Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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Hybrid Compound SA-2 is Neuroprotective in Animal Models of Retinal Ganglion Cell Death.

Sun, 07/28/2019 - 05:47
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Hybrid Compound SA-2 is Neuroprotective in Animal Models of Retinal Ganglion Cell Death.

Invest Ophthalmol Vis Sci. 2019 Jul 01;60(8):3064-3073

Authors: Stankowska DL, Dibas A, Li L, Zhang W, Krishnamoorthy VR, Chavala SH, Nguyen TP, Yorio T, Ellis DZ, Acharya S

Abstract
Purpose: Determine the toxicity, bioavailability in the retina, and neuroprotective effects of a hybrid antioxidant-nitric oxide donor compound SA-2 against oxidative stress-induced retinal ganglion cell (RGC) death in neurodegenerative animal models.
Methods: Optic nerve crush (ONC) and ischemia reperfusion (I/R) injury models were used in 12-week-old C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mice were treated intravitreally with either vehicle or SA-2. Retinal thickness was measured by spectral-domain optical coherence tomography (SD-OCT). The electroretinogram and pattern ERG (PERG) were used to assess retinal function. RGC survival was determined by counting RBPMS-positive RGCs and immunohistochemical analysis of superoxide dismutase 1 (SOD1) levels was carried out in the retina sections. Concentrations of SA-2 in the retina and choroid were determined using HPLC and MS. In addition, the direct effect of SA-2 treatment on RGC survival was assessed in ex vivo rat retinal explants under hypoxic (0.5% O2) conditions.
Results: Compound SA-2 did not induce any appreciable change in retinal thickness, or in a- or b-wave amplitude in naive animals. SA-2 was found to be bioavailable in both the retina and choroid after a single intravitreal injection (2% wt/vol). An increase in SOD1 levels in the retina of mice subjected to ONC and SA-2 treatment, suggests an enhancement in antioxidant activity. SA-2 provided significant (P < 0.05) RGC protection in all three of the tested RGC injury models in rodents. PERG amplitudes were significantly higher in both I/R and ONC mouse eyes following SA-2 treatment (P ≤ 0.001) in comparison with the vehicle and control groups.
Conclusions: Compound SA-2 was effective in preventing RGC death and loss of function in three different rodent models of acute RGC injury: ONC, I/R, and hypoxia.

PMID: 31348824 [PubMed - in process]

Examining the effect of weight conscious drinking on binge drinking frequency among college freshmen.

Sun, 07/28/2019 - 05:47
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Examining the effect of weight conscious drinking on binge drinking frequency among college freshmen.

J Am Coll Health. 2019 Jul 26;:1-8

Authors: Castañeda G, Colby SE, Barnett TE, Olfert MD, Zhou W, Leite WL, El Zein A, Mathews AE

Abstract
Objective: To examine the effect of weight-conscious drinking and compensatory behavior temporality on binge drinking frequency of college freshmen. Participants: Freshmen (n = 1149) from eight US universities, Fall 2015. Methods: Participants completed the Compensatory Eating Behaviors in Response to Alcohol Consumption Scale and Alcohol Use Disorders Identification Test-Consumption. Structural equation modeling was used to model the effect of weight-conscious drinking constructs on binge drinking frequency. Results: Bulimia, Dietary Restraint and Exercise, Restriction, proactive Alcohol Effects, during Alcohol Effects, and proactive Dietary Restraint and Exercise factors significantly predicted binge drinking frequency. Conclusion: Weight-conscious drinking among this cohort of college students comprises temporal factors significantly associated with binge drinking frequency. Relationships between Bulimia, Dietary Restraint and Exercise, and Restriction compensatory behaviors and binge drinking should be considered in interventions to address binge drinking among college students.

PMID: 31348733 [PubMed - as supplied by publisher]

Androgens modulate chronic intermittent hypoxia effects on brain and behavior.

Sun, 07/28/2019 - 05:47
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Androgens modulate chronic intermittent hypoxia effects on brain and behavior.

