Recent Research Articles from UNTHSC

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HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads.

Thu, 11/19/2015 - 10:34
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HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads.

Front Microbiol. 2015;6:1143

Authors: Borgmann K, Ghorpade A

Abstract
As a popular psychostimulant, methamphetamine (METH) use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10 and 15% of human immunodeficiency virus-1 (HIV-1) patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND) through direct and indirect mechanisms. Repetitive METH use impedes adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression toward AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte numbers and activity, cytokine signaling, phagocytic function and infiltration through the blood brain barrier. Further, METH triggers the dopamine reward pathway and leads to impaired neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation, which modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress, and excitotoxicity. Pathologically, reactive gliosis is a hallmark of both HIV-1- and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus, this review highlights alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, with special emphasis on HAND-associated neuroinflammation. Importantly, this review carefully evaluates interventions targeting astrocytes in HAND and METH as potential novel therapeutic approaches. This comprehensive overview indicates, without a doubt, that during HIV-1 infection and METH abuse, a complex dialog between all neural cells is orchestrated through astrocyte regulated neuroinflammation.

PMID: 26579077 [PubMed - as supplied by publisher]

HDL as a drug and nucleic acid delivery vehicle.

Thu, 11/19/2015 - 10:34
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HDL as a drug and nucleic acid delivery vehicle.

Front Pharmacol. 2015;6:247

Authors: Lacko AG, Sabnis NA, Nagarajan B, McConathy WJ

Abstract
This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s) of high density lipoprotein type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload) in their natural/physiological environment. The ability to accommodate highly water insoluble constituents in their core regions enables High density lipoproteins (HDL) type nanoparticles to effectively transport hydrophobic drugs subsequent to systemic administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents is compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

PMID: 26578957 [PubMed - as supplied by publisher]

High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: proof-of-concept.

Wed, 11/18/2015 - 14:34
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High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: proof-of-concept.

Brain Res Bull. 2015 Mar;112:35-41

Authors: Gatson JW, Simpkins JW, Uteshev VV

Abstract
There are currently no clinically efficacious drug therapies to treat brain damage secondary to traumatic brain injury (TBI). In this proof-of-concept study, we used a controlled cortical impact model of TBI in young adult rats to explore a novel promising approach that utilizes PNU-120596, a previously reported highly selective Type-II positive allosteric modulator (α7-PAM) of α7 nicotinic acetylcholine receptors (nAChRs). α7-PAMs enhance and prolong α7 nAChR activation, but do not activate α7 nAChRs when administered without an agonist. The rational basis for the use of an α7-PAM as a post-TBI treatment is tripartite and arises from: (1) the intrinsic ability of brain injury to elevate extracellular levels of choline (a ubiquitous cell membrane-building material and a selective endogenous agonist of α7 nAChRs) due to the breakdown of cell membranes near the site and time of injury; (2) the ubiquitous expression of functional α7 nAChRs in neuronal and glial/immune brain cells; and (3) the potent neuroprotective and anti-inflammatory effects of α7 nAChR activation. Therefore, both neuroprotective and anti-inflammatory effects can be achieved post-TBI by targeting only a single player (i.e., the α7 nAChR) using α7-PAMs to enhance the activation of α7 nAChRs by injury-elevated extracellular choline. Our data support this hypothesis and demonstrate that subcutaneous administration of PNU-120596 post-TBI in young adult rats significantly reduces both brain cell damage and reactive gliosis. Therefore, our results introduce post-TBI systemic administration of α7-PAMs as a promising therapeutic intervention that could significantly restrict brain injury post-TBI and facilitate recovery of TBI patients.

PMID: 25647232 [PubMed - indexed for MEDLINE]

Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Wed, 11/18/2015 - 14:34
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Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Leg Med (Tokyo). 2015 Mar;17(2):123-7

Authors: Davis C, Peters D, Warshauer D, King J, Budowle B

Abstract
Mitochondrial DNA testing is a useful tool in the analysis of forensic biological evidence. In cases where nuclear DNA is damaged or limited in quantity, the higher copy number of mitochondrial genomes available in a sample can provide information about the source of a sample. Currently, Sanger-type sequencing (STS) is the primary method to develop mitochondrial DNA profiles. This method is laborious and time consuming. Massively parallel sequencing (MPS) can increase the amount of information obtained from mitochondrial DNA samples while improving turnaround time by decreasing the numbers of manipulations and more so by exploiting high throughput analyses to obtain interpretable results. In this study 18 buccal swabs, three different tissue samples from five individuals, and four bones samples from casework were sequenced at hypervariable regions I and II using STS and MPS. Sample enrichment for STS and MPS was PCR-based. Library preparation for MPS was performed using Nextera® XT DNA Sample Preparation Kit and sequencing was performed on the MiSeq™ (Illumina, Inc.). MPS yielded full concordance of base calls with STS results, and the newer methodology was able to resolve length heteroplasmy in homopolymeric regions. This study demonstrates short amplicon MPS of mitochondrial DNA is feasible, can provide information not possible with STS, and lays the groundwork for development of a whole genome sequencing strategy for degraded samples.

