Feed aggregator

Introduction to EER Special Issue on ocular fibrosis.

Recent Research Articles from UNTHSC - Tue, 04/19/2016 - 06:31
Related Articles

Introduction to EER Special Issue on ocular fibrosis.

Exp Eye Res. 2016 Jan;142:1

Authors: O'Brien C, Clark AF

PMID: 26253011 [PubMed - indexed for MEDLINE]

The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders.

Recent Research Articles from UNTHSC - Tue, 04/19/2016 - 06:31
Related Articles

The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders.

Sci Transl Med. 2015 Jul 22;7(297):297ra113

Authors: Prokai L, Nguyen V, Szarka S, Garg P, Sabnis G, Bimonte-Nelson HA, McLaughlin KJ, Talboom JS, Conrad CD, Shughrue PJ, Gould TD, Brodie A, Merchenthaler I, Koulen P, Prokai-Tatrai K

Abstract
Many neurological and psychiatric maladies originate from the deprivation of the human brain from estrogens. However, current hormone therapies cannot be used safely to treat these conditions commonly associated with menopause because of detrimental side effects in the periphery. The latter also prevents the use of the hormone for neuroprotection. We show that a small-molecule bioprecursor prodrug, 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), converts to 17β-estradiol in the brain after systemic administration but remains inert in the rest of the body. The localized and rapid formation of estrogen from the prodrug was revealed by a series of in vivo bioanalytical assays and through in vivo imaging in rodents. DHED treatment efficiently alleviated symptoms that originated from brain estrogen deficiency in animal models of surgical menopause and provided neuroprotection in a rat stroke model. Concomitantly, we determined that 17β-estradiol formed in the brain from DHED elicited changes in gene expression and neuronal morphology identical to those obtained after direct 17β-estradiol treatment. Together, complementary functional and mechanistic data show that our approach is highly relevant therapeutically, because administration of the prodrug selectively produces estrogen in the brain independently from the route of administration and treatment regimen. Therefore, peripheral responses associated with the use of systemic estrogens, such as stimulation of the uterus and estrogen-responsive tumor growth, were absent. Collectively, our brain-selective prodrug approach may safely provide estrogen neuroprotection and medicate neurological and psychiatric symptoms developing from estrogen deficiency, particularly those encountered after surgical menopause, without the adverse side effects of current hormone therapies.

PMID: 26203081 [PubMed - indexed for MEDLINE]

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress.

Recent Research Articles from UNTHSC - Tue, 04/19/2016 - 06:31
Related Articles

Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress.

Neuroscience. 2015 Aug 20;301:193-203

Authors: Ryou MG, Choudhury GR, Li W, Winters A, Yuan F, Liu R, Yang SH

Abstract
UNLABELLED: Brain ischemia and reperfusion (I/R) injury occurs in various pathological conditions, but there is no effective treatment currently available in clinical practice. Methylene blue (MB) is a century-old drug with a newly discovered protective function in the ischemic stroke model. In the current investigation we studied the MB-induced neuroprotective mechanism focusing on stabilization and activation of hypoxia-inducible factor-1α (HIF-1α) in an in vitro oxygen and glucose deprivation (OGD)-reoxygenation model.
METHODS: HT22 cells were exposed to OGD (0.1% O2, 6h) and reoxygenation (21% O2, 24h). Cell viability was determined with the calcein AM assay. The dynamic change of intracellular O2 concentration was monitored by fluorescence lifetime imaging microscopy (FLTIM). Glucose uptake was quantified using the 2-[N-(7-Nitrobenz-2-Oxa-1,3-Diazol-4-yl)Amino]-2-Deoxy-d-Glucose (2-NBDG) assay. ATP concentration and glycolytic enzyme activity were examined by spectrophotometry. Protein content changes were measured by immunoblot: HIF-1α, prolyl hydroxylase 2 (PHD2), erythropoietin (EPO), Akt, mTOR, and PIP5K. The contribution of HIF-1α activation in the MB-induced neuroprotective mechanism was confirmed by blocking HIF-1α activation with 2-methoxyestradiol-2 (2-MeOE2) and by transiently transfecting constitutively active HIF-1α.
RESULTS: MB increases cell viability by about 50% vs. OGD control. Compared to the corresponding control, MB increases intracellular O2 concentration and glucose uptake as well as the activities of hexokinase and G-6-PDH, and ATP concentration. MB activates the EPO signaling pathway with a corresponding increase in HIF-1α. Phosphorylation of Akt was significantly increased with MB treatment followed by activation of the mTOR pathway. Importantly, we observed, MB increased nuclear translocation of HIF-1α vs. control (about three folds), which was shown by a ratio of nuclear:cytoplasmic HIF-1α protein content.
CONCLUSION: We conclude that MB protects the hippocampus-derived neuronal cells against OGD-reoxygenation injury by enhancing energy metabolism and increasing HIF-1α protein content accompanied by an activation of the EPO signaling pathway.

PMID: 26047733 [PubMed - indexed for MEDLINE]

Changes in biomechanical dysfunction and low back pain reduction with osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Recent Research Articles from UNTHSC - Tue, 04/19/2016 - 06:31
Related Articles

Changes in biomechanical dysfunction and low back pain reduction with osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Man Ther. 2014 Aug;19(4):324-30

Authors: Licciardone JC, Kearns CM, Crow WT

Abstract
The purpose of this study was to measure changes in biomechanical dysfunction following osteopathic manual treatment (OMT) and to assess how such changes predict subsequent low back pain (LBP) outcomes. Secondary analyses were performed with data collected during the OSTEOPATHIC Trial wherein a randomized, double-blind, sham-controlled, 2 × 2 factorial design was used to study OMT for chronic LBP. At baseline, prevalence rates of non-neutral lumbar dysfunction, pubic shear, innominate shear, restricted sacral nutation, and psoas syndrome were determined in 230 patients who received OMT. Five OMT sessions were provided at weeks 0, 1, 2, 4, and 6, and the prevalence of each biomechanical dysfunction was again measured at week 8 immediately before the final OMT session. Moderate pain improvement (≥30% reduction on a 100-mm visual analogue scale) at week 12 defined a successful LBP response to treatment. Prevalence rates at baseline were: non-neutral lumbar dysfunction, 124 (54%); pubic shear, 191 (83%); innominate shear, 69 (30%); restricted sacral nutation, 87 (38%), and psoas syndrome, 117 (51%). Significant improvements in each biomechanical dysfunction were observed with OMT; however, only psoas syndrome remission occurred more frequently in LBP responders than non-responders (P for interaction = 0.002). Remission of psoas syndrome was the only change in biomechanical dysfunction that predicted subsequent LBP response after controlling for the other biomechanical dysfunctions and potential confounders (odds ratio, 5.11; 95% confidence interval, 1.54-16.96). These findings suggest that remission of psoas syndrome may be an important and previously unrecognized mechanism explaining clinical improvement in patients with chronic LBP following OMT.

PMID: 24704126 [PubMed - indexed for MEDLINE]

HIV/neuroAIDS biomarkers.

Recent Research Articles from UNTHSC - Sun, 04/17/2016 - 06:33

HIV/neuroAIDS biomarkers.

Prog Neurobiol. 2016 Apr 12;

Authors: Rahimian P, He JJ

Abstract
HIV infection often causes neurological symptoms including cognitive and motor dysfunction, which have been collectively termed HIV/neuroAIDS. Neuropsychological assessment and clinical symptoms have been the primary diagnostic criteria for HIV/neuroAIDS, even for the mild cognitive and motor disorder, the most prevalent form of HIV/neuroAIDS in the era of combination antiretroviral therapy. Those performance-based assessments and symptoms are generally descriptive and do not have the sensitivity and specificity to monitor the diagnosis, progression, and treatment response of the disease when compared to objective and quantitative laboratory-based biological markers, or biomarkers. In addition, effects of demographics and comorbidities such as substance abuse, psychiatric disease, nutritional deficiencies, and co-infection on HIV/neuroAIDS could be more readily determined using biomarkers than using neuropsychological assessment and clinical symptoms. Thus, there have been great efforts in identification of HIV/neuroAIDS biomarkers over the past two decades. The need for reliable biomarkers of HIV/neuroAIDS is expected to increase as the HIV-infected population ages and their vulnerability to neurodegenerative diseases, particularly Alzheimer's disease increases. Currently, three classes of HIV/neuroAIDS biomarkers are being pursued to establish objective laboratory-based definitions of HIV-associated neurologic injury: cerebrospinal fluid biomarkers, blood biomarkers, and neuroimaging biomarkers. In this review, we will focus on the current knowledge in the field of HIV/neuroAIDS biomarker discovery.

PMID: 27084354 [PubMed - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Fri, 04/15/2016 - 06:32

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

Am J Forensic Med Pathol. 2016 Apr 12;

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

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

PMID: 27075592 [PubMed - as supplied by publisher]

Estimating sleep from multisensory armband measurements: validity and reliability in teens.

Recent Research Articles from UNTHSC - Fri, 04/15/2016 - 06:32
Related Articles

Estimating sleep from multisensory armband measurements: validity and reliability in teens.

