Birmingham Veterans Administration Medical Center

Birmingham, AL, United States

Birmingham Veterans Administration Medical Center

Birmingham, AL, United States
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Fogger S.A.,University of Alabama at Birmingham | Hart J.J.,Birmingham Veterans Administration Medical Center
Journal of Addictions Nursing | Year: 2017

Purpose: The aim of this editorial is to explore and highlight the importance of identifying both the alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) in the veteran population. Review: Determining if the patient has military experience can assist in both an accurate and complete assessment. Being aware of the patient’s military service time can help better understand some of the presenting physical and mental complaints that may incorrectly be attributed to substances. Although not all veterans had trauma exposure while in the military, asking about PTSD may help identify additional issues needing attention. Having a PTSD diagnosis increases the likelihood that there is an underlying substance use disorder. Veterans with PTSD have a 65% likely comorbidity with alcohol use (Smith, Goldstein, & Grant, 2016). Conclusion: Recognition of PTSD as a co-occurring disorder with AUD can begin the dialogue to address treatment of both disorders to optimize recovery. Copyright © 2017 International Nurses Society on Addictions.


Yang S.,University of Alabama at Birmingham | Abraham E.,University of Alabama at Birmingham | Agarwal A.,Birmingham Veterans Administration Medical Center | Liu G.,University of Alabama at Birmingham
American Journal of Physiology - Renal Physiology | Year: 2011

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis. © 2011 the American Physiological Society.


Xing D.,Vascular Biology and Hypertension Program | Kapadia A.,University of Alabama at Birmingham | Chen Y.-F.,Vascular Biology and Hypertension Program | Oparil S.,Vascular Biology and Hypertension Program | And 2 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

OBJECTIVE - 17β-Estradiol (E2) offers cardiovascular protection in young female animals and postmenopausal women. In contrast, randomized trials of menopausal hormones performed in older women have shown harm or no cardiovascular benefit. We hypothesize that E2 effects on vascular inflammation are age dependent. APPROACH AND RESULTS - Young (10 weeks) and aged (52 weeks) female C57BL/6 mice were used as source for primary cultures of bone marrow-derived macrophages (BMMs) and vascular smooth muscle cells (VSMCs). E2 pretreatment of cells derived from young mice attenuated C-reactive protein (CRP)-induced expression of inflammatory mediators. In contrast, E2 pretreatment of cells from aged mice did not alter (BMMs) or paradoxically exaggerated (VSMCs) inflammatory mediator response to CRP. Using E2 receptor (ER) knockout mice, we demonstrated that E2 regulates inflammatory response to CRP in BMMs via ERα and in VSMCs via ERβ. BMMs derived from aged (versus young) mice expressed significantly less ERα mRNA and protein. A selective ligand of the novel ER GPR30 reproduced the E2 effects in BMMs and VSMCs. Unlike in young mice, E2 did not reduce neointima formation in ligated carotid arteries of aged CRP transgenic mice. CONCLUSIONS - E2 attenuates inflammatory response to CRP in BMMs and VSMCs derived from young but not aged mice and reduces neointima formation in injured carotid arteries of young but not aged CRP transgenic mice. ERα expression in BMMs is greatly diminished with aging. These data suggest that vasoprotective effects of E2 are age dependent and may explain the vasotoxic effects of E2 seen in clinical trials of postmenopausal women. © 2014 American Heart Association, Inc.


