Recent Research Articles from UNTHSC

Syndicate content NCBI pubmed
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]
Updated: 2 hours 53 min ago

Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender.

Sun, 07/13/2014 - 4:04am
Related Articles

Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender.

Dement Geriatr Cogn Disord. 2014 Jul 4;38(5-6):300-309

Authors: Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Cunningham R, Singh M, O'Bryant SE

Abstract
Background: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. Methods: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. Results: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. Conclusion: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC. © 2014 S. Karger AG, Basel.

PMID: 25011444 [PubMed - as supplied by publisher]

ANGIOTENSIN II RECEPTOR SUBTYPE 1A (AT1AR) GENE KNOCKDOWN IN THE SUBFORNICAL ORGAN (SFO) PREVENTS INCREASED DRINKING BEHAVIOR IN BILE DUCT LIGATED RATS.

Sat, 07/12/2014 - 4:05am
Related Articles

ANGIOTENSIN II RECEPTOR SUBTYPE 1A (AT1AR) GENE KNOCKDOWN IN THE SUBFORNICAL ORGAN (SFO) PREVENTS INCREASED DRINKING BEHAVIOR IN BILE DUCT LIGATED RATS.

Am J Physiol Regul Integr Comp Physiol. 2014 Jul 9;

Authors: Walch JD, Nedungadi TP, Cunningham JT

Abstract
Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes resulting in dilutional hyponatremia due to increased water intake and vasopressin release. This project tested the hypothesis that angiotensin signaling at the subfornical organ (SFO) augments drinking behavior in BDL rats. A genetically modified adeno-associated virus containing shRNA for angiotensin II receptor subtype 1a (AT1aR) gene was microinjected into the subfornical organ (SFO) of rats to knockdown expression. Two weeks later, BDL or sham surgery was performed. Rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. The rats were euthanized 28 days after BDL surgery for analysis. A group of rats was perfused for immunohistochemistry and a second group was used for laser-capture microdissection for analysis of SFO AT1aR gene expression. BDL rats showed increased water intake that was attenuated in rats that received SFO microinjection of AT1aR shRNA. Among BDL rats treated with scrambled (control) and AT1aR shRNA, we observed an increased number of vasopressin positive cells in the supraoptic nucleus (SON) that colocalized with ΔFosB staining suggesting increased vasopressin release in both groups. These results indicate that angiotensin signalling through the SFO contributes to increased water intake, but not dilutional hyponatremia, during congestive liver failure.

PMID: 25009217 [PubMed - as supplied by publisher]

Response: Observational Study Demonstrates That OMT Is Associated With Reduced Analgesic Prescribing and Fewer Missed Work Days.

Fri, 07/11/2014 - 12:04pm

Response: Observational Study Demonstrates That OMT Is Associated With Reduced Analgesic Prescribing and Fewer Missed Work Days.

J Am Osteopath Assoc. 2014 Jul;114(7):530-1

Authors: Prinsen JK, Hensel KL, Snow RJ

PMID: 25002441 [PubMed - in process]

The OSTEOPATHIC Trial Demonstrates Significant Improvement in Patients With Chronic Low Back Pain as Manifested by Decreased Prescription Rescue Medication Use.

Fri, 07/11/2014 - 12:04pm

The OSTEOPATHIC Trial Demonstrates Significant Improvement in Patients With Chronic Low Back Pain as Manifested by Decreased Prescription Rescue Medication Use.

J Am Osteopath Assoc. 2014 Jul;114(7):528-9

Authors: Licciardone JC

PMID: 25002440 [PubMed - in process]

A high volume extraction and purification method for recovering DNA from human bone.

Wed, 07/09/2014 - 12:05pm
Related Articles

A high volume extraction and purification method for recovering DNA from human bone.

Forensic Sci Int Genet. 2014 Jun 18;12C:155-160

Authors: Marshall PL, Stoljarova M, Schmedes SE, King JL, Budowle B

Abstract
DNA recovery, purity and overall extraction efficiency of a protocol employing a novel silica-based column, Hi-Flow(®) (Generon Ltd., Maidenhead, UK), were compared with that of a standard organic DNA extraction methodology. The quantities of DNA recovered by each method were compared by real-time PCR and quality of DNA by STR typing using the PowerPlex(®) ESI 17 Pro System (Promega Corporation, Madison, WI) on DNA from 10 human bone samples. Overall, the Hi-Flow method recovered comparable quantities of DNA ranging from 0.8ng±1 to 900ng±159 of DNA compared with the organic method ranging from 0.5ng±0.9 to 855ng±156 of DNA. Complete profiles (17/17 loci tested) were obtained for at least one of three replicates for 3/10 samples using the Hi-Flow method and from 2/10 samples with the organic method. All remaining bone samples yielded partial profiles for all replicates with both methods. Compared with a standard organic DNA isolation method, the results indicated that the Hi-Flow method provided equal or improved recovery and quality of DNA without the harmful effects of organic extraction. Moreover, larger extraction volumes (up to 20mL) can be employed with the Hi-Flow method which enabled more bone sample to be extracted at one time.

