Recent Research Articles from UNTHSC

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Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

Fri, 04/11/2014 - 3:24am

Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

J Cereb Blood Flow Metab. 2014 Apr 9;

Authors: Tang Y, Wang J, Lin X, Wang L, Shao B, Jin K, Wang Y, Yang GY

Abstract
Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein(+) (GFAP(+)) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.Journal of Cerebral Blood Flow & Metabolism advance online publication, 9 April 2014; doi:10.1038/jcbfm.2014.61.

PMID: 24714034 [PubMed - as supplied by publisher]

Diversity of piroplasms detected in blood-fed and questing ticks from several states in the United States.

Thu, 04/10/2014 - 4:39am

Diversity of piroplasms detected in blood-fed and questing ticks from several states in the United States.

Ticks Tick Borne Dis. 2014 Apr 4;

Authors: Shock BC, Moncayo A, Cohen S, Mitchell EA, Williamson PC, Lopez G, Garrison LE, Yabsley MJ

Abstract
Piroplasms in the genera Babesia, Theileria, and Cytauxzoon are tick-borne parasites that may be animal and human pathogens. Most piroplasms with known life cycles are transmitted by ixodid ticks; however, for many species, the vector is unknown. This study was conducted to determine the prevalence and diversity of piroplasms in ticks from several US states. Piroplasm-specific polymerase chain reaction (PCR) assays were used to test 1631 ticks from Georgia (n=486), Kentucky (n=103), Pennsylvania (n=1), Tennessee (n=626), and Texas (n=414). Ticks were either questing (n=42) or collected from animals (n=627) or humans (n=962). The 2 primary species tested were Dermacentor variabilis (n=702) and Amblyomma americanum (n=743), but Amblyomma cajennense (n=99), Amblyomma maculatum (n=16), Ixodes scapularis (n=4), I. woodi (n=1), and unidentified Amblyomma spp. nymphs (n=64) were also tested. A low prevalence of piroplasms was detected with 37 (2.3%), 35 (2.1%), and 9 (0.6%) ticks positive for Theileria spp., Babesia spp., or Cytauxzoon felis, respectively. Based on sequence analysis, at least 6 Babesia spp. were detected and 15 of the 35 (41%) Babesia-positive ticks were A. americanum, 19 (56%) were D. variabilis, and one (3%) was an I. scapularis. Nine Babesia-positive ticks were removed from humans from Kentucky (n=1), Georgia (n=2), Texas (n=5), and Pennsylvania (n=1). Three Babesia-positive ticks were questing A. americanum which represents the first report of Babesia-infected questing Amblyomma in the US. Theileria infections were only detected in A. americanum, and all sequences were similar to white-tailed deer associated Theileria spp. C. felis was only detected in D. variabilis. These data suggest that A. americanum may be a vector of Babesia spp., although experimental studies are needed to confirm vector competence. Finally, these data demonstrate a high diversity of piroplasms in both questing and partially fed ticks in the US; although, host-blood meals can be present in non-questing ticks.

PMID: 24709338 [PubMed - as supplied by publisher]

Internal Validation of Human Mitochondrial DNA Quantification Using Real-Time PCR.

Thu, 04/10/2014 - 4:39am

Internal Validation of Human Mitochondrial DNA Quantification Using Real-Time PCR.

J Forensic Sci. 2014 Apr 7;

Authors: Sprouse ML, Phillips NR, Kavlick MF, Roby RK

Abstract
The quantity of mitochondrial DNA (mtDNA) template added for amplification and subsequent dye terminator reactions is critical for obtaining quality sequence data. Validation of a human mtDNA real-time quantitative PCR (qPCR) assay demonstrated its high degree of reproducibility and precision as well as an extremely sensitive threshold of detection (0.0001 pg/μL or approximately six human mtDNA copies/μL). A study of 35 nonprobative bone and teeth evidence samples revealed that 20 pg of mtDNA template is recommended for successful HV1 and HV2 sequence analysis; however, as little as 0.013 pg can generate a full mtDNA profile when using enhanced amplification reactions. The assay can also detect PCR inhibition and is useful for identifying samples that may benefit from re-purification. Overall, the assay is an excellent method to quantify mtDNA and is useful for determining the best analytical approach for successful sequencing.

PMID: 24708529 [PubMed - as supplied by publisher]

Erratum to: Modeling one complete versus triplicate analyses in low template DNA typing.

Wed, 04/09/2014 - 4:24am

Erratum to: Modeling one complete versus triplicate analyses in low template DNA typing.

Int J Legal Med. 2014 Apr 6;

Authors: Ge J, Budowle B

PMID: 24705733 [PubMed - as supplied by publisher]

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

Wed, 04/09/2014 - 4:24am

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

Man Ther. 2014 Mar 18;

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 - as supplied by publisher]

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.

Tue, 04/08/2014 - 4:24am

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia.

