Recent Research Articles from UNTHSC

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M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

Wed, 11/04/2015 - 11:29
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M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

J Immunol. 2015 Nov 2;

Authors: Tsuchimoto Y, Asai A, Tsuda Y, Ito I, Nishiguchi T, Garcia MC, Suzuki S, Kobayashi M, Higuchi K, Suzuki F

Abstract
Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.

PMID: 26525287 [PubMed - as supplied by publisher]

Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.

Wed, 11/04/2015 - 11:29
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Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.

Anticancer Drugs. 2015 Mar;26(3):293-300

Authors: He W, Liu R, Yang SH, Yuan F

Abstract
Tamoxifen, a selective estrogen receptor modulator, is widely used in the chemotherapy of estrogen receptor-positive breast cancer. Recent studies have indicated that tamoxifen might have a potential chemotherapeutic effect on glioma. In the present study, we determined the chemotherapeutic action of tamoxifen on human glioma cell lines. Methylation of 06-methylguanine-DNA methyltransferase was identified in A172, U251, and BT325 glioma cell lines, but not in the U87 cell line. Consistently, A172, U251, and BT325 cell lines are resistant to temozolomide. Tamoxifen induced significant cytotoxic action in A172, U251, BT325, and U87 cell lines. Further, Hoechst 33342 staining and apoptosis flow cytometric analysis demonstrated that tamoxifen induced apoptosis in the BT325 cell line. Mitochondrial complex analysis indicated that tamoxifen, but not other estrogen receptor modulators, dose-dependently inhibits complex I activity. In summary, our study suggests that tamoxifen might have a chemotherapeutic effect on temozolomide-resistant glioma through its direct action on mitochondrial complex I inhibition and could provide further evidence to support future clinical trials of tamoxifen for the treatment of glioblastoma.

PMID: 25535979 [PubMed - indexed for MEDLINE]

High Alcohol Concentration Products Associated With Poverty and State Alcohol Policies.

Sat, 10/31/2015 - 11:29
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High Alcohol Concentration Products Associated With Poverty and State Alcohol Policies.

Am J Public Health. 2015 Sep;105(9):1886-92

Authors: Rossheim ME, Thombs DL, Wagenaar AC, Xuan Z, Aryal S

Abstract
OBJECTIVES: We examined the associations among zip code demographics, the state alcohol policy environment, and the retail outlet availability of multiple fruit-flavored alcoholic drinks in a can (MFAC).
METHODS: In a nationally representative sample of zip codes (n = 872), we merged data from 4 sources: publicly available marketing information from 2 major MFAC producers, the US Census Bureau, state alcohol regulatory agencies, and recent research on state alcohol policies. We used zero-inflated negative binomial regression models to examine MFAC outlet availability in the United States.
RESULTS: More than 98% of MFAC outlets were off-premises alcohol establishments. After we controlled for population size and the number of licensed on- and off-premises alcohol outlets within zip codes, more families below the poverty line and weaker state alcohol control policies were associated with greater MFAC outlet availability.
CONCLUSIONS: Economic conditions and alcohol policy environment appeared to be related to MFAC outlet availability, after adjusting for the general availability of alcohol. Research is needed to determine whether MFACs are disproportionately contributing to alcohol-related harm in socially and economically disadvantaged communities. Policies to better regulate the off-premises sale of alcohol are needed.

PMID: 26180984 [PubMed - indexed for MEDLINE]

Differences in the Limits of Stability Between Older Rolling Walker Users and Older Single-Tip-Cane Users - A Preliminary Study.

Tue, 10/27/2015 - 07:29
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Differences in the Limits of Stability Between Older Rolling Walker Users and Older Single-Tip-Cane Users - A Preliminary Study.

