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.

Role of matrix metalloproteinase activity in the neurovascular protective effects of Angiotensin antagonism.

Abstract: Background and Purpose. Oxidative stress and matrix metalloproteinase (MMP) activity have been identified as key mediators of early vascular damage after ischemic stroke. Somewhat surprisingly, the angiotensin II type 1 receptor (AT1) blocker, candesartan, has been shown to acutely increase MMP activity while providing neurovascular protection. We aimed to determine the contribution of MMP and nitrative stress to the effects of angiotensin blockade in experimental stroke. Methods. Wistar rats (n = 9–14/group; a total of 99) were treated in a factorial design with candesartan 1 mg/kg IV, alone or in combination with either a peroxynitrite decomposition catalyst, FeTPPs, 30 mg/kg IP or GM6001 50 mg/kg IP (MMP inhibitor). Neurological deficit, infarct, size and hemorrhagic transformation (HT) were measured after 3 h of middle cerebral artery occlusion (MCAO) and 21 h of reperfusion. MMP activity and nitrotyrosine expression were also measured. Results. Candesartan reduced infarct size and HT when administered alone () and in combination with FeTPPs (). GM6001 did not significantly affect HT when administered alone, but the combination with candesartan caused increased HT () and worsened neurologic score (). Conclusions. Acute administration of candesartan reduces injury after stroke despite increasing MMP activity, likely by an antioxidant mechanism.

Floating anterior lens capsule: an unusual case of true exfoliation.

Abstract: A rare case of delamination and replication of the anterior lens capsule into prominent floating folds in the anterior chamber approximately 55 years after a penetrating injury to the eye and anterior lens capsule is reported. Classically, true exfoliation of the anterior lens capsule has been reported in individuals who have been exposed to intense heat over a prolonged period. However, more recently cases of true exfoliation of the anterior lens capsule have been reported in patients who have not been occupationally exposed to high temperatures and associated infrared radiation. A brief review of the literature concerning true exfoliation of the lens capsule in the absence of intense heat exposure is included. Associations with trauma, inflammation, advanced age, hyperopia, glaucoma, and capsular protein abnormality have been reported, but the pathogenesis of this rare clinical finding remains conjectural.

Authors' Response: Health Benefits/Hazards Associated with Companion Animal-Exposure Might be Endpoint-and-Animal Specific.

Abstract: We thank Dr. Richard Gillum for his interest in our study [1] and critical viewpoints [2]. It’s true that both Dr. Gillum’s and ours used the data collected from roughly the same cohort, i.e. the participants of the National Health and Nutritional Examination Survey, 1988–1994. The two studies, however, are fundamentally different as Dr. Gillum summarized in his letter. It might be inappropriate to assess the consistency of the conclusions from studies with different study populations using different endpoints. As Dr. Gillum correctly pointed out that study population in ours were the ‘‘persons under 50 (vs. 40) at baseline and those with chronic medical conditions were excluded (vs. included); the sample was followed 6 years longer; endpoints were restricted to deaths from cardiovascular disease including stroke (vs. all causes)’’ [2]. It is in particular relevant that Dr. Gillum’s study used all cause deaths [3] and ours instead examined deaths from cardiovascular events [1]. Companion animals include various species, from mammals to reptiles. The impact of living with companion animals might be not ‘‘all-or-nothing’’ or ‘‘black-andwhite’’, not only in terms of the types of animals but also the endpoints selected. The health benefits may be overshadowed by health drawbacks for selected animals with selected health endpoints. The heterogeneity of exposures (types of animal) and outcomes (causes of death, in this case) may explain a substantial part of the inconsistency of the literature, certainly, including the discrepancy between Dr. Gillum’s and ours. A beneficial association between pet ownership and cardiovascular disease was observed from numerous studies, including ours. Potential health hazards from keeping a pet were also reported from others, with a majority using cancer, in particular, leukemia and lung cancer [4], as the endpoint. With that said, we believe it is not surprising to find no or a weak relationship between having a pet and all—cause mortality in Dr. Gillum’s study [3] since the hazardous and beneficial effects on different health outcomes may be counter acting each other. We agree with Dr. Gillum that ‘‘we need to wait for better studies before making any firm conclusions about pets and survival among their owners’’ [2], and we are short of an overall assessment of the associations of companion animals with human health, in particular, among general population. For these reasons, we believe that our study [1], in nature, was exploratory, as such, we tried to minimize the type II error and did not adjust for multiple comparisons, which in turn may end with an increased type I error as Dr. Gillum was concerned. We had no intention to ‘‘emphasize findings that likely were due to chance (i.e. not statistically significant) and a single finding (women living with cats and stroke) [2]’’. As a matter of fact, in addition to the ‘‘single finding (women living with cats and stroke)’’, all the estimates for women were below the null value regardless of the cardiovascular endpoints (last & Jian Zhang jianzhang@georgiasouthern.edu