News Article | October 26, 2016
Site: www.eurekalert.org

A newly published study of people with chronic obstructive pulmonary disease (COPD) concludes that long-term supplemental oxygen treatment results in little or no change in time to death, time to first hospitalizations or significant quality of life improvements for those with moderately low blood oxygen levels. The findings, published in the New England Journal of Medicine on Oct. 27, are based on research examining oxygen treatment outcomes in 738 COPD patients with moderately low blood oxygen levels at 42 clinical centers in the United States. The study began in 2009 and ended in 2015. Patients who received supplemental oxygen over the course of the study showed no significant differences in rate of hospitalizations, time to death after diagnosis, exercise capacity or quality of life when compared to patients who did not receive supplemental oxygen. The results of the study, believed by the investigators to be the largest of its kind to date, show that most people with moderately low blood oxygen levels do not receive the same benefits from long-term oxygen therapy as COPD patients with severely low blood oxygen levels. "The benefits of long-term oxygen supplements for COPD patients with severe oxygen deficiency are clear," says Robert Wise, M.D., professor of medicine in the Johns Hopkins University School of Medicine's Division of Pulmonary and Critical Care Medicine and the paper's corresponding author. "However, it's never been established what benefits, if any, exist for patients with less severe oxygen deficiency." For the study, moderate oxygen deficiency was defined as having a blood oxygen saturation between 89 and 93 percent at rest, or a blood oxygen saturation below 90 percent during a six-minute walk test. A normal blood oxygen saturation level is generally defined as between 94 and 99 percent. Blood oxygen saturation levels are a measure of oxygen-carrying hemoglobin in circulating blood and a marker of lung function, and low levels are a hallmark of people with COPD. To examine the benefits of supplemental oxygen, the researchers studied two types of COPD patients: those who suffered from moderate oxygen deficiency while resting, and those who suffered from moderate oxygen deficiency only during exercise. Some 133 patients had resting oxygen deficiency, 319 had only exercise-induced oxygen deficiency and 268 had both. Participants in each of the two groups were randomly assigned to get supplemental oxygen or no supplemental oxygen at the start of the study, and all visited clinics annually for follow-up examinations that included oxygen levels at rest and exercise, oxygen use, respiratory symptoms and quality of life. All participants also completed telephone interviews biannually and completed mailed questionnaires regarding symptoms and health care use at four and 16 months. Of the 738 total patients studied with moderate oxygen deficiency, 368 received supplemental oxygen, and 370 did not. Wise says the primary outcomes measured -- time to death or time to first hospitalization -- were essentially the same in both groups. The risk of death in the no-oxygen group was 5.7 percent per year, compared to 5.2 percent per year for the oxygen group. Overall, the risk of death or hospitalization was not different between the two treatment groups. The researchers also found no significant differences between the oxygen treatment and non-oxygen treatment groups in all hospitalization rates; COPD exacerbations, defined as sudden worsening of COPD symptoms, such as shortness of breath and phlegm production that lasts for several days; self-reported quality of life; lung function; or measures of walk distance. Even when researchers controlled for variables such as total hours of oxygen use, race, sex and smoking status, no significant differences in the primary outcomes arose, Wise says. "No matter what measure we looked at, it made no apparent difference whether a patient with moderate oxygen deficiency received long-term oxygen treatments or not. I think the evidence is strong and shows that some patients may not need those treatments at all," says Wise. Wise cautioned that "we don't want to imply that everyone with COPD now using oxygen should stop; some individual patients may find that they can do more activities or have more effective exercise training if they use oxygen. Every patient should discuss his or her specific needs with his or her health care provider, but the data show, very clearly, that for many COPD patients with moderately low blood oxygen levels, supplemental oxygen won't help you live any longer or keep you out of the hospital." Supplemental oxygen therapy can be considered burdensome and expensive for many. From 2009 to 2011, Medicare reimbursements for oxygen-related costs for COPD patients exceeded $2 billion per year. Supplemental oxygen therapy requires those using it to carry or cart around heavy and bulky oxygen delivery equipment, sometimes resulting in adverse events, such as tripping over equipment or the start of fires. According to the COPD Foundation, an estimated 24 million people in the U.S. suffer from COPD, and it is the third leading cause of death in the nation. Other authors on this study include Amanda L. Blackford, David Shade, James Tonascia and Alice L. Sternberg of The Johns Hopkins University; Richard K. Albert of the University of Colorado at Denver; Richard Casaburi of the University of California at Los Angeles Medical Center; Allen Cooper Jr. of the Birmingham Veterans Administration Medical Center; Gerard J. Criner of the Lewis Katz School of Medicine at Temple University; Philip Diaz of Ohio State University; Anne L. Fuhlbrigge of Brigham and Women's Hospital; Steven E. Gay of the University of Michigan; Richard E. Kanner of the University of Utah Health Sciences Center; Neil MacIntyre of the Duke University Medical Center; Fernando J. Martinez of the Weill Cornell Medical Center; Ralph J. Panos of Cincinnati Veterans Administration Medical Center; Steven Piantadosi of the Cedars-Sinai Medical Center; Frank Sciurba of the University of Pittsburgh; Thomas Stibolt of the Kaiser Permanente Center for Health Research; Roger D. Yusen of the Washington University School of Medicine; and William Bailey of the University of Alabama. This study was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (HHSN268200736183C, HHSN268200736184C, HHSN268200736185C, HHSN268200736186C, HHSN268200736187C, HHSN268200736188C, HHSN268200736189C, HHSN268200736190C, HHSN268200736191C, HHSN268200736192C, HHSN268200736193C, HHSN268200736194C, HHSN268200736195C, HHSN268200736196C, HHSN268200736197C, Y1-HR-7019-01, Y1-HR-8076-01) in cooperation with the Centers for Medicare and Medicaid Services.


