Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constipation is a risk factor of colorectal cancer. Mucin is a major component of lumenal mucus, which protects the colorectal mucosa against mechanical and chemical damage. The aim of this study was to evaluate mucus production and to quantitate lumen mucus in a rat model of spastic constipation. We induced constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus production and the thickness of the mucus layer at the fecal surface. We quantitated the mucus attached to the mucosal surface using colonic perfusion with N-acetylcysteine. While more feces remained in the colon, there was less fecal excretion and lower fecal water content in loperamide-administered rats than in control rats. Crypt epithelial cells contained less mucus in constipated rats than in control rats. The mucus layer at the fecal surface was thinner and less mucus was recovered from the mucosal surface in constipated rats than in control rats. Mucus production of crypt epithelial cells and mucus at the fecal and mucosal surface were reduced by loperamide-induced constipation.
Comp Biochem Physiol A Mol Integr Physiol 2000 Jun
PMID:Decreased colonic mucus in rats with loperamide-induced constipation. 1093 60

The clinical presentation of patients with vitamin B(12) deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B(12) deficiency. The aim of this study was to evaluate the effect of vitamin B(12) deficiency on autonomic nervous system function by studying gastric emptying times ( T(1/2)). Twenty patients with newly diagnosed vitamin B(12) deficiency and 12 control patients with gastritis and normal vitamin B(12) levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B(12) replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T(1/2) in patients before and after treatment and in controls were 103.83+/-48.80 min, 90.00+/-17.29 min and 74.55+/-8.52 min, respectively. The difference in mean gastric emptying T(1/2) between patients before treatment and controls was statistically significant ( P<0.01). The statistically significant difference persisted after vitamin B(12) treatment ( P<0.05), though mean gastric emptying T(1/2) was somewhat shorter. There were no positive or negative correlations between gastric emptying T(1/2) and the following parameters: haemoglobin, vitamin B(12) level and Helicobacter pylori positivity. In conclusion, gastric emptying T(1/2) was prolonged in patients with vitamin B(12) deficiency and this prolongation was not corrected after vitamin B(12) replacement therapy. Although autonomic nervous system dysfunction due to vitamin B(12) deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B(12) does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies.
Eur J Nucl Med Mol Imaging 2002 Sep
PMID:Gastric emptying in patients with vitamin B(12) deficiency. 1219 55

The beneficial effect of plant foods on human health is unmistakable. Time and time again, studies have found foods of plant origin to reduce the risk of most major chronic illnesses suffered by the human population. Possible mechanisms for the preventative effects of these foods are discussed. Each of the plant groups reviewed was found to reduce the risk of one or more of the following: cardiovascular disease, cancer (lung, breast, colon, rectal, prostate, epithelial, stomach, esophageal, oral, pharynx, larynx, urinary tract, endometrium, pancreas, thyroid, liver, ovary, gallbladder, bladder, and kidney), diabetes, hypertension, bone degeneration, diverticulitis, constipation, gallstones, age-related blindness. Almost no evidence was found to suggest a negative effect on health due to consumption of these plant foods. Based on this material and a review of conserved animal signaling molecules we surmise that animals require these chemicals to enhance specific mammalian cellular processes, demonstrating phyto-zooidal signaling. Further, this diet dependency coupling between plants and animals probably evolved because of the abundance of a particular plant material in a local environment, which is now broken because of technological advances. In conclusion, the overwhelming majority of evidence shows that people may significantly decrease their risks of the aforementioned diseases by increasing their intake of these foods since they represent a natural method to enhance animal processes and signaling.
Int J Mol Med 2002 Oct
PMID:Communication between animal cells and the plant foods they ingest: phyto-zooidal dependencies and signaling (Review). 1223 87

Indium-111 is currently the radionuclide of choice for colonic transit study. However, it is expensive and not available in many hospitals. Technetium-99m has been proposed for colonic transit study but the short half-life has limited its use. Gallium-67 citrate is inexpensive and available in most countries. Most importantly, it has a suitable half-life for colonic transit study. Attempts have been made in some studies to use (67)Ga citrate to label activated charcoal, but the results have not been good because of poor stability. In this study, we successfully labelled activated charcoal()with (67)Ga citrate by adding alcohol and 5% glucose solution. To evaluate the in vitro stability, the (67)Ga-activated charcoal was incubated in a milieu mimicking the intestinal content, containing lipase, trypsin and glycochenodeoxycholate at different pH values (6.0, 7.0, 7.4 and 8.0) and for different durations (0 h, 24 h, 48 h, 72 h and 96 h). For the in vivo study, the (67)Ga-activated charcoal was loaded into a commercial empty enteric capsule. Colonic transit scintigraphy was performed in five volunteers, including three healthy people and two constipated patients, after intake of the radioactive capsule. Images were obtained at 2 h, 4 h, 6 h, 8 h, 24h, 48 h, 72 h etc. until no radioactivity was detected in the bowel. Our data show that the in vitro stability of (67)Ga-activated charcoal was good. The labelling efficiency still exceeded 91% at 96 h at pH values of 6.0, 7.0 and 7.4. In the group with a pH value of 8.0, the labelling efficiency gradually fell during the 4-day incubation but was still higher than 88% at the end of the fourth day. In the in vivo study, most capsules disintegrated in the caecum/colon region, and the (67)Ga-activated charcoal mixed very well with bowel content. In addition, the radioactive charcoal could be detected clearly on the 72-h image, which is very important for the evaluation of colonic transit time in patients with constipation. In conclusion, activated charcoal labelled with (67)Ga citrate is a potential radioactive marker for colonic transit study.
Eur J Nucl Med Mol Imaging 2003 Jun
PMID:Gallium-67 activated charcoal: a new method for preparation of radioactive capsules for colonic transit study. 1273 86

