Recent Research Articles from UNTHSC

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Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation.

Fri, 05/23/2014 - 4:05am
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Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation.

Age (Dordr). 2013 Oct;35(5):1821-34

Authors: Shetty RA, Forster MJ, Sumien N

Abstract
Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.

PMID: 23138632 [PubMed - indexed for MEDLINE]

Membrane Topology of Human Presenilin-1 in SK-N-SH Cells Determined by Fluorescence Correlation Spectroscopy and Fluorescent Energy Transfer.

Wed, 05/21/2014 - 4:04am

Membrane Topology of Human Presenilin-1 in SK-N-SH Cells Determined by Fluorescence Correlation Spectroscopy and Fluorescent Energy Transfer.

Cell Biochem Biophys. 2014 May 18;

Authors: Midde K, Rich R, Saxena A, Gryczynski I, Borejdo J, Das HK

Abstract
Presenilin-1 (PS1) protein acts as passive ER Ca(2+) leak channels that facilitate passive Ca(2+) leak across ER membrane. Mutations in the gene encoding PS1 protein cause neurodegeneration in the brains of patients with familial Alzheimer's disease (FAD). FADPS1 mutations abrogate the function of ER Ca(2+) leak channel activity in human neuroblastoma SK-N-SH cells in vitro (Das et al., J Neurochem 122(3):487-500, 2012) and in mouse embryonic fibroblasts. Consequently, genetic deletion or mutations of the PS1 gene cause calcium (Ca(2+)) signaling abnormalities leading to neurodegeneration in FAD patients. By analogy with other known ion channels it has been proposed that the functional PS1 channels in ER may be multimers of several PS1 subunits. To test this hypothesis, we conjugated the human PS1 protein with an NH2-terminal YFP-tag and a COOH-terminal CFP-tag. As expected YFP-PS1, and PS1-CFP were found to be expressed on the plasma membranes by TIRF microscopy, and both these fusion proteins increased ER Ca(2+) leak channel activity similar to PS1 (WT) in SK-N-SH cells, as determined by functional calcium imaging. PS1-CFP was either expressed alone or together with YFP-PS1 into SK-N-SH cell line and the interaction between YFP-PS1 and PS1-CFP was determined by Förster resonance energy transfer analysis. Our results suggest interaction between YFP-PS1 and PS1-CFP confirming the presence of a dimeric or multimeric form of PS1 in SK-N-SH cells. Lateral diffusion of PS1-CFP and YFP-PS1 in the plasma membrane of SK-N-SH cells was measured in the absence or in the presence of glycerol by fluorescence correlation spectroscopy to show that both COOH-terminal and NH2-terminal of human PS1 are located on the cytoplasmic side of the plasma membrane. Therefore, we conclude that both COOH-terminal and NH2-terminal of human PS1 may also be oriented on the cytosolic side of ER membrane.

PMID: 24839116 [PubMed - as supplied by publisher]

Enhancing Nurses' Knowledge Regarding the Complex Care of Hospitalized Patients on Insulin.

Tue, 05/20/2014 - 4:04am
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Enhancing Nurses' Knowledge Regarding the Complex Care of Hospitalized Patients on Insulin.

J Nurses Prof Dev. 2014 May 12;

Authors: Wakefield PL, Wilson MA

Abstract
A randomized controlled study assessed a self-paced, online educational course addressing the complex nursing care of hospitalized patients on basal-bolus insulin. Interactive quizzes and scenarios were used to reinforce learning. Knowledge in the intervention group increased significantly and was retained 3-months postintervention. Nursing professional development educators will find this article useful regarding methods for annual competency evaluation and for increasing staff's knowledge as part of a system approach for safely caring for patients with diabetes.

PMID: 24823888 [PubMed - as supplied by publisher]

Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Tue, 05/20/2014 - 4:04am
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Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Exp Biol Med (Maywood). 2014 Feb;239(2):240-9

Authors: Gurji HA, White DW, Hoxha B, Sun J, Harbor JP, Schulz DR, Williams AG, Olivencia-Yurvati AH, Mallet RT

