Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Updated: 1 hour 32 min ago

Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

Wed, 04/18/2018 - 07:39
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Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

Alcohol Clin Exp Res. 2017 Aug;41(8):1492-1501

Authors: Rossheim ME, Barry AE, Thombs DL, Weiler RM, Krall JR, Stephenson CJ, Walters ST, Reed MB, Clapp JD, Suzuki S, Barnett TE, Cannell MB

Abstract
BACKGROUND: Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons' self-estimated BrAC in high-risk college town settings.
METHODS: Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas.
RESULTS: Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std β = 0.014, p < 0.001), number of alcoholic drinks consumed (std β = 0.006, p < 0.01), and perceived drunkenness (std β = 0.024, p < 0.001) had significant positive associations with BrAC self-estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self-recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05).
CONCLUSIONS: These findings highlight the inaccuracy of self-estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self-estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self-estimates and deter driving after drinking.

PMID: 28683518 [PubMed - indexed for MEDLINE]

Cardioprotection by Intermittent Hypoxia Conditioning: Evidence, Mechanisms and Therapeutic Potential.

Sat, 04/14/2018 - 07:34
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Cardioprotection by Intermittent Hypoxia Conditioning: Evidence, Mechanisms and Therapeutic Potential.

Am J Physiol Heart Circ Physiol. 2018 Apr 13;:

Authors: Mallet RT, Manukhina EB, Ruelas SS, Caffrey JL, Downey HF

Abstract
The calibrated application of limited duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias following coronary artery occlusion and reperfusion, and in many cases, improved contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease, and produced robust, persistent anti-hypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that employ protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC, clearly merits further clinical evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions.

PMID: 29652543 [PubMed - as supplied by publisher]

Role and Possible Mechanisms of Sirt1 in Depression.

Fri, 04/13/2018 - 07:34

Role and Possible Mechanisms of Sirt1 in Depression.

Oxid Med Cell Longev. 2018;2018:8596903

Authors: Lu G, Li J, Zhang H, Zhao X, Yan LJ, Yang X

Abstract
Depression is a common, devastating illness. Due to complicated causes and limited treatments, depression is still a major problem that plagues the world. Silent information regulator 1 (Sirt1) is a deacetylase at the consumption of NAD+ and is involved in gene silencing, cell cycle, fat and glucose metabolism, cellular oxidative stress, and senescence. Sirt1 has now become a critical therapeutic target for a number of diseases. Recently, a genetic study has received considerable attention for depression and found that Sirt1 is a potential gene target. In this short review article, we attempt to present an up-to-date knowledge of depression and Sirt1 of the sirtuin family, describe the different effects of Sirt1 on depression, and further discuss possible mechanisms of Sirt1 including glial activation, neurogenesis, circadian control, and potential signaling molecules. Thus, it will open a new avenue for clinical treatment of depression.

PMID: 29643977 [PubMed - in process]

Evidence-based approaches to reduce cancer health disparities: Discover, develop, deliver, and disseminate.

Fri, 04/13/2018 - 07:34

Evidence-based approaches to reduce cancer health disparities: Discover, develop, deliver, and disseminate.

J Carcinog. 2018;17:1

Authors: Desai PP, Lampe JB, Bakre SA, Basha RM, Jones HP, Vishwanatha JK

Abstract
The Texas Center for Health Disparities (TCHD) at the University of North Texas Health Science Center is a National Institute on Minority Health and Health Disparities-funded, specialized center of excellence for health disparities. TCHD organized its 12th annual conference focusing on "Evidence-Based Approaches to Reduce Cancer Health Disparities: Discover, Develop, Deliver, and Disseminate." At this conference, experts in health care, biomedical sciences, and public health gathered to discuss the current status and strategies for reducing cancer health disparities. The meeting was conducted in three sessions on breast cancer, prostate cancer, and colorectal cancer disparities, in addition to roundtable discussions and a poster session. Each session highlighted differences in the effects of cancer, based on factors such as race/ethnicity, gender, socioeconomic status, and geographical location. In each session, expert speakers presented their findings, and this was followed by a discussion panel made up of experts in that field and cancer survivors, who responded to questions from the audience. This article summarizes the approaches to fundamental, translational, clinical, and public health issues in cancer health disparities discussed at the conference.