Emerging urinary alpha-synuclein and miRNA biomarkers in Parkinson’s disease

Abstract: Parkinson's disease (PD) is one of the most common neurodegenerative diseases after Alzheimer's disease (AD), afflicting adults above the age of sixty irrespective of gender, race, ethnicity, and social status. PD is characterized by motor dysfunctions, displaying resting tremor, rigidity, bradykinesia, and postural imbalance. Non-motor symptoms, including rapid eye movement (REM) behavior disorder, constipation, and loss of sense of smell, typically occur many years before the appearance of the PD motor symptoms that lead to a diagnosis. The loss of dopaminergic neurons in the substantia nigra, which leads to the motor symptoms seen in PD, is associated with the deposition of aggregated, misfolded α-Synuclein (α-Syn, SNCA) proteins forming Lewy Bodies. Additionally, dysregulation of miRNA (a short form of mRNA) may contribute to the developing pathophysiology in PD and other diseases such as cancer. Overexpression of α-Syn and miRNA in human samples has been found in PD, AD, and dementia. Therefore, evaluating these molecules in urine, present either in the free form or in association with extracellular vesicles of biological fluids, may lead to early biomarkers for clinical diagnosis. Collection of urine is non-invasive and thus beneficial, particularly in geriatric populations, for biomarker analysis. Considering the expression and function of α-Syn and miRNA, we predict that they can be used as early biomarkers in the diagnosis and prognosis of neurodegenerative diseases.

Monomethylfumarate protects against ovariectomy-related changes in body composition.

Abstract: Osteoporosis, low bone mass that increases fracture susceptibility, affects approximately 75 million individuals in the United States, Europe and Japan, with the number of osteoporotic fractures expected to increase by more than 3-fold over the next 50 years. Bone mass declines with age, although the mechanisms for this decrease are unclear. Aging enhances production of reactive oxygen species, which can affect bone formation and breakdown. The multiple sclerosis drug Tecfidera contains dimethylfumarate, which is rapidly metabolized to monomethylfumarate (MMF); MMF is thought to function through nuclear factor erythroid-derived-2-like-2 (Nrf2), a transcription factor activated by oxidative stress which induces the expression of endogenous anti-oxidant systems. We hypothesized that MMF-elicited increases in anti-oxidants would inhibit osteopenia induced by ovariectomy, as a model of aging-related osteoporosis and high oxidative stress. We demonstrated that MMF activated Nrf2 and induced anti-oxidant Nrf2 target gene expression in bone marrow-derived mesenchymal stem cells. Sham-operated or ovariectomized adult female mice were fed chow with or without MMF and various parameters monitored. Ovariectomy produced the expected effects, decreasing bone mineral density and increasing body weight, fat mass, bone marrow adiposity and serum receptor activator of nuclear factor-kappa-B ligand (RANKL) levels. MMF decreased fat but not lean mass. MMF improved trabecular bone microarchitecture after adjustment for body weight, although the unadjusted data showed few differences; MMF also tended to increase adjusted cortical bone and to reduce bone marrow adiposity and serum RANKL levels. Because these results suggest the possibility that MMF might be beneficial for bone, further investigation seems warranted.