Recent Research Articles from UNTHSC

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Measurement Properties of the Sedentary Behavior Strategy Self-management Instrument in African-American Breast Cancer Survivors.

Tue, 01/13/2015 - 4:29am

Measurement Properties of the Sedentary Behavior Strategy Self-management Instrument in African-American Breast Cancer Survivors.

Am J Health Behav. 2015 Mar;39(2):175-182

Authors: Paxton RJ, Gao Y, Herrmann SD, Norman GJ

Abstract
OBJECTIVES: To examine the validity and reliability of a modified Sedentary Behavior Strategy Self-Management Scale (SBSMS) in a sample of breast cancer survivors.
METHODS: A total of 291 African-American (AA) breast cancer survivors completed the SBSMS, which was subjected to tests of reliability, structural validity, and tests of measurement equivalence/invariance (ME/I).
RESULTS: A revised measurement model fit the data and demonstrated internal reliability and structural validity. Tests for ME/I revealed that the revised model had appropriate levels of invariance among weight status, educational, and years out from diagnosis groups, but not among age groups.
CONCLUSION: The reliability and structural validity of the instrument was supported overall; however, revisions may be needed to support its validity in older AA breast cancer survivors.

PMID: 25564829 [PubMed - as supplied by publisher]

Preoperative decision making in the treatment of high-angle "vertical" femoral neck fractures in young adult patients. An expert opinion survey of the Orthopaedic Trauma Association's (OTA) membership.

Thu, 01/08/2015 - 4:29am
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Preoperative decision making in the treatment of high-angle "vertical" femoral neck fractures in young adult patients. An expert opinion survey of the Orthopaedic Trauma Association's (OTA) membership.

J Orthop Trauma. 2014 Sep;28(9):e221-5

Authors: Luttrell K, Beltran M, Collinge CA

Abstract
OBJECTIVE: To identify the current implant and diagnostic imaging preferences among orthopaedic trauma experts for the treatment of high-energy vertical femoral neck fractures in young adult patients.
DESIGN: Web-based survey.
SETTING: Not available.
PARTICIPANTS: Active members of the OTA.
METHODS: A cross-sectional expert opinion survey was administered to the 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-degree Pauwels angle fracture in a healthy 30-year-old patient). Questions were also asked regarding the reason why this implant was selected, whether the surgeon felt that their choice was supported by the literature, and what imaging studies are routinely obtained to guide decision making. Data were collected using simple multiple-choice questions and/or a 5-point Likert item.
RESULTS: Two hundred 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." Most surgeons required anteroposterior pelvis (70%) and standard hip (88%) radiographs; however only 29% of surgeons required a computed tomography (59% found computed tomography 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" orthopaedic 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: 25148589 [PubMed - indexed for MEDLINE]

The impact of APOE status on relationship of biomarkers of vascular risk and systemic inflammation to neuropsychiatric symptoms in Alzheimer's disease.

Thu, 01/08/2015 - 4:29am
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The impact of APOE status on relationship of biomarkers of vascular risk and systemic inflammation to neuropsychiatric symptoms in Alzheimer's disease.

J Alzheimers Dis. 2014;40(4):887-96

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

Abstract
Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered.

PMID: 24577461 [PubMed - indexed for MEDLINE]

Dehydrated Amnion/Chorion Membrane and Venous Leg Ulcers.

Wed, 01/07/2015 - 4:30am

Dehydrated Amnion/Chorion Membrane and Venous Leg Ulcers.

Wound Repair Regen. 2014 Dec 30;

Authors: Dickerson JE, Slade HB

PMID: 25556326 [PubMed - as supplied by publisher]

Characterization of [(3) H]LS-3-134, a novel arylamide phenylpiperazine D3 dopamine receptor selective radioligand.

Wed, 01/07/2015 - 4:30am
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Characterization of [(3) H]LS-3-134, a novel arylamide phenylpiperazine D3 dopamine receptor selective radioligand.