World J Crit Care Med. 2013 Nov 4;2(4):56-64

Authors: Gurji HA, White DW, Hoxha B, Sun J, Olivencia-Yurvati AH, Mallet RT

Abstract
AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate (PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's (LR) during hypovolemia and hindlimb ischemia-reperfusion.
METHODS: Male domestic goats (25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mmHg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls (TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation (n = 6 per group) or 3.5 h later (n = 9 LR, 10 PR, 8 TC).
RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval (QTc) variability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR (P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC (P < 0.05), but was stable post-PR (P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR (P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.
CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvate-enriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemia-reperfusion.

PMID: 24701417 [PubMed]

Protein Kinase C-ε Promotes EMT in Breast Cancer.

Tue, 04/08/2014 - 4:24am

Protein Kinase C-ε Promotes EMT in Breast Cancer.

Breast Cancer (Auckl). 2014;8:61-7

Authors: Jain K, Basu A

Abstract
Protein kinase C (PKC), a family of serine/threonine kinases, plays critical roles in signal transduction and cell regulation. PKCε, a member of the novel PKC family, is known to be a transforming oncogene and a tumor biomarker for aggressive breast cancers. In this study, we examined the involvement of PKCε in epithelial to mesenchymal transition (EMT), the process that leads the way to metastasis. Overexpression of PKCε was sufficient to induce a mesenchymal phenotype in non-tumorigenic mammary epithelial MCF-10 A cells. This was accompanied by a decrease in the epithelial markers, such as E-cadherin, zonula occludens (ZO)-1, and claudin-1, and an increase in mesenchymal marker vimentin. Transforming growth factor β (TGFβ) induced Snail expression and mesenchymal morphology in MCF-10 A cells, and these effects were partially reversed by the PKCε knockdown. PKCε also mediated cell migration and anoikis resistance, which are hallmarks of EMT. Thus, our study demonstrates that PKCε is an important mediator of EMT in breast cancer.

PMID: 24701121 [PubMed]

Pre-operative Decision-Making in the Treatment of High-Angle "Vertical" Femoral Neck Fractures in Young Adult Patients.

Sat, 04/05/2014 - 12:22pm

Pre-operative Decision-Making in the Treatment of High-Angle "Vertical" Femoral Neck Fractures in Young Adult Patients.

J Orthop Trauma. 2014 Apr 1;

Authors: Luttrell K, Beltran M, Collinge C

Abstract
OBJECTIVE:: To identify the current implant and diagnostic imaging preferences among orthopedic trauma experts for the treatment of high-energy vertical femoral neck fractures in young adult patients.
DESIGN:: Web-based survey SETTING:: N/A PARTICIPANTS:: Active members of the Orthopaedic Trauma Association (OTA) METHODS:: A cross sectional expert opinion survey was administered to active members of the OTA to determine their preferences for implant use and imaging in the surgical treatment of a vertical femoral neck fracture in a young adult patient (e.g. 60° Pauwels' angle fracture in a healthy 30 year old patient). Questions were also asked regarding the reason this implant was selected, whether the surgeon felt their choice was supported by the literature, and what imaging studies are routinely obtained to guide decision-making. Data was collected using simple multiple-choice questions and/or a 5-point Likert item.
RESULTS:: Two-hundred and seventy-two surgeons (47%) responded to the survey. The preferred constructs for a vertical femoral neck fracture in a healthy young patient were a sliding hip screw with or without an anti-rotation screw (47%), parallel cannulated screws with an off-axis screw (28%), and parallel cannulated screw constructs (15%). When asked if their designated construct "was clearly supported by the literature," 46% were either unsure or disagreed. Seventy percent of surgeons chose their preferred implant because it was "biomechanically most stable." The majority of surgeons required AP pelvis (70%) and standard hip (88%) radiographs, however only 29% of surgeons required a CT scan (59% found CT helpful but not required). Twenty seven percent of surgeons have changed their implant choice intraoperatively.
CONCLUSIONS:: Femoral neck fractures in young adult patients are a challenging problem with high rates of failed treatment. Many options for treatment exist and a consensus on the best method remains elusive. Our survey demonstrates the diversity and disagreement among OTA member "expert" orthopedic traumatologists for the "best" treatment choice for this important clinical scenario. Our survey shows a divided level of confidence in the current literature and highlights the need for further study of this problem.
LEVEL OF EVIDENCE:: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

PMID: 24694558 [PubMed - as supplied by publisher]

Pharmacological Modulation of Abnormal Involuntary DOI-Induced Head Twitch Response in Male DBA/2J Mice: I. Effects of D2/D3 and D2 Dopamine Receptor Selective Compounds.

Fri, 04/04/2014 - 3:37am

Pharmacological Modulation of Abnormal Involuntary DOI-Induced Head Twitch Response in Male DBA/2J Mice: I. Effects of D2/D3 and D2 Dopamine Receptor Selective Compounds.

