Recent Research Articles from UNTHSC

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Introduction to the suicide prevention research prioritization task force special supplement: the topic experts.

Wed, 08/27/2014 - 4:05am
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Introduction to the suicide prevention research prioritization task force special supplement: the topic experts.

Am J Prev Med. 2014 Sep;47(3 Suppl 2):S102-5

Authors: Pearson JL, Claassen CA, Booth CL, Research Prioritization Task Force of the National Action Alliance for Suicide Prevention

PMID: 25145726 [PubMed - in process]

Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.

Tue, 08/26/2014 - 4:06am
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Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.

Neuropsychopharmacology. 2014 Jan;39(2):380-8

Authors: Paris JJ, Carey AN, Shay CF, Gomes SM, He JJ, McLaughlin JP

Abstract
As a major neuropathogenic factor associated with human immunodeficiency virus (HIV) infection, HIV-1 Tat protein is known to synergize with psychostimulant drugs of abuse to cause neurotoxicity and exacerbate the progression of central nervous system pathology. However, the functional consequences of the interaction between HIV-1 Tat and abused drugs on behavior are little known. We tested the hypothesis that HIV-1 Tat expression in brain would modulate the psychostimulant effects of cocaine. Using the GT-tg bigenic mouse model, where brain-selective Tat expression is induced by activation of a doxycycline (Dox) promotor, we tested the effects of Tat on cocaine (10 mg/kg, s.c.) induced locomotion and conditioned place preference (CPP). Compared with uninduced littermates or C57BL/6J controls, cocaine-induced hyperlocomotion was sustained for a significantly longer duration among Tat-induced mice. Moreover, although all groups displayed similar saline-CPP, Tat-induced GT-tg mice demonstrated a three-fold increase in cocaine-CPP over the response of either uninduced littermates or Dox-treated C57BL/6J control mice. Induction of Tat also increased the magnitude of a previously established cocaine-CPP after an additional cycle of cocaine place-conditioning. Despite Tat-induced potentiation, extinction of place preference occurred within 21 days, commensurate with cocaine-extinction among saline-treated littermates and C57BL/6J controls. Re-exposure to cocaine produced reinstatement of an equivalent place preference in Tat-induced GT-tg or C57BL/6J mice; however, induction of Tat protein after the extinction of CPP also produced reinstatement without additional exposure to cocaine. Together, these data suggest that central HIV-1 Tat expression can potentiate the psychostimulant behavioral effects of cocaine in mice.

PMID: 23945478 [PubMed - indexed for MEDLINE]

Multiple biomarker panels for early detection of breast cancer in peripheral blood.

Fri, 08/22/2014 - 4:05am
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Multiple biomarker panels for early detection of breast cancer in peripheral blood.

Biomed Res Int. 2013;2013:781618

Authors: Zhang F, Deng Y, Drabier R

Abstract
Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

PMID: 24371830 [PubMed - indexed for MEDLINE]

mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia.

Fri, 08/22/2014 - 4:05am
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mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia.

J Immunol. 2014 Jun 15;192(12):6009-19

Authors: Xie L, Sun F, Wang J, Mao X, Xie L, Yang SH, Su DM, Simpkins JW, Greenberg DA, Jin K

Abstract
Signaling by the mammalian target of rapamycin (mTOR) plays an important role in the modulation of both innate and adaptive immune responses. However, the role and underlying mechanism of mTOR signaling in poststroke neuroinflammation are largely unexplored. In this study, we injected rapamycin, a mTOR inhibitor, by the intracerebroventricular route 6 h after focal ischemic stroke in rats. We found that rapamycin significantly reduced lesion volume and improved behavioral deficits. Notably, infiltration of γδ T cells and granulocytes, which are detrimental to the ischemic brain, was profoundly reduced after rapamycin treatment, as was the production of proinflammatory cytokines and chemokines by macrophages and microglia. Rapamycin treatment prevented brain macrophage polarization toward the M1 type. In addition, we also found that rapamycin significantly enhanced anti-inflammation activity of regulatory T cells (Tregs), which decreased production of proinflammatory cytokines and chemokines by macrophages and microglia. Depletion of Tregs partially elevated macrophage/microglia-induced neuroinflammation after stroke. Our data suggest that rapamycin can attenuate secondary injury and motor deficits after focal ischemia by enhancing the anti-inflammation activity of Tregs to restrain poststroke neuroinflammation.