J Neurochem. 2014 Nov;131(4):418-31

Authors: Rangel-Barajas C, Malik M, Taylor M, Neve KA, Mach RH, Luedtke RR

Abstract
LS-3-134 is a substituted N-phenylpiperazine derivative that has been reported to exhibit: (i) high-affinity binding (Ki value 0.2 nM) at human D3 dopamine receptors, (ii) > 100-fold D3 versus D2 dopamine receptor subtype binding selectivity, and (iii) low-affinity binding (Ki  > 5000 nM) at sigma 1 and sigma 2 receptors. Based upon a forskolin-dependent activation of the adenylyl cyclase inhibition assay, LS-3-134 is a weak partial agonist at both D2 and D3 dopamine receptor subtypes (29% and 35% of full agonist activity, respectively). In this study, [(3) H]-labeled LS-3-134 was prepared and evaluated to further characterize its use as a D3 dopamine receptor selective radioligand. Kinetic and equilibrium radioligand binding studies were performed. This radioligand rapidly reaches equilibrium (10-15 min at 37°C) and binds with high affinity to both human (Kd  = 0.06 ± 0.01 nM) and rat (Kd  = 0.2 ± 0.02 nM) D3 receptors expressed in HEK293 cells. Direct and competitive radioligand binding studies using rat caudate and nucleus accumbens tissue indicate that [(3) H]LS-3-134 selectively binds a homogeneous population of binding sites with a dopamine D3 receptor pharmacological profile. Based upon these studies, we propose that [(3) H]LS-3-134 represents a novel D3 dopamine receptor selective radioligand that can be used for studying the expression and regulation of the D3 dopamine receptor subtype.

PMID: 25041389 [PubMed - indexed for MEDLINE]

Collaborative EDNAP exercise on the IrisPlex system for DNA-based prediction of human eye colour.

Wed, 01/07/2015 - 4:30am
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Collaborative EDNAP exercise on the IrisPlex system for DNA-based prediction of human eye colour.

Forensic Sci Int Genet. 2014 Jul;11:241-51

Authors: Chaitanya L, Walsh S, Andersen JD, Ansell R, Ballantyne K, Ballard D, Banemann R, Bauer CM, Bento AM, Brisighelli F, Capal T, Clarisse L, Gross TE, Haas C, Hoff-Olsen P, Hollard C, Keyser C, Kiesler KM, Kohler P, Kupiec T, Linacre A, Minawi A, Morling N, Nilsson H, Norén L, Ottens R, Palo JU, Parson W, Pascali VL, Phillips C, Porto MJ, Sajantila A, Schneider PM, Sijen T, Söchtig J, Syndercombe-Court D, Tillmar A, Turanska M, Vallone PM, Zatkalíková L, Zidkova A, Branicki W, Kayser M

Abstract
The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.

PMID: 24880832 [PubMed - indexed for MEDLINE]

Developmental validation of the EX20+4 system.

Wed, 01/07/2015 - 4:30am
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Developmental validation of the EX20+4 system.

Forensic Sci Int Genet. 2014 Jul;11:207-13

Authors: Li S, Liu C, Liu H, Ge J, Budowle B, Liu C, Zheng W, Li F, Ge B

Abstract
The EX20+4Y System is a polymerase chain reaction (PCR)-based amplification kit that enables typing of 19 autosomal short tandem repeat (STR) loci (i.e., CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, TH01, TPOX, vWA, Penta D, Penta E, D2S1338, D19S433, D12S391, D6S1043), four widely used Y chromosome-specific STR (Y-STR) loci (DYS458, DYS456, DYS391, DYS635), and amelogenin. In this study, this multiplex system was validated for sensitivity of detection, DNA mixtures, inhibitor tolerance, species specificity based on the Scientific Working Group on DNA Analysis methods (SWGDAM) developmental validation guidelines, and the Chinese criteria for the human fluorescent STR multiplex PCR reagent. The results show that the EX20+4 System is a robust and reliable amplification kit which can be used for human identification testing.

PMID: 24815370 [PubMed - indexed for MEDLINE]

Erythropoietin: powerful protection of ischemic and post-ischemic brain.