PMID: 24997320 [PubMed - as supplied by publisher]

Hypertrophic Cardiomyopathy Associated Lys104Glu Mutation in the Myosin Regulatory Light Chain Causes Diastolic Disturbance in Mice.

Wed, 07/09/2014 - 12:05pm
Related Articles

Hypertrophic Cardiomyopathy Associated Lys104Glu Mutation in the Myosin Regulatory Light Chain Causes Diastolic Disturbance in Mice.

J Mol Cell Cardiol. 2014 Jun 30;

Authors: Huang W, Liang J, Kazmierczak K, Muthu P, Duggal D, Farman GP, Sorensen L, Pozios I, Abraham TP, Moore JR, Borejdo J, Szczesna-Cordary D

Abstract
We have examined, for the first time, the effects of the familial hypertrophic cardiomyopathy (HCM)- associated Lys104Glu mutation in the myosin regulatory light chain (RLC). Transgenic mice expressing the Lys104Glu substitution (Tg-MUT) were generated and the results compared to Tg-WT (wild-type human ventricular RLC) mice. Echocardiography with pulse wave Doppler in 6month-old Tg-MUT showed early signs of diastolic disturbance with significantly reduced E/A transmitral velocities ratio. Invasive hemodynamics in 6month-old Tg-MUT mice also demonstrated a borderline significant prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, suggesting alterations in diastolic function in Tg-MUT. Six month-old mutant animals had no LV hypertrophy; however, at >13months they displayed significant hypertrophy and fibrosis. In skinned papillary muscles from 5-6 month-old mice a mutation induced reduction in maximal tension and slower muscle relaxation rates were observed. Mutated cross-bridges showed increased rates of binding to the thin filaments and a faster rate of the power stroke. In addition, ~2-fold lower level of RLC phosphorylation was observed in the mutant compared to Tg-WT. In line with the higher mitochondrial content seen in Tg-MUT hearts, the MUT-myosin ATPase activity was significantly higher than WT-myosin, indicating increased energy consumption. In the in vitro motility assay, MUT-myosin produced higher actin sliding velocity under zero load, but the velocity drastically decreased with applied load in the MUT vs. WT myosin. Our results suggest that diastolic disturbance (impaired muscle relaxation, lower E/A) and inefficiency of energy use (reduced contractile force and faster ATP consumption) may underlie the Lys104Glu-mediated HCM phenotype.

PMID: 24992035 [PubMed - as supplied by publisher]

Cancer-associated Isocitrate Dehydrogenase 1 (IDH1) R132H Mutation and D-2-hydroxyglutarate Stimulate Glutamine Metabolism under Hypoxia.

Wed, 07/09/2014 - 12:05pm
Related Articles

Cancer-associated Isocitrate Dehydrogenase 1 (IDH1) R132H Mutation and D-2-hydroxyglutarate Stimulate Glutamine Metabolism under Hypoxia.

J Biol Chem. 2014 Jul 1;

Authors: Reitman ZJ, Duncan CG, Poteet E, Winters A, Yan LJ, Gooden DM, Spasojevic I, Boros LG, Yang SH, Yan H

Abstract
Mutations in the cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations target a critical step in reductive glutamine metabolism, the metabolic pathway that converts glutamine ultimately to acetyl-CoA for biosynthetic processes. While IDH1-mutated cells are sensitive to therapies that target glutamine metabolism, the effect of IDH1 mutations on reductive glutamine metabolism remains poorly understood. To explore this issue, we investigated the effect of a knock-in, single-codon IDH1-R132H mutation on the metabolism of the HCT116 colorectal adenocarcinoma cell line. Here we report the R132H-isobolome by using targeted 13C isotopomer tracer fate analysis to trace the metabolic fate of glucose and glutamine in this system. We show that introduction of the R132H mutation into IDH1 upregulates the contribution of glutamine to lipogenesis in hypoxia, but not in normoxia. Treatment of cells with a D-2-hydroxyglutarate (D-2HG) ester recapitulated these changes, indicating that the alterations observed in the knocked-in cells were mediated by D-2HG produced by the IDH1 mutant. These studies provide a dynamic mechanistic basis for metabolic alterations observed in IDH1-mutated tumors and uncover potential therapeutic targets in IDH1-mutated cancers.

PMID: 24986863 [PubMed - as supplied by publisher]

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Wed, 07/09/2014 - 12:05pm
Related Articles

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Psychopharmacology (Berl). 2014 Jul 3;

Authors: Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB

Abstract
RATIONALE: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens.
OBJECTIVE: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT).
METHODS: Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT.
RESULTS: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro.
CONCLUSIONS: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

PMID: 24985890 [PubMed - as supplied by publisher]

Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15.

