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]
Updated: 1 hour 46 min ago

Impact of air quality guidelines on COPD sufferers.

Sat, 01/14/2017 - 07:43
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Impact of air quality guidelines on COPD sufferers.

Int J Chron Obstruct Pulmon Dis. 2016;11:839-72

Authors: Liu Y, Yan S, Poh K, Liu S, Iyioriobhe E, Sterling DA

Abstract
BACKGROUND: COPD is one of the leading causes of morbidity and mortality in both high- and low-income countries and a major public health burden worldwide. While cigarette smoking remains the main cause of COPD, outdoor and indoor air pollution are important risk factors to its etiology. Although studies over the last 30 years helped reduce the values, it is not very clear if the current air quality guidelines are adequately protective for COPD sufferers.
OBJECTIVE: This systematic review was to summarize the up-to-date literature on the impact of air pollution on the COPD sufferers.
METHODS: PubMed and Google Scholar were utilized to search for articles related to our study's focus. Search terms included "COPD exacerbation", "air pollution", "air quality guidelines", "air quality standards", "COPD morbidity and mortality", "chronic bronchitis", and "air pollution control" separately and in combination. We focused on articles from 1990 to 2015. We also used articles prior to 1990 if they contained relevant information. We focused on articles written in English or with an English abstract. We also used the articles in the reference lists of the identified articles.
RESULTS: Both short-term and long-term exposures to outdoor air pollution around the world are associated with the mortality and morbidity of COPD sufferers even at levels below the current air quality guidelines. Biomass cooking in low-income countries was clearly associated with COPD morbidity in adult nonsmoking females.
CONCLUSION: There is a need to continue to improve the air quality guidelines. A range of intervention measures could be selected at different levels based on countries' socioeconomic conditions to reduce the air pollution exposure and COPD burden.

PMID: 27143874 [PubMed - indexed for MEDLINE]

Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Wed, 01/11/2017 - 07:33
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Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Int J Legal Med. 2017 Jan 09;:

Authors: Pakstis AJ, Kang L, Liu L, Zhang Z, Jin T, Grigorenko EL, Wendt FR, Budowle B, Hadi S, Al Qahtani MS, Morling N, Mogensen HS, Themudo GE, Soundararajan U, Rajeevan H, Kidd JR, Kidd KK

Abstract
Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful.

PMID: 28070634 [PubMed - as supplied by publisher]

DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Wed, 01/11/2017 - 07:33
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DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Forensic Sci Int. 2016 Apr;261:148-53

Authors: Rahikainen AL, Palo JU, de Leeuw W, Budowle B, Sajantila A

Abstract
Blood samples preserved on FTA cards offer unique opportunities for genetic research. DNA recovered from these cards should be stable for long periods of time. However, it is not well established as how well the DNA stored on FTA card for substantial time periods meets the demands of forensic or genomic DNA analyses and especially so for from post-mortem (PM) samples in which the quality can vary upon initial collection. The aim of this study was to evaluate the time-dependent degradation on DNA quality and quantity extracted from up to 16 years old post-mortem bloodstained FTA cards. Four random FTA samples from eight time points spanning 1998 to 2013 (n=32) were collected and extracted in triplicate. The quantity and quality of the extracted DNA samples were determined with Quantifiler(®) Human Plus (HP) Quantification kit. Internal sample and sample-to-sample variation were evaluated by comparing recovered DNA yields. The DNA from the triplicate samplings were subsequently combined and normalized for further analysis. The practical effect of degradation on DNA quality was evaluated from normalized samples both with forensic and pharmacogenetic target markers. Our results suggest that (1) a PM change, e.g. blood clotting prior to sampling, affects the recovered DNA yield, creating both internal and sample-to-sample variation; (2) a negative correlation between the FTA card storage time and DNA quantity (r=-0.836 at the 0.01 level) was observed; (3) a positive correlation (r=0.738 at the level 0.01) was found between FTA card storage time and degradation levels. However, no inhibition was observed with the method used. The effect of degradation was manifested clearly with functional applications. Although complete STR-profiles were obtained for all samples, there was evidence of degradation manifested as decreased peak heights in the larger-sized amplicons. Lower amplification success was notable with the large 5.1 kb CYP2D6 gene fragment which strongly supports degradation of the stored samples. According to our results, DNA stored on FTA cards is rather stable over a long time period. DNA extracted from this storage medium can be used as human identification purposes as the method used is sufficiently sensitive and amplicon sizes tend to be <400 bp. However, DNA integrity was affected during storage. This effect should be taken into account depending on the intended application especially if high quality DNA and long PCR amplicons are required.