PMID: 29643743 [PubMed]

Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

Wed, 04/11/2018 - 16:53
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Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

J Physiol. 2018 Apr 10;:

Authors: Moralez G, Jouett NP, Tian J, Zimmerman MC, Bhella P, Raven PB

Abstract
We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): Perindopril ((high-lipid soluble Captopril (low-lipid soluble), and/or placebo. Repeated measurements of whole venous blood (N = 8), MSNA (N = 7) and arterial blood pressures (N = 14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady-state dynamic exercise. Arterial baroreflex (ABR) function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance (ESR) spectroscopy were elevated during exercise and were not altered by ACEi at rest (P ≥ 0.4) or during exercise (P ≥ 0.3). Baseline MSNA and mean arterial pressure (MAP) were unchanged at rest (P ≥ 0.1; P ≥ 0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P < 0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise induced increases in MSNA. This article is protected by copyright. All rights reserved.

PMID: 29635787 [PubMed - as supplied by publisher]

Beyond Body Mass Index: Are Weight-loss Programs the Best Way to Improve the Health of African American Women?

Tue, 04/10/2018 - 07:36
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Beyond Body Mass Index: Are Weight-loss Programs the Best Way to Improve the Health of African American Women?

Prev Chronic Dis. 2017 Jun 15;14:E48

Authors: Dodgen L, Spence-Almaguer E

Abstract
African American women have higher prevalence (82%) of overweight (body mass index [BMI] 25-29) and obesity (BMI ≥30) than white women (63.2%) or Hispanic women (77.2%), and weight-loss programs yield minimal results in this population. We examine the concept of BMI as a measure of health for African American women and suggests a more holistic, multifaceted approach to preventing chronic disease.

PMID: 28617664 [PubMed - indexed for MEDLINE]

The Role of Wnt/β-Catenin Signaling and K-Cadherin in the Regulation of Intraocular Pressure.

Sat, 04/07/2018 - 07:34

The Role of Wnt/β-Catenin Signaling and K-Cadherin in the Regulation of Intraocular Pressure.

Invest Ophthalmol Vis Sci. 2018 Mar 01;59(3):1454-1466

Authors: Webber HC, Bermudez JY, Millar JC, Mao W, Clark AF

Abstract
Purpose: Wnt/β-catenin signaling in the trabecular meshwork (TM) is required for maintaining normal intraocular pressure (IOP), although the mechanism(s) behind this are unknown. We hypothesize that Wnt/β-catenin signaling regulates IOP via β-catenin's effects on cadherin junctions.
Methods: Nonglaucomatous primary human TM (NTM) cells were treated with or without 100 ng/ml Wnt3a, 1 μg/ml sFRP1, or both for 4 to 48 hours. Cells were immunostained for β-catenin, total cadherins, or cadherin isoforms. Membrane proteins or whole-cell lysates were isolated for Western immunoblotting and probed for cadherin isoforms. RNA was extracted for cDNA synthesis and qPCR analysis of cadherin expression. Some NTM cells were cultured on electric plates for cell impedance assays. Ad5.CMV recombinant adenoviruses encoding K-cadherin, and/or sFRP1 were injected into eyes of 4- to 6-month-old female BALB/cJ mice (n = 8-10). Conscious IOPs were assessed for 35 days.
Results: Upon Wnt3a treatment, total cadherin expression increased and β-catenin accumulated at the TM cell membrane and on processes formed between TM cells. qPCR showed that Wnt3a significantly increased K-cadherin expression in NTM cells (P < 0.01, n = 3), and Western immunoblotting showed that Wnt3a increased K-cadherin in NTM cells, which was inhibited by the addition of sFRP1. Cell impedance assays showed that Wnt3a treatment increased transcellular resistance and anti-K-cadherin siRNA decreased transcellular resistance (P < 0.001, n = 4-6). Our in vivo study showed that K-cadherin significantly decreased sFRP1-induced ocular hypertension (P < 0.05, n = 6). Western immunoblotting also showed that K-cadherin alleviated sFRP1-induced β-catenin decrease in mouse anterior segments.
Conclusions: Our results suggest that cadherins play important roles in the regulation of TM homeostasis and IOP via the Wnt/β-catenin pathway.

