Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

Treating Posttraumatic Stress Disorder Symptoms With Low Amplitude Seizure Therapy (LAP-ST) Compared With Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial.

Abstract: Objectives An important barrier to further studying electroconvulsive therapy (ECT) in posttraumatic stress disorder (PTSD) is the cognitive adverse effects However, recent data suggest that low amplitude seizure therapy (LAP-ST) has no or minimal cognitive adverse effects The aims of this report were to examine the efficacy of LAP-ST in PTSD and to compare LAP-ST with standard right unilateral (RUL) ECT using a pilot randomized clinical trial Methods Patients were randomized to LAP-ST or RUL ECT Posttraumatic stress disorder was assessed using clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and symptom severity with PTSD Checklist (PCL) The scores pertaining to PCL were analyzed using descriptive analysis for this pilot study Results Eleven patients consented to be enrolled Seven were randomly allocated to LAP-ST or RUL ECT Five completed the study and had completed PCL before and after the course In both groups, PTSD symptoms showed fast improvement The effect size of improvement seems promising The mean baseline PCL score for patients in the LAP-ST group was 425 (SD = 1626) and the mean end point PCL score after treatment was 31 (SD = 1556) The mean baseline PCL score for patients in the standard RUL ECT group was 647 (SD = 115) and the mean end point was 41 (SD = 1562) Conclusions Both LAP-ST and standard RUL ECT showed reduction in PTSD symptoms with fast improvement This first PTSD LAP-ST study adds support to the prior LAP-ST proof-of-concept clinical trial that LAP-ST can produce effective therapeutic outcomes Replication of this trial is warranted in larger clinical trials (ClinicalTrialsgov ID: NCT02583490)

PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress.

Abstract: Renal fibrosis is the final common pathway to chronic kidney diseases regardless of etiology Parkinson disease protein 7 (PARK7) is a multifunctional protein involved in various cellular processes, but its pathophysiological role in kidneys remain largely unknown Here, we have determined the role of PARK7 in renal fibrosis and have further elucidated the underlying mechanisms by using the in vivo mouse model of unilateral ureteric obstruction (UUO) and the in vitro model of transforming growth factor-b (TGFB1) treatment of cultured kidney proximal tubular cells PARK7 decreased markedly in atrophic kidney tubules in UUO mice, and Park7 deficiency aggravated UUO-induced renal fibrosis, tubular cell apoptosis, ROS production and inflammation In vitro, TGFB1 treatment induced fibrotic changes in renal tubular cells, which was accompanied by alterations of PARK7 Park7 knockdown exacerbated TGFB1-induced fibrotic changes, cell apoptosis and ROS production, whereas Park7 overexpression or treatment with ND-13 (a PARK7-derived peptide) attenuated these TGFB1-induced changes Mechanistically, PARK7 translocated into the nucleus of renal tubular cells following TGFB1 treatment or UUO, where it induced the expression of SOD2, an antioxidant enzyme Taken together, these results indicate that PARK7 protects against chronic kidney injury and renal fibrosis by inducing SOD2 to reduce oxidative stress in tubular cells

Modulation of p75NTR on Mesenchymal Stem Cells Increases Their Vascular Protection in Retinal Ischemia-Reperfusion Mouse Model.

Abstract: Mesenchymal stem cells (MSCs) are a promising therapy to improve vascular repair, yet their role in ischemic retinopathy is not fully understood. The aim of this study is to investigate the impact of modulating the neurotrophin receptor; p75NTR on the vascular protection of MSCs in an acute model of retinal ischemia/reperfusion (I/R). Wild type (WT) and p75NTR-/- mice were subjected to I/R injury by increasing intra-ocular pressure to 120 mmHg for 45 min, followed by perfusion. Murine GFP-labeled MSCs (100,000 cells/eye) were injected intravitreally 2 days post-I/R and vascular homing was assessed 1 week later. Acellular capillaries were counted using trypsin digest 10-days post-I/R. In vitro, MSC-p75NTR was modulated either genetically using siRNA or pharmacologically using the p75NTR modulator; LM11A-31, and conditioned media were co-cultured with human retinal endothelial cells (HREs) to examine the angiogenic response. Finally, visual function in mice undergoing retinal I/R and receiving LM11A-31 was assessed by visual-clue water-maze test. I/R significantly increased the number of acellular capillaries (3.2-Fold) in WT retinas, which was partially ameliorated in p75NTR-/- retinas. GFP-MSCs were successfully incorporated and engrafted into retinal vasculature 1 week post injection and normalized the number of acellular capillaries in p75NTR-/- retinas, yet ischemic WT retinas maintained a 2-Fold increase. Silencing p75NTR on GFP-MSCs coincided with a higher number of cells homing to the ischemic WT retinal vasculature and normalized the number of acellular capillaries when compared to ischemic WT retinas receiving scrambled-GFP-MSCs. In vitro, silencing p75NTR-MSCs enhanced their secretome, as evidenced by significant increases in SDF-1, VEGF and NGF release in MSCs conditioned medium; improved paracrine angiogenic response in HREs, where HREs showed enhanced migration (1.4-Fold) and tube formation (2-Fold) compared to controls. In parallel, modulating MSCs-p75NTR using LM11A-31 resulted in a similar improvement in MSCs secretome and the enhanced paracrine angiogenic potential of HREs. Further, intervention with LM11A-31 significantly mitigated the decline in visual acuity post retinal I/R injury. In conclusion, p75NTR modulation can potentiate the therapeutic potential of MSCs to harness vascular repair in ischemic retinopathy diseases.

Skeletal stem cells for bone development, homeostasis and repair: one or many?

Abstract: Regenerative Bioscience Center, Rhodes Center for ADS, and College of Engineering, University of Georgia, Athens, GA, USA. Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA. Department of Orthopaedic Surgery, Medical College of Georgia, Augusta University, Augusta, GA, USA. The Institute for Regenerative and Reparative Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA. Charlie Norwood VA Medical Center, Augusta, GA, USA.

Soluble CD14 and fracture risk

Abstract: Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture. Soluble CD14, a proinflammatory cytokine, is primarily derived from macrophages/monocytes that can differentiate into osteoclasts. The purpose of this study was to examine the relationship between sCD14 levels and osteoporotic fractures. In the Cardiovascular Health Study, 5462 men and women had sCD14 levels measured at baseline. Incident hip fractures (median follow-up time 12.5 years) and incident composite fractures (defined as the first hip, pelvis, humerus, or distal radius fracture, median follow-up 8.6 years) were identified from hospital discharge summaries and/or Medicare claims data. Cox proportional hazards models were used to model the association between sCD14 levels and time to incident hip or composite fracture, overall and as a function of race and gender. In unadjusted models, there was a positive association between sCD14 levels (per 1 standard deviation increase, i.e., 361.6 ng/mL) and incident hip (HR, 1.26; 95 % CI, 1.17, 1.36) and composite (HR, 1.20; 95 % CI, 1.12, 1.28) fractures. When models were fully adjusted for demographics, lifestyle factors, and medication use, these associations were no longer significant. However, in whites, the association of sCD14 levels with hip fractures remained significant in fully adjusted models (HR, 1.11; 95 % CI, 1.01–1.23). Associations of sCD14 levels with hip and composite fracture did not differ between men and women. In this large cohort of community-dwelling older adults, higher sCD14 levels were associated with an increased risk of incident hip fractures in whites.