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: 54 min 42 sec ago

Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens.

Fri, 03/03/2017 - 07:31
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Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens.

mSphere. 2017 Jan-Feb;2(1):

Authors: Grossman TH, Fyfe C, O'Brien W, Hackel M, Minyard MB, Waites KB, Dubois J, Murphy TM, Slee AM, Weiss WJ, Sutcliffe JA

Abstract
TP-271 is a novel, fully synthetic fluorocycline antibiotic in clinical development for the treatment of respiratory infections caused by susceptible and multidrug-resistant pathogens. TP-271 was active in MIC assays against key community respiratory Gram-positive and Gram-negative pathogens, including Streptococcus pneumoniae (MIC90 = 0.03 µg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC90 = 0.25 µg/ml), methicillin-resistant S. aureus (MRSA; MIC90 = 0.12 µg/ml), Streptococcus pyogenes (MIC90 = 0.03 µg/ml), Haemophilus influenzae (MIC90 = 0.12 µg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 µg/ml). TP-271 showed activity (MIC90 = 0.12 µg/ml) against community-acquired MRSA expressing Panton-Valentine leukocidin (PVL). MIC90 values against Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae were 0.004, 1, and 4 µg/ml, respectively. TP-271 was efficacious in neutropenic and immunocompetent animal pneumonia models, generally showing, compared to the burden at the start of dosing, ~2 to 5 log10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log10 CFU reductions when given orally (p.o.). TP-271 was potent against key community-acquired bacterial pneumonia (CABP) pathogens and was minimally affected, or unaffected, by tetracycline-specific resistance mechanisms and fluoroquinolone or macrolide drug resistance phenotypes. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP.

PMID: 28251179 [PubMed - in process]

Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma.

Fri, 03/03/2017 - 07:31
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Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma.

BMC Neurosci. 2017 Mar 01;18(1):27

Authors: McGrady NR, Minton AZ, Stankowska DL, He S, Jefferies HB, Krishnamoorthy RR

Abstract
BACKGROUND: Primary open angle glaucoma is a heterogeneous group of optic neuropathies that results in optic nerve degeneration and a loss of retinal ganglion cells (RGCs) ultimately causing blindness if allowed to progress. Elevation of intraocular pressure (IOP) is the most attributable risk factor for developing glaucoma and lowering of IOP is currently the only available therapy. However, despite lowering IOP, neurodegenerative effects persist in some patients. Hence, it would be beneficial to develop approaches to promote neuroprotection of RGCs in addition to IOP lowering therapies. The endothelin system is a key target for intervention against glaucomatous neurodegeneration. The endothelin family of peptides and receptors, particularly endothelin-1 (ET-1) and endothelin B (ETB) receptor, has been shown to have neurodegenerative roles in glaucoma. The purpose of this study was to examine changes in endothelin A (ETA) receptor protein expression in the retinas of adult male Brown Norway rats following IOP elevation by the Morrison's model of ocular hypertension and the impact of ETA receptor overexpression on RGC viability in vitro.
RESULTS: IOP elevation was carried out in one eye of Brown Norway rats by injection of hypertonic saline through episcleral veins. After 2 weeks of IOP elevation, immunohistochemical analysis of retinal sections from rat eyes showed an increasing trend in immunostaining for ETA receptors in multiple retinal layers including the inner plexiform layer, ganglion cell layer and outer plexiform layer. Following 4 weeks of IOP elevation, a significant increase in immunostaining for ETA receptor expression was found in the retina, primarily in the inner plexiform layer and ganglion cells. A modest increase in staining for ETA receptors was also found in the outer plexiform layer in the retina of rats with IOP elevation. Cell culture studies showed that overexpression of ETA receptors in 661W cells as well as primary RGCs decreases cell viability, compared to empty vector transfected cells. Adeno-associated virus mediated overexpression of the ETA receptor produced an increase in the ETB receptor in primary RGCs.
CONCLUSIONS: Elevated IOP results in an appreciable change in ETA receptor expression in the retina. Overexpression of the ETA receptor results in an overall decrease in cell viability, accompanied by an increase in ETB receptor levels, suggesting the involvement of both ETA and ETB receptors in mediating cell death. These findings raise possibilities for the development of ETA/ETB dual receptor antagonists as neuroprotective treatments for glaucomatous neuropathy.