PMID: 26937857 [PubMed - indexed for MEDLINE]

A Brief Report Describing the Union of Medical Training and Agricultural Health.

Wed, 01/11/2017 - 07:33
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A Brief Report Describing the Union of Medical Training and Agricultural Health.

J Agromedicine. 2016;21(1):123-6

Authors: Levin JL, Bowling J, Wickman AJ, Harris M

Abstract
This brief report describes a mutually beneficial partnership forged to extend agricultural medicine training to physicians, nurses, veterinarians, public health workers, health care professionals, medical residents, and students. Agricultural Medicine: Occupational and Environmental Health for Rural Health Professionals originated at the University of Iowa, Iowa's Center for Agricultural Safety and Health, and the Great Plains Center for Agricultural Health. Through a National Institute for Occupational Safety and Health (NIOSH)-funded Training Project Grant, The University of Texas Health Northeast worked with the University of Iowa and regional experts to adapt the agricultural medicine content for the southwestern United States. Further partnerships were developed with the Southwest Center for Agricultural Health, Injury Prevention and Education, The University of North Texas Health Science Center College of Osteopathic Medicine, and the Texas Rural Health Association to extend the reach of this training to other important stakeholders. Each of the collaborators offered unique resources to the coordination of the agricultural medicine course. Likewise, each organization benefited from extending regionally relevant agricultural medicine training to current and future health care providers. The long-term goal for the partnership is to train a broad array of health care providers with the basics of anticipation, recognition, diagnosis, treatment, and the prevention of occupational and environmental illnesses and injuries within rural and agricultural communities, customized to the Southwest Region. This brief descriptive report highlights the process by which strategic partners collaborated to conduct a regional agricultural medicine course, such that other organizations interested in offering a similar training might gain insight to best practices from our experience.

PMID: 26479683 [PubMed - indexed for MEDLINE]

A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing.

Tue, 01/10/2017 - 10:35
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A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing.

PLoS One. 2017;12(1):e0169671

Authors: Bermudez JY, Webber HC, Brown B, Braun TA, Clark AF, Mao W

Abstract
The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain. Based on maximum IOP change in the perfused eye, the BTM cell strain was identified as a DEX-responder or non-responder strain. Three responder and three non-responder BTM cell strains were cultured, treated with 0.1% ethanol or 100nM DEX for 7 days. RNA and proteins were extracted for RNA sequencing (RNAseq), qPCR, and Western immunoblotting (WB), respectively. Data were analyzed using the human and bovine genome databases as well as Tophat2 software. Genes were grouped and compared using Student's t-test. We found that DEX induced fibronectin expression in responder BTM cells but not in non-responder cells using WB. RNAseq showed between 93 and 606 differentially expressed genes in different expression groups between responder and non-responder BTM cells. The data generated by RNAseq were validated using qPCR. Pathway analyses showed 35 pathways associated with differentially expressed genes. These genes and pathways may play important roles in GC-induced OHT and will help us to better understand differential ocular responsiveness to GCs.

PMID: 28068412 [PubMed - in process]

mGlu5 negative allosteric modulators: a patent review (2013-2016).

Tue, 01/10/2017 - 10:35
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mGlu5 negative allosteric modulators: a patent review (2013-2016).

