Glucose-mediated induction of TGF-beta 1 and MCP-1 in mesothelial cells in vitro is osmolality and polyol pathway dependent.

BACKGROUND: Glucose is converted to sorbitol and then to fructose via the polyol pathway that has been implicated in the pathogenesis of organ damage. The contribution of the polyol pathway to mesothelial cell activation has, however, not been fully determined. METHODS: The effect of increasing glucose concentrations on transforming growth factor-beta 1 (TGF-beta 1) and monocyte chemoattractant protein-1 (MCP-1) secretion by human peritoneal mesothelial cells (HPMC) was examined. The importance of the polyol pathway was identified by its specific inhibition with an aldose reductase inhibitor. RESULTS: Incubation of HPMC with 5 to 100 mmol/L glucose resulted in an induction of aldose reductase mRNA and intracellular sorbitol accumulation accompanied by the induction of TGF-beta 1 and MCP-1 mRNA expression and protein secretion. Mannitol at the same concentrations also induced aldose reductase, TGF-beta 1 and MCP-1 mRNA and protein expression but at a lower level than glucose. Sorbinil dose-dependently reduced both intracellular sorbitol levels (79.8% reduction of 60 mmol/L D-glucose induced intracellular sorbitol with 100 micromol/L sorbinil (N = 3, P < 0.01) and glucose-induced TGF-beta 1 and MCP-1 secretion. Mannitol induced TGF-beta 1 and MCP-1 secretion was not reduced by sorbinil. The addition of 15 to 40 mmol/L sodium lactate, either alone or in the presence of D-glucose enhanced TGF-beta 1 and MCP-1 secretion, which was inhibited by sorbinil. In contrast, sodium pyruvate appeared to antagonize D-glucose-induced TGF-beta 1 and MCP-1 secretion. CONCLUSION: These data suggest that the polyol pathway and osmolality contribute to the regulation of HPMC function by glucose. Control of polyol pathway activation might reduce glucose-mediated damage to the peritoneal membrane and promote its long-term survival.

Prevalence of sleep disturbances in Chinese patients with end stage renal failure on maintenance hemodialysis.

BACKGROUND: Sleep disorders, such as daytime sleepiness, insomnia, restless legs syndrome (RLS) and obstructive sleep apnea syndrome (OSAS) have been reported as prevalent among patients with end stage renal failure(ESRF). MATERIAL/METHODS: As there is little published data from Southeast Asia, a sleep questionnaire was administered to all patients (N=43, 27 males) on chronic hemodialysis (HD) at the Prince of Wales Hospital, Hong Kong, to assess their sleep complaints. RESULTS: The mean age was 49.5 +/- 11.3 years (mean I SD) with mean body mass index (BMI) of 22.6 +/- 3.6 kg/m2. Frequent awakenings and sleep onset insomnia were the most frequent complaints (79% each), while daytime sleepiness occurred in 74% of patients. Sleep maintenance insomnia and pruritus occurred in 64% and 60% of patients respectively. Symptoms of RLS were reported by 70% of patients. The prevalence of OSAS was estimated by the frequency of observed choking (4.7% of cases), witnessed apnea (14%), snoring and witnessed apnea (9.3%), disruptive snoring (14%), disruptive snoring and witnessed apnea (2.3%), extremely loud snoring (4.7%). CONCLUSIONS: Our questionnaire survey revealed a high prevalence of sleep complaints such as frequent awakenings, daytime sleepiness, insomnia and RLS in patients with ESRF on maintenance HD, but a relatively low prevalence of OSAS, which may be related to the low BMI of our ESRF patients.