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Biomedical subjects

M A Hull

Publications and source records attributed to M A Hull.

29 records · Page 2Linked to original sources
PubMed1998

Evaluation of the developmental toxicities of coumarin, 4-hydroxycoumarin, and 7-hydroxycoumarin using FETAX.

The developmental toxicities of coumarin and hydroxycoumarin metabolites were evaluated using FETAX. Young X. laevis embryos were exposed to coumarin, 4-hydroxycoumarin, and 7-hydroxycoumarin in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO), cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450 activity. The MAS was also treated with cyclohexene oxide (CHO) to selectively modulate epoxide hydrolase activity. Without the MAS or inhibited MAS, coumarin and 7-hydroxycoumarin were nearly equitoxic, whereas 4-hydroxycoumarin was nearly 2-fold less developmentally toxic than coumarin on an equimolar basis. Addition of the MAS and CIM-MAS increased the developmental toxicities of coumarin and, particularly, 4-hydroxycoumarin. Addition of the CHO-MAS greatly increased the developmental toxicity of coumarin and, especially, 4-hydroxycoumarin. Addition of the ELL- or CO-inhibited MAS did not increase the developmental toxicity of coumarin. However, addition of the intact MAS did not alter the developmental toxicity of 7-hydroxycoumarin. Results from these studies suggested that P-450; specifically ELL-inhibited P-450 (arylhydrocarbon hydroxylase) may have been responsible for increasing the developmental toxicity of coumarin. Furthermore, the increased toxicity of coumarin or 4-hydroxycoumarin following co-incubation with CHO-treated microsomes indicated that highly toxic epoxide intermediates may be produced from oxidative P-450 metabolism and that epoxide hydrolase may play a role in detoxification of the reactive intermediates.

4-Hydroxycoumarins↗
PubMed1997

Healing with basic fibroblast growth factor is associated with reduced indomethacin induced relapse in a human model of gastric ulceration.

BACKGROUND: Acid stable basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats and reduces subsequent non-steroidal anti-inflammatory drug (NSAID) induced relapse. AIMS: To test in a double blind, placebo controlled, three way crossover study whether bFGF promotes healing and reduces subsequent relapse in a human model of gastric ulceration. SUBJECTS: Twelve healthy volunteers. METHODS: Subjects took aspirin 900 mg twice daily (days 1-3) with bFGF 0.1 mg twice daily or cimetidine 400 mg twice daily or placebo (days 1-14) and then indomethacin 50 mg thrice daily (days 15-21). Endoscopy was performed on days 1, 4, 8, 15, and 22 during each treatment period. Eight antral biopsy specimens were taken on day 1 and the number of unhealed biopsy induced mini-ulcers and NSAID induced erosions counted during subsequent endoscopies. RESULTS: Basic FGF and cimetidine were protective against aspirin and indomethacin induced duodenal (but not gastric) injury compared with placebo. There was significant relapse of biopsy induced mini-ulcers after indomethacin only in the placebo group (0 (0-0) before v 1 (0-4.5) after; p > 0.05). TGP-580 was detected in serum of one volunteer. CONCLUSIONS: Healing with bFGF (and cimetidine) was associated with reduced NSAID induced ulcer relapse in this model of gastric ulceration.

Adult↗
PubMed1996

Isolation and culture of human gastric endothelial cells.

