Correlates of utilization of PTSD specialty treatment among recently diagnosed veterans at the VA.

Objectives: This study described utilization of specialty treatment for posttraumatic stress disorder (PTSD) at U.S. Department of Veterans Affairs (VA) facilities among veterans of Operation Enduring Freedom (OEF), in Afghanistan, or of Operation Iraqi Freedom (OIF), in Iraq, and non-OEF-OIF veterans recently diagnosed as having PTSD.

Characterization of clonal vascular smooth muscle cell lines derived from young and old Fischer 344 rats.

A significant finding with aging humans (and aging animal models) is that blood vessels lose their ability to respond to beta-adrenergic receptor stimuli. Therefore, they produce less cyclic adenosine monophosphate (cAMP) and have decreased vasorelaxation with advancing age. This change likely contributes to hypertension, insufficient blood flow, and atherosclerosis.

Biomarkers of myocardial stress and systemic inflammation in patients who engage in heart failure self-care management.

Background: Self-care is believed to improve heart failure (HF) outcomes, but the mechanisms by which such improvement occurs remain unclear.

Methods: We completed a secondary analysis of cross-sectional data collected on adults with symptomatic HF to test our hypothesis that effective self-care is associated with less myocardial stress and systemic inflammation. Multivariate logistic regression modeling was used to determine if better HF self-care reduced the odds of having serum levels of amino-terminal pro-B-type natriuretic peptide and soluble tumor necrosis factor α receptor type 1 at or greater than the sample median.

CD4+FoxP3+ regulatory T-cells in cerebral ischemic stroke.

Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and is accompanied by systemic increases in CD4+CD25+Foxp3+ regulatory T-cells (Treg). To determine their effect on ischemic brain injury, Treg were depleted in Foxp3(DTR) mice prior to stroke induction. In contrast to a recent Nature Medicine report, our results demonstrate unequivocally that Treg depletion did not affect stroke infarct volume, thus failing to implicate this regulatory pathway in limiting stroke damage.

RTL therapy for multiple sclerosis: a Phase I clinical study.

A human recombinant T cell receptor ligand (RTL1000) consisting of DR2 α1 and β1 domains linked covalently to MOG-35-55 peptide can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE), and was evaluated for safety in a Phase 1 randomized, placebo-controlled, escalating dose study in 34 subjects with multiple sclerosis (MS). RTL1000 was safe and well tolerated at a dose of ≤60 mg that is well within the effective dose range for EAE and did not cause worsening of MS disease at doses ≤200 mg. RTL1000 represents a novel approach for the treatment of MS that promises potent immunoregulation and CNS repair without global immunosuppression.

Inhibition of soluble epoxide hydrolase preserves cardiomyocytes: role of STAT3 signaling.

Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), primarily 14,15-EET. EETs are derived from arachidonic acid via P-450 epoxygenases and are cardioprotective. We tested the hypothesis that sEH deficiency and pharmacological inhibition elicit tolerance to ischemia via EET-mediated STAT3 signaling in vitro and in vivo.

MR imaging of inflammation during myelin-specific T cell-mediated autoimmune attack in the EAE mouse spinal cord.

Purpose: The purpose of this study is to detect myelin-specific T cells, key pathological mediators in early multiple sclerosis, and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), in the mouse spinal cord.

Procedures: T cells were labeled with the iron-based, magnetic resonance (MR) contrast reagent, Feridex, and the transfection reagent, protamine sulfate, resulting in approximately 100% iron-labeling efficiency. Feridex-labeling did not alter the induction of EAE by T cells, and recipients were imaged by a 12-T MR instrument.

Neuroimmune mechanisms of cytokine-induced depression: current theories and novel treatment strategies.

The relationships between immune and neural function are an increasingly important area of study for neuropsychiatric disorders, in particular depression. This is exemplified by the growing number of publications on cytokines and depression during the last 10 years, as compared to earlier decades. This review summarizes the current theories and novel treatment strategies for depression, with a focus on cytokine-induced depression.

The multidimensional burden of hepatitis C and its treatment: a case study.

The purpose of this case study was to gain an in-depth understanding of the mental, physical, and emotional burden of being infected with the hepatitis C virus (HCV) from the perspective of an individual living with the disease and undergoing antiviral treatment. Interviews were conducted during and after antiviral therapy with 1 participant chosen from a Midwest HCV clinic population. Interviews were audio recorded, transcribed verbatim, and coded.

Influencing patient adherence to treatment guidelines.

Background: As chronic disease continues to weigh more heavily on health care resources, lifestyle management and compliance to treatment become paramount to patient care and care coordination. Although a wealth of information is available to the public regarding the basic tenets on exercise, nutrition, weight management, power of medications, and so forth, patients do not always modify their behavior accordingly to improve their overall health. Motivation seems to be both the key element as well as the central puzzle in efforts to change behavior.

Questions unanswered: propofol use in the pediatric intensive care unit.

As professionals who care for the sickest children, we want to provide the best evidence-based care available. While there are questions still to be answered, it is clear that when propofol is administered to children, it should be done in a manner that is intentional, well planned, and consistent with national guidelines and regulatory groups. Haphazard administration of propofol will place children at risk.

Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice.

