Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042961 (volvulus)
 4,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.
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PMID:Gastrointestinal manifestations in cystic fibrosis. 886 67

The alternatively-spliced Caenorhabditis elegans gbr-2/avr-14 gene encodes two subunits of the nematode ligand-gated chloride channel family which forms an important molecular target for the avermectin and related anthelminthics. We used reverse transcriptase-polymerase chain reaction (RT-PCR) techniques to isolate cDNAs encoding the products of the gbr-2/avr-14 orthologues from the parasitic nematodes Haemonchus contortus and Ascaris suum. The predicted polypeptides possess all the characteristics of subunits of the ligand-gated chloride channels, sharing greater than 80% amino-acid identity with their counterparts in C. elegans and with partial sequences from the filarial species Onchocerca volvulus and Dirofilaria immitis. The pattern of alternative splicing of the gbr-2/avr-14 gene observed in C. elegans is conserved in H. contortus but may not be in A. suum. Affinity-purified anti-GBR-2 antibodies were used to study the expression of these subunits in adult worms and they reacted specifically with the nerve ring, the ventral and dorsal nerve cords, the anterior portion of the dorsal sub-lateral cord and motor-neuron commissures in H. contortus. Specific immunofluorescence of the nerve cords was confirmed in A. suum; isolated muscle cells did not react with the antibody.
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PMID:Ligand-gated chloride channel subunits encoded by the Haemonchus contortus and Ascaris suum orthologues of the Caenorhabditis elegans gbr-2 (avr-14) gene. 1055 58

Heartworm prophylaxis is currently largely dependent on the ability of avermectins and milbemycins to arrest the development of third and fourth stages of Dirofilaria immitis for prolonged periods, without producing adulticidal effects. Major control programs, dependent on the activity of ivermectin, are being implemented for human onchocerciasis and lymphatic filariasis. The avermectins and milbemycins act on glutamate-gated and gamma-aminobutyrate-gated chloride channel subunit proteins in nematodes. Ivermectin resistance has been widely described in trichostrongylid nematodes of ruminants. There is evidence that when ivermectin resistance occurs in nematodes, there may be selection on some, but not all of the genes that code for ligand-gated chloride channel subunit proteins as well as on some ABC-transporter genes, whose products may be involved in regulating macrocyclic lactone drug concentrations at receptors, and on some structural protein genes of amphidial neurones. Although ivermectin resistance has not been reported in filarial nematodes, there have recently been reports of suboptimal responses to ivermectin in Onchocerca volvulus. Evidence has been found of ivermectin selection on at least ABC-transporter genes and some neuronal structural protein genes in O. volvulus. To date, there is no evidence of avermectin/milbemycin resistance in D. immitis, also a filarial nematode. Chemotherapy against trichostrongylids of animals, human filariae, and D. immitis, relies on avermectins or milbemycins. However, control involves targeting different stages or processes in the nematode life cycles, different control strategies, different proportions of the nematode population in refugia, and different drug dosage rates. Consideration of the proportion of the D. immitis population normally in refugia, the life cycle stage targeted, and the anthelmintic dosages used suggest that it is unlikely that significant avermectin/milbemycin resistance will be selected in D. immitis with current treatment strategies.
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PMID:Is anthelmintic resistance a concern for heartworm control? What can we learn from the human filariasis control programs? 1619 24

In some trichostrongyloid nematodes, the early stages of ivermectin (IVM) resistance have been characterized by a shift in allele frequency and reduced polymorphism at loci of P-glycoprotein genes, glutamate-gated chloride channel genes and gamma-aminobutyric acid receptor genes. Mass treatment with IVM is an integral component of the onchocerciasis control programmes. Genetic variation of an Onchocerca volvulus ABC transporter homologue (OvABC-3) from several populations in Africa was examined to determine whether an association exists between alleles of this gene and IVM treatment. Allelic variation in a non-treated population from Ghana showed this locus to be highly polymorphic. However, variability was reduced in IVM-treated populations. chi2 analysis of polymorph frequencies showed significant differences between untreated and treated samples collected in Ghana in 1999. There was less variability in this gene in samples collected in 2002 compared with the 1999 samples. In some treated populations, there appeared to be selection on OvABC-3-C. The observed reduction in variability could be expected in a control programme in which prevalence and intensity of infections are markedly reduced after years of vector control and IVM distribution. The reduction in polymorphism may not in itself indicate that these O. volvulus are IVM resistant, although it could indicate that selection for resistance is occurring.
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PMID:Reduced genetic variation of an Onchocerca volvulus ABC transporter gene following treatment with ivermectin. 1790 99