BACKGROUND & AIMS: Angiogenesis plays an important role in gastric ulcer healing. Considerable heterogeneity exists between endothelial cells from different blood vessels in vitro. Hitherto, it has not been possible to study gastric angiogenesis using relevant endothelial cells. The aim of this study was to isolate and culture human gastric endothelial (HuGE) cells to allow investigation of gastric ulcer angiogenesis. METHODS: Gastric mucosa underwent mechanical and enzymatic disruption. Microvessel fragments and endothelial cells were selected using superparamagnetic beads (Dynabeads; Dynal, Wirral, England) coated with a murine monoclonal anti-human platelet-endothelial cell adhesion molecule 1 antibody. Contaminating nonendothelial cells were removed by mechanical weeding and further Dynabead separation of endothelial cells. RESULTS: HuGE cells have been cultured up to passage 19. HuGE cells formed contact-inhibited monolayers on gelatin coated surfaces and tube-like structures on basement membrane matrices. Indirect immunofluorescence studies confirmed the endothelial nature of these cells. Basic and acidic fibroblast growth factors and vascular endothelial growth factor promoted proliferation (but not epidermal growth factor). HuGE cells synthesized less prostaglandin I2 and E2 compared with human umbilical vein endothelial cells. CONCLUSIONS: Pure cultures of HuGE cells can be obtained. Physiologically important differences from large vessel endothelial cells require further investigation.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Evaluation of the developmental toxicity of theophylline, dimethyluric acid, and methylxanthine metabolites using Xenopus.

The developmental toxicities of theophylline and theophylline metabolites were evaluated using FETAX (Frog Embryo Teratogenesis Assay - Xenopus). Young X. laevis embryos were exposed to theophylline, 1-methylxanthine, 3-methylxanthine, or 1, 3-dimethyluric acid in each of two separate concentration-response experiments with and without an exogenous metabolic activation system (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO), cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450 activity. Addition of the MAS and CIM-MAS reduced the developmental toxicity of theophylline. Addition of the ELL- or CO-inhibited MAS did not reduce the developmental toxicity of theophylline. Addition of the intact MAS did not alter the developmental toxicity of 1-methyl- or 3-methylxanthine which were slightly more developmentally toxic on an equimolar basis than theophylline itself. 1, 3-dimethyluric acid was not developmentally toxic at maximum soluble concentrations in 1% (V/V) DMSO. Results from these studies suggested that P-450, specifically ELL-inhibited P-450 (aryl hydrocarbon hydroxylase) may have been responsible for detoxification of theophylline and that 1, 3 dimethyluric acid represented the primary detoxification metabolite of theophylline.

Abnormalities, Drug-Induced↗
PubMed1995

Basic fibroblast growth factor treatment for non-steroidal anti-inflammatory drug associated gastric ulceration.

An open, pilot study tested the safety and efficacy of an acid stable form of the angiogenic protein basic fibroblast growth factor (bFGF) for healing of non-steroidal anti-inflammatory drug (NSAID) associated gastric ulcers in five patients with nine gastric ulcers that were resistant to conventional treatment (4) or had relapsed (5). Oral bFGF treatment for four weeks was safe and well tolerated. There was no evidence of systemic absorption. After four weeks, four ulcers had healed and there was a 89 (3)% mean (SEM) reduction in the area of the others. A controlled, comparative trial of this novel growth factor treatment is warranted.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Audit of outcome of long-term enteral nutrition by percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is the preferred method for administration of long-term enteral tube feeding. However, most published studies describe only short-term follow-up in any detail. We report the long-term outcome and complication rate after PEG insertion in 49 patients (mean [SE] age 64 [2] years) whose mean length of PEG feeding was 175 days (range 30-560). Data were collected prospectively. PEG insertion was technically successful in all cases, with a procedure-related mortality of 2%. Early (< 30 days) mortality and morbidity were 8% and 22%, respectively. Of 45 patients surviving for more than 30 days, 76% were able to return home and 6 patients were eventually able to revert to oral feeding. There were 27 late complications: 2 site infections, 17 mechanical problems, and 8 episodes of gastrointestinal dysfunction. 51% of patients had no problems at all and 22% had 2 or more complications. 47% of complications required a hospital visit for resolution. Long-term enteral feeding by PEG was safe, effective, and had a low complication rate. Our patients were managed by a specialist nutrition team, a policy that may reduce the complication rate and hospital visits for patients being fed at home, and allow early discharge of dysphagic patients, thereby reducing costs.

Aged↗
PubMed1987

Ciguatera toxicity.

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Ciguatera Poisoning↗