Ghimire G.,University of Alabama at Birmingham | Hage F.G.,University of Alabama at Birmingham | Hage F.G.,Birmingham Veterans Administration Medical Center | Heo J.,University of Alabama at Birmingham | Iskandrian A.E.,University of Alabama at Birmingham
Journal of Nuclear Cardiology | Year: 2013

Since its approval by the Food and Drug Administration in 2008, regadenoson has become the most commonly used vasodilator in the United States. Previous reviews have summarized the pre-clinical and clinical data on the use of regadenoson for myocardial perfusion imaging (MPI). Since then, data have emerged on the safety of this agent in special groups of patients such as those with chronic kidney disease, airway disease (asthma and chronic obstructive pulmonary disease), and liver disease. There has also been recent interest in the use of regadenoson in hybrid protocols with exercise as a way to improve patient tolerance and image quality. Finally, although regadenoson was approved for clinical use based on the agreement rate of regadenoson MPI and adenosine MPI with regards to perfusion abnormalities, data are now available on the prognostic data derived from regadenoson MPI. We will briefly summarize these recent reports here in a focused update on the use of regadenoson for MPI. © 2012 American Society of Nuclear Cardiology.


Larson-Casey J.L.,University of Alabama at Birmingham | Deshane J.S.,University of Alabama at Birmingham | Ryan A.J.,University of Iowa | Thannickal V.J.,University of Alabama at Birmingham | And 3 more authors.
Immunity | Year: 2016

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder with increasing incidence. Mitochondrial oxidative stress in alveolar macrophages is directly linked to pulmonary fibrosis. Mitophagy, the selective engulfment of dysfunctional mitochondria by autophagasomes, is important for cellular homeostasis and can be induced by mitochondrial oxidative stress. Here, we show Akt1 induced macrophage mitochondrial reactive oxygen species (ROS) and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages (Akt1-/-Lyz2-cre) and Park2-/- mice had impaired mitophagy and reduced active transforming growth factor-β1 (TGF-β1). Although Akt1 increased TGF-β1 expression, mitophagy inhibition in Akt1-overexpressing macrophages abrogated TGF-β1 expression and fibroblast differentiation. Importantly, conditional Akt1-/- Lyz2-cre mice and Park2-/- mice had increased macrophage apoptosis and were protected from pulmonary fibrosis. Moreover, IPF alveolar macrophages had evidence of increased mitophagy and displayed apoptosis resistance. These observations suggest that Akt1-mediated mitophagy contributes to alveolar macrophage apoptosis resistance and is required for pulmonary fibrosis development. © 2016 Elsevier Inc.


Hage F.G.,University of Alabama at Birmingham | Hage F.G.,Birmingham Veterans Administration Medical Center | Oparil S.,University of Alabama at Birmingham
Current Opinion in Cardiology | Year: 2013

PURPOSE OF REVIEW: Observational studies have shown benefit of hormone therapy, particularly estrogen, in women who begin treatment in the perimenopausal/early postmenopausal period, whereas randomized controlled trials of such therapy in older postmenopausal women have reported harm. These apparently paradoxical findings have led to the 'timing hypothesis' which proposes that estrogen signaling is altered in older women, converting vasoprotective to vasotoxic effects. We reviewed recent literature on age-dependent effects of hormones (particularly estrogen) on the vasculature of women and the fundamental cellular/molecular mechanisms responsible for those effects. RECENT FINDINGS: Observational studies have shown that early menopause is associated with adverse cardiovascular disease outcomes and that starting hormone therapy in the perimenopausal period reduces these outcomes. Mechanistic studies have shown that estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and vascular smooth muscle cells isolated from young women but that these vasoprotective mechanisms are lost in women who are aged and/or deprived of estrogen for prolonged periods of time. SUMMARY: The vasoprotective effects of estrogen are age-dependent and disappear with aging and/or estrogen deprivation. Future studies designed to preserve the vasoprotective effects of estrogen in older women are needed and may lead to innovative approaches to improving women's cardiovascular health. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Hull T.D.,University of Alabama at Birmingham | Agarwal A.,University of Alabama at Birmingham | Agarwal A.,Birmingham Veterans Administration Medical Center | George J.F.,University of Alabama at Birmingham
Antioxidants and Redox Signaling | Year: 2014