Treatment of human autoimmune diseases such as multiple sclerosis (MS) will likely require agents that can prevent or reverse the inflammatory process that results in clinical relapses and disease progression. We evaluated the ability of a newly designed monomeric recombinant TCR ligand (RTL342M) containing HLA-DR2 peptide-binding domains covalently linked to MOG-35-55 peptide to prevent and treat both the initial episode and subsequent relapses of experimental autoimmune encephalomyelitis (EAE) in HLA-DR2 transgenic mice. Single doses of RTL342M given either i.

Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney.

Experimental diabetes is associated with complex changes in renal nitric oxide (NO) bioavailability. We explored the effect of diabetes on renal cortical protein expression of endothelial NO synthase (eNOS) with respect to several determinants of its enzymatic function, such as eNOS expression, membrane localization, phosphorylation, and dimerization, in moderately hyperglycemic streptozotocin-induced diabetic rats compared with nondiabetic control rats and diabetic rats with intensive insulin treatment to achieve near-normal metabolic control. We studied renal cortical expression and localization of caveolin-1 (CAV-1), an endogenous modulator of eNOS function.

TRPV4 and the mammalian kidney.

Transient receptor potential vanilloid 4 (TRPV4) was identified as the mammalian homologue of the Caenorhabditis elegans osmosensory channel protein, OSM-9. In mammals, TRPV4 is activated by a variety of stimuli including thermal stress, fatty acid metabolites, and hypotonicity. Two distinct mechanisms have been described through which TRPV4 may be activated by hypotonicity: one involves the Src family of nonreceptor protein tyrosine kinases, whereas a second is mediated via arachidonic acid metabolites.

Double feature at the signalplex.

In this issue of Molecular Pharmacology, Oliveras-Reyes et al. (p. 356) describe the agonist-stimulated formation of a caveolin-dependent signalplex that includes both the angiotensin AT(1) receptor and the epidermal growth factor receptor, and probably also a number of other signal transduction intermediates.

5-Hydroxytryptophan plus SSRIs for interferon-induced depression: synergistic mechanisms for normalizing synaptic serotonin.

Interferon-alpha (IFN) is widely used in the treatment of certain cancers and viral infections, including hepatitis C (HCV). Unfortunately, depression is a common side effect of IFN therapy, affecting approximately a third of HCV patients receiving IFN therapy. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) can effectively treat IFN-induced depression in only 63-75% of cases.

Common channel length predicts outcomes of biliopancreatic diversion alone and with the duodenal switch surgery.

Background: The optimal common channel (CC) length for malabsorptive weight loss surgeries is unknown even though these surgeries were developed in the 1970s (biliopancreatic diversion [BPD]) and the 1990s (biliopancreatic diversion with a duodenal switch [BPD DS]). We hypothesized that the length of the CC correlates with a successful weight loss result.

Methods: We evaluated 3 groups of patients based on the length of the CC whose duration of follow-up evaluation was at least 1 year.

Improved detection of prostate cancer using classification and regression tree analysis.

Purpose: To build a decision tree for patients suspected of having prostate cancer using classification and regression tree (CART) analysis.

Patients And Methods: Data were uniformly collected on 1,433 referred men with a serum prostate-specific antigen (PSA) levels of < or = 10 ng/mL who underwent a prostate biopsy. Factors analyzed included demographic, laboratory, and ultrasound data (ie, hypoechoic lesions and PSA density [PSAD]).

SRC family kinases in cell volume regulation.

SRC family kinases are a group of nine cytoplasmic protein tyrosine kinases essential for many cell functions. Some appear to be ubiquitously expressed, whereas others are highly tissue specific. The ability of members of the SRC family to influence ion transport has been recognized for several years.

Met5-enkephalin-induced cardioprotection occurs via transactivation of EGFR and activation of PI3K.

Our previous studies indicated that opioid-induced cardioprotection occurs via activation of mitochondrial ATP-sensitive K(+) (K(ATP)) channels. However, other elements of the Met(5)-enkephalin (ME) cardioprotection pathway are not fully characterized. In the present study, we investigated the role of tyrosine kinase, MAPK, and phosphatidylinositol 3-kinase (PI3K) signaling in ME-induced protection.

Long-term infusion of Met5-enkephalin fails to protect murine hearts against ischemia-reperfusion injury.

Recently, we reported that exogenous administration of Met(5)-enkephalin (ME) for 24 h reduces infarct size after ischemia-reperfusion in rabbits. In the present study, we tested whether ME-induced cardioprotection is exhibited in murine hearts and whether chronic infusion of this peptide can render hearts tolerant to ischemia. Barbiturate-anesthetized open-chest mice (C57BL/6J) were subjected to regional myocardial ischemia-reperfusion (45 min of occlusion and 20 min of reperfusion).

Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor.

Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST.

Patients And Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA.

Dietary intake and risk of postmenopausal breast cancer (United States).

Objectives: While there is good evidence from cell-culture and animal studies to indicate that dietary intake impacts breast cancer risk, results of epidemiologic studies have been inconsistent. Additionally, while the etiology of breast cancer in premenopausal versus postmenopausal women may be quite different, most studies have not chosen to focus solely on one group or the other. In this case-control study, we evaluate the associations between red meat, fish, dairy products, and fruits and vegetables, and risk of breast cancer in postmenopausal women.