Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats

Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto–Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 μg/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2–4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions

Depression and quality of life among heart failure patients in Georgia, Eastern Europe

The goal of the study was to assess longitudinal changes in quality of life among patients who screened positive for depression and patients who did not enroll in an outpatient heart failure disease management program (HFDMP). Patients with an ejection fraction ≤40% and clinical signs and symptoms of heart failure were enrolled over 11 months from August 2007 to July 2008. Study participants (n=314) were divided at baseline into "depressed" (9-Question Patient Health Questionnaire [PHQ-9] ≥10) and "nondepressed" (PHQ-9 <10) groups. The two cohort groups had quality of life assessed by the Minnesota Living With Heart Failure Questionnaire at baseline and at 1 year while enrolled in the HFDMP. Both groups showed improved quality of life scores, with the depressed group experiencing a greater mean score decrease (14.4 vs 10.8 for nondepressed patients; P<.01). Both patients who screened positive for depression and those who did not enroll in an HFDMP improved their quality of life scores, with depressed patients experiencing a statistically significant greater mean score reduction (better quality of life)

Prevalence of Stroke in Systolic Heart Failure

Heart disease is a major independent risk factor for stroke, ranking third after age and hypertension. Heart failure (HF) patient constitutes an important subgroup of patients with stroke, because of their poor outcome and high rates of mortality and stroke recurrence. We examined the prevalence of stroke in patients with heart failure from 3 different geographic regions. We compared the prevalence of self-reported history of stroke in participants with systolic HF from 3 different geographic regions (Houma, LA; Miami, FL; and Tbilisi, Georgia, Eastern Europe). We examined the prevalence of stroke/adjusting for patient demographic and health characteristics. Stroke prevalence was reported by 79 (7.8%) of 1017 participants from Louisiana, 51 (9.2%) of 556 participants from Florida, and 5 (1.3%) of 383 participants from Georgia. After multivariable adjustment, the prevalence of stroke was significantly lower in Georgia compared to Florida and Louisiana sites. Patients on β-blocker medication were 3.58 times (95% CI 1.96-6.55) more likely to report stroke compared to those without β-blockers (×2 = 19.5, P ≤ .0001). There were significantly fewer participants on β-blockers from Georgia (7%) compared to participants from Florida (87%) and Louisiana (94%; (×2 = 24.3, P<.001). Self-reported stroke prevalence in participants with HF was not consistent among the 3 sites. These differences in prevalence may in part be explained by the lower reported use of β-blockers in the Georgia site. Longitudinal studies are needed to determine whether β-blockers increase the risk of stroke in HF population

Comparative genomic analysis of four multidrug-resistant isolates of Acinetobacter baumannii from Georgia

Objectives: This study reports the draft genomes of four newly isolated multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates (0830, 0365, 4022, and 2846) from western Georgia to identify putative antimicrobial resistance genes (ARGs) and to determine the clonal subtypes of local clinical isolates. Methods: An Illumina MiSeq sequencer was used to perform whole-genome sequencing (WGS). The Vitek 2 automated system was used for microbial identification and antimicrobial resistance profiling. Results: Taxonomical identification as A. baumannii was confirmed by WGS. In silico analyses resolved their ARG content and clonal relatedness using the Oxford (Oxf) and Pasteur (Pas) multi-locus sequence typing schemes. Isolates 0365 and 4022 displayed similar allelic profiles corresponding to ST944Oxf/ST78Pas. Isolate 2846 displayed a different allelic profile consistent with ST19Pas/IC 1 (International or European Clone I) and exhibited a novel Oxford ST that was designated as 1868. Isolate 0830 displayed the ST78Pas allelic profile, similar to isolates 0365 and 4022, and also possessed a single allelic mismatch in the gpi gene, resulting in an ST1104Oxf allele profile in the Oxford typing scheme. Conclusion: Circulating MDR A. baumannii exhibited genetic heterogeneity with variations in the structure and content of genomic A. baumannii resistance islands and encoded multiple putative ARGs. This report represents the first clonal subtype information and genomic characterization of MDR A. baumannii in Georgia and may inform future epidemiological investigations

Glucagonlike peptide-1 receptor activation reduces ischaemic brain damage following stroke

A B S T R A C T Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic animal model, a drug administration paradigm and a dose that mimics a diabetic patient on Ex-4 therapy. Furthermore, we investigated inflammation and neurogenesis as potential cellular mechanisms underlying the Ex-4 efficacy. A total of seven 9-month-old Type 2 diabetic Goto-Kakizaki rats were treated peripherally for 4 weeks with Ex-4 at 0.1, 1 or 5 μg/kg of body weight before inducing stroke by transient middle cerebral artery occlusion and for 2-4 weeks thereafter. The severity of ischaemic damage was measured by evaluation of stroke volume and by stereological counting of neurons in the striatum and cortex. We also quantitatively evaluated stroke-induced inflammation, stem cell proliferation and neurogenesis. We show a profound anti-stroke efficacy of the clinical dose of Ex-4 in diabetic rats, an arrested microglia infiltration and an increase of stroke-induced neural stem cell proliferation and neuroblast formation, while stroke-induced neurogenesis was not affected by Ex-4. The results show a pronounced anti-stroke, neuroprotective and anti-inflammatory effect of peripheral and chronic Ex-4 treatment in middle-aged diabetic animals in a preclinical setting that has the potential to mimic the clinical treatment. Our results should provide strong impetus to further investigate GLP-1R agonists for their neuroprotective action in diabetes, and for their possible use as anti-stroke medication in non-diabetic conditions