Abstract
Tourniquet-imposed ischemia-reperfusion of extremities generates reactive oxygen and nitrogen species (RONS), which can disrupt intermediary metabolism and ATP production. This study tested the hypothesis that fluid resuscitation with pyruvate, a natural antioxidant and metabolic fuel, ameliorates the deleterious effects of ischemia-reperfusion on intermediary metabolism in skeletal muscle. Anesthetized male goats (∼25 kg) were bled to a mean arterial pressure of 48 ± 1 mmHg and then subjected to 90 min hindlimb ischemia with a tourniquet and femoral crossclamp, followed by 4-h reperfusion. Lactated Ringers (LR) or pyruvate Ringers (PR) was infused intravenous for 90 min, from 30 min ischemia to 30 min reperfusion, to deliver 0.05 mmol kg(-1) min(-1) lactate or pyruvate. Time controls (TC) underwent neither hemorrhage nor hindlimb ischemia. Lipid peroxidation product 8-isoprostane, RONS-sensitive aconitase and creatine kinase activities, antioxidant superoxide dismutase activity, and phosphocreatine phosphorylation potential ([PCr]/[{Cr}{P(i)}]), an index of tissue energy state, were measured in reperfused gastrocnemius at 90 min resuscitation (n = 6 all groups) and 3.5 h post-resuscitation (n = 8 TC, 9 LR, 10 PR). PR more effectively than LR suppressed 8-isoprostane formation, prevented inactivation of aconitase and creatine kinase, doubled superoxide dismutase activity, and augmented [PCr]/([Cr][P(i)]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.

PMID: 24414481 [PubMed - indexed for MEDLINE]

Evaluating factors affecting patellar component fixation strength in total knee arthroplasty.

Tue, 05/20/2014 - 4:04am
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Evaluating factors affecting patellar component fixation strength in total knee arthroplasty.

Am J Orthop (Belle Mead NJ). 2013 Sep;42(9):416-9

Authors: Wagner RA, Lesley NE, Coté RE, Tayag TJ

Abstract
Complications related to the patellofemoral joint after total knee arthroplasty (TKA) represent up to 50% of TKA reoperations. Shear forces across the knee produce wear and occasionally result in failure of fixation of all-polyethylene patellar components. We conducted a study to evaluate the effect of 2 factors on the shear strength of patellar component fixation: time between cement mixing and application of the patellar component, and amount of pressure applied during implantation. Fifty-four patellae were harvested from 27 cadavers and were prepared as for a TKA, allowing 3 different amounts of time for the cement to set or cure before application, and using 3 different pressures. The patellae were mounted and tested for fixation strength with a materials testing machine. Fixation was significantly stronger (P = .006) at 42 pounds of pressure after curing the cement for 8 minutes (compared with 2 minutes) and was significantly stronger (P = .005) after 2 minutes of curing at 42 pounds of pressure (compared with 62 pounds of pressure). We concluded that allowing the cement to cure while cementing the femoral and tibial components does not jeopardize fixation of the patellar component and that excessive compression of a patellar clamp may weaken fixation.

PMID: 24078966 [PubMed - indexed for MEDLINE]

Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Fri, 05/16/2014 - 4:05am

Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Surg Radiol Anat. 2014 May 10;

Authors: Fraser PR, Howard LW, Rosales AA, Guttmann GD

Abstract
During a routine dissection of a 51-year-old Caucasian male cadaver, bilateral symmetrical supernumerary heads (SH) of the biceps brachii muscles with insertion into the pectoralis major (PM) muscles were discovered. Multiple case reports have documented supernumerary heads for the biceps brachii; however, none have shown bilateral insertion into the pectoralis major. This study describes a previously undocumented variation of the SH that has potential for clinical impact. Healthcare providers could be confounded by patients presenting with shoulder pain or muscle tears as a result of the anomaly. Furthermore, MRI studies on patients with possible shoulder muscle tears could reveal unexpected results. Such cases would warrant consideration of SH anomaly and treatment should be adjusted accordingly. The significant bulk and angle of the SH insertion on the PM we observed changes force vectors which would have an unknown effect in performance, surgical interventions and pain syndromes. A second biceps brachii anomaly was observed on the left brachium in addition to the bilateral SH. We postulate that these variants provide the potential for clinical complications regarding muscular injury to these aforementioned muscle groups.

PMID: 24817560 [PubMed - as supplied by publisher]

Developmental validation of the EX20+4 system.

Fri, 05/16/2014 - 4:05am

Developmental validation of the EX20+4 system.