Wed, 01/07/2015 - 4:30am
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Erythropoietin: powerful protection of ischemic and post-ischemic brain.

Exp Biol Med (Maywood). 2014 Nov;239(11):1461-75

Authors: Nguyen AQ, Cherry BH, Scott GF, Ryou MG, Mallet RT

Abstract
Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10-15 min of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side-effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO's membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain's resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the prospects for induction of EPO production within the brain by the intermediary metabolite, pyruvate.

PMID: 24595981 [PubMed - indexed for MEDLINE]

Menu-labeling usage and its association with diet and exercise: 2011 BRFSS Sugar Sweetened Beverage and Menu Labeling module.

Wed, 01/07/2015 - 4:30am
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Menu-labeling usage and its association with diet and exercise: 2011 BRFSS Sugar Sweetened Beverage and Menu Labeling module.

Prev Chronic Dis. 2014;11:130231

Authors: Bowers KM, Suzuki S

Abstract
INTRODUCTION: The primary objective of our study was to investigate the association between menu-labeling usage and healthy behaviors pertaining to diet (consumption of fruits, vegetables, sodas, and sugar-sweetened beverages) and exercise.
METHODS: Data from the 2011 Behavioral Risk Factor Surveillance System, Sugar Sweetened Beverage and Menu-Labeling module, were used. Logistic regression was used to determine the association between menu-labeling usage and explanatory variables that included fruit, vegetable, soda, and sugar-sweetened beverage consumption as well as exercise.
RESULTS: Nearly half (52%) of the sample indicated that they used menu labeling. People who used menu labeling were more likely to be female (odds ratio [OR], 2.29; 95% confidence interval [CI], 2.04-2.58), overweight (OR, 1.13; 95% CI, 1.00-1.29) or obese (OR, 1.29; 95% CI, 1.12-1.50), obtain adequate weekly aerobic exercise (OR, 1.18; 95% CI, 1.06-1.32), eat fruits (OR, 1.20; 95% CI, 1.12-1.29) and vegetables (OR, 1.12; 95% CI, 1.05-1.20), and drink less soda (OR, 0.76; 95% CI, 0.69-0.83).
CONCLUSION: Although obese and overweight people were more likely to use menu labeling, they were also adequately exercising, eating more fruits and vegetables, and drinking less soda. Menu labeling is intended to combat the obesity epidemic; however the results indicate an association between menu-labeling usage and certain healthy behaviors. Thus, efforts may be necessary to increase menu-labeling usage among people who are not partaking in such behaviors.

PMID: 24384303 [PubMed - indexed for MEDLINE]

Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands.

Tue, 01/06/2015 - 12:29am

Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands.

Bioorg Med Chem Lett. 2014 Dec 17;

Authors: Peng X, Wang Q, Mishra Y, Xu J, Reichert DE, Malik M, Taylor M, Luedtke RR, Mach RH

Abstract
A series of 2-methoxyphenyl piperazine analogues containing a triazole ring were synthesized and their in vitro binding affinities at human dopamine D2 and D3 receptors were evaluated. Compounds 5b, 5c, 5d, and 4g, demonstrate high affinity for dopamine D3 receptors and moderate selectivity for the dopamine D3 versus D2 receptor subtypes. To further examine their potential as therapeutic agents, their intrinsic efficacy at both D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay. Affinity at dopamine D4 and serotonin 5-HT1A receptors was also determined. In addition, information from previous molecular modeling studies of the binding of a panel of 163 structurally-related benzamide analogues at dopamine D2 and D3 receptors was applied to this series of compounds. The results of the modeling studies were consistent with our previous experimental data. More importantly, the modeling study results explained why the replacement of the amide linkage with the hetero-aromatic ring leads to a reduction in the affinity of these compounds at D3 receptors.

PMID: 25556097 [PubMed - as supplied by publisher]

Joint pain in a man with lung cancer.

Sun, 01/04/2015 - 4:29am

Joint pain in a man with lung cancer.

