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)

Juvenile rats fed a diet containing 1% lead acetate for 7 weeks, in addition to an impaired growth rate and renal function derangements, suffered malabsorption of glucose and certain amino acids, as assessed by an in vivo perfusion technique. The reduction in glucose absorption ranged between 10% and 31% when the carbohydrate was pumped in concentrations of 2-80 mM. This alteration was compatible with a noncompetitive type of transport inhibition. The intestinal absorption of glycine, lysine, and phenylalanine were, respectively, decreased 22, 18, and 15% when these amino acids were present at 1 mM levels. Sodium transport was severely reduced (57.6 +/- 17.9 (SEM) vs. 124.2 +/- 17.4 muEq/min-cm) and intestinal mucosa (Na+-K+)-ATPase was concomitantly lower in the lead-intoxicated rats (186.4 +/- 19.0 vs 268.4 +/- 29.8 nmol P/min-mg protein). However, this enzyme was not altered in liver and kidney. Furthermore, intestinal mucosa fructose-1,6-diphosphatase, succinic dehydrogenase, pyruvate kinase, and tryptophan hydroxylase were not different in experimental and control animals. These studies substantiate the presence of functional and biochemical abnormalities in the intestinal mucosa of young rats when fed substantial amounts of a soluble lead salt. It is, therefore, reasonable to accept the possibility that physiologic damage occurs in tissues directly subjected to high and persistent levels of a toxic agents, as it occurs in other organs, underscoring the parallelism between transport mechanisms at the renal and intestinal levels.
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PMID:Experimental lead poisoning and intestinal transport of glucose, amino acids, and sodium. 13 38

Patients with autoimmune polyendocrine syndrome type 1 (APS-1) frequently have autoantibodies directed against the aromatic amino acid hydroxylases tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH). We aimed to characterize these autoantibodies with regard to their antigenic determinants, their influence on enzymatic activity and their clinical associations. In particular, we wanted to compare autoantibodies against the two different isoforms of TPH, which display different tissue distribution. Using sera from 48 Scandinavian APS-1 patients we identified 36 patients (75%) with antibodies against one or more of these three enzymes. Antibodies against TPH1, but not TPH2, were associated with malabsorption in the whole Scandinavian cohort, while TH antibodies were associated with dental enamel hypoplasia in Norwegian patients. Subsequent experiments with selected patient sera indicated that while the C-terminal domain was the immunodominant part of TPH1, the epitopes of TPH2 and TH were mainly located in the N-terminal regulatory domains. We also identified a TPH1 specific epitope involved in antibody mediated inhibition of enzyme activity, a finding that provides new insight into the enzymatic mechanisms of the aromatic amino acid hydroxylases and knowledge about structural determinants of enzyme autoantigens. In conclusion, TPH1, TPH2 and TH all have unique antigenic properties in spite of their structural similarity.
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PMID:Autoantibodies against aromatic amino acid hydroxylases in patients with autoimmune polyendocrine syndrome type 1 target multiple antigenic determinants and reveal regulatory regions crucial for enzymatic activity. 2318 18

Autoimmune polyendocrinopathy-candidiasis-ectodermal-distrophy (APECED) is a rare autosomal recessive disease, which is mainly characterized by the association of many autoimmune diseases, with a classic triad including chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Its clinical spectrum has significantly enlarged in the last years and other non-classic components have been recently described. Aim of this review was to alert pediatricians to these novel clinical aspects of this syndrome, that have been recently included among the autoimmune APECED manifestations: a) chronic lung disease, that may evolve to cor pulmonale and terminal respiratory failure; b) chronic inflammatory demyelinating polineuropathy, with progressive muscular weakness of both arms and legs and sensory loss; c) gastrointestinal dysfunction, with recurrent diarrhea, malabsorption and steatorrhea or chronic constipation. For each of these novel components of APECED, specific autoantibodies against either lung autoantigens or peripheral nerves or tryptophan hydroxylase have been just recently identified.
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PMID:APECED syndrome in childhood: clinical spectrum is enlarging. 2550 18

Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.
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PMID:Management of Diarrhea in Patients With Carcinoid Syndrome. 3142 82

Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.
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PMID:Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors. 3275 58