PMID: 24829408 [PubMed - indexed for MEDLINE]

A useful mouse model of glucocorticoid-induced ocular hypertension.

Tue, 08/19/2014 - 4:06am
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A useful mouse model of glucocorticoid-induced ocular hypertension.

Invest Ophthalmol Vis Sci. 2014;55(8):4934

Authors: Clark AF

PMID: 25108005 [PubMed - in process]

Neuronal injury from cardiac arrest: aging years in minutes.

Tue, 08/19/2014 - 4:06am
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Neuronal injury from cardiac arrest: aging years in minutes.

Age (Dordr). 2014 Aug;36(4):9680

Authors: Cherry BH, Sumien N, Mallet RT

Abstract
Cardiac arrest is a leading cause of death and permanent disability. Most victims succumb to the oxidative and inflammatory damage sustained during cardiac arrest/resuscitation, but even survivors typically battle long-term neurocognitive impairment. Although extensive research has delineated the complex mechanisms that culminate in neuronal damage and death, no effective treatments have been developed to interrupt these mechanisms. Of importance, many of these injury cascades are also active in the aging brain, where neurons and other cells are under persistent oxidative and inflammatory stress which eventually damages or kills the cells. In light of these similarities, it is reasonable to propose that the brain essentially ages the equivalent of several years within the few minutes taken to resuscitate a patient from cardiac arrest. Accordingly, cardiac arrest-resuscitation models may afford an opportunity to study the deleterious mechanisms underlying the aging process, on an accelerated time course. The aging and resuscitation fields both stand to gain pivotal insights from one another regarding the mechanisms of injury sustained during resuscitation from cardiac arrest and during aging. This synergism between the two fields could be harnessed to foster development of treatments to not only save lives but also to enhance the quality of life for the elderly.

PMID: 25104136 [PubMed - as supplied by publisher]

Capsule Commentary on Albrecht et al., Hospital Discharge Instructions: Comprehension and Compliance Among Older Adults.

Tue, 08/19/2014 - 4:06am
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Capsule Commentary on Albrecht et al., Hospital Discharge Instructions: Comprehension and Compliance Among Older Adults.

J Gen Intern Med. 2014 Aug 8;

Authors: Tak HJ

PMID: 25103123 [PubMed - as supplied by publisher]

The future of blood-based biomarkers for Alzheimer's disease.

Tue, 08/19/2014 - 4:06am
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The future of blood-based biomarkers for Alzheimer's disease.

Alzheimers Dement. 2014 Jan;10(1):115-31

Authors: Henriksen K, O'Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lönneborg A, Wyss-Coray T, Soares H, Bazenet C, Sjögren M, Hu W, Lovestone S, Karsdal MA, Weiner MW, Blood-Based Biomarker Interest Group

Abstract
Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field.

PMID: 23850333 [PubMed - indexed for MEDLINE]

Validation of high throughput sequencing and microbial forensics applications.

Tue, 08/12/2014 - 4:05am

Validation of high throughput sequencing and microbial forensics applications.

Investig Genet. 2014;5:9

Authors: Budowle B, Connell ND, Bielecka-Oder A, Colwell RR, Corbett CR, Fletcher J, Forsman M, Kadavy DR, Markotic A, Morse SA, Murch RS, Sajantila A, Schmedes SE, Ternus KL, Turner SD, Minot S

Abstract
High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security.

PMID: 25101166 [PubMed]

Assessing long-term health and cost outcomes of patient-centered medical homes serving adults with poor diabetes control.