Cleve Clin J Med. 2015 Jan;82(1):18-9

Authors: Jernigan E, Siddiqi N, Peddi P

PMID: 25552621 [PubMed - in process]

Organizational downsizing and depressive symptoms in the European recession: the experience of workers in France, Hungary, Sweden and the United kingdom.

Fri, 01/02/2015 - 4:30am
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Organizational downsizing and depressive symptoms in the European recession: the experience of workers in France, Hungary, Sweden and the United kingdom.

PLoS One. 2014;9(5):e97063

Authors: Brenner MH, Andreeva E, Theorell T, Goldberg M, Westerlund H, Leineweber C, Hanson LL, Imbernon E, Bonnaud S

Abstract
BACKGROUND: Organizational downsizing has become highly common during the global recession of the late 2000s with severe repercussions on employment. We examine whether the severity of the downsizing process is associated with a greater likelihood of depressive symptoms among displaced workers, internally redeployed workers and lay-off survivors.
METHODS: A cross-sectional survey involving telephone interviews was carried out in France, Hungary, Sweden and the United Kingdom. The study analyzes data from 758 workers affected by medium- and large-scale downsizing, using multiple logistic regression.
MAIN RESULTS: Both unemployment and surviving layoffs were significantly associated with depressive symptoms, as compared to reemployment, but the perceived procedural justice of a socially responsible downsizing process considerably mitigated the odds of symptoms. Perception of high versus low justice was assessed along several downsizing dimensions. In the overall sample, chances to have depressive symptoms were significantly reduced if respondents perceived the process as transparent and understandable, fair and unbiased, well planned and democratic; if they trusted the employer's veracity and agreed with the necessity for downsizing. The burden of symptoms was significantly greater if the process was perceived to be chaotic. We further tested whether perceived justice differently affects the likelihood of depressive symptoms among distinct groups of workers. Findings were that the odds of symptoms largely followed the same patterns of effects across all groups of workers. Redeploying and supporting surplus employees through the career change process-rather than forcing them to become unemployed-makes a substantial difference as to whether they will suffer from depressive symptoms.
CONCLUSIONS: While depressive symptoms affect both unemployed and survivors, a just and socially responsible downsizing process is important for the emotional health of workers.

PMID: 24841779 [PubMed - indexed for MEDLINE]

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

Thu, 01/01/2015 - 4:30am
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Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

Int J Mol Med. 2014 Jul;34(1):167-76

Authors: Sun L, Li W, Li W, Xiong L, Li G, Ma R

Abstract
Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

PMID: 24718766 [PubMed - indexed for MEDLINE]

Platelet Activation after Presyncope by Lower Body Negative Pressure in Humans.

Wed, 12/31/2014 - 4:30am

Platelet Activation after Presyncope by Lower Body Negative Pressure in Humans.

PLoS One. 2014;9(12):e116174

Authors: Zaar M, Fedyk CG, Pidcoke HF, Scherer MR, Ryan KL, Rickards CA, Hinojosa-Laborde C, Convertino VA, Cap AP