Neuropharmacology. 2014 Mar 25;

Authors: Rangel-Barajas C, Malik M, Vangveravong S, Mach RH, Luedtke RR

Abstract
Because of the complexity and heterogeneity of human neuropsychiatric disorders, it has been difficult to identify animal models that mimic the symptoms of these neuropathologies and can be used to screen for antipsychotic agents. For this study we selected the murine 5HT2A/2C receptor agonist-induced head twitch response (HTR) induced by the administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has been proposed as an animal model of symptoms associated with a variety of behavioral and psychiatric conditions. We investigated the DOI-induced HTR in male DBA/2J mice using a panel of D2-like (D2, D3 and D4) and D2 dopamine receptor selective compounds. When DBA/2J mice were administered a daily dose of DOI (5 mg/kg), tolerance to the DOI occurs. However, administrations of the same dose of DOI every other day (48 hrs.) or on a weekly basis did not lead to tolerance and the ability to induce tolerance after daily administration of DOI remains intact after repeated weekly administration of DOI. Subsequently, a panel of D2-like dopamine receptor antagonists was found to effectively inhibit the DOI-induced HTR in DBA/2J mice. However, the benzamide eticlopride, which is a high affinity D2-like antagonist, was a notable exception. SV 293, SV-III-130s and N-methylbenperidol, which exhibit a high affinity for D2 versus the D3 dopamine receptor subtypes (60- to 100-fold binding selectivity), were also found to inhibit the HTR in DBA/2J mice. This observation suggests a functional interaction between dopaminergic and serotonergic systems through D2 dopamine receptors and the 5-HT2A serotonin receptors in vivo.

PMID: 24680675 [PubMed - as supplied by publisher]

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

Fri, 04/04/2014 - 3:37am

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

J Surg Res. 2014 Feb 28;

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 - as supplied by publisher]

Effective removal of co-purified inhibitors from extracted DNA samples using synchronous coefficient of drag alteration (SCODA) technology.

Tue, 04/01/2014 - 4:40am
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Effective removal of co-purified inhibitors from extracted DNA samples using synchronous coefficient of drag alteration (SCODA) technology.

Int J Legal Med. 2013 Jul;127(4):749-55

Authors: Schmedes S, Marshall P, King JL, Budowle B

Abstract
Various types of biological samples present challenges for extraction of DNA suitable for subsequent molecular analyses. Commonly used extraction methods, such as silica membrane columns and phenol-chloroform, while highly successful may still fail to provide a sufficiently pure DNA extract with some samples. Synchronous coefficient of drag alteration (SCODA), implemented in Boreal Genomics' Aurora Nucleic Acid Extraction System (Boreal Genomics, Vancouver, BC), is a new technology that offers the potential to remove inhibitors effectively while simultaneously concentrating DNA. In this initial study, SCODA was tested for its ability to remove various concentrations of forensically and medically relevant polymerase chain reaction (PCR) inhibitors naturally found in tissue, hair, blood, plant, and soil samples. SCODA was used to purify and concentrate DNA from intentionally contaminated DNA samples containing known concentrations of hematin, humic acid, melanin, and tannic acid. The internal positive control (IPC) provided in the Quantifiler™ Human DNA Quantification Kit (Life Technologies, Foster City, CA) and short tandem repeat (STR) profiling (AmpFℓSTR® Identifiler® Plus PCR Amplification Kit; Life Technologies, Foster City, CA) were used to measure inhibition effects and hence purification. SCODA methodology yielded overall higher efficiency of purification of highly contaminated samples compared with the QIAquick® PCR Purification Kit (Qiagen, Valencia, CA). SCODA-purified DNA yielded no cycle shift of the IPC for each sample and yielded greater allele percentage recovery and relative fluorescence unit values compared with the QIAquick® purification method. The Aurora provided an automated, minimal-step approach to successfully remove inhibitors and concentrate DNA from challenged samples.

PMID: 23254459 [PubMed - indexed for MEDLINE]

Associations between bar patron alcohol intoxication and tobacco smoking.

Tue, 04/01/2014 - 4:40am
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Associations between bar patron alcohol intoxication and tobacco smoking.

Am J Health Behav. 2013 Nov;37(6):794-9

Authors: Rossheim ME, Thombs DL, O'Mara RJ, Bastian N, Suzuki S

Abstract
OBJECTIVE: To examine the event-specific relationship between alcohol intoxication and nighttime tobacco smoking among college bar patrons.
METHODS: In this secondary analysis of existing data, we examined event-specific associations between self-report measures of tobacco smoking and breath alcohol concentration (BrAC) readings obtained from 424 patrons exiting on-premise drinking establishments.
RESULTS: In a multivariable logistic regression analysis, acute alcohol intoxication was positively associated with same-night incidents of smoking tobacco, adjusting for the effects of established smoking practices and other potential confounders.
CONCLUSIONS: This investigation is the first known study using data collected in an on-premise drinking setting to link alcohol intoxication to specific incidents of tobacco smoking.

PMID: 24001628 [PubMed - indexed for MEDLINE]