Rehabil Nurs. 2015 Oct 25;

Authors: Liu HH, Quiben M, Holmes C, Connors M, Salem Y

Abstract
PURPOSE: To identify the differences in the limits of stability (LOS) between older rolling walker and single-tip-cane users.
DESIGN: This was a matched paired t-test design with respected measure.
METHODS: Eighteen older subjects were matched based on age, gender, and functional level. The subjects were assessed using the multidirectional reach test initially and 5-month later in four directions: forward, backward, leftward, and rightward.
FINDINGS: Initially, there were no differences between cane users and rolling walker users in the LOS in all directions. However, 5-month later, the cane users who held their canes in their right hand had significantly better stability in forward and rightward reach than the walker users (p < .05). Further, the walker users demonstrated significantly decreased functional reach in forward reach (p < .05).
CONCLUSION: Cane users might have better stability than walker users in the forward direction and in the direction toward the side holding the cane. This study may provide guide for clinicians including nurses for selecting appropriate rehabilitative interventions for older adults using walkers and canes.

PMID: 26497836 [PubMed - as supplied by publisher]

Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Tue, 10/27/2015 - 07:29
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Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Mol Neurobiol. 2015 Oct 26;

Authors: Wei X, Gao H, Zou J, Liu X, Chen D, Liao J, Xu Y, Ma L, Tang B, Zhang Z, Cai X, Jin K, Xia Y, Wang Q

Abstract
Recent evidence suggests that nerve growth factor IB (Nur77) and nuclear receptor related1 (Nurr1) are differentially involved in dopaminergic neurodegeneration. Since memantine has shown clinically relevant efficacy in Parkinson's disease (PD) and displayed a potent protective effect on dopaminergic neurons in experimental PD models, we asked if it exerts its neuroprotection by regulating Nur77 and Nurr1 signaling. We adopted a well-established in vitro PD model, 6-hydroxydopamine (OHDA)-lesioned PC12 cells, to test our hypothesis. Different concentrations of memantine were incubated with 6-OHDA-lesioned PC12 cells, and Nur77/Nurr1 and their related signaling molecules were examined by Western blot and immunocytochemistry. Nur77-deficient PC12 cells were used to verify the influences of Nur77 on neurodegeneration and memantine-mediated neuroprotection. We found that memantine reversed Nur77 upregulation and restored Nurr1 downregulation in 6-OHDA-lesioned PC12 cells. 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and induced co-localization of Cyt c/HSP60/Nur77 in the cytosol. Memantine strongly reduced the sub-cellular translocations of Nur77/Cyt c/HSP60 under 6-OHDA-induced oxidative condition. Knockdown of Nur77 enhanced the viability of PC12 cells exposed to 6-OHDA, while memantine-induced neuroprotection was much less in the cells with Nur77 knockdown than in those without it. We conclude that Nur77 plays a crucial role in modulating mitochondrial impairment and contributes to neurodegeneration under the experimental PD condition. Memantine effectively suppresses such Nur77-mediated neurodegeneration and promotes survival signaling through post-translational modification of Nurr1. Nur77 and Nurr1 present a contra-directionally coupling interaction in memantine-mediated neuroprotection.

PMID: 26497037 [PubMed - as supplied by publisher]

Bilorrhea secondary to bronchobiliary fistula.

Tue, 10/27/2015 - 07:29
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Bilorrhea secondary to bronchobiliary fistula.

Int Surg. 2014 Jul-Aug;99(4):438-41

Authors: Olivencia-Yurvati AH, Rollins C

Abstract
Bronchobiliary fistula (BBF) is a rare condition which occurs most commonly as a complication of hydatid cyst liver disease. The following report describes a patient who presented with biliptysis 6 months following decortication of an empyema that had occurred following partial hepatectomy of a colon cancer metastasis. This is the only case to our knowledge that describes the presentation of a BBF in this context. The patient was diagnosed with BBF and successfully underwent open thoracotomy for fistulectomy and repair.