Abstract
Central hypovolemia elevates hemostatic activity which is essential for preventing exsanguination after trauma, but platelet activation to central hypovolemia has not been described. We hypothesized that central hypovolemia induced by lower body negative pressure (LBNP) activates platelets. Eight healthy subjects were exposed to progressive central hypovolemia by LBNP until presyncope. At baseline and 5 min after presyncope, hemostatic activity of venous blood was evaluated by flow cytometry, thrombelastography, and plasma markers of coagulation and fibrinolysis. Cell counts were also determined. Flow cytometry revealed that LBNP increased mean fluorescence intensity of PAC-1 by 1959±455 units (P<0.001) and percent of fluorescence-positive platelets by 27±18%-points (P = 0.013). Thrombelastography demonstrated that coagulation was accelerated (R-time decreased by 0.8±0.4 min (P = 0.001)) and that clot lysis increased (LY60 by 6.0±5.8%-points (P = 0.034)). Plasma coagulation factor VIII and von Willebrand factor ristocetin cofactor activity increased (P = 0.011 and P = 0.024, respectively), demonstrating increased coagulation activity, while von Willebrand factor antigen was unchanged. Plasma protein C activity and tissue-type plasminogen activator increased (P = 0.007 and P = 0.017, respectively), and D-dimer increased by 0.03±0.02 mg l-1 (P = 0.031), demonstrating increased fibrinolytic activity. Plasma prothrombin time and activated partial thromboplastin time were unchanged. Platelet count increased by 15±13% (P = 0.014) and red blood cells by 9±4% (P = 0.002). In humans, LBNP-induced presyncope activates platelets, as evidenced by increased exposure of active glycoprotein IIb/IIIa, accelerates coagulation. LBNP activates fibrinolysis, similar to hemorrhage, but does not alter coagulation screening tests, such as prothrombin time and activated partial thromboplastin time. LBNP results in increased platelet counts, but also in hemoconcentration.

PMID: 25546432 [PubMed - as supplied by publisher]

Neither the HIV Protease Inhibitor Lopinavir-Ritonavir nor the Antimicrobial Trimethoprim-Sulfamethoxazole Prevent Malaria Relapse in Plasmodium cynomolgi-Infected Non-Human Primates.

Wed, 12/31/2014 - 4:30am

Neither the HIV Protease Inhibitor Lopinavir-Ritonavir nor the Antimicrobial Trimethoprim-Sulfamethoxazole Prevent Malaria Relapse in Plasmodium cynomolgi-Infected Non-Human Primates.

PLoS One. 2014;9(12):e115506

Authors: Hobbs CV, Dixit S, Penzak SR, Sahu T, Orr-Gonzalez S, Lambert L, Zeleski K, Chen J, Neal J, Borkowsky W, Wu Y, Duffy PE

Abstract
Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. vivax relapses. HIV and P. vivax malaria geographically overlap in many areas of the world, including South America and Asia. Despite the increasing body of knowledge regarding HIV protease inhibitors (HIV PIs) on P. falciparum malaria, there are no data regarding the effects of these treatments on P. vivax's hypnozoite form and clinical relapses of malaria. We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium actively dividing liver stages in rodent malarias and in vitro in P. falciparum, but effect against Plasmodium dormant hypnozoite forms remains untested. Separately, although other antifolates have been tested against hypnozoites, the antibiotic trimethoprim sulfamethoxazole, commonly used in HIV infection and exposure management, has not been evaluated for hypnozoite-killing activity. Since Plasmodium cynomolgi is an established animal model for the study of liver stages of malaria as a surrogate for P. vivax infection, we investigated the antimalarial activity of these drugs on Plasmodium cynomolgi relapsing malaria in rhesus macaques. Herein, we demonstrate that neither TMP-SMX nor LPV-RTV kills hypnozoite parasite liver stage forms at the doses tested. Because HIV and malaria geographically overlap, and more patients are being managed for HIV infection and exposure, understanding HIV drug impact on malaria infection is important.

PMID: 25541998 [PubMed - in process]

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

Wed, 12/31/2014 - 4:30am

Molecular mechanisms of maternal vascular dysfunction in preeclampsia.

Trends Mol Med. 2014 Dec 2;

Authors: Goulopoulou S, Davidge ST

Abstract
In preeclampsia, as a heterogeneous syndrome, multiple pathways have been proposed for both the causal as well as the perpetuating factors leading to maternal vascular dysfunction. Postulated mechanisms include imbalance in the bioavailability and activity of endothelium-derived contracting and relaxing factors and oxidative stress. Studies have shown that placenta-derived factors [antiangiogenic factors, microparticles (MPs), cell-free nucleic acids] are released into the maternal circulation and act on the vascular wall to modify the secretory capacity of endothelial cells and alter the responsiveness of vascular smooth muscle cells to constricting and relaxing stimuli. These molecules signal their deleterious effects on the maternal vascular wall via pathways that provide the molecular basis for novel and effective therapeutic interventions.