J Sleep Res. 2015 Dec;24(6):714-21

Authors: Roane BM, Van Reen E, Hart CN, Wing R, Carskadon MA

Abstract
Given the recognition that sleep may influence obesity risk, there is increasing interest in measuring sleep parameters within obesity studies. The goal of the current analyses was to determine whether the SenseWear(®) Pro3 Armband (armband), typically used to assess physical activity, is reliable at assessing sleep parameters. The armband was compared with the AMI Motionlogger(®) (actigraph), a validated activity monitor for sleep assessment, and with polysomnography, the gold standard for assessing sleep. Participants were 20 adolescents (mean age = 15.5 years) with a mean body mass index percentile of 63.7. All participants wore the armband and actigraph on their non-dominant arm while in-lab during a nocturnal polysomnographic recording (600 min). Epoch-by-epoch sleep/wake data and concordance of sleep parameters were examined. No significant sleep parameter differences were found between the armband and polysomnography; the actigraph tended to overestimate sleep and underestimate wake compared with polysomnography. Both devices showed high sleep sensitivity, but lower wake detection rates. Bland-Altman plots showed large individual differences in armband sleep parameter concordance rates. The armband did well estimating sleep overall, with group results more similar to polysomnography than the actigraph; however, the armband was less accurate at an individual level than the actigraph.

PMID: 26126746 [PubMed - indexed for MEDLINE]

Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Recent Research Articles from UNTHSC - Thu, 04/14/2016 - 06:36
Related Articles

Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Am J Cancer Res. 2016;6(1):105-13

Authors: Tao MH, Dai Q, Millen AE, Nie J, Edge SB, Trevisan M, Shields PG, Freudenheim JL

Abstract
Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio.

PMID: 27073728 [PubMed]

Role of Tat-interacting protein of 110 kDa and microRNAs in the regulation of hematopoiesis.

Recent Research Articles from UNTHSC - Thu, 04/14/2016 - 06:36
Related Articles

Role of Tat-interacting protein of 110 kDa and microRNAs in the regulation of hematopoiesis.

Curr Opin Hematol. 2016 Apr 8;

Authors: Liu Y, He JJ

Abstract
PURPOSE OF REVIEW: Hematopoiesis is regulated by cellular factors including transcription factors, microRNAs, and epigenetic modifiers. Understanding how these factors regulate hematopoiesis is pivotal for manipulating them to achieve their desired potential. In this review, we will focus on HIV-1 Tat-interacting protein of 110 kDa (Tip110) and its regulation of hematopoiesis.
RECENT FINDINGS: There are several pathways in hematopoiesis that involve Tip110 regulation. Tip110 is expressed in human cord blood CD34 cells; its expression decreases when CD34 cells begin to differentiate. Tip110 is also expressed in mouse marrow hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC). Tip110 expression increases the number, survival, and cell cycling of HPC. Tip110-mediated regulation of hematopoiesis has been linked to its reciprocal control of c-Myc expression. Small noncoding microRNAs (miRs) have been shown to play important roles in regulation of hematopoiesis. miR-124 specifically targets 3'-untranslated region of Tip110 and subsequently regulates Tip110 expression in HSC.
SUMMARY: Our recent findings for manipulating expression levels of Tip110 in HSC and HPC could be useful for expanding HSC and HPC and for improving engraftment of cord blood HSC/HPC.

PMID: 27071021 [PubMed - as supplied by publisher]

Cerebral Blood-Flow Regulation During Hemorrhage.

Recent Research Articles from UNTHSC - Thu, 04/14/2016 - 06:36
Related Articles

Cerebral Blood-Flow Regulation During Hemorrhage.

Compr Physiol. 2015 Oct;5(4):1585-621

Authors: Rickards CA

Abstract
Massive uncontrolled blood loss can occur under a variety of conditions including trauma, as a complication of childbirth or surgery, ruptured ulcers, clotting disorders, and hemorrhagic fevers. Across the continuum of hemorrhage, loss of blood volume is a significant challenge to the maintenance of cerebral perfusion. During the initial stages of hemorrhage, reflex mechanisms are activated to protect cerebral perfusion, but persistent blood loss will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Hemorrhage represents a unique physiological stress to the brain, as it influences each of these regulatory mechanisms, resulting in complex interplay that ultimately challenges the ability of the brain to maintain adequate perfusion. Early studies of actual hemorrhage in humans employed blood loss protocols up to 1000 mL, but did not include any measurements of cerebral blood flow. As ethical considerations necessarily constrain the use of human volunteers for massive blood loss studies that induce irreversible shock, most of what is known about cerebral blood-flow responses to hemorrhage has been determined from animal models. Limitations of species differences regarding regulatory mechanisms, anatomy, and the effect of anesthesia, however, must be considered. Advances in monitoring technologies, and a recent renewed interest in understanding cerebral blood-flow regulation in humans, however, is rapidly accelerating knowledge in this field.

PMID: 26426461 [PubMed - indexed for MEDLINE]

Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Recent Research Articles from UNTHSC - Tue, 04/12/2016 - 06:34
Related Articles

Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3168-71

Authors: Visalli RJ, Ziobrowski H, Badri KR, He JJ, Zhang X, Arumugam SR, Zhao H

Abstract
Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼ 0.1-10 μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9 μM for compounds 1-5, respectively.

PMID: 26112446 [PubMed - indexed for MEDLINE]

Pages