PMID: 29625468 [PubMed - in process]

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

Fri, 04/06/2018 - 11:12
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Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

J Mass Spectrom. 2016 Oct;51(10):900-907

Authors: Prokai L, Fryčák P, Nguyen V, Forster MJ

Abstract
We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip-based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time provided the required soft ionization, shortcomings of a tandem mass spectrometry-based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples was necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time-resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 27747995 [PubMed - indexed for MEDLINE]

Oral bisphosphonate use and lung cancer incidence among postmenopausal women.

Thu, 04/05/2018 - 07:36
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Oral bisphosphonate use and lung cancer incidence among postmenopausal women.

Ann Oncol. 2018 Mar 29;:

Authors: Tao MH, Chen S, Freudenheim JL, Cauley JA, Johnson KC, Mai X, Sarto GE, Wakelee H, Boffetta P, Wactawski-Wende J

Abstract
Background: Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women's Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI.
Patients and methods: The association between oral bisphosphonate use and lung cancer risk was examined in 151,432 postmenopausal women enrolled into the WHI in 1993-1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates.
Results: After a mean follow-up of 13.3 years, 2,511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio (HR), 0.91; 95% confidence intervals (CI), 0.80-1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (HR = 0.57, 95% CI, 0.39-0.84; P < 0.01).
Conclusion: In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.

PMID: 29617712 [PubMed - as supplied by publisher]

Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection.

Thu, 04/05/2018 - 07:36
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Mutacin 1140 Lantibiotic Variants Are Efficacious Against Clostridium difficile Infection.

Front Microbiol. 2018;9:415

Authors: Kers JA, Sharp RE, Defusco AW, Park JH, Xu J, Pulse ME, Weiss WJ, Handfield M

Abstract
Lantibiotics offer an untapped pipeline for the development of novel antibiotics to treat serious Gram-positive (+) infections including Clostridium difficile. Mutacin 1140 (MU1140) is a lantibiotic produced by Streptococcus mutans and acts via a novel mechanism of action, which may limit the development of resistance. This study sought to identify a lead compound for the treatment of C. difficile associated diarrhea (CDAD). Compounds were selected from a saturation mutagenesis library of 418 single amino acid variants of MU1140. Compounds were produced by small scale fermentation, purified, characterized and then subjected to a panel of assays aimed at identifying the best performers. The screening assays included: in vitro susceptibility testing [MIC against Micrococcus luteus, Clostridium difficile, vancomycin-resistant enterococci (VRE), Staphylococcus aureus, Streptococcus pneumonia, Mycobacterium phlei, and Pseudomonas aeruginosa; cytotoxicity screening on HepG2 hepatocytes; in vitro pharmacological profiling with the Safety Screen 44TM, metabolic and chemical stability in biologically relevant fluids (FaSSGF, FaSSIF and serum); and efficacy in vivo]. Several lantibiotic compounds had better MIC against C. difficile, compared to vancomycin, but not against other bacterial species tested. The Safety Screen 44TMin vitro pharmacological profiling assay suggested that this class of compounds has relatively low overall toxicity and that compound OG253 (MU1140, Phe1Ile) is not likely to present inadvertent off-target effects, as evidenced by a low promiscuity score. The in vitro cytotoxicity assay also indicated that this class of compounds was characterized by low toxicity; the EC50 of OG253 was 636 mg/mL on HepG2 cells. The half-life in simulated gastric fluid was >240 min. for all compound tested. The stability in simulated intestinal fluid ranged between a half-life of 5 min to >240 min, and paralleled the half-life in serum. OG253 ultimately emerged as the lead compound based on superior in vivo efficacy along with an apparent lack of relapse in a hamster model of infection. The lessons learned from this report are applicable to therapeutic lanthipeptides in general and may assist in the design of novel molecules with improved pharmacological, therapeutic and physicochemical profiles. The data presented also support the continued clinical development of OG253 as a novel antibiotic against CDAD that could prevent recurrence of the infection.