PMID: 25541377 [PubMed - as supplied by publisher]

Angiotensin II Type 1a Receptors in Subfornical Organ contributes towards Chronic Intermittent Hypoxia associated sustained increase in Mean Arterial Pressure.

Wed, 12/31/2014 - 4:30am

Angiotensin II Type 1a Receptors in Subfornical Organ contributes towards Chronic Intermittent Hypoxia associated sustained increase in Mean Arterial Pressure.

Am J Physiol Heart Circ Physiol. 2014 Dec 24;:ajpheart.00747.2014

Authors: Saxena A, Little JT, Nedungadi TP, Cunningham JT

Abstract
Sleep apnea is associated with hypertension. The mechanisms contributing to sustained increase in mean arterial pressure (MAP) even during normoxic awake-state remain unknown. Rats exposed to chronic intermittent hypoxia for 7 days, a model of the hypoxemia associated with sleep apnea, exhibit sustained increases in MAP even during the normoxic dark phase. Activation of the renin-angiotensin system (RAS) has been implicated in CIH hypertension. Since the subfornical organ (SFO) serves as a primary target for the central actions of circulating ANG II, we tested the effects of ANG II type1a receptor (AT1aR) knockdown in SFO on the sustained increase in mean arterial pressure in this CIH model. Adeno-associated virus carrying GFP and shRNA against either AT1aR or a scrambled control sequence (SCM) was stereotaxically injected in the SFO of rats. After recovery, MAP, heart rate, respiratory rate, and activity were continuously recorded using radio-telemetry. In the normoxic groups, the recorded variables did not deviate from the baseline values. Both CIH groups exhibited significant increases in MAP during CIH exposures (p<0.05). During the normoxic dark phase in the CIH groups, only the SCM injected group exhibited a sustained increase in MAP (p<0.05). The AT1aR-CIH group showed significant decreases in FosB/∆FosB staining in the median preoptic nucleus and the paraventricular nuclei of the hypothalamus as compared to the SCM-CIH group. Our data indicate that AT1aRs in the SFO are critical for the sustained elevation in MAP and increased FosB/∆FosB expression in forebrain autonomic nuclei associated with CIH.

PMID: 25539713 [PubMed - as supplied by publisher]

Protein redox modification as a cellular defense mechanism against tissue ischemic injury.

Wed, 12/31/2014 - 4:30am
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Protein redox modification as a cellular defense mechanism against tissue ischemic injury.

Oxid Med Cell Longev. 2014;2014:343154

Authors: Yan LJ

Abstract
Protein oxidative or redox modifications induced by reactive oxygen species (ROS) or reactive nitrogen species (RNS) not only can impair protein function, but also can regulate and expand protein function under a variety of stressful conditions. Protein oxidative modifications can generally be classified into two categories: irreversible oxidation and reversible oxidation. While irreversible oxidation usually leads to protein aggregation and degradation, reversible oxidation that usually occurs on protein cysteine residues can often serve as an "on and off" switch that regulates protein function and redox signaling pathways upon stress challenges. In the context of ischemic tolerance, including preconditioning and postconditioning, increasing evidence has indicated that reversible cysteine redox modifications such as S-sulfonation, S-nitrosylation, S-glutathionylation, and disulfide bond formation can serve as a cellular defense mechanism against tissue ischemic injury. In this review, I highlight evidence of cysteine redox modifications as protective measures in ischemic injury, demonstrating that protein redox modifications can serve as a therapeutic target for attenuating tissue ischemic injury. Prospectively, more oxidatively modified proteins will need to be identified that can play protective roles in tissue ischemic injury, in particular, when the oxidative modifications of such identified proteins can be enhanced by pharmacological agents or drugs that are available or to be developed.

PMID: 24883175 [PubMed - indexed for MEDLINE]

Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.

Tue, 12/30/2014 - 4:31am

Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.

Anticancer Drugs. 2014 Dec 22;

Authors: He W, Liu R, Yang S, 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 - as supplied by publisher]

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