Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017536 (giardiasis)
 1,714 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giardia lamblia trophozoites are flagellated protozoa that inhabit the human small intestine, where they are exposed to various dietary lipids and fatty acids. It is believed that G. lamblia, which colonizes a lipid-rich environment of the human small intestine, is unable to synthesize phospholipids, long-chain fatty acids, and sterols de novo. Therefore, it is possible that this protozoan has developed a special process for acquiring lipids from its host. We have previously shown that G. lamblia can take up saturated fatty acids and incorporate them into phosphatidylglycerol (PG) and other glycerol-based phospholipids (Stevens et al., Experimental Parasitology, 86, 133-143, 1997). In the present study, an attempt has been made to investigate the underlying mechanisms of transesterification and interesterification reactions of giardial phospholipids by free and conjugated fatty acids. Results show that exogenously supplied, unsaturated, fatty acids were taken up by Giardia and incorporated into various phosphoglycerides, including PG. To test whether this intestinal pathogen can utilize conjugated fatty acids, live trophozoites were exposed to either [3]H;cbphosphatidylcholine (PC), where the fatty acid was 3H-labeled at its sn2 position, or to [14C]lyso-PC (fatty acid was 14C-labeled at the sn1 position) for 90 min, followed by phospholipid analysis using thin-layer chromatography. The results suggest that conjugated fatty acids, like free fatty acids, were incorporated into PG. It was also observed that aristolochic acid, an inhibitor of Ca2+-ionophore-stimulated phospholipase A2, decreased the transfer of fatty acids from [3H]PC to PG, indicating that giardial phospholipases were involved in these esterification reactions. Additional experiments, which include culturing trophozoites in serum-supplemented and serum-deprived medium, along with numerous biochemical analyses suggest that (i) PG is a major transesterified and interesterified product, (ii) it is likely that giardial phospholipases are involved in esterification reactions, (iii) in G. lamblia, PG is localized in perinuclear membranes, as well as intracellularly, but not in the plasma membrane, and (iv) various synthetic analogs of PG inhibit the growth of the parasite in vitro. These studies suggest that PG is an important phospholipid of Giardia and a potential target for lipid-based chemotherapy against giardiasis.
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PMID:Giardia lamblia: incorporation of free and conjugated fatty acids into glycerol-based phospholipids. 1032 59

The mechanisms of epithelial injury in giardiasis remain unknown. The effects of live Giardia lamblia on cellular G-actin, F-actin, alpha-actinin, and electrical resistance of human intestinal epithelial monolayers were investigated using SCBN and Caco2 cell lines grown on chamber slides or Transwell filter membranes. In separate experiments, some monolayers were also exposed to sonicated trophozoites, some to supernatant from live G. lamblia cultures, and some with or without the Ca2+ channel blocker verapamil. After 2, 24, or 48 hr of coincubation with G. lamblia, monolayers were assessed for cytoskeletal arrangement under fluorescence and confocal laser microscopy, and transepithelial electrical resistance was measured. Exposure to live G. lamblia trophozoites induced localized condensation of F-actin and loss of perijunctional alpha-actinin while G-actin remained unchanged. Confocal laser microscopy indicated that F-actin rearrangement was not affected by verapamil and was localized within the terminal web area. Coincubation of monolayers with G. lamblia lysates or with spent medium alone similarly rearranged F-actin. Verapamil alone did not alter F-actin. Electrical resistance of SCBN and Caco2 monolayers exposed to G. lamblia was significantly decreased versus controls regardless of whether live or lysed trophozoite samples were used. The results indicate that G. lamblia-induced epithelial injury is associated with F-actin and alpha-actinin rearrangements in the terminal web area via mechanisms independent of extracellular Ca2+. These alterations are associated with reduced transepithelial electrical resistance and are due at least in part to trophozoite products.
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PMID:Giardia lamblia rearranges F-actin and alpha-actinin in human colonic and duodenal monolayers and reduces transepithelial electrical resistance. 1095 59

Alpha-11 Giardin, a protein from the annexin superfamily, is a 35.0 kDa protein from the intestinal protozoan parasite Giardia lamblia which triggers a form of diarrhea called giardiasis. Here, the cloning, expression, purification and the crystallization of alpha-11 giardin under two different conditions and in two different space groups is reported. Crystals from the first condition diffracted to 1.1 A and belong to a primitive orthorhombic space group, while crystals from the second condition, which included calcium in the crystallization solution, diffracted to 2.93 A and belong to a primitive monoclinic space group. Determination of the detailed atomic structure of alpha-11 giardin will provide a better insight into its biological function and might establish whether this class of proteins is a potential drug target against giardiasis.
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PMID:Expression, purification, crystallization and preliminary X-ray diffraction analysis of alpha-11 giardin from Giardia lamblia. 1707 90