PMID: 29615987 [PubMed]

Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.

Wed, 04/04/2018 - 07:48
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Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.

Free Radic Biol Med. 2017 Oct;111:235-243

Authors: Awasthi YC, Ramana KV, Chaudhary P, Srivastava SK, Awasthi S

Abstract
Glutathione-S-Transferases (GSTs) have primarily been thought to be xenobiotic metabolizing enzymes that protect cells from toxic drugs and environmental electrophiles. However, in last three decades, these enzymes have emerged as the regulators of oxidative stress-induced signaling and toxicity. 4-Hydroxy-trans 2-nonenal (HNE) an end-product of lipid peroxidation, has been shown to be a major determinant of oxidative stress-induced signaling and toxicity. HNE is involved in signaling pathways, including apoptosis, proliferation, modulation of gene expression, activation of transcription factors/repressors, cell cycle arrest, and differentiation. In this article, available evidence for a major role of GSTs in the regulation of HNE-mediated cell signaling processes through modulation of the intracellular levels of HNE is discussed.

PMID: 27794453 [PubMed - indexed for MEDLINE]

Effectiveness of a computerized motivational intervention on treatment initiation and substance use: Results from a randomized trial.

Tue, 04/03/2018 - 07:34
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Effectiveness of a computerized motivational intervention on treatment initiation and substance use: Results from a randomized trial.

J Subst Abuse Treat. 2017 Sep;80:59-66

Authors: Lerch J, Walters ST, Tang L, Taxman FS

Abstract
As many as 80% of the nearly five million adults under community supervision (i.e., probation, parole) are substance involved; however, treatment utilization is low. Using a multi-site randomized controlled trial, we tested the efficacy of in-person motivational interviewing (MI), a motivational computer intervention (MAPIT), or standard probation intake (SAU) to encourage treatment initiation among 316 substance-involved probationers in Dallas, Texas and Baltimore City, Maryland. Ninety-three percent (n=295) of participants completed the 2-month follow-up and 90% (n=285) completed the 6-month follow-up. At 2-months, individuals in the MAPIT condition were more likely to report treatment initiation compared to the SAU condition (OR=2.40, 95% CI=1.06, 5.47) via intent-to-treat analysis, especially among those completing both sessions (RE=0.50, 95% CI=0.05, 0.95) via instrumental variable analysis. At 6-months, MAPIT approached significance for treatment initiation in both analyses. MI did not achieve significance in any model. We did not find any differential impact on substance use. The success of MAPIT suggests that an integrated health-justice computerized intervention as part of a Screening, Brief Intervention, and Referral to Treatment (SBIRT) can be used to address public safety and health issues.

PMID: 28755774 [PubMed - indexed for MEDLINE]

The influence of vitamins E and C and exercise on brain aging.

Tue, 04/03/2018 - 07:34
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The influence of vitamins E and C and exercise on brain aging.

Exp Gerontol. 2017 Aug;94:69-72

Authors: Mock JT, Chaudhari K, Sidhu A, Sumien N

Abstract
Age-related declines in motor and cognitive function have been associated with increases in oxidative stress. Accordingly, interventions capable of reducing the oxidative burden would be capable of preventing or reducing functional declines occurring during aging. Popular interventions such as antioxidant intake and moderate exercise are often recommended to attain healthy aging and have the capacity to alter redox burden. This review is intended to summarize the outcomes of antioxidant supplementation (more specifically of vitamins C and E) and exercise training on motor and cognitive declines during aging, and on measures of oxidative stress. Additionally, we will address whether co-implementation of these two types of interventions can potentially further their individual benefits. Together, these studies highlight the importance of using translationally-relevant parameters for interventions and to study their combined outcomes on healthy brain aging.

PMID: 27939444 [PubMed - indexed for MEDLINE]

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