Fri, 08/08/2014 - 4:05am
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Assessing long-term health and cost outcomes of patient-centered medical homes serving adults with poor diabetes control.

J Prim Care Community Health. 2013 Oct;4(4):281-5

Authors: Pagán JA, Carlson EK

Abstract
The patient-centered medical home (PCMH) is an integrated primary care delivery model particularly suited for patients with poor diabetes control. Although PCMH models targeting adults with diabetes have shown some early success, little is known about the long-term benefits of medical homes in terms of health and cost outcomes. The performance of a PCMH model in adults with poor diabetes control was assessed using simulated controlled trial data obtained from the Archimedes model of disease progression and health care utilization. Using the Cardio-Metabolic Risk data set, we compared health and cost outcomes over a 20-year period between adults with poor diabetes control (HbA1c >9%) receiving standard care and these same adults receiving care under a PCMH model with a 49% HbA1c intervention improvement rate at a per-beneficiary per-month care management cost of $20 per month. The results suggest that the PCMH model has the potential to not only reduce the proportion of the population with bilateral blindness, foot amputations, and myocardial infarctions-and the mortality rate-but it can also do so in a cost-effective manner ($7898 per quality-adjusted life year). The PCMH model is cost saving for the population 50 to 64 years old and it is particularly cost-effective for men ($883 per quality-adjusted life year). Moreover, these effects are relatively large for adults 30 to 49 years old (lower bilateral blindness and death rates), women (lower foot amputation and death rates), and men (lower bilateral blindness and myocardial infarction rates). The PCMH model has potential long-term benefits to both patients with poor diabetes control as well as health care systems and providers willing to invest in this health care delivery approach.

PMID: 23799676 [PubMed - indexed for MEDLINE]

Influencing referral of adolescents and young adults with cancer to sites with higher rates of trial enrollment.

Thu, 08/07/2014 - 4:04am
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Influencing referral of adolescents and young adults with cancer to sites with higher rates of trial enrollment.

Pediatrics. 2014 Jun;133 Suppl 3:S104-8

Authors: Albritton KH, Coccia P

Abstract
Adolescents and young adults (AYAs) have lower rates of clinical trial enrollment than younger or older patients with cancer. Multiple approaches to change policy and practice need to be used to improve this statistic. This article examines the option of increasing referral to 3 types of centers that are known to have relatively higher rates of enrollment of AYAs: pediatric cancer centers, AYA oncology programs, and National Cancer Institute-designated cancer centers. There are reasonable challenges to changing referral patterns, and more research, as well as education of those diagnosing AYAs, is required.

PMID: 24918207 [PubMed - indexed for MEDLINE]

The effect of in-office waiting time on physician visit frequency among working-age adults.

Wed, 08/06/2014 - 4:05am
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The effect of in-office waiting time on physician visit frequency among working-age adults.

Soc Sci Med. 2014 Jul 27;118C:43-51

Authors: Tak HJ, Hougham GW, Ruhnke A, Ruhnke GW

Abstract
Disparities in unmet health care demand resulting from socioeconomic, racial, and financial factors have received a great deal of attention in the United States. However, out-of-pocket costs alone do not fully reflect the total opportunity cost that patients must consider as they seek medical attention. While there is an extensive literature on the price elasticity of demand for health care, empirical evidence regarding the effect of waiting time on utilization is sparse. Using the nationally representative 2003 Community Tracking Study Household Survey, the most recent iteration containing respondents' physician office visit frequency and estimated in-office waiting time in the United States (N = 23,484), we investigated the association between waiting time and calculated time cost with the number of physician visits among a sample of working-age adults. To avoid the bias that literature suggests would result from excluding respondents with zero physician visits, we imputed waiting time for the essential inclusion of such individuals. On average, respondents visited physician offices 3.55 times, during which time they waited 28.7 min. The estimates from a negative binomial model indicated that a doubling of waiting time was associated with a 7.7 percent decrease (p-value < 0.001) in physician visit frequency. For women and unemployed respondents, who visited physicians more frequently, the decrease was even larger, suggesting a stronger response to greater waiting times. We believe this finding reflects the discretionary nature of incremental visits in these groups, and a consequent lower perceived marginal benefit of additional visits. The results suggest that in-office waiting time may have a substantial influence on patients' propensity to seek medical attention. Although there is a belief that expansions in health insurance coverage increase health care utilization by reducing financial barriers to access, our results suggest that unintended consequences may arise if in-office waiting time increases.

PMID: 25089963 [PubMed - as supplied by publisher]

An evaluation of the RapidHIT(®) system for reliably genotyping reference samples.

Wed, 08/06/2014 - 4:05am
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An evaluation of the RapidHIT(®) system for reliably genotyping reference samples.

Forensic Sci Int Genet. 2014 Jul 18;13C:104-111

Authors: LaRue BL, Moore A, King JL, Marshall PL, Budowle B

Abstract
Short tandem repeat (STR) typing is used routinely for associating or excluding individuals with biological evidence left at a crime scene. Improvements have been made to reduce the turnaround time and labor involved with profile generation, but there is still some lag time between sample collection and interpretation of results. The RapidHIT(®) (IntegenX; Pleasanton, CA, USA) system is an automated instrument that is configured to perform DNA extraction, bead-based DNA normalization, amplification, electrophoresis of PCR amplicons, and data analysis of five reference swabs simultaneously. The RapidHIT system provided reliable STR profiles from reference buccal swabs in approximately 90min with nominal "hands-on" sample loading time with no evidence of contamination between samples. The overall success rate of typing buccal swabs was comparable to standard typing systems. In the event of a failed run due to instrument failure, the swab can be removed from the cartridge and reanalyzed in the RapidHIT system or with standard STR genotyping workflows.

PMID: 25086874 [PubMed - as supplied by publisher]

Resonance energy transfer between fluorescent BSA protected Au nanoclusters and organic fluorophores.

Wed, 08/06/2014 - 4:05am
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Resonance energy transfer between fluorescent BSA protected Au nanoclusters and organic fluorophores.

Nanoscale. 2014 Jan 7;6(1):385-91

Authors: Raut S, Rich R, Fudala R, Butler S, Kokate R, Gryczynski Z, Luchowski R, Gryczynski I

Abstract
Bovine serum albumin (BSA) protected nanoclusters (Au and Ag) represent a group of nanomaterials that holds great promise in biophysical applications due to their unique fluorescence properties and lack of toxicity. These metal nanoclusters have utility in a variety of disciplines including catalysis, biosensing, photonics, imaging and molecular electronics. However, they suffer from several disadvantages such as low fluorescence quantum efficiency (typically near 6%) and broad emission spectrum (540 nm to 800 nm). We describe an approach to enhance the apparent brightness of BSA Au clusters by linking them with a high extinction donor organic dye pacific blue (PB). In this conjugate PB acts as a donor to BSA Au clusters and enhances its brightness by resonance energy transfer (RET). We found that the emission of BSA Au clusters can be enhanced by a magnitude of two-fold by resonance energy transfer (RET) from the high extinction donor PB, and BSA Au clusters can act as an acceptor to nanosecond lifetime organic dyes. By pumping the BSA Au clusters using a high extinction donor, one can increase the effective brightness of less bright fluorophores like BSA Au clusters. Moreover, we prepared another conjugate of BSA Au clusters with the near infrared (NIR) dye Dylight 750 (Dy750), where BSA Au clusters act as a donor to Dy750. We observed that BSA Au clusters can function as a donor, showing 46% transfer efficiency to the NIR dye Dy750 with a long lifetime component in the acceptor decay through RET. Such RET-based probes can be used to prevent the problems of a broad emission spectrum associated with the BSA Au clusters. Moreover, transferring energy from BSA Au clusters to Dy750 will result in a RET probe with a narrow emission spectrum and long lifetime component which can be utilized in imaging applications.

PMID: 24201559 [PubMed - indexed for MEDLINE]

Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.