Expert Opin Ther Pat. 2017 Jan 08;:

Authors: Emmitte KA

Abstract
INTRODUCTION: The pursuit of small molecule mGlu5 NAMs as treatments for a variety of psychiatric and neurodegenerative disorders has developed into a mature field. In addition to extensive preclinical studies, multiple compounds have advanced into clinical trials with the most advanced studies occurring in patients with FXS, PD-LID, and MDD. Areas covered: This review begins with an update of the clinical activity with mGlu5 NAMs, and then moves into a summary of patent applications filed since 2013. The summaries are organized into three separate sections: (1) inventions centered on improvements to existing clinical compounds; (2) new small molecules that maintain the prototypical disubstituted alkyne chemotype found in many mGlu5 NAM compounds; and (3) new small molecules that are not from a disubstituted alkyne chemotype. Expert Opinion: It is a critical moment for mGlu5 NAM research as recent reports from clinical trials have included some significant disappointments that have blunted prior optimism. Still, research in this area remains active, and recent years have added several more attractive small molecules to this field. There is now an arsenal of diverse chemotypes available to continue to probe this target in the hopes that a drug may yet emerge.

PMID: 28067079 [PubMed - as supplied by publisher]

Social support for physical activity: Comparison of family, friends, and coworkers.

Sat, 01/07/2017 - 10:37

Social support for physical activity: Comparison of family, friends, and coworkers.

Work. 2016;55(4):893-899

Authors: Sarkar S, Taylor WC, Lai D, Shegog R, Paxton RJ

Abstract
BACKGROUND: Few studies have examined the associations among family, friend, and coworker social support for physical activity. It is important to know the sources of social support that facilitate and promote physical activity among fulltime working adults.
OBJECTIVE: We analyzed the associations among family, friend, and coworker social support for physical activity and moderate-to-vigorous physical activity among participants in a worksite study.
METHODS: This study was a cross-sectional analysis of baseline data from 144 participants from four worksites in a large, southwestern city in the United States. The intervention for the worksite study was Booster Breaks (a physical activity routine of 15 minutes) practiced daily to break-up prolonged sitting time. Descriptive statistics and multiple linear regressions were conducted using SPSS version 20.
RESULTS: Age was inversely associated (p = 0.001), and social support from friends (p = 0.04) and coworkers (p = 0.003) were positively associated with physical activity in the unadjusted model. After controlling for all the covariates (age, sex, marital status, BMI, education, and income) in the model, only coworker social support was positively (p = 0.027) associated with physical activity among participants in the workplace study.
CONCLUSIONS: Coworker social support is an important correlate of physical activity and should be incorporated in workplace health promotion programs.

PMID: 28059824 [PubMed - in process]

Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation.

Sat, 01/07/2017 - 10:37
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Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation.

Physiol Rep. 2017 Jan;5(1):

Authors: Burnley B, P Jones H

Abstract
The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin-releasing hormone (CRH) is a neuropeptide released from the hypothalamic-pituitary-adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks.

PMID: 28057851 [PubMed - in process]

Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study.

Thu, 01/05/2017 - 07:38
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Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study.

Circulation. 2016 Jun 14;133(24):2423-33

Authors: Chang CH, Chen HC, Caffrey JL, Hsu J, Lin JW, Lai MS, Chen YS

Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides circulatory and respiratory support for patients with severe acute cardiopulmonary failure. The objective of this study was to examine the survival outcomes for patients who received ECMO.
METHODS AND RESULTS: Adult patients who received ECMO from September 1, 2002, to December 31, 2012, were identified from the Taiwan National Health Insurance Database associated with coronary artery bypass graft surgery, myocardial infarction/cardiogenic shock, injury, and infection/septic shock. A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates with the myocardial infarction/cardiogenic shock group used as the reference. The mean±SD age of the 4227-patient cohort was 57±17 years, and 72% were male. The overall mortalities were 59.8% and 76.5% at 1 month and 1 year. Survival statistics deteriorated sharply when ECMO was required for >3 days. Acute (30-day) survival was more favorable in the infection/septic shock (n=1076; hazard ratio, 0.61; 95% confidence interval, 0.55-0.67), coronary artery bypass graft surgery (n=1077; hazard ratio, 0.68; 95% confidence interval, 0.61-0.75), and injury (n=369, hazard ratio, 0.82; 95% confidence interval, 0.70-0.95) groups. The extended survival rapidly approached an asymptote near 20% for the infection/septic shock, myocardial infarction/cardiogenic shock (n=1705), and coronary artery bypass graft surgery groups. The pattern of survival for the injury group was somewhat better, exceeding 30% at year-end.
CONCLUSIONS: Regardless of initial pathology, patients requiring ECMO were critically ill with similar guarded prognoses. Those in the trauma group had somewhat better outcomes. Determining the efficacy and cost-effectiveness of ECMO should be a critical future goal.

PMID: 27199466 [PubMed - indexed for MEDLINE]

A Post-Hurricane Katrina Examination of Substance Abuse Treatment Discharges with Co-Occurring Psychiatric and Substance Use Disorders.

Wed, 01/04/2017 - 07:33

A Post-Hurricane Katrina Examination of Substance Abuse Treatment Discharges with Co-Occurring Psychiatric and Substance Use Disorders.

J Dual Diagn. 2017 Jan 03;:0

Authors: Shuler M, Suzuki S, Podesta A, Qualls-Hampton R, Wallington SF

Abstract
OBJECTIVES: There is increasing literature supporting the adverse effects of disasters on substance use and psychiatric disorders. The co-occurrence of psychiatric disorders with substance use intensifies the challenge of treatment delivery. Thus the aim of this study was to examine the prevalence of substance use, treatment characteristics, and demographics of discharges from substance abuse treatment in New Orleans, post-Hurricane Katrina. Trends associated with discharges that have a co-occurring psychiatric and substance use disorder (COD) were also assessed. The secondary aim of this study was to examine the association of successful substance abuse treatment completion among those with a COD post-Hurricane Katrina.
METHODS: Substance abuse treatment discharge data (N = 16,507) from New Orleans, Louisiana, for years 2006 through 2011 was obtained from the Treatment Episode Data Set -Discharge (TEDS-D). Multiple logistic regression was employed to examine the association of discharges with a COD and completion of substance abuse treatment. Demographic, psychiatric, and treatment characteristics of discharges in 2006 were compared to characteristics in 2011. Trends of characteristics were also assessed through the study period.
RESULTS: Roughly a third (35.2%) of all discharges in New Orleans from 2006 to 2011 had a COD. After controlling for race, employment, treatment service setting at discharge, primary substance problem, and the discharge's principal source of referral, discharges with a COD were 29% less likely to complete treatment as compared to those with no COD (AOR: 0.71, 95% CI: [0.56, 0.90], p = 0.004). Treatment completion among discharges with a COD has significantly declined from 36.8% in 2006 to 18.7% in 2011 (p < .0001). Notable significant trends in homelessness, criminality, and heroin use were identified among discharges with a COD.
CONCLUSIONS: Substance abuse treatment undergoes various changes in the event of a natural disaster. These changes may increase challenges for successful treatment completion for vulnerable populations such as those with a COD. Results of this study demonstrate that discharges with a COD are less likely to complete treatment as compared to those with no COD disorder. Unmet treatment needs may also increase odds of criminalization and homelessness.

PMID: 28045601 [PubMed - as supplied by publisher]

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Wed, 01/04/2017 - 07:33
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N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Exp Physiol. 2016 Mar;101(3):387-96

Authors: Jouett NP, Moralez G, White DW, Eubank WL, Chen S, Tian J, Smith ML, Zimmerman MC, Raven PB

Abstract
NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

PMID: 27027616 [PubMed - indexed for MEDLINE]

Association Between Healthcare Provider Type and Intent to Breastfeed Among Expectant Mothers.

Wed, 01/04/2017 - 07:33
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Association Between Healthcare Provider Type and Intent to Breastfeed Among Expectant Mothers.

Matern Child Health J. 2016 May;20(5):993-1000

Authors: Balyakina E, Fulda KG, Franks SF, Cardarelli KM, Hinkle K

Abstract
BACKGROUND: The primary purpose of this study was to determine the association between type of healthcare provider delivering prenatal care and intent to exclusively breastfeed.
METHODS: A self-report survey was administered to 455 expectant mothers. Logistic regression was performed to determine the association between prenatal care provider type [obstetrician; other primary care physician (family doctor/general practitioner/internist/or other physician); midwife/nurse midwife; more than one provider; and other] with intent to breastfeed (exclusive/non-exclusive).
RESULTS: Having a midwife/nurse midwife as a prenatal care provider was associated with intent to breastfeed compared to having an obstetrician (OR 2.544, 95 % CI 1.385-4.675). There was no difference in intent between women with another primary care physician and an obstetrician. Women with another type of health care provider, no prenatal care from a health professional, or no knowledge of who is providing prenatal care were less likely to intend to breastfeed (OR 0.228, CI 0.068-0.766) as compared to those with an obstetrician.
DISCUSSION/CONCLUSIONS: Provider type is associated with intent to breastfeed among pregnant women. Women's intent to breastfeed is an important predictor of breastfeeding initiation, continuation, and duration that may be assessed by healthcare providers during the prenatal period. A consideration of what features of provider care are associated with improved breastfeeding outcomes and characteristics of women seeking prenatal care with midwives may serve to formulate future prenatal care policies and education during prenatal care visits.

PMID: 26699790 [PubMed - indexed for MEDLINE]

Emerging therapeutics for targeting Akt in cancer.

Fri, 12/30/2016 - 07:33
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Emerging therapeutics for targeting Akt in cancer.

Front Biosci (Landmark Ed). 2016 Jan 01;21:757-68

Authors: Gdowski A, Panchoo M, Treuren TV, Basu A

Abstract
The ultimate goal of cancer therapeutic research is to develop effective, targeted therapeutics that exploit the vulnerabilities of cancer cells. The three isoforms of Akt, also known as protein kinase B (PKB), are important mediators of various pathways that transmit mitogenic signals from the cell's exterior to the effector proteins of the cell's interior. Due to Akt\\\\\\\'s importance in cell functions such as growth, proliferation and cell survival, many cancer cells rely on this pathway to aid in their survival. This dependence can lead to chemoresistance and selection of more adapted populations of cancer cells. Thus, it is important to understand the functional significance of isoform specificity and its relation to chemoresistance. In this review, we have summarized recent studies on Akt isoform specific regulation as well as each isoform's role in chemoresistance, emphasizing their potential as targets for cancer therapy. We have also condensed ongoing clinical studies involving various types of Akt inhibitors while highlighting the type of study, rationale and co-therapies involved in identifying Akt isoforms as promising therapeutic targets.

PMID: 26709804 [PubMed - indexed for MEDLINE]

Tissue loss with subcutaneous immunotherapy--Nicolau syndrome.

Fri, 12/30/2016 - 07:33
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Tissue loss with subcutaneous immunotherapy--Nicolau syndrome.

J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):154-5

Authors: Tierce ML, Schultz SM, Lanier BQ

PMID: 26362220 [PubMed - indexed for MEDLINE]

Targeting specificity protein 1 transcription factor and survivin using tolfenamic acid for inhibiting Ewing sarcoma cell growth.

Wed, 12/28/2016 - 07:42
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Targeting specificity protein 1 transcription factor and survivin using tolfenamic acid for inhibiting Ewing sarcoma cell growth.

Invest New Drugs. 2016 Dec 26;:

