Prognostic importance of tissue Doppler imaging of systolic and diastolic functions in dogs with severe sepsis and septic shock.

The goal of this study was to determine the distribution of left ventricular (LV) systolic and diastolic dysfunctions and their prognostic value in canine parvovirus-infected dogs suffering from severe sepsis and septic shock (SS/SS). Twenty dogs with SS/SS (experimental group) and 18 healthy dogs (control group) were used in the study. Systolic and diastolic dysfunction was present in three (15%) and 14 (70%) diseased dogs, respectively, with both types of dysfunction present in two (10%) of the patients. These dogs were split into two groups: survivors (Sv, n = 14) and non-survivors (non-Sv, n = 6). The pulsed wave tissue Doppler (PW-TDI) septal mitral annulus systolic velocity (LVS'), an index of systolic dysfunction, had a high sensitivity and specificity to differentiate Sv and non-Sv animals, with values of 83.3% (95% CI: 41.6-98.4) and 83.3% (95% CI: 59.8-94.8), respectively, at an optimum cut-off point of ≥ 9.90. The PW-TDI septal early mitral annulus early-diastolic peak velocity (E'), an index of diastolic dysfunction, had the best sensitivity and specificity to differentiate Sv and non-Sv dogs, with values of 100% (95% CI: 55.2-100) and 100% (95% CI: 78.9-100), respectively, at an optimum cut-off point of ≤ 6.50. Therefore, diastolic dysfunction determined by E' is a good independent outcome predictor.

Exenatide upregulates gene expression of glucagon-like peptide-1 receptor and nerve growth factor in streptozotocin/nicotinamide-induced diabetic mice.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has modulating effects on insulin release. GLP-1 and receptors for GLP-1 are widely expressed throughout the body including the brain. The expression of GLP-1 receptors is very specific to large neurons in hippocampus, neocortex, and cerebellum. GLP-1 receptor stimulation enhances glucose-dependent insulin secretion and lowers blood glucose in type 2 diabetes mellitus. Studies on adipobiology of neurotrophins have focused on nerve growth factor (NGF) as an example of adipose-derived neurotrophins. Compromised trophic factor signaling may underlie neurodegenerative diseases ranging from Alzheimer's disease to diabetic neuropathies. Exenatide, a potent and selective agonist for the GLP-1 receptor, is currently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to assess the effect of chronic exenatide treatment on the hippocampal gene expression levels of GLP-1 receptor and NGF in diabetic mice. The effects of chronic exenatide treatment (0.1 µg/kg, s.c., twice daily for 2 weeks) on GLP-1 receptor and NGF gene expression levels in the hippocampus of streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice were assessed by quantitative real-time polymerase chain reaction (RT-PCR). The results of this study revealed that hippocampal gene expression of GLP-1 receptor and NGF were downregulated in diabetic mice. Importantly, a significant increase in the gene expression level of GLP-1 receptor and NGF was determined after 2 weeks of exenatide administration. Increased gene expression level of GLP-1 receptor and NGF may underlie the beneficial action of exenatide in STZ/NA-induced diabetes.

Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice.

Exenatide is a potent and selective agonist for the GLP-1 (glucagon-like peptide-1) receptor. Recent studies are focused on the effects of GLP-1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 µg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real-time polymerase chain reaction (RT-PCR). This study revealed that in the mEPM and PA tests, type-2 diabetes-induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP-1 receptor agonist exenatide. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA-induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder.