Gibson D. Lewis Library

Recent Research Articles from UNTHSC

Syndicate content NCBI pubmed
NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 3 hours 43 min ago

Observational study fails to demonstrate the effectiveness of OMT in decreasing low back pain.

Sun, 05/24/2015 - 3:29am
Related Articles

Observational study fails to demonstrate the effectiveness of OMT in decreasing low back pain.

J Am Osteopath Assoc. 2014 Nov;114(11):e119-20

Authors: Licciardone JC

PMID: 25352411 [PubMed - indexed for MEDLINE]

Response: observational study demonstrates that OMT is associated with reduced analgesic prescribing and fewer missed work days.

Sun, 05/24/2015 - 3:29am
Related Articles

Response: observational study demonstrates that OMT is associated with reduced analgesic prescribing and fewer missed work days.

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

Authors: Prinsen JK, Hensel KL, Snow RJ

PMID: 25002441 [PubMed - indexed for MEDLINE]

The OSTEOPATHIC trial demonstrates significant improvement in patients with chronic low back pain as manifested by decreased prescription rescue medication use.

Sun, 05/24/2015 - 3:29am
Related Articles

The OSTEOPATHIC trial demonstrates significant improvement in patients with chronic low back pain as manifested by decreased prescription rescue medication use.

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

Authors: Licciardone JC

PMID: 25002440 [PubMed - indexed for MEDLINE]

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

Sun, 05/24/2015 - 3:29am
Related Articles

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

Int J Biochem Cell Biol. 2014 Sep;54:10-9

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

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

PMID: 24984263 [PubMed - indexed for MEDLINE]

Statin therapy for venous ulcers.

Sat, 05/23/2015 - 3:30am
Related Articles

Statin therapy for venous ulcers.

Br J Dermatol. 2015 Apr;172(4):1132-3

Authors: Dickerson JE, Slade HB

PMID: 25123223 [PubMed - indexed for MEDLINE]

In vivo assessment of SMT19969 in a hamster model of clostridium difficile infection.

Sat, 05/23/2015 - 3:30am
Related Articles

In vivo assessment of SMT19969 in a hamster model of clostridium difficile infection.

Antimicrob Agents Chemother. 2014 Oct;58(10):5714-8

Authors: Weiss W, Pulse M, Vickers R

Abstract
SMT19969 [2,2'-bis(4-pyridyl)3H,3'-H 5,5-bibenzimidazole] is a novel narrow-spectrum nonabsorbable antibiotic currently in development for the treatment of Clostridium difficile infection. The comparative activities of SMT19969 and vancomycin against nonepidemic and epidemic strains of C. difficile were studied in an established hamster model. Against nonepidemic (VA11) strains, the survival rates of SMT19969-treated animals ranged from 80% to 95%. Vancomycin exhibited 100% protection during treatment, with relapse observed starting on day 9 and 50% survival at day 20. At 50 mg/kg of body weight, SMT19969 administered orally once daily for 5 days provided full protection of treated animals on the dosing days and through day 12 against epidemic strains. Vancomycin also protected during the dosing interval, but apparent relapse occurred earlier, starting on day 11. SMT19969 exhibited excellent in vitro activity, with MICs of 0.25 μg/ml for all isolates. The MICs for vancomycin were 2- to 4-fold higher at ≤0.5 to 1 μg/ml. All plasma sample concentrations of SMT19969 were below the limit of quantification (25 ng/ml) at all time points, consistent with the reported lack of bioavailability of the compound. Cecal concentrations were significantly above the MIC (ranging from 96 μg/ml to 172 μg/ml).

PMID: 25022586 [PubMed - indexed for MEDLINE]

Large-scale recent expansion of European patrilineages shown by population resequencing.

Thu, 05/21/2015 - 3:29am

Large-scale recent expansion of European patrilineages shown by population resequencing.