PMID: 28249604 [PubMed - in process]

Glutamate Impairs Mitochondria Aerobic Respiration Capacity and Enhances Glycolysis in Cultured Rat Astrocytes.

Thu, 03/02/2017 - 07:33
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Glutamate Impairs Mitochondria Aerobic Respiration Capacity and Enhances Glycolysis in Cultured Rat Astrocytes.

Biomed Environ Sci. 2017 Jan;30(1):44-51

Authors: Yan X, Shi ZF, Xu LX, Li JX, Wu M, Wang XX, Jia M, Dong LP, Yang SH, Yuan F

Abstract
OBJECTIVE: To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes.
METHODS: After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates (OCR) and extra cellular acidification rate (ECAR) was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit.
RESULTS: Compared with the control group, treatment with 1 mmol/L glutamate decreased the astrocytes' maximal respiration and spare respiratory capacity but increased their glycolytic capacity and glycolytic reserve. Further analysis found that 1-h treatment with different concentrations of glutamate (0.1-1 mmol/L) increased lactate release from astrocytes, however the cell viability was not affected by the glutamate treatment.
CONCLUSION: The current study provided direct evidence that exogenous glutamate treatment impaired the mitochondrial respiration capacity of astrocytes and enhanced aerobic glycolysis, which could be involved in glutamate injury or protection mechanisms in response to neurological disorders.

PMID: 28245898 [PubMed - in process]

Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation.

Wed, 03/01/2017 - 07:32
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Association of Sp1 and survivin in epithelial ovarian cancer: Sp1 inhibitor and cisplatin, a novel combination for inhibiting epithelial ovarian cancer cell proliferation.

Tumour Biol. 2016 Oct;37(10):14259-14269

Authors: Sankpal UT, Ingersoll SB, Ahmad S, Holloway RW, Bhat VB, Simecka JW, Daniel L, Kariali E, Vishwanatha JK, Basha R

Abstract
The expression of specificity protein 1 (Sp1) and survivin was evaluated in clinical specimens of epithelial ovarian cancer (EOC) patients. When compared to normal tissue, EOC samples showed high expression of Sp1 and survivin using qPCR (Sp1: ∼2-fold; survivin: ∼5-fold) and Western blot (Sp1: >2.6-fold; survivin: >100-fold). The Sp1 inhibitor, and anti-cancer small molecule, tolfenamic acid (TA), was tested to enhance the response of Cisplatin (Cis) in EOC cell lines. Cell viability (CellTiter-Glo), combination index (CalcuSyn software), apoptosis (Annexin-V staining), cell cycle analyses (flow cytometry), and reactive oxygen species (flow cytometry) were determined. Cell migration and invasion was assessed using matrigel coated transwell chambers. Agilent Technologies proteomics analysis identified potential signaling pathways involved. The combination of TA (50 μM) and Cis (5 μM) synergistically increased the growth inhibition in ES2 (∼80 %, p < 0.001) and OVCAR-3 (60 %, p < 0.001) cells. TA or TA + Cis treatment in ES2 cells caused cell cycle arrest in G1 Phase (TA) or S-Phase (TA + Cis) and unregulated reactive oxygen species. Invasion and migration was decreased in ES2 cells. Global proteomic profiling showed modulation of proteins associated with oxidative phosphorylation, apoptosis, electron transport chain, DNA damage, and cell cycle proteins. These results demonstrate an association of Sp1 and survivin in EOC and confirm targeting these candidates with TA potentially sensitizes EOC cells to cisplatin.

PMID: 27581819 [PubMed - indexed for MEDLINE]

TGFβ2 Induces the Formation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells Through the Smad and Non-Smad Dependent Pathways.

Tue, 02/28/2017 - 07:33

TGFβ2 Induces the Formation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells Through the Smad and Non-Smad Dependent Pathways.

Invest Ophthalmol Vis Sci. 2017 Feb 01;58(2):1288-1295

Authors: Montecchi-Palmer M, Bermudez JY, Webber HC, Patel GC, Clark AF, Mao W

Abstract
Purpose: Increased intraocular pressure results from increased aqueous humor (AH) outflow resistance at the trabecular meshwork (TM) due to pathologic changes including the formation of cross-linked actin networks (CLANs). Transforming growth factor β2 (TGFβ2) is elevated in the AH and TM of primary open angle glaucoma (POAG) patients and induces POAG-associated TM changes, including CLANs. We determined the role of individual TGFβ2 signaling pathways in CLAN formation.
Methods: Cultured nonglaucomatous human TM (NTM) cells were treated with control or TGFβ2, with or without the inhibitors of TGFβ receptor, Smad3, c-Jun N-terminal kinases (JNK), extracellular signal regulated kinase (ERK), P38, or Rho-associated protein kinase (ROCK). NTM cells were cotreated with TGFβ2 plus inhibitors for 10 days or pretreated with TGFβ2 for 10 days followed by 1-hour inhibitor treatment. NTM cells were immunostained with phalloidin-Alexa-488 and 4',6-diamidino-2-phenylindole (DAPI). Data were analyzed using 1-way ANOVA and Dunnett's post hoc test.
Results: TGFβ2 significantly induced CLAN formation (n = 6 to 12, P < 0.05), which was completely inhibited by TGFβ receptor, Smad3, and ERK inhibitors, as well as completely or partially inhibited by JNK, P38, and ROCK inhibitors, depending on cell strains. One-hour exposure to ROCK inhibitor completely resolved formed CLANs (P < 0.05), whereas TGFβ receptor, Smad3 inhibitor, and ERK inhibitors resulted in partial or complete resolution. The JNK and P38 inhibitors showed partial or no resolution. Among these inhibitors, the ROCK inhibitor was the most disruptive to the actin stress fibers, whereas ERK inhibition showed the least disruption.
Conclusions: TGFβ2-induced CLANs in NTM cells were prevented and resolved using various pathway inhibitors. Apart from CLAN inhibition, some of these inhibitors also had different effects on actin stress fibers.

PMID: 28241317 [PubMed - in process]

Non-Feminizing Estrogens Do Not Exhibit Antidepressant-like Activity.

Tue, 02/28/2017 - 07:33
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Non-Feminizing Estrogens Do Not Exhibit Antidepressant-like Activity.

J Pharm Drug Res. 2016;1(1):1-6

Authors: Prokai-Tatrai K, Nguyen V, Prokai L

Abstract
In this exploratory study, we performed an evaluation of non-feminizing estrogens as lead compounds for the safe treatment of menopausal symptoms. Despite confirming an enhancement of antioxidant potency as a consequence of increased lipophilicity of the prototype structures, our analyses have revealed serious shortcomings regarding pharmaceutically important properties and drug-likeness. In addition, our assessment in an animal model of estrogen deprivation has confirmed that genomic mechanisms are required for the alleviation of menopause-associated depression. Therefore, non-feminizing estrogens are not suitable to fulfill their implicated premise to address unmet needs to treat neurological and psychiatric conditions associated with estrogen deprivation of the brain.

PMID: 28239683 [PubMed - in process]

Cross-linked actin networks (CLANs) in glaucoma.

Tue, 02/28/2017 - 07:33
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Cross-linked actin networks (CLANs) in glaucoma.