Sun, 07/06/2014 - 4:04am
Related Articles

Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15.

Int J Biochem Cell Biol. 2014 Jun 28;

Authors: Timani KA, Liu Y, Suvannasankha A, He JJ

Abstract
Tip110 is a nuclear protein and has been shown to function in tumor antigenicity, regulation of gene transcription, pre-mRNA splicing, stem cell proliferation and differentiation, and embryonic development. To characterize the in vivo functions of Tip110, a transgene cassette expressing human Tip110 protein (hTip110) was used to generate hTip110 transgenic (Tg) mice. Unexpectedly, only Tip110 mRNA but not Tip110 protein was expressed in Tg MEF and tissues. Treatment of Tg MEF with proteasome inhibitors led to detection of hTip110 protein, which prompted us to investigate the regulatory mechanisms of Tip110 degradation in mouse cells. We found that hTip110 was more sensitive to ubiquitin-proteasome system (UPS)-mediated protein degradation than mouse Tip110 (mTip110), likely resulting from more hTip110 ubiquitination. Using affinity chromatography and proteomics, we identified USP15, a deubiquitinating enzyme, to be associated with Tip110. Tip110 expression led to re-distribution of USP15 from the cytoplasm to the nucleus and complete co-localization of Tip110 with USP15 in the nucleus, whereas USP15 expression resulted in hTip110 deubiquitination. Interestingly, USP15 knockdown restored hTip110 protein expression in Tg MEF and USP15 expression had little effects. Taken together, these results provide insights into the regulatory mechanism of human Tip110 degradation by USP15.

PMID: 24984263 [PubMed - as supplied by publisher]

Nanobiosensors: role in cancer detection and diagnosis.

Sun, 07/06/2014 - 4:04am
Related Articles

Nanobiosensors: role in cancer detection and diagnosis.

Adv Exp Med Biol. 2014;807:33-58

Authors: Gdowski A, Ranjan AP, Mukerjee A, Vishwanatha JK

Abstract
The ability to detect many cancers at an early stage in its clinical course has the potential to improve patient outcomes in terms of morbidity and mortality. Nanosized components incorporated into existing clinical diagnostic and detection systems as well as novel nanobiosensors have demonstrated improved sensitivity and specificity compared with traditional cancer testing approaches. Nanoparticles, nanowires, nanotubes, and nanocantilevers are examples of four nanobiosensor systems that have been used experimentally in the context of detection and diagnosis of prostate, breast, pancreatic, lung, and brain cancers over the past few years. Nanobiosensors will begin to transition into clinically validated tests as experimental and engineering techniques advance. This paper presents examples of some such nanobiosensors for cancer diagnosis and detection.

PMID: 24619617 [PubMed - indexed for MEDLINE]

Acute Effects of Muscle Fatigue on Anticipatory and Reactive Postural Control in Older Individuals: A Systematic Review of the Evidence.

Wed, 07/02/2014 - 4:05am
Related Articles

Acute Effects of Muscle Fatigue on Anticipatory and Reactive Postural Control in Older Individuals: A Systematic Review of the Evidence.

J Geriatr Phys Ther. 2014 Jun 27;

Authors: Papa EV, Garg H, Dibble LE

Abstract
BACKGROUND:: Falls are the leading cause of traumatic brain injury and fractures and the No. 1 cause of emergency department visits by older adults. Although declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. In an effort to increase awareness of the detrimental effects of skeletal muscle fatigue on postural control, we sought to systematically review research studies examining this issue.
PURPOSE:: The specific purpose of this review was to provide a detailed assessment of how anticipatory and reactive postural control tasks are influenced by acute muscle fatigue in healthy older individuals.
METHODS:: An extensive search was performed using the CINAHL, Scopus, PubMed, SPORTDiscus, and AgeLine databases for the period from inception of each database to June 2013. This systematic review used standardized search criteria and quality assessments via the American Academy for Cerebral Palsy and Developmental Medicine Methodology to Develop Systematic Reviews of Treatment Interventions (2008 version, revision 1.2, AACPDM, Milwaukee, Wisconsin).
RESULTS:: A total of 334 citations were found. Six studies were selected for inclusion, whereas 328 studies were excluded from the analytical review. The majority of articles (5 of 6) utilized reactive postural control paradigms. All studies incorporated extrinsic measures of muscle fatigue, such as declines in maximal voluntary contraction or available active range of motion. The most common biomechanical postural control task outcomes were spatial measures, temporal measures, and end-points of lower extremity joint kinetics.
CONCLUSION:: On the basis of systematic review of relevant literature, it appears that muscle fatigue induces clear deteriorations in reactive postural control. A paucity of high-quality studies examining anticipatory postural control supports the need for further research in this area. These results should serve to heighten awareness regarding the potential negative effects of acute muscle fatigue on postural control and support the examination of muscle endurance training as a fall risk intervention in future studies.

PMID: 24978932 [PubMed - as supplied by publisher]