PMID: 25459369 [PubMed - indexed for MEDLINE]

Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: a finite element study.

Wed, 11/18/2015 - 14:34
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Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: a finite element study.

Technol Health Care. 2015;23(1):83-92

Authors: Kosmopoulos V, Luedke C, Nana AD

Abstract
BACKGROUND: A smaller humerus in some patients makes the use of a large fragment fixation plate difficult. Dual small fragment plate constructs have been suggested as an alternative.
OBJECTIVE: This study compares the biomechanical performance of three single and one dual plate construct for mid-diaphyseal humeral fracture fixation.
METHODS: Five humeral shaft finite element models (1 intact and 4 fixation) were loaded in torsion, compression, posterior-anterior (PA) bending, and lateral-medial (LM) bending. A comminuted fracture was simulated by a 1-cm gap. Fracture fixation was modelled by: (A) 4.5-mm 9-hole large fragment plate (wide), (B) 4.5-mm 9-hole large fragment plate (narrow), (C) 3.5-mm 9-hole small fragment plate, and (D) one 3.5-mm 9-hole small fragment plate and one 3.5-mm 7-hole small fragment plate.
RESULTS: Model A showed the best outcomes in torsion and PA bending, whereas Model D outperformed the others in compression and LM bending. Stress concentrations were located near and around the unused screw holes for each of the single plate models and at the neck of the screws just below the plates for all the models studied. Other than in PA bending, Model D showed the best overall screw-to-screw load sharing characteristics.
CONCLUSION: The results support using a dual small fragment locking plate construct as an alternative in cases where crutch weight-bearing (compression) tolerance may be important and where anatomy limits the size of the humerus bone segment available for large fragment plate fixation.

PMID: 25408282 [PubMed - indexed for MEDLINE]

Attitudes associated with alcohol and marijuana referral actions by resident assistants.

Wed, 11/18/2015 - 14:34
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Attitudes associated with alcohol and marijuana referral actions by resident assistants.

J Prim Prev. 2014 Dec;35(6):429-37

Authors: Thombs DL, Osborn CJ, Rossheim ME, Suzuki S

Abstract
This exploratory study examined associations between resident assistant (RA) attitudes and referral actions to identify training strategies for strengthening the ability of these paraprofessionals to recognize and refer college students in their living units who misuse alcohol and marijuana. The study's hypotheses were that (1) referral self-efficacy and perceived referral norms would be positively associated with RA referral actions and (2) perceived referral barriers and referral anticipatory anxiety would be negatively associated with RAs' referral actions. A total of 317 RAs at eight residential campuses in different regions of the U.S. took part in the study. All participating RAs had at least one semester of work experience. Just prior to the Fall semester of 2012, RA's responded to an online survey that assessed their alcohol and marijuana referral attitudes and referral actions. Overall, RAs reported considerable anxiety about approaching and referring students who may have an alcohol and/or marijuana problem. Perceived referral norms among RAs indicated substantial variability in perceptions about others' expectations of them for referring students who may have alcohol and marijuana problems. Results from two multivariable logistic regression analyses showed that referral self-efficacy distinguished RAs who took alcohol referral actions and marijuana referral actions from those who did not do so. Neither length of RA service nor time spent on campus was associated with referral actions. RA training programs could give attention to strengthening referral self-efficacy through a series of increasingly difficult skill-building activities during pre- and in-service training. In addition, senior residence life and housing professional staff may consider assessing the extent to which RAs under their supervision follow established protocols for assisting students with possible alcohol and marijuana problems. The development of evidence-based RA training programs will require additional research.

PMID: 25245491 [PubMed - indexed for MEDLINE]

Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance in β Cell Function and Dysfunction.

Tue, 11/17/2015 - 10:30

Roles of Pyruvate, NADH, and Mitochondrial Complex I in Redox Balance and Imbalance in β Cell Function and Dysfunction.