Exp Eye Res. 2017 Feb 23;:

Authors: Bermudez JY, Montecchi-Palmer M, Mao W, Clark AF

Abstract
One of the major causes of decreased vision, irreversible vision loss and blindness worldwide is glaucoma. Increased intraocular pressure (IOP) is a major risk factor associated with glaucoma and its molecular mechanisms are not fully understood. The trabecular meshwork (TM) is the primary site of injury in glaucoma, and its dysfunction results in elevated IOP. The glaucomatous TM has increased extracellular matrix deposition as well as cytoskeletal rearrangements referred to as cross-linked actin networks (CLANs) that consist of dome like structures consisting of hubs and spokes. CLANs are thought to play a role in increased aqueous humor outflow resistance and increased IOP by creating stiffer TM cells and tissue. CLANs are inducible by glucocorticoids (GCs) and TGFβ2 in confluent TM cells and TM tissues. The signaling pathways of these induction agents give insight into the possible mechanisms of CLAN formation, but to date, the mechanism of CLANs regulation by these pathways has yet to be determined. Understanding the role CLANs play in IOP elevation and their mechanisms of induction and regulation may lead to novel treatment options to help prevent or intervene in glaucomatous damage to the trabecular meshwork.

PMID: 28238754 [PubMed - as supplied by publisher]

Intervention Mediators in a Randomized Controlled Trial to Increase Colonoscopy Uptake Among Individuals at Increased Risk of Familial Colorectal Cancer.

Mon, 02/27/2017 - 07:32
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Intervention Mediators in a Randomized Controlled Trial to Increase Colonoscopy Uptake Among Individuals at Increased Risk of Familial Colorectal Cancer.

Ann Behav Med. 2017 Feb 24;:

Authors: Brumbach BH, Birmingham WC, Boonyasiriwat W, Walters S, Kinney AY

Abstract
BACKGROUND: Understanding the pathways by which interventions achieve behavioral change is important for optimizing intervention strategies.
PURPOSE: We examined mediators of behavior change in a tailored-risk communication intervention that increased guideline-based colorectal cancer screening among individuals at increased familial risk.
METHODS: Participants at increased familial risk for colorectal cancer (N = 481) were randomized to one of two arms: (1) a remote, tailored-risk communication intervention (Tele-Cancer Risk Assessment and Evaluation (TeleCARE)) or (2) a mailed educational brochure intervention.
RESULTS: Structural equation modeling showed that participants in TeleCARE were more likely to get a colonoscopy. The effect was partially mediated through perceived threat (β = 0.12, p < 0.05), efficacy beliefs (β = 0.12, p < 0.05), emotions (β = 0.22, p < 0.001), and behavioral intentions (β = 0.24, p < 0.001). Model fit was very good: comparative fit index = 0.95, root-mean-square error of approximation = 0.05, and standardized root-mean-square residual = 0.08.
CONCLUSION: Evaluating mediating variables between an intervention (TeleCARE) and a primary outcome (colonoscopy) contributes to our understanding of underlying mechanisms that lead to health behavior change, thus leading to better informed and designed future interventions.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov , NCT01274143.

PMID: 28236077 [PubMed - as supplied by publisher]

Genetic redundancy of GATA factors in extraembryonic trophoblast lineage ensures progression of both pre and postimplantation mammalian development.

Sun, 02/26/2017 - 17:16
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Genetic redundancy of GATA factors in extraembryonic trophoblast lineage ensures progression of both pre and postimplantation mammalian development.

Development. 2017 Feb 23;:

Authors: Home P, Kumar RP, Ganguly A, Saha B, Milano-Foster J, Bhattacharya B, Ray S, Gunewardena S, Paul A, Camper SA, Fields PE, Paul S

Abstract
GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.

PMID: 28232602 [PubMed - as supplied by publisher]

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

Fri, 02/24/2017 - 07:33
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Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

Clin Infect Dis. 2016 May 01;62(9):1081-8

Authors: Luetkemeyer AF, Firnhaber C, Kendall MA, Wu X, Mazurek GH, Benator DA, Arduino R, Fernandez M, Guy E, Johnson P, Metchock B, Sattler F, Telzak E, Wang YF, Weiner M, Swindells S, Sanne IM, Havlir DV, Grinsztejn B, Alland D, AIDS Clinical Trials Group A5295 and Tuberculosis Trials Consortium Study 34 Teams

Abstract
BACKGROUND: The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation.
METHODS: Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa.
RESULTS: Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%.
CONCLUSIONS: In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

PMID: 26839383 [PubMed - indexed for MEDLINE]

Plasma Cystatin C and High-Density Lipoprotein Are Important Biomarkers of Alzheimer's Disease and Vascular Dementia: A Cross-Sectional Study.