Tue, 08/05/2014 - 4:05am
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Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.

J Biomater Appl. 2014 Aug 1;

Authors: Aghyarian S, Rodriguez LC, Chari J, Bentley E, Kosmopoulos V, Lieberman IH, Rodrigues DC

Abstract
Calcium phosphate fillers have been shown to increase cement osteoconductivity, but have caused drawbacks in cement properties. Hydroxyapatite and Brushite were introduced in an acrylic two-solution cement at varying concentrations. Novel composite bone cements were developed and characterized using rheology, injectability, and mechanical tests. It was hypothesized that the ample swelling time allowed by the premixed two-solution cement would enable thorough dispersion of the additives in the solutions, resulting in no detrimental effects after polymerization. The addition of Hydroxyapatite and Brushite both caused an increase in cement viscosity; however, these cements exhibited high shear-thinning, which facilitated injection. In gel point studies, the composite cements showed no detectable change in gel point time compared to an all-acrylic control cement. Hydroxyapatite and Brushite composite cements were observed to have high mechanical strengths even at high loads of calcium phosphate fillers. These cements showed an average compressive strength of 85 MPa and flexural strength of 65 MPa. A calcium phosphate-containing cement exhibiting a combination of high viscosity, pseudoplasticity and high mechanical strength can provide the essential bioactivity factor for osseointegration without sacrificing load-bearing capability.

PMID: 25085810 [PubMed - as supplied by publisher]

Erratum to: Pressure cycling technology (PCT) reduces effects of inhibitors of the PCR.

Sun, 08/03/2014 - 4:05am
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Erratum to: Pressure cycling technology (PCT) reduces effects of inhibitors of the PCR.

Int J Legal Med. 2014 Aug 1;

Authors: Marshall PL, King JL, Lawrence NP, Lazarev A, Gross VS, Budowle B

PMID: 25082499 [PubMed - as supplied by publisher]

Kinetic comparison of older men and women during walk-to-stair descent transition.

Sun, 08/03/2014 - 4:05am
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Kinetic comparison of older men and women during walk-to-stair descent transition.

Gait Posture. 2014 Jul 15;

Authors: Singhal K, Kim J, Casebolt J, Lee S, Han KH, Kwon YH

Abstract
Stair walking is one of the most challenging tasks for older adults, with women reporting higher incidence of falls. The purpose of this study was to investigate the gender differences in kinetics during stair descent transition. Twenty-eight participants (12 male and 16 female; 68.5 and 69.0 years of mean age, respectively) performed stair descent from level walking in a step-over-step manner at a self-selected speed over a custom-made three-step staircase with embedded force plates. Kinematic and force data were combined using inverse dynamics to generate kinetic data for gender comparison. The top and the first step on the staircase were chosen for analysis. Women showed a higher trail leg peak hip abductor moment (-1.0Nm/kg), lower trail leg peak knee extensor moment and eccentric power (0.74Nm/kg and 3.15W/kg), and lower peak concentric power at trail leg ankle joint (1.29W/kg) as compared to men (p<0.05; -0.82Nm/kg, 0.89Nm/kg, 3.83W/kg, and 1.78W/kg, respectively). The lead leg knee eccentric power was also lower in women (p<0.05). This decreased ability to exert knee control during stair descent transition may predispose women to a higher risk of fall.

PMID: 25082325 [PubMed - as supplied by publisher]

The novel histone deacetylase inhibitor thailandepsin A inhibits anaplastic thyroid cancer growth.

Sun, 08/03/2014 - 4:05am
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The novel histone deacetylase inhibitor thailandepsin A inhibits anaplastic thyroid cancer growth.

