ABSTRACT
Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.
Subject(s)
Brain/drug effects , Hypoglycemic Agents/pharmacology , Peptides/pharmacology , Venoms/pharmacology , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Animals , Brain/enzymology , Brain/metabolism , Cognition Disorders/drug therapy , Cognition Disorders/metabolism , Cognition Disorders/pathology , Diabetes Mellitus, Experimental/drug therapy , Disease Models, Animal , Electron Transport Complex IV/metabolism , Exenatide , Female , Hypoglycemic Agents/therapeutic use , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Male , Memory, Long-Term/drug effects , Memory, Short-Term/drug effects , Mice , Mice, Transgenic , Mitochondria/enzymology , Peptides/therapeutic use , Venoms/therapeutic use , tau Proteins/metabolismABSTRACT
The incidence of exit-site infections among peritoneal home-dialysis patients was quantified following for 1 year all home dialysis patients of 23 dialysis centres. The exit site conditions were observed and classified according to Twardowsky. When an infection occurred data on its treatment were collected. 393 patients were observed. The infection occurred in 40 patients (10.1%). 82.2% of patients wear a Tenckoff catheter, 3% do not protect the exit site with any kind of dressing. The strategies adopted by different centres vary for the choice of antiseptics, the suggested frequency of changes dressing and the routine use of nasal swabs. Due to the limited number of patients with infection no association was found between tunnel direction or frequency of dressing changes and infections occurrence. Discussion on controversial aspects and the definition of common guidelines for instance for frequency of dressing changes, use of antiseptics is warranted.