Thu, 02/23/2017 - 07:32
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Plasma Cystatin C and High-Density Lipoprotein Are Important Biomarkers of Alzheimer's Disease and Vascular Dementia: A Cross-Sectional Study.

Front Aging Neurosci. 2017;9:26

Authors: Wang R, Chen Z, Fu Y, Wei X, Liao J, Liu X, He B, Xu Y, Zou J, Yang X, Weng R, Tan S, McElroy C, Jin K, Wang Q

Abstract
Objectives: Cystatin C (Cys C) and high-density lipoprotein (HDL) play critical roles in neurodegenerative diseases, such as dementia, Alzheimer's disease (AD) and vascular dementia (VaD). However, whether they can be used as reliable biomarkers to distinguish patients with dementia from healthy subjects and to determine disease severity remain largely unknown. Methods: We conducted a cross-sectional study to determine plasma Cys C and HDL levels of 88 patients with dementia (43 AD patients, 45 VaD patients) and 45 healthy age-matched controls. The severity of dementia was determined based on the Schwab and England Activities of Daily Living (ADL) Scale, the Mini-mental State Examination (MMSE), the Global Deterioration Scale (GDS), the Lawton Instrumental ADL (IADL) Scale, and the Hachinski Ischemia Scale (Hachinski). Receiver operating characteristic (ROC) curves were calculated to determine the diagnostic accuracy of Cys C and HDL levels in distinguishing patients with dementia from healthy subjects. Results: We found that plasma Cys C levels were higher, but HDL levels were lower in AD and VaD patients respectively, compared to healthy control subjects. Yet, Cys C levels were highest among patients with VaD. Interestingly, plasma Cys C levels were significantly correlated with IADL Scale scores. In addition, the ROC curves for Cys C (area under the curve, AUC 0.816 for AD, AUC 0.841 for VaD) and HDL (AUC 0.800 for AD, AUC 0.731 for VaD) exhibited potential diagnostic value in distinguishing AD/VaD patients from healthy subjects. While the ROC curve for the combination of Cys C and HDL (AUC 0.873 for AD, AUC 0.897 for VaD) showed higher diagnostic accuracy in distinguishing AD/VaD patients from healthy subjects than the separate curves for each parameter. Conclusions: Our findings suggest that the inflammatory mediators Cys C and HDL may play important roles in the pathogenesis of dementia, and plasma Cys C and HDL levels may be useful screening tools for differentiating AD/VaD patients from healthy subjects.
HIGHLIGHTS: Plasma Cys C levels were higher in patients with AD/VaD than in healthy subjects.Plasma HDL levels were lower in patients with AD/VaD than in healthy subjects.Plasma Cys C levels were significantly correlated with dementia.The ROC curve for the combination of Cys C and HDL showed potential diagnostic value in distinguishing AD/VaD from healthy subjects.

PMID: 28223934 [PubMed - in process]

Analysis of Short Tandem Repeat and Single Nucleotide Polymorphism Loci From Single-Source Samples Using a Custom HaloPlex Target Enrichment System Panel.

Thu, 02/23/2017 - 07:32
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Analysis of Short Tandem Repeat and Single Nucleotide Polymorphism Loci From Single-Source Samples Using a Custom HaloPlex Target Enrichment System Panel.