Significance: Heme oxygenase-1 (HO-1) is a potential therapeutic target in many diseases, especially those mediated by oxidative stress and inflammation. HO-1 expression appears to regulate the homeostatic activity and distribution of mononuclear phagocytes (MP) in lymphoid tissue under physiological conditions. It also regulates the ability of MP to modulate the inflammatory response to tissue injury. Recent Advances: The induction of HO-1 within MP-particularly macrophages and dendritic cells-modulates the effector functions that they acquire after activation. These effector functions include cytokine production, surface receptor expression, maturation state, and polarization toward a pro-or anti-inflammatory phenotype. The importance of HO-1 in MP is emphasized by their expression of specific receptors that primarily function to ingest heme-containing substrate and deliver it to HO-1. Critical Issues: MP are the first immunological responders to tissue damage. They critically affect the outcome of injury to many organ systems, yet few therapies are currently available to specifically target MP during disease pathogenesis. Elucidation of the role of HO-1 expression in MP may help to direct broadly applicable therapies to clinical use that are based on the immunomodulatory capabilities of HO-1. Future Directions: Unraveling the complexities of HO-1 expression specifically within MP will more completely define how HO-1 provides cytoprotection in vivo. The use of models in which HO-1 expression is specifically modulated in bone marrow-derived cells will allow for a more complete characterization of its immunoregulatory properties. © Copyright 2014, Mary Ann Liebert, Inc. 2014.


Elmets C.A.,University of Alabama at Birmingham | Elmets C.A.,Birmingham Veterans Administration Medical Center | J. Ledet J.,University of Alabama at Birmingham | J. Ledet J.,Birmingham Veterans Administration Medical Center | Athar M.,University of Alabama at Birmingham
Journal of Investigative Dermatology | Year: 2014

Non-melanoma skin cancers (NMSCs) are among the most common human malignancies. Current methods for their prevention include avoidance of natural and artificial sources of UV radiation and using photoprotective clothing and sunscreens. However, these methods have proven to be inadequate in stemming the rise in skin cancer incidence over the past several years. There is accumulating evidence that cyclooxygenase-2 (COX-2), an enzyme involved in prostaglandin synthesis, may be involved in the pathogenesis of NMSC. In preclinical studies, animals genetically deficient in the COX-2 enzyme or that have been treated with pharmacological inhibitors of COX-2 develop significantly fewer tumors when subjected to a UV-induced skin carcinogenesis protocol compared with control mice. Several epidemiological studies in humans support the concept that this enzyme is intimately involved in UV-induced skin cancer development, and UV radiation is known to augment COX-2 expression in human skin. Recent studies suggest that drugs that block COX-2 expression may prevent the development of NMSCs. Thus, pharmacologic agents that inhibit the enzyme COX-2 may be effective chemopreventive agents for NMSCs.


Hage F.G.,Vascular Biology and Hypertension Program | Oparil S.,Vascular Biology and Hypertension Program | Xing D.,Vascular Biology and Hypertension Program | Chen Y.-F.,Vascular Biology and Hypertension Program | And 3 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010

Background: We previously demonstrated that vascular injury-induced neointima formation is exaggerated in human C-reactive protein (CRP) transgenic (CRPtg) compared to nontransgenic (NTG) mice. We now test the hypothesis that complement is required for this effect. Methods and results: CRPtg and NTG with a normal complement system versus their counterparts lacking expression of complement component 3 (C3) protein (CRPtg/C3-/- and NTG/C3 -/-) underwent carotid artery ligation. Twenty-eight days later, the injured vessels in CRPtg had thicker neointimas and more immunoreactive C3 in the surrounding adventitia compared with NTG. In CRPtg/C3-/-, there was no increase in neointimal thickness compared with NTG or NTG/C3 -/-. Decreasing human CRP blood levels through administration of a selective antisense oligonucleotide eliminated the depletion of serum C3 associated with vascular injury and reduced immunoreactive C3 in the resultant lesions. In injured vessels, C3 colocalized with F4/80 (macrophage marker), and in vitro, human CRP elicited increased expression of C3 by bone marrow-derived macrophages. Conclusion: Human CRP exaggeration of neointima formation in injured mouse carotid arteries associates with decreased circulating C3 and increased tissue-localized C3. C3 elimination or pharmacological reduction of human CRP prevents CRP-driven exacerbation of the injury response. In the CRPtg model system, mouse C3 is essential for the effect of human CRP. © 2010 American Heart Association, Inc.

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