Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emphasis has been put on the intensification of chemotherapy programs through high-dose chemotherapy regimens. While their myelosuppression is managed through the use of colony-stimulating factors and/or infusion of autologous peripheral blood progenitor cell transfusions (PBPCT), extramedullary dose-limiting toxicities, including gastrointestinal mucosal injury, are a treatment-limiting factor and their management is a critical issue in HSD-HDC. Octreotide is effective in the control of diarrhoea induced by fluoropyrimidines. We have studied its effect on hematopoietic support-dependent high-dose chemotherapy (HSD-HDC) related diarrhoea. HSD-HDC-treated patients were included in the study when they had > or =4 loose stools per day. Diagnostic work-up included physical examination, stool culture, Clostridium difficile toxin assay, abdominal plain films, complete blood counts, liver and renal function tests. Patients were treated with 0.1 mg octreotide, q 8 h, subcutaneously for 48 h. Responding patients (< or =2 loose stools per day) continued treatment at the same dose for an additional 24 h. Lack of response (> or =3 loose stools per day), led to dose escalation by 0.1 mg increments, up to a 0.5 mg/dose and the latter dose was maintained for 24 h. Patients not responding at 0.5 mg/8 h were considered failures. A consecutive cohort of 24 HSD-HDC treated patients was studied. Fourteen (n = 14) (58.33%) patients developed severe diarrhoea with a median number of 7.5 loose stools per day (range, 4-11). Diarrhoea started at a median of 8 days (2-18) from day 0 of the infusion of HSD-HDC. Seven patients (50%) had less than 500 ANC/mm3 (grade 4 neutropenia) simultaneously with the diarrhoea. Twelve of 14 patients (86%) had their diarrhoea controlled, seven of them (50%) at the starting dose level of octreotide. In five of the responding patients (35.7%), octreotide had to be increased to 0.2 mg (one patient), 0.3 mg (two patients) and 0.5 mg (two patients). No toxicity was observed, while one patient had a subcutaneous hematoma at the injection site. We have concluded that octreotide appears to be safe and effective in controlling the diarrhoea induced by HSD-HDC. Prospective controlled trials are needed to confirm its value.
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PMID:Octreotide (SMS 201-995) for hematopoietic support-dependent high-dose chemotherapy (HSD-HDC)-related diarrhoea: dose finding study and evaluation of efficacy. 938 71

Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.
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PMID:Proteome mining for the identification and in-silico characterization of putative drug targets of multi-drug resistant Clostridium difficile strain 630. 2823 60