Hypomagnesemia is a rare cause of hypoparathyroidism that can have a very serious clinical presentation. We report the case of a 62-year-old woman hospitalized for exploration of acute tetraparesis with vomiting and swallowing disorders associated with a severe hypocalcemia. Biological explorations revealed hypoparathyroidism (PTH=16ng/L) related to low plasma and erythrocyte magnesium (0.32 and 1.32mmol/L, respectively) as well as hypocalciuria and hypomagnesuria linked to gastrointestinal malabsorption. Etiologic investigations led to the discovery of Giardiasis lamblia on duodenal biopsies and a long-term treatment with proton pump inhibitors (PPI) (omeprazole followed by esomeprazole), both being recently described as causal factors of hypomagnesemic hypoparathyroidism. After treatment of the parasite (by metronidazole) and discontinuation of the PPI, both calcium and magnesium levels returned to normal. Selective malabsorption has been previously reported in patients with giardiasis. The specific mechanism of PPI participation in the genesis of hypomagnesemia remains a subject of debate.
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PMID:[Chronic use of proton-pump inhibitors associated with giardiasis: A rare cause of hypomagnesemic hypoparathyroidism?]. 1861 53

The aim of this study is to assess the prevalence of isolated short stature as a clinical presentation of celiac disease in Saudi Arab children and whether some of the routine laboratory tests performed to determine the cause of short stature could suggest the diagnosis of celiac disease. A total of 91 children with short stature were included in the study. Extensive endocrine and biochemical assessments, including total protein, serum albumin, calcium phosphate and alkaline phosphatase assays; renal function tests; coagulation profile; anti-endomysial antibodies and anti-tissue transglutaminase antibody, growth hormone, thyroid stimulating hormone, free-thyroxin (FT4) assays; stool tests for giardiasis; bone age; and endoscopic intestinal biopsies, were done for all children. Ten of the 91 children had positive intestinal biopsies in the form of total villous atrophy, an increase in crypt height, and an increase in intra-epithelial lymphocyte (IEL) numbers up to >40 IEL/100 EC (Type 3C) according to the Oberhuber classification, confirming the diagnosis of celiac disease. Five children had mild villous atrophy according to this classification (Type 3A), and they were considered to have potential celiac disease. Seventy-six children had normal intestinal biopsies. Therefore, the prevalence of celiac disease among Saudi children with short stature was 10.9%, and 4.3% of the children were diagnosed as having potential celiac disease. After confirming the diagnosis of celiac disease, all children were kept on a gluten-free diet and all of them showed improvement in their growth rate. We concluded that celiac disease is a very important cause of short stature in children without gastrointestinal complaints in Saudi Arabia. We highly recommend anti-tissue transglutaminase and anti-endomysial antibody screening tests, and a small bowel biopsy to confirm the diagnosis of celiac disease irrespective of the results of the antibody assays, in children with short stature in Saudi Arabia. Once the diagnosis is confirmed, children should be kept on a gluten-free diet so they can catch up their growth early before they develop permanent short stature.
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PMID:Isolated short stature as a presentation of celiac disease in Saudi children. 2158 40

Hyperparathyroidism is a rare finding in children. It is a typical sign of vitamin D-deficiency caused by different reasons. It may also be due to calcium wasting syndromes, and it can rarely be induced by adenomas of the parathyroid glands and in parathormone receptor mutations (pseudohyperparathyroidism). A 12-year old Gambian girl living in Hamburg, Germany, was developing abdominal and joint pain. Serum analysis revealed low serum-calcium, significantly elevated parathormone and decreased vitamin D. Immigrant rickets was assumed. Because of abdominal pain and iron deficiency, lambliasis was ruled out. Celiac disease was demonstrated by gliadin and endomysium antibodies as well as by intestinal mucosa biopsy. Despite of a gluten-free diet the joint pains persisted. They were declared by rheumatologists to be caused by a chronic juvenile arthritis (sister disease of celiac disease). However, there were no positive inflammation signals and no clear elevated rheuma-immunology. Follow up: Gluten-free diet and additional treatment with calcium and active vitamin D did not stop increasing parathormone levels, did not stop abdominal and joint pain, and did not stop increment of positive celiac disease antibodies. Assuming compliance problems the patient was then treated with vitamin D injections, which caused decreasing parathormone levels and vanishing joint pain. Celiac disease can cause intestinal rickets with elevated parathomone levels mimicking chronic juvenile arthritis, if gluten-free diet is not strictly performed by compliance problems.
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PMID:Hyperparathyroidism due to auto-immunological malabsorption in an African girl. 2161 78

Giardia lamblia causes malabsorption. The aim of this study was to evaluate serum and saliva calcium and magnesium levels in patients with giardiasis. Thirty patients with giardiasis as a case and 30 person without giardiasis as a control group were enrolled. The stimulated and unstimulated whole saliva and serum calcium and magnesium levels were assayed by Arsenazo reaction and xylidyl blue complex methods, respectively. Mean calcium and magnesium level was low in serum and stimulated saliva of case group than that of controls. However, they were higher in the unstimulated saliva of the case group. It is suggested that patients suffering from giardiasis have low calcium and magnesium levels, and they lose the most of calcium and magnesium by saliva during unstimulated condition.
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PMID:Stimulated and Unstimulated Saliva Levels of Calcium and Magnesium in Giardiasis. 2824 50