Am J Forensic Med Pathol. 2016 Jun;37(2):99-107

Authors: Wendt FR, Zeng X, Churchill JD, King JL, Budowle B

Abstract
Short tandem repeats and single nucleotide polymorphisms (SNPs) are used to individualize biological evidence samples. Short tandem repeat alleles are characterized by size separation during capillary electrophoresis (CE). Massively parallel sequencing (MPS) offers an alternative that can overcome limitations of the CE. With MPS, libraries are prepared for each sample, entailing target enrichment and bar coding, purification, and normalization. The HaloPlex Target Enrichment System (Agilent Technologies) uses a capture-based enrichment system with restriction enzyme digestion to generate fragments containing custom-selected markers. It offers another possible workflow for typing reference samples. Its efficacy was assessed using a panel of 275 human identity SNPs, 88 short tandem repeats, and amelogenin. The data analyzed included locus typing success, depth of sequence coverage, heterozygote balance, and concordance. The results indicate that the HaloPlex Target Enrichment System provides genetic data similar to that obtained by conventional polymerase chain reaction-CE methods with the advantage of analyzing substantially more markers in 1 sequencing run. The genetic typing performance of HaloPlex is comparable to other MPS-based sample preparation systems that utilize primer-based target enrichment.

PMID: 27075592 [PubMed - indexed for MEDLINE]

For the pursuit of oxygen and carbon dioxide channels in mitochondria.

Wed, 02/22/2017 - 07:32
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For the pursuit of oxygen and carbon dioxide channels in mitochondria.

Med Gas Res. 2016 Oct-Dec;6(4):237-238

Authors: Yang SH, Liu R

PMID: 28217298 [PubMed - in process]

What's the agreement between self-reported and biochemical verification of drug use? A look at permanent supportive housing residents.

Mon, 02/20/2017 - 07:33
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What's the agreement between self-reported and biochemical verification of drug use? A look at permanent supportive housing residents.

Addict Behav. 2017 Feb 10;70:90-96

Authors: Rendon A, Livingston M, Suzuki S, Hill W, Walters S

Abstract
Self-reported substance use is commonly used as an outcome measure in treatment research. We evaluated the validity of self-reported drug use in a sample of 334 adults with mental health problems who were residing in supportive housing programs. The primary analysis was the calculation of the positive predictive values (PPVs) of self-report compared to an oral fluid test taken at the same time. A sensitivity analysis compared the positive predictive values of two self-reported drug use histories: biological testing window (ranging between the past 96h to 30days depending on drug type) or the full past 90-day comparison window (maximum length recorded during interview). A multivariable logistic regression was used to predict discordance between self-report and the drug test for users. Self-reported drug use and oral fluid drug tests were compared to determine the positive predictive value for amphetamines/methamphetamines/PCP (47.1% agreement), cocaine (43.8% agreement), and marijuana (69.7% agreement) drug tests. Participants who misreported their drug use were more likely to be older, non-White, have no medical insurance, and not report any alcohol use. In general, amphetamine/methamphetamine/PCP and cocaine use was adequately captured by the biological test, while marijuana use was best captured by a combination of self-report and biological data. Using the full past 90day comparison window resulted in higher concordance with the oral fluid drug test, indicating that self-reported drug use in the past 90days may be a proxy for drug use within the biological testing window. Self-report has some disadvantages when used as the sole measure of drug use in this population.

PMID: 28214742 [PubMed - as supplied by publisher]

Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats.

Sat, 02/18/2017 - 07:33
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Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats.

Psychopharmacology (Berl). 2017 Feb 16;:

Authors: Gatch MB, Dolan SB, Forster MJ

Abstract
RATIONALE: Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds.
OBJECTIVES: The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: α-pyrrolidinopropiophenone (α-PPP), α-pyrrolidinohexiophenone (α-PHP), α-pyrrolidinopentiothiophenone (α-PVT), 3,4-methylenedioxybutiophenone (MDPBP), and ethylone.
METHODS: Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle.
RESULTS: Each of the compounds produced an inverted-U dose-effect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > α-PPP = α-PHP > ethylone > α-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. α-PPP, α-PHP, and ethylone fully substituted for cocaine. α-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%.
CONCLUSIONS: These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.

PMID: 28210779 [PubMed - as supplied by publisher]

Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

Fri, 02/17/2017 - 07:32
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Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice.