J Diabetes Res. 2015;2015:512618

Authors: Luo X, Li R, Yan LJ

Abstract
Pancreatic β cells not only use glucose as an energy source, but also sense blood glucose levels for insulin secretion. While pyruvate and NADH metabolic pathways are known to be involved in regulating insulin secretion in response to glucose stimulation, the roles of many other components along the metabolic pathways remain poorly understood. Such is the case for mitochondrial complex I (NADH/ubiquinone oxidoreductase). It is known that normal complex I function is absolutely required for episodic insulin secretion after a meal, but the role of complex I in β cells in the diabetic pancreas remains to be investigated. In this paper, we review the roles of pyruvate, NADH, and complex I in insulin secretion and hypothesize that complex I plays a crucial role in the pathogenesis of β cell dysfunction in the diabetic pancreas. This hypothesis is based on the establishment that chronic hyperglycemia overloads complex I with NADH leading to enhanced complex I production of reactive oxygen species. As nearly all metabolic pathways are impaired in diabetes, understanding how complex I in the β cells copes with elevated levels of NADH in the diabetic pancreas may provide potential therapeutic strategies for diabetes.

PMID: 26568959 [PubMed - as supplied by publisher]

The 'sweet' spot of cellular pluripotency: protein glycosylation in human pluripotent stem cells and its applications in regenerative medicine.

Tue, 11/17/2015 - 10:30
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The 'sweet' spot of cellular pluripotency: protein glycosylation in human pluripotent stem cells and its applications in regenerative medicine.

Expert Opin Biol Ther. 2015 May;15(5):679-87

Authors: Wang YC, Lin V, Loring JF, Peterson SE

Abstract
INTRODUCTION: Human pluripotent stem cells (hPSCs) promise for the future of regenerative medicine. The structural and biochemical diversity associated with glycans makes them a unique type of macromolecule modification that is involved in the regulation of a vast array of biochemical events and cellular activities including pluripotency in hPSCs. The primary focus of this review article is to highlight recent advances in stem cell research from a glycobiological perspective. We also discuss how our understanding of glycans and glycosylation may help overcome barriers hindering the clinical application of hPSC-derived cells.
AREAS COVERED: A literature survey using NCBI-PubMed and Google Scholar was performed in 2014.
EXPERT OPINION: Regenerative medicine hopes to provide novel strategies to combat human disease and tissue injury that currently lack effective therapies. Although progress in this field is accelerating, many critical issues remain to be addressed in order for cell-based therapy to become a practical and safe treatment option. Emerging evidence suggests that protein glycosylation may significantly influence the regulation of cellular pluripotency, and that the exploitation of protein glycosylation in hPSCs and their differentiated derivatives may lead to transformative and translational discoveries for regenerative medicine. In addition, hPSCs represent a novel research platform for investigating glycosylation-related disease.

PMID: 25736263 [PubMed - indexed for MEDLINE]

Neighborhood Disadvantage, Physical Activity Barriers, and Physical Activity among African American Breast Cancer Survivors.

Sat, 11/14/2015 - 07:32
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Neighborhood Disadvantage, Physical Activity Barriers, and Physical Activity among African American Breast Cancer Survivors.

Prev Med Rep. 2015;2:622-627

Authors: Jones A, Paxton RJ

Abstract
BACKGROUND: In view of evidence that African American cancer survivors experience the greatest challenges in maintaining adequate levels of physical activity, this cross-section study was designed to determine whether individual and residential environment characteristics are associated with physical activity in this population.
METHODS: A total of 275 breast cancer survivors completed self-report items measuring sociodemographic variables, physical activity, and select barriers to physical activity in Spring of 2012. Neighborhood disadvantage variables were extracted from national databases. Regression models were computed to assess relationships.
RESULTS: Traditional correlates of smoking status and the presence of health complications were associated with physical activity. In addition, the relative number of renters versus homeowners in one's neighborhood was associated with lower levels of physical activity in the context of individual level barriers (i.e., interest and space), which were also associated with lower levels of physical activity.
DISCUSSION: Higher renter rates and individual barriers both contribute to lower levels of physical activity in African American breast cancer survivors. These data suggest that the potential for constant residential turnover (via rentership) and perceived barriers may increase physical inactivity even where facilities may be available.

PMID: 26566472 [PubMed - as supplied by publisher]

Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

Thu, 11/12/2015 - 07:29
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Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse.

BMC Womens Health. 2015;15(1):98

Authors: Cannell MB, Weitlauf JC, Garcia L, Andresen EM, Margolis KL, Manini TM

Abstract
BACKGROUND: Exposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women's health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation.
METHODS: Multivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women's Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time.
RESULT: Abuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure.
CONCLUSIONS: Taken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician's vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women's diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood.

