Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine.HCl (DPPE) is a diphenylmethane analog of tamoxifen that antagonizes the intracellular binding of histamine to growth-regulatory sites, a proportion of which represents P450 enzymes, in microsomes and nuclei. We previously reported increased response rates and decreased myelotoxicity in patients with prostate and other cancers who received an intensive dose/schedule of DPPE plus single-agent chemotherapy. We now report the results of a study of DPPE combined with a standard dose/schedule of doxorubicin in twenty-three patients with metastatic breast cancer, sixteen of whom had received prior non-anthracycline chemotherapy. DPPE (6 mg/kg) was infused intravenously (i.v.) over 80 minutes. Doxorubicin (60 mg/m2) was administered i.v. over the last 20 minutes of the DPPE infusion. Treatment was repeated every 3 weeks (maximum, 7 cycles). Patients achieving complete response (CR) were followed off treatment until relapse. All patients were evaluable for toxicities and efficacy. Sixteen patients (69%; 95% C.I. = 47-87%) responded (7 CR and 9 PR). Eleven responders, including 6 with CR, had prior chemotherapy. Five responders (2CR, 3PR) had a poor (ECOG 3/4) performance status pre-treatment. Median CR duration was 11 (range 5-18) months. Hematological toxicity was low; GI toxicity (nausea/vomiting/dyspepsia) appeared somewhat higher than historical experience, but responded well to anti-emetics, ranitidine, and/or dexamethasone in most patients; a mean absolute drop in left ventricular ejection fraction of 8% occurred in 17 patients who received = or > 300 mg/m2 doxorubicin. The observed response rate in DPPE/doxorubicin-treated patients appeared to be higher than historically reported for doxorubicin alone in this setting, suggesting a chemopotentiating effect of DPPE. A multi-centre trial of this regimen in an additional 32 patients with early metastatic breast cancer has been conducted by the Clinical Trials Group, National Cancer Institute of Canada, and a phase 3 study is planned.
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PMID:The intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethamine.HCL, may potentiate doxorubicin in the treatment of metastatic breast cancer: Results of a pilot study. 969 12

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in irritable bowel syndrome (IBS) and gastric emptying but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups on the basis of bowel dysfunction. In 122 patients with IBS and 39 healthy controls, we assessed gastrointestinal somatic symptoms and affect by validated questionnaires. We measured: gastric volume (GV), maximum tolerated volume, rectal compliance, sensation thresholds and ratings, and genetic variations including alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T), and 5-HTTLPR. Demographics and genotype distributions were similar in the patients with IBS subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and the gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors, and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia.
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PMID:Candidate genes and sensory functions in health and irritable bowel syndrome. 1851 40

Male erectile dysfunction is common and frustrating after the age of forty years. Erectile dysfunction is a cause of misery, relationship difficulties, and significantly reduced quality of life. Sildenafil citrate (Viagra) has shown promising results in recently published clinical trials. Sildenafil is a potent and competitive inhibitor of cGMp specific phosphodiesterase-5, predominant isoenzyme in the human corpus cavernosum. It is effective in erectile dysfunction of diverse origin, however it requires a patent vascular system to be effective. It is not effective in patients with endocrinal impotence, loss of libido, premature ejaculation or infertility. Its main adverse effects are headache, flushing, dyspepsia, diarrhoea, nasal congestion, indigestion, visual disturbances, dizziness and rash. Ventricular tachycardia and acute myocardial infraction have been reported in patients of ischaemic heart disease after consumption of sildenafil. Six deaths have been reported in patients taking nitrates. In India it is likely to be prescribed by a primary care physician without complete evaluation of patient on complaint of impotence. Hence the ethical question of who should prescribe this drug should be addressed by medical fraternity and proper guidelines formulated to avoid misuse of sildenafil. Phosphodiesterase is distributed in nerve, central nervous system, and systemic vasculature, hence long-term effects of drug on these tissues has to be ascertained. It should be made mandatory to report all adverse drug reactions to ADR monitoring centres. It is a wonder for those who require it, but has potentially dangerous adverse effects and drug interactions and hence is and not a wonder pill for all kinds of impotence.
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PMID:VIAGRA : IS IT A WONDER DRUG ? 2736 78