Horm Behav. 2018 11;106:62-73

Authors: Snyder B, Duong P, Trieu J, Cunningham RL

Abstract
Sleep apnea is associated with testosterone dysregulation as well as increased risk of developing neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). A rodent model of the hypoxemic events of sleep apnea, chronic intermittent hypoxia (CIH), has been previously documented to impair cognitive function and elevate oxidative stress in male rats, while simultaneously decreasing testosterone. Therefore, androgens may modulate neuronal function under CIH. To investigate the role of androgens during CIH, male rats were assigned to one of four hormone groups: 1) gonadally intact, 2) gonadectomized (GDX), 3) GDX + testosterone (T) supplemented, or 4) GDX + dihydrotestosterone (DHT) supplemented. Each group was exposed to either normal room air or CIH exposure for one week, followed by memory and motor task assessments. Brain regions associated with AD and PD (entorhinal cortex, dorsal hippocampus, and substantia nigra) were examined for oxidative stress and inflammatory markers, key characteristics of AD and PD. Gonadally intact rats exhibited elevated oxidative stress due to CIH, but no significant memory and motor impairments. GDX increased memory impairments, regardless of CIH exposure. T preserved memory function and prevented detrimental CIH-induced changes. In contrast, DHT was not protective, as evidenced by exacerbated oxidative stress under CIH. Further, CIH induced significant spatial memory impairment in rats administered DHT. These results indicate androgens can have both neuroprotective and detrimental effects under CIH, which may have clinical relevance for men with untreated sleep apnea.

PMID: 30268884 [PubMed - indexed for MEDLINE]

Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.

Fri, 07/26/2019 - 05:23

Mutation of CEP72 Gene May Predispose Patients to Hepatotoxicity.

J Pediatr Hematol Oncol. 2019 Jul 23;:

Authors: Pham R, Hoeft A, Roberts C, Hamby T, Maloy C, Ray A

Abstract
Drug toxicities during treatment of acute lymphoblastic leukemia play a pivotal role in influencing the outcome as certain toxicities may impair treatment compliance. Polymorphisms in CEP72 have been linked to increased incidence of vincristine-induced toxicities, namely peripheral neuropathy. We hypothesize that polymorphisms in the same gene may increase a patient's risk of developing hepatotoxicity when receiving potentially hepatotoxic agents during chemotherapy. This report describes hepatotoxicity that first developed during consolidation in a patient homozygous for the CEP72 risk alleles. Bilirubin levels normalized following dose reduction of 6-mercaptopurine. The patient continues to tolerate maintenance therapy at a reduced dose of 6-mercaptopurine.

PMID: 31343483 [PubMed - as supplied by publisher]

Antiretroviral Adherence Level Necessary for HIV Viral Suppression using Real-World Data.

Fri, 07/26/2019 - 05:23

Antiretroviral Adherence Level Necessary for HIV Viral Suppression using Real-World Data.

J Acquir Immune Defic Syndr. 2019 Jul 18;:

Authors: Byrd KK, Hou JG, Hazen R, Kirkham H, Suzuki S, Clay PG, Bush T, Camp NM, Weidle PJ, Delpino A, Patient-centered HIV Care Model Team

Abstract
BACKGROUND: A benchmark of near-perfect adherence (≥95%) to antiretroviral therapy (ART) is often cited as necessary for HIV viral suppression. However, given newer, more effective ART medications the threshold for viral suppression might be lower. We estimated the minimum ART adherence level necessary to achieve viral suppression.
SETTINGS: The Patient-centered HIV Care Model demonstration project.
METHODS: Adherence to ART was calculated using the Proportion of Days Covered (PDC) measure for the 365-day period prior to each viral load test result, and grouped into five categories (<50%, 50%-<80%, 80%-<85%, 85%-<90%, and ≥90%). Binomial regression analyses were conducted to determine factors associated with viral suppression (HIV RNA <200 copies/mL); demographics, PDC category and ART regimen type were explanatory variables. Generalized estimating equations with an exchangeable working correlation matrix accounted for correlation within subjects. In addition, probit regression models were used to estimate adherence levels required to achieve viral suppression in 90% of HIV viral load tests.
RESULTS: The adjusted odds of viral suppression did not differ between persons with an adherence level of 80%-<85% or 85%-<90% and those with an adherence level of ≥90%. Additionally, the overall estimated adherence level necessary to achieve viral suppression in 90% of viral load tests was 82% and varied by regimen type; integrase inhibitor- and non-nucleoside reverse transcriptase inhibitor-based regimens achieved 90% viral suppression with adherence levels of 75% and 78%, respectively.
CONCLUSIONS: The ART adherence level necessary to reach HIV viral suppression may be lower than previously thought and may be regimen dependent.

PMID: 31343455 [PubMed - as supplied by publisher]

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.

Thu, 07/25/2019 - 05:15
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A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.

Sci Rep. 2017 10 25;7(1):14057

Authors: Pedrini S, Gupta VB, Hone E, Doecke J, O'Bryant S, James I, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Martins RN, AIBL Research Group

Abstract
Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

PMID: 29070909 [PubMed - indexed for MEDLINE]

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