PMID: 26554450 [PubMed - as supplied by publisher]

Comparison of phenology and pathogen prevalence, including infection with the Ehrlichia muris-like (EML) agent, of Ixodes scapularis removed from soldiers in the midwestern and the northeastern United States over a 15 year period (1997-2012).

Tue, 11/10/2015 - 07:30
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Comparison of phenology and pathogen prevalence, including infection with the Ehrlichia muris-like (EML) agent, of Ixodes scapularis removed from soldiers in the midwestern and the northeastern United States over a 15 year period (1997-2012).

Parasit Vectors. 2014;7:553

Authors: Stromdahl E, Hamer S, Jenkins S, Sloan L, Williamson P, Foster E, Nadolny R, Elkins C, Vince M, Pritt B

Abstract
BACKGROUND: Since 1997, human-biting ticks submitted to the Department of Defense Human Tick Test Kit Program (HTTKP) of the US Army Public Health Command have been tested for pathogens by PCR. We noted differences in the phenology and infection prevalence among Ixodes scapularis ticks submitted from military installations in different geographic regions. The aim of this study was to characterize these observed differences, comparing the phenology and pathogen infection rates of I. scapularis submitted from soldiers at two sites in the upper Midwest (Camp Ripley, MN, and Ft. McCoy, WI) and one site in the northeastern US (Ft. Indiantown Gap, PA).
METHODS: From 1997 through 2012, the HTTKP received 1,981 I. scapularis from the three installations and tested them for Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi and the Ehrlichia muris-like (EML) agent using PCR; pathogen presence was confirmed via sequencing or amplification of a second gene target. Pathogen and co-infection prevalence, tick engorgement status, and phenology were compared among installations.
RESULTS: Greater rates of A. phagocytophilum and Ba. microti infections were detected in ticks submitted from installations in Minnesota than in Wisconsin or Pennsylvania, and the EML agent was only detected in ticks from Minnesota and Wisconsin. Midwestern ticks were also more likely to be co-infected than those from Pennsylvania. Both adult and nymphal ticks showed evidence of feeding on people, although nymphs were more often submitted engorged. Adult I. scapularis were received more frequently in June from Minnesota than from either of the other sites. Minnesota adult and nymphal peaks overlapped in June, and submissions of adults exceeded nymphs in that month.
CONCLUSIONS: There were clear differences in I. scapularis phenology, pathogen prevalence and rates of co-infection among the three military installations. Seasonal and temperature differences between the three sites and length of time a population had been established in each region may contribute to the observed differences. The synchrony of adults and nymphs observed in the upper Midwest has implications for pathogen infection prevalence. The EML agent was only detected in Minnesota and Wisconsin, supporting the previous assertion that this pathogen is currently limited to the upper Midwest.

PMID: 25465046 [PubMed - indexed for MEDLINE]

Adherence, Healthcare Resource Use (Hru) And Costs: A Comparison Of Single-Tablet Regimen (Str) Versus Multi-Tablet Regimen (Mtr) Containing Fixed Dose Combination (Fdc) Regimens.

Thu, 11/05/2015 - 07:29
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Adherence, Healthcare Resource Use (Hru) And Costs: A Comparison Of Single-Tablet Regimen (Str) Versus Multi-Tablet Regimen (Mtr) Containing Fixed Dose Combination (Fdc) Regimens.

Value Health. 2015 Nov;18(7):A577

Authors: Narayanan S, Clay PG

PMID: 26533241 [PubMed - in process]

Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli.

Wed, 11/04/2015 - 11:29
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Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli.

Molecules. 2015;20(11):19690-19698

Authors: Koneru B, Shi Y, Wang YC, Chavala SH, Miller ML, Holbert B, Conson M, Ni A, Di Pasqua AJ

Abstract
Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect.

PMID: 26528964 [PubMed - as supplied by publisher]

Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels.

Wed, 11/04/2015 - 11:29
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Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels.

Blood. 2015 Nov 2;

Authors: Mullighan CG, Jeha S, Pei D, Payne-Turner D, Coustan-Smith E, Roberts KG, Waanders E, Choi JK, Ma X, Raimondi SC, Fan Y, Yang W, Song G, Yang JJ, Inaba H, Downing JR, Leung WH, Bowman WP, Relling MV, Evans WE, Zhang J, Campana D, Pui CH

PMID: 26527677 [PubMed - as supplied by publisher]

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]

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