J Surg Res. 2014 Jul;190(1):191-7

Authors: Weinlander E, Somnay Y, Harrison AD, Wang C, Cheng YQ, Jaskula-Sztul R, Yu XM, Chen H

Abstract
BACKGROUND: Anaplastic thyroid cancer (ATC) remains refractory to available surgical and medical interventions. Histone deacetylase (HDAC) inhibitors are an emerging targeted therapy with antiproliferative activity in a variety of thyroid cancer cell lines. Thailandepsin A (TDP-A) is a novel class I HDAC inhibitor whose efficacy remains largely unknown in ATC. Therefore, we aimed to characterize the effect of TDP-A on ATC.
METHODS: Human-derived ATC cells were treated with TDP-A. IC50 was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) rapid colorimetric assay, and cell proliferation was measured by viable cell count. Molecular mechanisms of cell growth inhibition were investigated by Western blot analysis of canonical apoptosis markers, intrinsic and extrinsic apoptosis regulators, and cell cycle regulatory proteins. Cell cycle staging was determined with propidium iodide flow cytometry.
RESULTS: TDP-A dose- and time-dependently reduced cell proliferation. Increased cleavage of the apoptosis markers Caspase-9, Caspase-3, and poly adenosine diphosphate ribose polymerase were observed with TDP-A treatment. Levels of the intrinsic apoptosis pathway proteins BAD, Bcl-XL, and BAX remained unchanged. Importantly, the extrinsic apoptosis activator cleaved Caspase-8 increased dose-dependently, and the antiapoptotic proteins Survivin and Bcl-2 decreased. Among the cell cycle regulatory proteins, levels of CDK inhibitors p21/WAF1 and p27/KIP increased. Flow cytometry showed that ATC cells were arrested in G2/M phase with diminished S phase after TDP-A treatment.
CONCLUSIONS: TDP-A induces a notable dose- and time-dependent antiproliferative effect on ATC, which is mainly attributed to extrinsic apoptosis with concomitant cell cycle arrest. TDP-A therefore warrants further preclinical and clinical investigations.

PMID: 24679699 [PubMed - indexed for MEDLINE]

Letter to the editor in regard to Peacock, Bruno, and Martin (2012): "the subjective physiological, psychological, and behavioral risk-taking consequences of alcohol and energy drink co-ingestion": misleading results and unjustified conclusions.

Sun, 08/03/2014 - 4:05am
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Letter to the editor in regard to Peacock, Bruno, and Martin (2012): "the subjective physiological, psychological, and behavioral risk-taking consequences of alcohol and energy drink co-ingestion": misleading results and unjustified conclusions.

Alcohol Clin Exp Res. 2013 Dec;37(12):2168-70

Authors: Rossheim ME, Suzuki S, Thombs DL

PMID: 23895400 [PubMed - indexed for MEDLINE]

Angiotensin II induces membrane trafficking of natively-expressed Transient Receptor Potential vanilloid type 4 channels in hypothalamic 4B cells.

Sat, 08/02/2014 - 4:06am

Angiotensin II induces membrane trafficking of natively-expressed Transient Receptor Potential vanilloid type 4 channels in hypothalamic 4B cells.

Am J Physiol Regul Integr Comp Physiol. 2014 Jul 30;

Authors: Saxena A, Bachelor M, Park YH, Carreno FR, Nedungadi TP, Cunningham JT

Abstract
Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that, in rodent a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (Ang II) on TRPV4 expression and function. Our results demonstrate the expression of transcripts for SRY (male genotype), AVP, CRF, TRPV4, and Ang II type 1a and 1b receptor in 4B cells. After a 1 hour incubation in Ang II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction and this effect was prevented by the Ang II type 1 receptor antagonist, Losartan (1 µM) , and by a Src kinase inhibitor, PP2 (10 µM). Radiometric calcium imaging experiments demonstrated that Ang II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM) induced calcium influx (Control 18.4 ± 2.8% n=5 and Ang II 80.5 ± 2.4% n=5). This Ang II induced increase in calcium influx was also blocked by 1 µM Losartan and 10 µM PP2 (Losartan 26.4 ± 3.8% n=5 and PP2 19.7 ± 3.9% n=5). Our data suggests that Ang II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway.

PMID: 25080500 [PubMed - as supplied by publisher]