Authors: Shelake S, Sankpal UT, Paul Bowman W, Wise M, Ray A, Basha R

Abstract
Transcription factor Specificity protein 1 (Sp1) and its downstream target survivin (inhibitor of apoptosis protein), play major roles in the pathogenesis of various cancers. Ewing Sarcoma (ES) is a common soft tissue/bone tumor in adolescent and young adults. Overexpression of survivin is also linked to the aggressiveness and poor prognosis of ES. Small molecule Tolfenamic acid (TA) inhibits Sp1 and survivin in cancer cells. In this investigation, we demonstrate a strategy to target Sp1 and survivin using TA and positive control Mithramycin A (Mit) to inhibit ES cell growth. Knock down of Sp1 using small interfering RNA (siRNA) resulted in significant (p < 0.05) inhibition of CHLA-9 and TC-32 cell growth as assessed by CellTiter-Glo assay kit. TA or Mit treatment caused dose/time-dependent inhibition of cell viability, and this inhibition was correlated with a decrease in Sp1 and survivin protein levels in ES cells. Quantitative PCR results showed that Mit treatment decreased the mRNA expression of both survivin and Sp1, whereas TA diminished only survivin but not Sp1. Proteasome inhibitor restored TA-induced inhibition of Sp1 protein expression suggesting that TA might cause proteasome-dependent degradation. Gel shift assay using ES cell nuclear extract and biotinylated Sp1 consensus oligonucleotides confirmed that both TA and Mit decreased DNA-binding activity of Sp1. These results demonstrate that both Mit and TA reduce expression of Sp1 and survivin, disrupt Sp1 DNA-binding and inhibit ES cell proliferation. This investigation suggests that targeting Sp1 and survivin could be an effective strategy for inhibiting ES cell growth.

PMID: 28025760 [PubMed - as supplied by publisher]

Analogs of microgravity: head-down tilt and water immersion.

Wed, 12/28/2016 - 07:42
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Analogs of microgravity: head-down tilt and water immersion.

J Appl Physiol (1985). 2016 Apr 15;120(8):904-14

Authors: Watenpaugh DE

Abstract
This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. DI is less common but well accepted for long-duration studies. Very few studies exist that attempt to validate a specific simulation mode against actual microgravity. Many fundamental physical, and thus physiological, differences exist between microgravity and our methods to simulate it, and between the different methods. Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability.

PMID: 26869710 [PubMed - indexed for MEDLINE]

Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging.

Tue, 12/27/2016 - 07:32
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Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging.

Front Pharmacol. 2016;7:466

Authors: Mooberry LK, Sabnis NA, Panchoo M, Nagarajan B, Lacko AG

Abstract
Malignant tumors display remarkable heterogeneity to the extent that even at the same tissue site different types of cells with varying genetic background may be found. In contrast, a relatively consistent marker the scavenger receptor type B1 (SR-B1) has been found to be consistently overexpressed by most tumor cells. Scavenger Receptor Class B Type I (SR-BI) is a high density lipoprotein (HDL) receptor that facilitates the uptake of cholesterol esters from circulating lipoproteins. Additional findings suggest a critical role for SR-BI in cholesterol metabolism, signaling, motility, and proliferation of cancer cells and thus a potential major impact in carcinogenesis and metastasis. Recent findings indicate that the level of SR-BI expression correlate with aggressiveness and poor survival in breast and prostate cancer. Moreover, genomic data show that depending on the type of cancer, high or low SR-BI expression may promote poor survival. This review discusses the importance of SR-BI as a diagnostic as well as prognostic indicator of cancer to help elucidate the contributions of this protein to cancer development, progression, and survival. In addition, the SR-B1 receptor has been shown to serve as a potential gateway for the delivery of therapeutic agents when reconstituted high density lipoprotein nanoparticles are used for their transport to cancer cells and tumors. Opportunities for the development of new technologies, particularly in the areas of cancer therapy and tumor imaging are discussed.

PMID: 28018216 [PubMed]

The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Tue, 12/27/2016 - 07:32
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The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Disabil Health J. 2016 Apr;9(2):289-97

