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.

Is targeting Akt a viable option to treat advanced-stage COVID-19 patients?

Abstract: One of the primary reasons for high mortality in the advanced stage coronavirus disease-2019 (COVID-19) patients is the uncontrolled inflammation in the lungs leading to acute respiratory distress syndrome (ARDS). Controlling the pathological inflammation in the ARDS lungs without compromising the immune system's fight against the virus is indeed a daunting task. In this situation, an appropriate therapeutic target would be the one that will not only reverse the damaging inflammation and promote resolution but also helps to check the root cause of the virus infection. Akt is a potential therapeutic target for the advanced stage COVID-19 patients; its inhibition will potentially suppress the pathological inflammation, cytokine storm, fibroproliferation, and platelet activation associated with COVID-19, and at the same time prevent scarring and promote resolution in injured lungs. As pharmacological inhibition of Akt has also been reported to inhibit ACE2 expression, a receptor for the virus entry into the lung cells, targeting Akt for COVID-19 looks a viable option.

Ultraviolet B irradiation and activation of protein kinase D in primary mouse epidermal keratinocytes.

Abstract: Our previous studies demonstrated that protein kinase D (PKD), a serine/threonine kinase implicated in various cell processes, is upregulated in basal cell carcinoma (BCC), supporting a possible tumorigenic role for PKD in skin. As the greatest risk factor for BCC is sun exposure, the ability of ultraviolet B (UVB) irradiation to activate PKD in primary mouse keratinocytes was investigated. Using western analysis with two autophosphorylation-specific antibodies, we show for the first time that UVB activated PKD in a time- and dose-dependent manner. UVB-induced PKD activation was verified using an in vitro kinase assay. Furthermore, activation was reduced by antioxidant pretreatment, suggesting a link with oxidative stress. UVB-induced PKD activation was mediated primarily by Src family tyrosine kinases rather than protein kinase C (PKC), and in fact, UVB did not alter PKC-mediated transphosphorylation. UVB induced apoptosis dose dependently, and this death could be prevented by overexpression of wild-type PKD, but not mutant PKD or the empty adenovirus. Indeed, a mutant that cannot be phosphorylated by Src kinases exacerbated UVB-elicited apoptosis. Thus, our data indicate that UVB irradiation of keratinocytes induces Src-mediated activation of PKD, which protects cells from UVB-stimulated apoptosis, providing a possible explanation for the observed upregulation of PKD in BCC.

Vascular access surveillance: case study of a false paradigm.

Abstract: The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria include four components: undesired condition, screening test, intervention, and desired outcome. The WHO criteria show that surveillance as currently practiced fails all four components and provides little or no significant benefit, suggesting that surveillance is a false paradigm. Once a paradigm is established, however, challenges to its validity are usually resisted even as new evidence indicates the paradigm is not valid. Thus, it is paramount to apply rigorous criteria when developing guidelines. Regulators may help promote needed changes in paradigms when cost and safety considerations coincide.