G protein-coupled receptor desensitization and trafficking are important regulators of opioid receptor signaling that can dictate overall drug responsiveness in vivo. Furthermore, different mu-opioid receptor (muOR) ligands can lead to varying degrees of receptor regulation, presumably because of distinct structural conformations conferred by agonist binding. For example, morphine binding produces a muOR with low affinity for beta-arrestin proteins and limited receptor internalization, whereas enkephalin analogs promote robust trafficking of both beta-arrestins and the receptors. Here, we evaluate muOR trafficking in response to activation by a novel mu-selective agonist derived from the naturally occurring plant product, salvinorin A. It is interesting that this compound, termed herkinorin, does not promote the recruitment of beta-arrestin-2 to the muOR and does not lead to receptor internalization. Moreover, whereas G protein-coupled receptor kinase overexpression can promote morphine-induced beta-arrestin interactions and muOR internalization, such manipulations do not promote herkinorin-induced trafficking. Studies in mice have shown that beta-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression. Therefore, drugs that can activate the receptor without recruiting the arrestins may be a promising step in the development of opiate analgesics that distinguish between agonist activity and receptor regulation and may ultimately lead to therapeutics designed to provide pain relief without the adverse side effects normally associated with the opiate narcotics.
Mol Pharmacol 2007 Feb
PMID:An opioid agonist that does not induce mu-opioid receptor--arrestin interactions or receptor internalization. 1709 Jul 5

Microbia Inc is developing the oral guanylate cyclase C agonist linaclotide, a 14mer peptide for the potential treatment of constipation-predominant irritable bowel syndrome and chronic idiopathic constipation. Phase II clinical trials are underway for both indications.
Curr Opin Mol Ther 2007 Aug
PMID:Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. 1769 54

General gastrointestinal dysmotility occurs in patients with irritable bowel syndrome (IBS). Ghrelin seems to play an important role in regulating gastrointestinal motility. The present study was undertaken, therefore, to establish the possible role of ghrelin in the pathophysiology of IBS. Thirty-seven patients with IBS (19 had IBS-constipation and 18 IBS-diarrhoea) were included in this study. Ten healthy volunteers served as controls. After overnight fast, blood samples were drawn from patients and controls, and a gastroduodenal endoscopy was performed. Biopsies were taken from oxyntic mucosa and duodenum. Ghrelin cell density was determined by computer image analysis after immunohistochemical staining of the tissues. Total and active ghrelin were detected in tissue extracts and plasma by commercially available RIA and ELISA Kits. The density of ghrelin-immunoreactive cells in the oxyntic mucosa was significantly lower in IBS-constipation and significantly higher in IBS-diarrhoea patients than healthy controls (P<0.0001 and <0.0001, respectively). There was no statistical difference in total or active ghrelin between IBS patients and controls, regarding tissue extracts or plasma. In order to compensate for the increase and decrease in the ghrelin cell density, the synthesis and release of ghrelin may be decreased and increased in IBS-diarrhoea and IBS-constipation patients, respectively. It has been speculated that this compensatory mechanism may be subjected from time to time to fatigue with the subsequent increased and decreased synthesis and release of ghrelin in IBS-diarrhoea and IBS-constipation with a subsequent intermittent diarrhoea or constipation seen in these patients, respectively.
Int J Mol Med 2009 Jun
PMID:Ghrelin in patients with irritable bowel syndrome. 1942 95

Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.
Int J Mol Sci 2009 Aug 27
PMID:The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. 1986 17

Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is familial. Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD. We set out to develop transgenic mice expressing mutant alpha-synuclein (either A53T or A30P) from insertions of an entire human SNCA gene as models for the familial disease. Both the A53T and A30P lines show robust abnormalities in enteric nervous system (ENS) function and synuclein-immunoreactive aggregates in ENS ganglia by 3 months of age. The A53T line also has abnormal motor behavior but neither demonstrates cardiac autonomic abnormalities, olfactory dysfunction, dopaminergic neurotransmitter deficits, Lewy body inclusions or neurodegeneration. These animals recapitulate the early gastrointestinal abnormalities seen in human PD. The animals also serve as an in vivo system in which to investigate therapies for reversing the neurological dysfunction that target alpha-synuclein toxicity at its earliest stages.
Hum Mol Genet 2010 May 01
PMID:Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes. 2010 67

Two TP53 gene polymorphisms at codon 47 (TP53 Pro47Ser) and at codon 72 (TP53 Arg72Pro) have been associated with susceptibility to various cancers. We carried out a case-control study and examined the genotype distribution of TP53 Pro47Ser and Arg72Pro single nucleotide polymorphisms (SNPs), using a PCR-RFLP approach, to determine if these two SNPs are risk factors for colorectal cancer (CRC) development and to look for a possible correlation of these two SNPs with clinicopathological variables of CRC. We investigated the genotype distribution of these SNPs in 86 CRC cases in comparison with 160 healthy subjects in an ethnic Kashmiri population. TP53 Arg72Pro SNP genotype frequencies differed significantly (P = 0.000001) between the groups; the frequency of the Pro/Pro mutant was almost 20% in the general population. We also found significant association of the Pro/Pro mutant with tumor location, nodal status/higher tumor grade and bleeding per rectum/constipation. We conclude that Arg72Pro SNP is associated with susceptibility to developing CRC in this ethnic Kashmiri population.
Genet Mol Res 2010 Apr 13
PMID:TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. 2044 97


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