Aging Dis. 2017 Feb;8(1):17-30

Authors: Thangthaeng N, Rutledge M, Wong JM, Vann PH, Forster MJ, Sumien N

Abstract
Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

PMID: 28203479 [PubMed]

Potential Biochemical Mechanisms of Lung Injury in Diabetes.

Fri, 02/17/2017 - 07:32
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Potential Biochemical Mechanisms of Lung Injury in Diabetes.

Aging Dis. 2017 Feb;8(1):7-16

Authors: Zheng H, Wu J, Jin Z, Yan LJ

Abstract
Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury.

PMID: 28203478 [PubMed]

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

Fri, 02/17/2017 - 07:32
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Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

Am J Physiol Regul Integr Comp Physiol. 2017 Feb 15;:ajpregu.00120.2016

Authors: Lalley PM, Mifflin SW

Abstract
μ-Opioid receptors are distributed widely in the brainstem respiratory network, and opioids with selectivity for μ-type receptors slow in-vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and inter-spike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brainstem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid mediated disinhibition and postsynaptic enhancement of NMDA receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brainstem respiratory network to override opioid blunting of CO2/pH chemosensitivity.

PMID: 28202437 [PubMed - as supplied by publisher]

Managing Spaghetti Syndrome in Critical Care With a Novel Device: A Nursing Perspective.

Thu, 02/16/2017 - 10:37
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Managing Spaghetti Syndrome in Critical Care With a Novel Device: A Nursing Perspective.

Crit Care Nurse. 2015 Dec;35(6):38-45

Authors: Haynes J, Bowers K, Young R, Sanders T, Schultz KE

Abstract
BACKGROUND: Managing "spaghetti syndrome," the tangle of therapeutic cables, tubes, and cords at patients' bedsides, can be challenging.
OBJECTIVES: To assess nurses' perceptions of the effectiveness of a novel banding device in management of spaghetti syndrome.
METHODS: A simple color-coded elastomeric banding strap with ribbed flaps was attached to bed rails of adult critical care patients to help organize therapeutic cables, tubes, wires, and cords. Nurses were surveyed before and after use of the bands and after the nursing shift to assess the burden of spaghetti syndrome and the effectiveness of using the bands.
RESULTS: Use of the bands decreased the time spent untangling cords, reduced the frequency of contact of tubing with the floor, and diminished disruptions in care.
CONCLUSIONS: Use of a simple flexible latex-free elastomeric band may help organize therapeutic tubing at patients' bedsides and may promote improvements in nursing care.

PMID: 26628544 [PubMed - indexed for MEDLINE]

FRET study in oligopeptide-linked donor-acceptor system in PVA matrix.

Tue, 02/14/2017 - 07:32

FRET study in oligopeptide-linked donor-acceptor system in PVA matrix.

Methods Appl Fluoresc. 2016 Dec 13;4(4):047002

Authors: Shah S, Mandecki W, Li J, Gryczynski Z, Borejdo J, Gryczynski I, Fudala R

Abstract
An oligopeptide: Lys-Gly-Pro-Arg-Ser-Leu-Ser-Gly-Lys-NH2, cleaved specifically by a matrix metalloproteinase 9 (MMP-9) at the Ser-Leu bond, was labeled on the ε-NH2 groups of lysine with donor (5, 6 TAMRA) and acceptor (HiLyte647) dye. The donor control was a peptide labeled with 5, 6 TAMRA only on the C-terminal lysine, and the acceptor control was free HiLyte647. Following three products were studied by dissolving in 10% (w/w) poly(vinyl alcohol) and dried on glass slides forming 200 micron films. Absorption spectra of the films show full additivity of donor and acceptor absorptions. A strong Fluorescence Resonance Energy Transfer (FRET) with an efficiency of about 85% was observed in the fluorescence emission and excitation spectra. The lifetime of the donor was shorter and heterogeneous compared with the donor control.

PMID: 28192309 [PubMed - in process]

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