Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds.

OBJECTIVE: This study compares treatment with a polihexanide-containing biocellulose wound dressing (BWD+PHMB) versus the best local standard of silver dressings (Ag) in painful, critically colonised (wounds-at-risk) or locally-infected wounds. METHOD: Patients with wounds of various aetiologies, a baseline VAS pain score >4 and a semi-quantitative bacterial load of ++ or higher were randomly allocated to receive treatment with either BWD+PHMB or Ag. Patients with systemic infections and/or using systemic antibiotics were excluded. The primary endpoint, patient-reported pain (VAS total pain, including the sub-scores pain at night, during the day, before, and 15min after dressing changes), was compared between treatment groups and scored on days 0, 1, 3, 7, 14, 21 and 28. Secondary outcomes of bacterial load, wound bed and periwound skin condition, quality of life and dressing handling were assessed at the same visits. RESULTS: Thirty-eight patients (BWD+PHMB, n=21 [24 wounds]; Ag, n=17 [18 wounds]) were included in the analyses. Baseline variables showed no significant differences. Wound pain was reduced significantly in both groups, with a better pain reduction noted for BWD+ PHMB (p<0.001) before dressing changes. Compared with Ag, in the BWD+PHMB group critical colonisation and local wound infection had been reduced significantly faster and better (p<0.001) over the 28-day study period. Improved quality of life, good tolerability and no adverse events were demonstrated for both groups. CONCLUSION: Both BWD+PHMB and AG were effective in reducing pain and bacterial burden. However, that BWD+PHMB was significantly faster and better in removing the critical bacterial load, makes this dressing an attractive therapeutic option to treat critically colonised and locally-infected wounds.

A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.

AIMS/HYPOTHESIS: The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical. This notion has been addressed in different lines of HSL knockout mice with contradictory results. METHODS: To resolve this, we created a transgenic mouse lacking HSL specifically in beta cells, and characterised this model with regard to glucose metabolism and insulin secretion, using both in vivo and in vitro methods. RESULTS: We found that fasting basal plasma glucose levels were significantly elevated in mice lacking HSL in beta cells. An IVGTT at 12 weeks revealed a blunting of the initial insulin response to glucose with delayed elimination of the sugar. Additionally, arginine-stimulated insulin secretion was markedly diminished in vivo. Investigation of the exocytotic response in single HSL-deficient beta cells showed an impaired response to depolarisation of the plasma membrane. Beta cell mass and islet insulin content were increased, suggesting a compensatory mechanism, by which beta cells lacking HSL strive to maintain normoglycaemia. CONCLUSIONS/INTERPRETATION: Based on these results, we suggest that HSL, which is located in close proximity of the secretory granules, may serve as provider of a lipid-derived signal essential for normal insulin secretion.

Cardiac dysfunction in adipose triglyceride lipase deficiency: treatment with a PPARα agonist.

BACKGROUND AND PURPOSE: Adipose triglyceride lipase (ATGL) has been identified as a rate-limiting enzyme of mammalian triglyceride catabolism. Deletion of the ATGL gene in mice results in severe lipid accumulation in a variety of tissues including the heart. In the present study we investigated cardiac function in ATGL-deficient mice and the potential therapeutic effects of the PPARα and γ agonists Wy14,643 and rosiglitazone, respectively. EXPERIMENTAL APPROACH: Hearts isolated from wild-type (WT) mice and ATGL(-/-) mice treated with Wy14,643 (PPARα agonist), rosiglitazone (PPARγ agonist) or vehicle were perfused at a constant flow using the Langendorff technique. Left ventricular (LV) pressure-volume relationships were established, and the response to adrenergic stimulation was determined with noradrenaline (NA). KEY RESULTS: Hearts from ATGL(-/-) mice generated higher LV end-diastolic pressure and lower LV developed pressure as a function of intracardiac balloon volume compared to those from WT mice. Likewise, passive wall stress was increased and active wall stress decreased in ATGL(-/-) hearts. Contractile and microvascular responses to NA were substantially reduced in ATGL(-/-) hearts. Cardiac contractility was improved by treating ATGL(-/-) mice with the PPARα agonist Wy14,643 but not with the PPARγ agonist rosiglitazone. CONCLUSIONS AND IMPLICATIONS: Our results indicate that lipid accumulation in mouse hearts caused by ATGL gene deletion severely affects systolic and diastolic function, as well as the response to adrenergic stimulation. The beneficial effects of Wy14,643 suggest that the cardiac phenotype of these mice is partially due to impaired PPARα signalling.