Nat Commun. 2015;6:7152

Authors: Batini C, Hallast P, Zadik D, Delser PM, Benazzo A, Ghirotto S, Arroyo-Pardo E, Cavalleri GL, de Knijff P, Dupuy BM, Eriksen HA, King TE, de Munain AL, López-Parra AM, Loutradis A, Milasin J, Novelletto A, Pamjav H, Sajantila A, Tolun A, Winney B, Jobling MA

Abstract
The proportion of Europeans descending from Neolithic farmers ∼10 thousand years ago (KYA) or Palaeolithic hunter-gatherers has been much debated. The male-specific region of the Y chromosome (MSY) has been widely applied to this question, but unbiased estimates of diversity and time depth have been lacking. Here we show that European patrilineages underwent a recent continent-wide expansion. Resequencing of 3.7 Mb of MSY DNA in 334 males, comprising 17 European and Middle Eastern populations, defines a phylogeny containing 5,996 single-nucleotide polymorphisms. Dating indicates that three major lineages (I1, R1a and R1b), accounting for 64% of our sample, have very recent coalescent times, ranging between 3.5 and 7.3 KYA. A continuous swathe of 13/17 populations share similar histories featuring a demographic expansion starting ∼2.1-4.2 KYA. Our results are compatible with ancient MSY DNA data, and contrast with data on mitochondrial DNA, indicating a widespread male-specific phenomenon that focuses interest on the social structure of Bronze Age Europe.

PMID: 25988751 [PubMed - as supplied by publisher]

Carbon Disulfide (CS2) Mechanisms in Formation of Atmospheric Carbon Dioxide (CO2) Formation from Unconventional Shale Gas Extraction and Processing Operations and Global Climate Change.

Thu, 05/21/2015 - 3:29am

Carbon Disulfide (CS2) Mechanisms in Formation of Atmospheric Carbon Dioxide (CO2) Formation from Unconventional Shale Gas Extraction and Processing Operations and Global Climate Change.

Environ Health Insights. 2015;9(Suppl 1):35-9

Authors: Rich AL, Patel JT

Abstract
Carbon disulfide (CS2) has been historically associated with the production of rayon, cellophane, and carbon tetrachloride. This study identifies multiple mechanisms by which CS2 contributes to the formation of CO2 in the atmosphere. CS2 and other associated sulfide compounds were found by this study to be present in emissions from unconventional shale gas extraction and processing (E&P) operations. The breakdown products of CS2; carbonyl sulfide (COS), carbon monoxide (CO), and sulfur dioxide (SO2) are indirect greenhouse gases (GHGs) that contribute to CO2 levels in the atmosphere. The heat-trapping nature of CO2 has been found to increase the surface temperature, resulting in regional and global climate change. The purpose of this study is to identify five mechanisms by which CS2 and the breakdown products of CS2 contribute to atmospheric concentrations of CO2. The five mechanisms of CO2 formation are as follows: Chemical Interaction of CS2 and hydrogen sulfide (H2S) present in natural gas at high temperatures, resulting in CO2 formation;Combustion of CS2 in the presence of oxygen producing SO2 and CO2;Photolysis of CS2 leading to the formation of COS, CO, and SO2, which are indirect contributors to CO2 formation;One-step hydrolysis of CS2, producing reactive intermediates and ultimately forming H2S and CO2;Two-step hydrolysis of CS2 forming the reactive COS intermediate that reacts with an additional water molecule, ultimately forming H2S and CO2. CS2 and COS additionally are implicated in the formation of SO2 in the stratosphere and/or troposphere. SO2 is an indirect contributor to CO2 formation and is implicated in global climate change.

PMID: 25987843 [PubMed]

Aerosol optical depth as a measure of particulate exposure using imputed censored data, and relationship with childhood asthma hospital admissions for 2004 in athens, Greece.

Thu, 05/21/2015 - 3:29am

Aerosol optical depth as a measure of particulate exposure using imputed censored data, and relationship with childhood asthma hospital admissions for 2004 in athens, Greece.

Environ Health Insights. 2015;9(Suppl 1):27-33

Authors: Higgs G, Sterling DA, Aryal S, Vemulapalli A, Priftis KN, Sifakis NI

Abstract
An understanding of human health implications from atmosphere exposure is a priority in both the geographic and the public health domains. The unique properties of geographic tools for remote sensing of the atmosphere offer a distinct ability to characterize and model aerosols in the urban atmosphere for evaluation of impacts on health. Asthma, as a manifestation of upper respiratory disease prevalence, is a good example of the potential interface of geographic and public health interests. The current study focused on Athens, Greece during the year of 2004 and (1) demonstrates a systemized process for aligning data obtained from satellite aerosol optical depth (AOD) with geographic location and time, (2) evaluates the ability to apply imputation methods to censored data, and (3) explores whether AOD data can be used satisfactorily to investigate the association between AOD and health impacts using an example of hospital admission for childhood asthma. This work demonstrates the ability to apply remote sensing data in the evaluation of health outcomes, that the alignment process for remote sensing data is readily feasible, and that missing data can be imputed with a sufficient degree of reliability to develop complete datasets. Individual variables demonstrated small but significant effect levels on hospital admission of children for AOD, nitrogen oxides (NOx), relative humidity (rH), temperature, smoke, and inversely for ozone. However, when applying a multivari-able model, an association with asthma hospital admissions and air quality could not be demonstrated. This work is promising and will be expanded to include additional years.

PMID: 25987842 [PubMed]

Prognostic models to detect and monitor the near-term risk of suicide: state of the science.

Wed, 05/20/2015 - 3:29am
Related Articles

Prognostic models to detect and monitor the near-term risk of suicide: state of the science.

Am J Prev Med. 2014 Sep;47(3 Suppl 2):S181-5

Authors: Claassen CA, Harvilchuck-Laurenson JD, Fawcett J

Abstract
Aspirational Goal 3 of the National Action Alliance for Suicide Prevention's Research Prioritization Task Force research agenda is to "find ways to assess who is at risk for attempting suicide in the immediate future." Suicide risk assessment is the practice of detecting patient-level conditions that may rapidly progress toward suicidal acts. With hundreds of thousands of risk assessments occurring every year, this single activity arguably represents the most broadly implemented, sustained suicide prevention activity practiced in the U.S. Given this scope of practice, accurate and reliable risk assessment capabilities hold a central and irreplaceable position among interventions mounted as part of any public health approach to suicide prevention. Development of more reliable methods to detect and measure the likelihood of impending suicidal behaviors, therefore, represents one of the more substantial advancements possible in suicide prevention science today. Although past "second-generation" risk models using largely static risk factors failed to show predictive capabilities, the current "third-generation" dynamic risk prognostic models have shown initial promise. Methodologic improvements to these models include the advent of real-time, in vivo data collection processes, common data elements across studies and data sharing to build knowledge around key factors, and analytic methods designed to address rare event outcomes. Given the critical need for improved risk detection, these promising recent developments may well foreshadow advancement toward eventual achievement of this Aspirational Goal.

PMID: 25145737 [PubMed - indexed for MEDLINE]

Introduction to the Suicide Prevention Research Prioritization Task Force special supplement: the topic experts.

Wed, 05/20/2015 - 3:29am
Related Articles

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 - indexed for MEDLINE]

Shortening femoral osteotomy with stemmed resurfacing total knee arthroplasty for severe flexion contracture in Juvenile Rheumatoid Arthritis.

Sat, 05/16/2015 - 3:31am

Shortening femoral osteotomy with stemmed resurfacing total knee arthroplasty for severe flexion contracture in Juvenile Rheumatoid Arthritis.

J Orthop. 2015 Jun;12(2):118-21

Authors: Kitchen B, Sanchez HB, Wagner RA

Abstract
Juvenile Rheumatoid Arthritis (JRA) is a progressive disease characterized by pain, swelling, and loss of motion in the joints of adolescents. Total knee arthroplasty (TKA) can be indicated, during the adolescent years, in patients with advanced JRA to alleviate pain and improve function. Because of the relative infrequency of TKA in patients with JRA, evaluation of the type of TKA performed and the results merit review. This case report present two distinct operations performed to obtain full extension. 1. Distal femoral resection with conversion to hinged arthroplasty. 2. Femoral shortening osteotomy with resurfacing TKA.

PMID: 25972704 [PubMed]

Electrophoretic characterization of the Mammalian nuclear matrix proteome, nuclear envelope, nucleoli and covalently bound ADP-ribose polymers: potential applications to cancer.

Sat, 05/16/2015 - 3:31am
Related Articles

Electrophoretic characterization of the Mammalian nuclear matrix proteome, nuclear envelope, nucleoli and covalently bound ADP-ribose polymers: potential applications to cancer.

Cancer Genomics Proteomics. 2014 Sep-Oct;11(5):217-23

Authors: Aranda XG, Racho RG, Pacheco-Rodríguez G, Alvarez-González R

Abstract
BACKGROUND/AIM: Nucleic acid metabolism is biochemically compartmentalized to the nucleus. Thus, it is necessary to define the proteome of the various macromolecular structures within this organelle.
MATERIALS AND METHODS: We isolated the nuclear matrix (NM) fraction from rat liver by sequential centrifugation steps at 13,000 rpm, staggered between endogenous nuclease treatment for 2 h at 37°C, followed by high-salt (H.S.; 2.0 M NaCl) and non-ionic detergent extractions (0.1%- or 1.0% Triton X-100) to eliminate the bulk of chromosomal DNA/RNA, histone proteins and the nuclear envelope (NE).
RESULTS: Integrity of the NM and NE structures was confirmed by electron microscopy. Next, we analyzed the NM proteome on a 20% polyacrylamide gel using the PhastSystem. We observed the absence of histone proteins and the characteristic presence of the lamins by Coomassie blue staining. By contrast, upon silver staining, following electrophoretic separation with a Tris-Borate-EDTA buffer, we observed the NM-associated nucleic RNA and protein-free ADP-ribose polymers. While polymers are found in much lower concentration than RNA in NM, they were purified by affinity chromatography on boronate resin prior to electrophoresis. We observed the electrophoretic resolution of free ADP-ribose chains (5-25 units) by silver staining.
CONCLUSION: The significance of our observations to cancer studies and carcinogenesis is discussed.

PMID: 25331794 [PubMed - indexed for MEDLINE]

Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

Fri, 05/15/2015 - 3:29am

Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

J Foot Ankle Surg. 2015 May 8;

Authors: Thorud JC, Jolley T, Shibuya N, Lew E, Britt M, Butterfield T, Boike A, Hardy M, Brancheau S, Motley T, Jupiter DC

Abstract
Few studies have investigated the complications that occur after hallux interphalangeal joint arthrodesis. The present study evaluated complications in 152 patients aged 18 to 80 years from 2005 to 2012 from 4 different academic institutions after hallux interphalangeal joint arthrodesis. Overall, 65.8% of the patients had ≥1 complication. Infections occurred in 16.5%, dehiscence in 12.5%, and reoperations in 27.0%. The clinical nonunion rate was ≥17.8%, and the radiographic nonunion rate was ≥13.8%. After logistic regression analysis, only the study site and peripheral neuropathy were associated with having ≥1 complication (p < .01 and p < .05, respectively). Single screw fixation compared with other fixation did not have a statistically significant influence on the postoperative complications. However, when fixation was expanded to 4 categories, single screw fixation had lower infection and reoperation rates than either crossed Kirschner wires or other fixation category but not compared with crossed screws on multivariate logistic regression analysis. Although additional studies are warranted, the findings from the present study might aid in both the prognosis of complications and the support of the use of a single screw over crossed Kirchner wire fixation in hallux interphalangeal joint arthrodesis.

PMID: 25960055 [PubMed - as supplied by publisher]

Caloric restriction and the aging process: a critique.

Fri, 05/15/2015 - 3:29am
Related Articles

Caloric restriction and the aging process: a critique.

Free Radic Biol Med. 2014 Aug;73:366-82

Authors: Sohal RS, Forster MJ

Abstract
The main objective of this review is to provide an appraisal of the current status of the relationship between energy intake and the life span of animals. The concept that a reduction in food intake, or caloric restriction (CR), retards the aging process, delays the age-associated decline in physiological fitness, and extends the life span of organisms of diverse phylogenetic groups is one of the leading paradigms in gerontology. However, emerging evidence disputes some of the primary tenets of this conception. One disparity is that the CR-related increase in longevity is not universal and may not even be shared among different strains of the same species. A further misgiving is that the control animals, fed ad libitum (AL), become overweight and prone to early onset of diseases and death, and thus may not be the ideal control animals for studies concerned with comparisons of longevity. Reexamination of body weight and longevity data from a study involving over 60,000 mice and rats, conducted by a National Institute on Aging-sponsored project, suggests that CR-related increase in life span of specific genotypes is directly related to the gain in body weight under the AL feeding regimen. Additionally, CR in mammals and "dietary restriction" in organisms such as Drosophila are dissimilar phenomena, albeit they are often presented to be the very same. The latter involves a reduction in yeast rather than caloric intake, which is inconsistent with the notion of a common, conserved mechanism of CR action in different species. Although specific mechanisms by which CR affects longevity are not well understood, existing evidence supports the view that CR increases the life span of those particular genotypes that develop energy imbalance owing to AL feeding. In such groups, CR lowers body temperature, rate of metabolism, and oxidant production and retards the age-related pro-oxidizing shift in the redox state.

PMID: 24941891 [PubMed - indexed for MEDLINE]

Reduced Vascular Responses to Soluble Guanylyl Cyclase but Increased Sensitivity to Sildenafil in Female Rats with Type 2 Diabetes.

Tue, 05/12/2015 - 3:29am

Reduced Vascular Responses to Soluble Guanylyl Cyclase but Increased Sensitivity to Sildenafil in Female Rats with Type 2 Diabetes.

Am J Physiol Heart Circ Physiol. 2015 May 8;:ajpheart.00079.2015

Authors: Goulopoulou S, Hannan JL, Matsumoto T, Ogbi S, Ergul A, Webb RC

Abstract
Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC) and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (activators). In this study, we hypothesized that resistance arteries from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats) would have reduced vasodilatory responses to heme-dependent sGC activation and increased responses to heme-independent sGC activation as compared to control rats (Wistar). Endothelium-dependent and -independent relaxation was assessed in isolated segments from mesenteric resistance arteries (MA) mounted in a wire myograph. GK MA had reduced responses to acetylcholine (ACh; pEC50: 7.96 ± 0.06 vs. 7.66 ± 0.05, p<0.05) and sodium nitroprusside (SNP; pEC50: 8.34 ± 0.05 vs. 7.77 ± 0.04, p<0.05). There were no group differences in 8-Br-cGMP-induced relaxation and protein kinase G-1 (PKG-1) expression (p>0.05). GK MA had attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56 ± 0.05 vs. 6.93 ± 0.06, p<0.05) and BAY 58-2667 (heme-independent sGC activator; pEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, p<0.05) and increased sensitivity to sildenafil [phosphodiestarase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, p<0.05]. Isolated resistance arteries from female rats of reproductive age that spontaneously develop type 2 diabetes have increased sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and stimulators.

PMID: 25957216 [PubMed - as supplied by publisher]

Thymic Involution Perturbs Negative Selection Leading to Autoreactive T Cells That Induce Chronic Inflammation.

Tue, 05/12/2015 - 3:29am

Thymic Involution Perturbs Negative Selection Leading to Autoreactive T Cells That Induce Chronic Inflammation.

J Immunol. 2015 May 8;

Authors: Coder BD, Wang H, Ruan L, Su DM

Abstract
Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non-lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).

PMID: 25957168 [PubMed - as supplied by publisher]

Tip110 regulates the cross-talk between p53 and HIF-1α under hypoxia and promotes survival of cancer cells.

Sun, 05/10/2015 - 3:29am

Tip110 regulates the cross-talk between p53 and HIF-1α under hypoxia and promotes survival of cancer cells.

Mol Cell Biol. 2015 May 4;

Authors: Timani KA, Liu Y, Fan Y, Mohammad KS, He JJ

Abstract
Hypoxia often occurs under various physiological and pathophysiological conditions including solid tumors; it is linked to malignant transformation, metastatic progression and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes including cancers. Thus, in the current study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated HIF-1α, likely through enhancement of its protein stability. Furthermore, Tip110 up-regulated p300, a known co-activator for both p53 and HIF-1α. Expression of p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Lastly, significantly less Tip110, p53, and HIF-1α were detected in the hypoxic region of bone metastases tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 as an important mediator in the cross-talk between p53 and HIF-1α in response to hypoxic stress.

PMID: 25939381 [PubMed - as supplied by publisher]

Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer's disease.

Sun, 05/10/2015 - 3:29am
Related Articles

Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer's disease.

Alzheimers Res Ther. 2015;7(1):24

Authors: Hall JR, Wiechmann AR, Cunningham RL, Johnson LA, Edwards M, Barber RC, Singh M, Winter S, O'Bryant SE, Texas Alzheimer’s Research and Care Consortium

Abstract
INTRODUCTION: There has been a significant increase in the use of testosterone in aging men, but little investigation into its impact on men with Alzheimer's disease (AD). The findings of the few studies that have been done are inconsistent. In the present study, we investigated the relationship between total testosterone (TT) and neuropsychiatric symptoms (NPS) in a well-characterized sample of elderly men with mild to moderate AD.
METHODS: The sample, which was drawn from the Texas Alzheimer's Research Care Consortium Longitudinal Research Cohort, included 87 men who met the criteria for mild to moderate AD. The occurrence of NPS was gathered from caregivers and/or family members with the Neuropsychiatric Inventory. TT was analyzed, and the sample was divided into a low-testosterone group (TT ≤2.5 ng/ml; n = 44) and a borderline/normal group (TT ≥2.6 ng/ml; n = 43).
RESULTS: TT was correlated with symptoms of hallucinations, delusions, agitation, irritability and motor activity. The borderline/normal group was significantly more likely to have hallucinations (odds ratio (OR) = 5.56), delusions (OR = 3.87), motor activity (OR = 3.13) and irritability (OR = 2.77) than the low-testosterone group. Health status and apolipoprotein E ε4 status were not significant factors.
CONCLUSIONS: The findings of the present study have implications for the use of testosterone replacement therapy in men with AD or the prodromal stage of the disease.

PMID: 25937840 [PubMed]

AMPA receptor desensitization is the determinant of AMPA receptor mediated excitotoxicity in purified retinal ganglion cells.

Sun, 05/10/2015 - 3:29am
Related Articles

AMPA receptor desensitization is the determinant of AMPA receptor mediated excitotoxicity in purified retinal ganglion cells.

Exp Eye Res. 2015 Mar;132:136-50

Authors: Park YH, Mueller BH, McGrady NR, Ma HY, Yorio T

Abstract
The ionotropic glutamate receptors (iGLuR) have been hypothesized to play a role in neuronal pathogenesis by mediating excitotoxic death. Previous studies on iGluR in the retina have focused on two broad classes of receptors: NMDA and non-NMDA receptors including the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) and kainate receptor. In this study, we examined the role of receptor desensitization on the specific excitotoxic effects of AMPAR activation on primary retinal ganglion cells (RGCs). Purified rat RGCs were isolated from postnatal day 4-7 Sprague-Dawley rats. Calcium imaging was used to identify the functionality of the AMPARs and selectivity of the s-AMPA agonist. Phosphorylated CREB and ERK1/2 expression were performed following s-AMPA treatment. s-AMPA excitotoxicity was determined by JC-1 mitochondrial membrane depolarization assay, caspase 3/7 luciferase activity assay, immunoblot analysis for α-fodrin, and Live (calcein AM)/Dead (ethidium homodimer-1) assay. RGC cultures of 98% purity, lacking Iba1 and GFAP expression were used for the present studies. Isolated prenatal RGCs expressed calcium permeable AMPAR and s-AMPA (100 μM) treatment of cultured RGCs significantly increased phosphorylation of CREB but not that of ERK1/2. A prolonged (6 h) AMPAR activation in purified RGCs using s-AMPA (100 μM) did not depolarize the RGC mitochondrial membrane potential. In addition, treatment of cultured RGCs with s-AMPA, both in the presence and absence of trophic factors (BDNF and CNTF), did not increase caspase 3/7 activities or the cleavage of α-fodrin (neuronal apoptosis marker), as compared to untreated controls. Lastly, a significant increase in cell survival of RGCs was observed after s-AMPA treatment as compared to control untreated RGCs. However, preventing the desensitization of AMPAR with the treatment with either kainic acid (100 μM) or the combination of s-AMPA and cyclothiazide (50 μM) significantly reduced cell survivability. Activation of the AMPAR in RGCs does not appear to activate a signaling cascade to apoptosis, suggesting that RGCs in vitro are not susceptible to AMPA excitotoxicity as previously hypothesized. Conversely, preventing AMPAR desensitization through differential agonist activation caused AMPAR mediated excitotoxicity. Activation of the AMPAR in increasing CREB phosphorylation was dependent on the presence of calcium, which may help explain this action in increasing RGC survival.

PMID: 25643624 [PubMed - indexed for MEDLINE]

Contact Us