Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

BACKGROUND: The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva. METHODS: Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models. RESULTS: EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF. CONCLUSION: Basic FGF may be effective for refractory oral mucosal lesions.     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

The effects of KATP channel modulators on counterregulatory responses and cognitive function during acute controlled hypoglycaemia in healthy men: a pilot study.

AIMS: To examine the effects of agents that alter potassium adenosine triphosphate (KATP) channel activity in beta-cells on cognitive function and counterregulatory hormone responses during acute hypoglycaemia, given the physiological similarities between the pancreatic beta-cell and the hypothalamic glucose-sensitive neurones (GSN) and the widespread distribution of sulphonylurea receptors in neuronal cells throughout the brain. METHODS: Ten healthy males were studied on four occasions and in random order underwent three stepped hypoglycaemic (plasma glucose aims: 3.4, 2.8, 2.4 mmol/l) and one euglycaemic (plasma glucose aim: 5 mmol/l) insulin clamps. Prior to each hypoglycaemic study, volunteers received either 10 mg glibenclamide, or 5 mg/kg diazoxide or placebo orally. Cognitive function, symptom scores and counterregulatory hormone responses were measured at each glycaemic level. RESULTS: There was no statistically significant effect of either drug on the symptoms generated or the counterregulatory hormonal response during hypoglycaemia. However, cognitive function was better preserved during hypoglycaemia in the glibenclamide-treated arm, particularly four-choice reaction time which deteriorated at a plasma glucose 2.5 mmol/l compared with 3.0 mmol/l with diazoxide (P = 0.015) and 2.9 mmol/l with placebo (P = 0.114). CONCLUSIONS: Single doses of pharmacological agents which alter membrane KATP channel activity do not affect the counterregulatory response to hypoglycaemia but may modify cognitive function during cerebral glucopenia. The unexpected effects of glibenclamide on cortical function suggest a novel action of sulphonylureas that warrants further investigation.     

Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells.

The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has been investigated. TSE significantly (P<0.001) reduced the time-dependent cell proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses) suppressed the proliferating cell nuclear antigen expression in both the cells. It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562 cells at G1 phase of the cell cycle. Confocal microscopy showed the altered fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937 and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were observed through scanning electron microscope. TSE-induced DNA fragmentation in U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE significantly (P<0.001) increase the length-width ratio of DNA mass as compared to control in comet assay. The flow cytometric analysis of annexin-V binding to the cancer cells further supported the apoptotogenic activity of TSE. The effect of TSE on normal human peripheral blood mononuclear cells viability and cytotoxicity was studied in culture and found to be less cytotoxic than on the U937 and K562 cells. The findings from the present study suggested that TSE might possess potent antineoplastic agent having antiproliferative, cytotoxic and apoptogenic activity against U937 and K562 myeloid leukemic cells.