PMID: 25058780 [PubMed - indexed for MEDLINE]

Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Tue, 10/27/2015 - 07:29
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Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Dement Geriatr Cogn Disord. 2014;38(5-6):300-9

Authors: Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Cunningham R, Singh M, O'Bryant SE

Abstract
BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD.
METHODS: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed.
RESULTS: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC.
CONCLUSION: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

PMID: 25011444 [PubMed - indexed for MEDLINE]

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

Sat, 10/24/2015 - 07:33
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The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Disabil Health J. 2015 Sep 25;

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

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

PMID: 26493638 [PubMed - as supplied by publisher]

Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

Sat, 10/24/2015 - 07:33
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Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

J Neurophysiol. 2015 Feb 15;113(4):1165-74

Authors: Xu H, Boychuk JA, Boychuk CR, Uteshev VV, Smith BN

Abstract
The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.

PMID: 25429117 [PubMed - indexed for MEDLINE]

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Fri, 10/23/2015 - 07:29

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Int J Sports Phys Ther. 2015 Oct;10(5):602-11

Authors: Garrison JC, Bothwell JM, Wolf G, Aryal S, Thigpen CA

Abstract
BACKGROUND: Restoration of symmetrical strength, balance, and power following anterior cruciate ligament reconstruction (ACL-R) are thought to be important factors for successful return to sports. Little information is available regarding early rehabilitation outcomes and achieving suggested limb indices of 90% on functional performance measures at the time of return to sports (RTS).
HYPOTHESIS/PURPOSE: To examine the relationship between symmetry of the anterior reach of the Y Balance Test™ at 12 weeks and functional performance measures at time of return to sports after anterior cruciate ligament (ACL) reconstruction.
STUDY DESIGN: Retrospective Cohort.
METHODS: Forty subjects (mean ± SD age, 17.2 ± 3.8 years) who were in the process of rehabilitation following ACL reconstruction. Each subject volunteered and was enrolled in the study during physical therapy following ACL-R. Participants averaged two visits per week in physical therapy until the time of testing for RTS. The Y Balance Test™ was assessed at 12 weeks. Participants completed a battery of tests at RTS (6.4 ± 1.1 months) including triple hop distance (THD), single hop distance (SHD), isometric knee extension strength (KE), and the Vail Sport Test™. Side to side difference was calculated for the Y Balance Test™ anterior reach and limb symmetry indices (LSI) were computed for THD, SHD, and KE. Multiple regression models were used to study the relationship between variables at 12 weeks and RTS while controlling for age, gender, type of graft, and pain score. In addition, subjects were dichotomized based on a side-to-side Y Balance anterior reach difference into high risk (>4 cm) or low risk (≤4 cm) categories. A receiver operating characteristic (ROC) curve was used to identify individuals at 12 weeks who do not achieve 90% limb symmetry indices at time of RTS testing. .
RESULTS: A statistically significant association was seen between Y Balance ANT at 12 weeks and SHD at RTS (β = -1.46, p = 0.0005, R(2) = 0.395), THD at RTS (β = -1.08, p = 0.0011, R(2) = 0.354) and KE at RTS (β = -1.00, p = 0.0025, R(2) = 0.279) after adjusting for age, gender, type of graft and pain score at week 12. There was no significant association between Y Balance ANT at 12 weeks and Vail Sport Test at RTS (p = 0.273). ROC curves indicated that the Y Balance ANT at 12 weeks identified participants who did not achieve 90% LSI for the SHD (AUC = 0.82 p = 0.02) and THD (AUC=0.85, p = 0.01) at RTS with a sensitivity of 0.96 (SHD) and 0.92 (THD) respectively.
CONCLUSIONS: Participants following ACL-R who demonstrated > 4 cm Y Balance ANT deficits at 12 weeks on their involved limb did not tend to achieve 90% LSI for the SHD and THD at time of return to sports. The Y Balance ANT at 12 weeks and Vail Sport Test™ appear to measure different constructs following ACL-R.
LEVELS OF EVIDENCE: Level 3.

PMID: 26491610 [PubMed]

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