Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the intestinal epithelium the rapidly proliferating crypt cells, the precursors of the mature enterocytes are extremely sensitive to the effects of cytostatic agents. The symptoms of intestinal impairment: nausea, vomiting, diarrhea, ulceration, are well known both in clinical practice and in experimental chemotherapy. To obtain information about the biochemical nature of these side effects, a study was performed by investigating the influence of clinically used alkylating hexitol derivatives, dianhydrogalactitol and diacetyl-dianhydrogalactitol, on rat intestinal mucosa cells. The biochemical parameters were investigated in isolated intestinal mucosa cells. Cell proliferation was characterized by measuring the activity of thymidine kinase, while digestion was evaluated by assaying the alkaline phosphatase, sucrase and maltase activities localized in the brush border membrane of the villus cells. The dose response studies of the different enzyme activities indicated that inhibition in all cases was dose dependent. The nadir of the intestinal damage and the time of regeneration were influenced both by the dose and the dosage schedule of the drugs.
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PMID:Biochemical changes of intestinal epithelial cells induced by cytostatic agents in rats. 386 86

Imipenem, the first of a new class of carbapenem antibiotics, has potent activity against most clinically important species of bacteria, including isolates resistant to other antibiotics. The drug is well distributed to most tissues and fluids after intravenous administration; however, levels in cerebrospinal fluid are modest. Most of the drug is eliminated in the urine, where it is metabolized by an enzyme on the brush border of the renal tubular cells; cilastatin is given simultaneously to inhibit this inactivation. Adverse effects include a syndrome of nausea and hypotension, especially after rapid intravenous infusion, and a predisposition to seizures in certain high-risk patients. Superinfections by resistant bacteria and fungi are infrequent. This new drug may be particularly useful in the treatment of infections caused by mixtures of bacteria for which a combination of antibiotics, often including an aminoglycoside, would otherwise be necessary. Examples include pulmonary, intra-abdominal, and soft-tissue infections.
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PMID:Imipenem: first of a new class of beta-lactam antibiotics. 389 54

The pharmacokinetics of imipenem were evaluated in four studies involving 49 healthy men, several of whom participated in more than one study. Within a dose-range of 150 to 1000 mg, imipenem was found to give high plasma concentrations, proportional to the size of the dose. The half life in the beta-phase was about 1 h in 48 subjects with normal renal function and about 80 min in one subject with a glomerular filtration rate (GFR) of about 50 ml/min/1 X 73 m2. The volume of distribution in the central compartment was about 101. Co-administration of imipenem with probenecid resulted in a slight but significant increase of the plasma half life and a corresponding increase of the area under the plasma concentration curve (AUC). The renal excretion of imipenem was characterized by low urinary recovery (UR) of imipenem. That was in agreement with findings by others that in animals, imipenem undergoes renal metabolism by a dipeptidase, dehydropeptidase I, located to the brush border of the proximal tubular cells. There was a very high degree of between-subject variability of the UR with values varying from about 5% to more than 40% of the dose. Comparing the results obtained after several administrations of imipenem to the same subjects, a small within-subject variability was found. Co-administration of imipenem with inhibitors of the dehydropeptidase MK0789 or MK0791 (cilastatin), resulted in a uniform increase of the imipenem UR to about 70% of the dose irrespective of the degree of metabolism when imipenem was given alone. The effects of the inhibitors on the plasma kinetics of imipenem were an increase of the AUC by about 20% and a proportional decrease of the plasma clearance (VClp) while the plasma half life remained unaffected. Testing various ratios of imipenem and the inhibitors and using incremental data, it could be demonstrated that an increase of the imipenem/cilastatin ratio resulted in a prolonged inhibition of the renal metabolism. Optimal inhibition seemed to be achieved at a ratio of 1:1 between imipenem and cilastatin. A practical consequence of the inhibition of renal metabolism by cilastatin was that high urine concentrations were maintained for longer periods when the combination was given than when imipenem was administered alone. In all subjects, imipenem and the inhibitors were well tolerated and the only adverse reaction observed was nausea during infusion, observed in one subject.
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PMID:Pharmacokinetics of imipenem in healthy volunteers. 658 94

Carbohydrates are hydrolyzed in the intestinal lumen by specific enzymes to monosaccharides before transport across the brush border membrane of epithelial cells into the cell interior. The enzymes implicated in the digestion of carbohydrates in the intestinal lumen are membrane-bound glycoproteins that are expressed at the apical domain of the enterocytes. Absent or reduced activity of one of these enzymes is the cause of disaccharide intolerance and malabsorption, the symptoms of which are abdominal pain, cramps or distention, flatulence, nausea and osmotic diarrhea. Lactose intolerance is the most common intestinal disorder that is associated with an absence or drastically reduced levels of an intestinal enzyme, in this case lactase-phlorizin hydrolase (LPH). The pattern of reduction of activity has been termed late onset of lactase deficiency or adult type hypolactasia. It was thought that the regulation of LPH was post-translational and was associated with altered structural features of the enzyme. Recent studies, however, suggest that the major mechanism of regulation of LPH is transcriptional. Other forms of lactose intolerance include the rare congenital lactase deficiency and secondary forms, such as those caused by mucosal injury, due to infectious gastroenteritis, celiac disease, parasitic infection, drug-induced enteritis and Crohn's disease. This review will shed light on important strucural and biosynthetic aspects of LPH, the role played by particular regions of the LPH protein in its transport, polarized sorting, and function, as well as on the gene expession and regulation of the activity of the enzyme.
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PMID:Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase. 1133 11

Giardia intestinalis infection causes enterocytes damage and loss of brush border of the epithelial cells of the intestine that leads to shortening of microvilli and altered epithelial barrier function. This pathology results in aqueous diarrhoea, steatorrhea, nausea, abdominal pain, vomiting and weight loss. However, most infections are asymptomatic. The main consequence of Giardia colonization is nutrients malabsorption. Several families of drugs with good efficacy are used for Giardia treatment, but sometime dosing regimens are suboptimal and emerging resistance begins to question their clinical value. Moreover, some of these drugs can cause side effects that result in patient discomfort and low adherence to the treatment. This paper reviews the drugs currently used for the treatment against Giardia: the mechanism of action, the efficacy, the normal dosing, side effects and in vitro and clinical studies. In addition, new therapies against Giardia such as those based on phytochemicals, Lactobacillus and nanotechnology are collected in this paper, trying to find the ideal treatment for this disease with maximum efficacy and minimum adverse effects.
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PMID:Giardiasis: Characteristics, Pathogenesis and New Insights About Treatment. 3027 55