Forensic Sci Int Genet. 2014 Mar 19;11C:207-213

Authors: Li S, Liu C, Liu H, Ge J, Budowle B, Liu C, Zheng W, Li F, Ge B

Abstract
The EX20+4Y System is a polymerase chain reaction (PCR)-based amplification kit that enables typing of 19 autosomal short tandem repeat (STR) loci (i.e., CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, TH01, TPOX, vWA, Penta D, Penta E, D2S1338, D19S433, D12S391, D6S1043), four widely used Y chromosome-specific STR (Y-STR) loci (DYS458, DYS456, DYS391, DYS635), and amelogenin. In this study, this multiplex system was validated for sensitivity of detection, DNA mixtures, inhibitor tolerance, species specificity based on the Scientific Working Group on DNA Analysis methods (SWGDAM) developmental validation guidelines, and the Chinese criteria for the human fluorescent STR multiplex PCR reagent. The results show that the EX20+4 System is a robust and reliable amplification kit which can be used for human identification testing.

PMID: 24815370 [PubMed - as supplied by publisher]

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Fri, 05/16/2014 - 4:05am

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Int J Cardiol. 2014 Apr 26;

Authors: Rosanio S, Keylani AM, D'Agostino DC, Delaughter CM, Vitarelli A

Abstract
This systematic review aims to provide an update on pharmacology, efficacy and safety of the newer oral direct thrombin and factor Xa inhibitors, which have emerged for the first time in ~60years as cogent alternatives to warfarin for stroke prophylaxis in non-valvular atrial fibrillation. We also discuss on four of the most common clinical scenarios with several unsolved questions and areas of uncertainty that may play a role in physicians' reluctance to prescribe the newer oral anticoagulants such as 1) patients with renal failure; 2) the elderly; 3) patients presenting with atrial fibrillation and acute coronary syndromes and/or undergoing coronary stenting; and 4) patients planning to receive AF ablation with the use of pulmonary vein isolation. New aspects presented in current guidelines are covered and we also propose an evidence-based anticoagulation management algorithm.

PMID: 24814537 [PubMed - as supplied by publisher]

Assessment of the role of DNA repair in damaged forensic samples.

Tue, 05/13/2014 - 4:04am

Assessment of the role of DNA repair in damaged forensic samples.

Int J Legal Med. 2014 May 3;

Authors: Ambers A, Turnbough M, Benjamin R, King J, Budowle B

Abstract
Previous studies on DNA damage and repair have involved in vitro laboratory procedures that induce a single type of lesion in naked templates. Although repair of singular, sequestered types of DNA damage has shown some success, forensic and ancient specimens likely contain a number of different types of lesions. This study sought to (1) develop protocols to damage DNA in its native state, (2) generate a pool of candidate samples for repair that more likely emulate authentic forensic samples, and (3) assess the ability of the PreCR(TM) Repair Mix to repair the resultant lesions. Complexed, native DNA is more difficult to damage than naked DNA. Modified procedures included the use of higher concentrations and longer exposure times. Three types of samples, those that demonstrated damage based on short tandem repeat (STR) profile signals, were selected for repair experiments: environmentally damaged bloodstains, bleach-damaged whole blood, and human skeletal remains. Results showed trends of improved performance of STR profiling of bleach-damaged DNA. However, the repair assay did not improve DNA profiles from environmentally damaged bloodstains or bone, and in some cases resulted in lower RFU values for STR alleles. The extensive spectrum of DNA damage and myriad combinations of lesions that can be present in forensic samples appears to pose a challenge for the in vitro PreCR(TM) assay. The data suggest that the use of PreCR in casework should be considered with caution due to the assay's varied results.

PMID: 24792635 [PubMed - as supplied by publisher]

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Tue, 05/13/2014 - 4:04am
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Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Neurobiol Dis. 2013 Nov;59:18-25

Authors: Li W, Huang R, Shetty RA, Thangthaeng N, Liu R, Chen Z, Sumien N, Rutledge M, Dillon GH, Yuan F, Forster MJ, Simpkins JW, Yang SH

Abstract
Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague-Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both hippocampi was reduced at 30days after stroke. This LTP impairment was prevented by blocking GABAA receptors. In addition, ERK activity was significantly reduced in both hippocampi. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke.

PMID: 23845275 [PubMed - indexed for MEDLINE]

Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Tue, 05/13/2014 - 4:04am
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Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Environ Res. 2014 Apr;130:59-69

Authors: Gong G, Mattevada S, O'Bryant SE

Abstract
Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular.

PMID: 24559533 [PubMed - indexed for MEDLINE]