE.
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PMID:Is there a difference in gastric emptying between Parkinson's disease patients under long-term L-dopa therapy with and without motor fluctuations? An analysis using the 13C-acetate breath test. 1957 60

The proton-coupled folate transporter (PCFT) plays a key role in intestinal folate absorption, and loss-of-function mutations in the gene encoding this transporter are the molecular basis for hereditary folate malabsorption. Using a stable transfectant with high expression of PCFT, physiologic levels of bicarbonate produced potent and rapidly reversible inhibition of PCFT-mediated transport at neutral pH. Bisulfite and nitrite also inhibited PCFT function at neutral pH, whereas sulfate, nitrate, and phosphate had no impact at all. At weakly acidic pH (6.5), bisulfite and nitrite exhibited much stronger inhibition of PCFT-mediated transport, whereas sulfate and nitrate remained noninhibitory. Inhibition by bisulfite and nitrite at pH 6.5 was associated with a marked decrease in the influx Vmax and collapse of the transmembrane proton gradient attributed to the diffusion of the protonated forms into these cells. Monocarboxylates such as pyruvate and acetate also collapsed the pH gradient and were also inhibitory, whereas citrate and glycine neither altered the proton gradient nor inhibited PCFT-mediated transport. These observations add another dimension to the unfavorable pH environment for PCFT function in systemic tissues: the presence of high concentrations of bicarbonate.
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PMID:Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions. 2360 45


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