Authors: Cannell MB, Bouldin ED, Teigen K, Akhtar WZ, Andresen EM

Abstract
BACKGROUND: Research has demonstrated a clear association between cognitive decline and non-cognitive disability; however, all of these studies focus on disability as a correlate or result of some level of cognitive impairment or dysfunction. The relationship between disability and cognition is likely a complex one, that is currently incompletely described in the literature.
OBJECTIVES: Our objective was to estimate the prevalence of long-term, non-cognitive disability using a population-representative sample of adults aged 18 and older, and then estimate the association between long-term, non-cognitive disability and self-reported worsening memory.
METHODS: Using the 2009 Florida Behavioral Risk Factor Surveillance System (BRFSS), we measured the relationship between non-cognitive disability and worsening memory using multivariable logistic regression analysis weighted to account for the complex sampling design of the BRFSS. We also estimated the adjusted odds of worsening memory by disability severity, classified according to the types of assistance needed.
RESULTS: Approximately 18% (95% confidence interval = (16%, 19%)) of Floridians were living with a long-term, non-cognitive disability in 2009. Among adults with no disability during or prior to the last year, only 5% reported worsening memory. The proportion of Floridians reporting worsening memory increases with increasing severity of disability-related limitations. In a multivariable logistic regression model, odds of worsening memory increased significantly with severity of disability-related limitations.
CONCLUSIONS: These results highlight the association between non-cognitive disability and subsequent increased odds of worsening memory, independent of several other known risk factors, and a dose-response association with disability-related limitations.

PMID: 26493638 [PubMed - indexed for MEDLINE]

Compact NMR relaxometry of human blood and blood components.

Fri, 12/23/2016 - 16:46
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Compact NMR relaxometry of human blood and blood components.

Trends Analyt Chem. 2016 Nov;83(A):53-64

Authors: Cistola DP, Robinson MD

Abstract
Nuclear magnetic resonance relaxometry is a uniquely practical and versatile implementation of NMR technology. Because it does not depend on chemical shift resolution, it can be performed using low-field compact instruments deployed in atypical settings. Early relaxometry studies of human blood were focused on developing a diagnostic test for cancer. Those efforts were misplaced, as the measurements were not specific to cancer. However, important lessons were learned about the factors that drive the water longitudinal (T1) and transverse (T2) relaxation times. One key factor is the overall distribution of proteins and lipoproteins. Plasma water T2 can detect shifts in the blood proteome resulting from inflammation, insulin resistance and dyslipidemia. In whole blood, T2 is sensitive to hemoglobin content and oxygenation, although the latter can be suppressed by manipulating the static and applied magnetic fields. Current applications of compact NMR relaxometry include blood tests for candidiasis, hemostasis, malaria and insulin resistance.

PMID: 28003711 [PubMed]

The Role of Angiotensin Converting Enzyme 1 within the median preoptic nucleus following chronic intermittent hypoxia.

Fri, 12/23/2016 - 16:46
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The Role of Angiotensin Converting Enzyme 1 within the median preoptic nucleus following chronic intermittent hypoxia.

Am J Physiol Regul Integr Comp Physiol. 2016 Dec 21;:ajpregu.00472.2016

Authors: Faulk K, Shell B, Nedungadi TP, Cunningham JT

Abstract
Sustained hypertension is an important consequence of obstructive sleep apnea. An animal model of the hypoxemia associated with sleep apnea, chronic intermittent hypoxia (CIH), produces increased sympathetic nerve activity (SNA) and sustained increases in blood pressure. Many mechanisms have been implicated in the hypertension associated with CIH including the role of ΔFosB within the median preoptic nucleus (MnPO). Also, the renin-angiotensin system (RAS) has been associated with CIH hypertension. We conducted experiments in order to determine the possible association of FosB/ΔFosB with a RAS component, angiotensin converting enzyme 1 (ACE1), within the MnPO following 7 days of CIH. Retrograde tract tracing from the paraventricular nucleus (PVN), a downstream region of the MnPO, was utilized in order to establish a potential pathway for FosB/ΔFosB activation of MnPO ACE1 neurons. After CIH, ACE1 cells with FosB/ΔFosB expression increased colocalization with a retrograde tracer that was injected unilaterally within the PVN. Also, Western blot examination showed ACE1 protein expression increasing within the MnPO following CIH. Chromatin immunoprecipitation (ChIP) assays demonstrated an increase in FosB/ΔFosB association with the ACE1 gene within the MnPO following CIH. FosB/ΔFosB may transcriptionally target ACE1 within the MnPO following CIH in order to affect the downstream PVN region, which may influence SNA and blood pressure.

PMID: 28003214 [PubMed - as supplied by publisher]

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