Context. Contraception is increasingly used as a management technique to reduce fertility in wildlife populations; however, the feasibility of contraceptive formulations has been limited until ...recently because they have required multiple treatments to achieve prolonged infertility. Aims. We tested the efficacy and evaluated potential side effects of two contraceptive formulations, a porcine zona pellucida (PZP) formulation, SpayVac and a gonadotrophin-releasing hormone (GnRH) formulation GonaCon-Btrade mark sign, in a population of free-roaming feral horses (Equus caballus). Both formulations were developed to provide several years of infertility with one injection. Methods. Females were treated in June 2005 with either GonaCon-B (n=24), SpayVac (n=20), adjuvant only (n=22), or received no injection (n=18). Females were monitored for fertility status year round for 3 years after treatment. Key results. Both contraceptive treatments significantly reduced fertility for 3 years. Fertility rates for GonaCon-B mares were 39%, 42% and 31%, respectively, and 37%, 50% and 44% for SpayVac mares. During the same seasons, 61%, 67% and 76% of control females were fertile. We found no significant effects from contraceptive treatment on the sex ratio of foals, birthing season or foal survival. Conclusions. These results demonstrated that both vaccines are capable of significantly reducing fertility for several years without boosters. Implications. Contraceptive vaccines examined in the present study represent a useful tool for the management of feral horses, because of their being efficacious for 3 years in the absence of booster immunisations.
Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an ...additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.
To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent microglia exposed to the prototypical inflammatory mediator lipopolysaccharide (LPS).
(3)H-Saquinavir accumulation by microglia was rapid, and was increased up to two-fold in the presence of the specific P-glycoprotein inhibitor, PSC833. After six or 24 hours of exposure to 10 ng/ml LPS, saquinavir accumulation was decreased by up to 45%. LPS did not directly inhibit saquinavir transport, and did not affect P-glycoprotein protein expression. LPS exposure did not alter RNA and/or protein expression of other transporters including multidrug resistance-associated protein 1 and several solute carrier uptake transporters.
The decrease in saquinavir accumulation in microglia following treatment with LPS is likely multi-factorial, since drug accumulation was attenuated by inhibitors of NF-κβ and the MEK1/2 pathway in the microglia cell line HAPI, and in primary microglia cultures from toll-like receptor 4 deficient mice. These data provide new pharmacological insights into why microglia act as a difficult-to-treat viral sanctuary site.
Previous studies have shown that killifish (Fundulus heteroclitus) renal proximal tubules express a luminal membrane transporter that is functionally and immunologically analogous to the mammalian ...multidrug resistance-associated protein isoform 2 (Mrp2, ABCC2). Here we used confocal microscopy to investigate in killifish tubules the transport of a fluorescent cAMP analog (fluo-cAMP), a putative substrate for Mrp2 and Mrp4 (ABCC4). Steady-state luminal accumulation of fluo-cAMP was concentrative, specific, and metabolism-dependent, but not reduced by high K+ medium or ouabain. Transport was not affected by p-aminohippurate (organic anion transporter inhibitor) or p-glycoprotein inhibitor (PSC833), but cell-to-lumen transport was reduced in a concentration-dependent manner by Mrp inhibitor MK571, leukotriene C4 (LTC4), azidothymidine (AZT), cAMP, and adefovir; the latter two compounds are Mrp4 substrates. Although MK571 and LTC4 reduced transport of the Mrp2 substrate fluorescein-methotrexate (FL-MTX), neither cAMP, adefovir, nor AZT affected FL-MTX transport. Fluo-cAMP transport was not reduced when tubules were exposed to endothelin-1, Na nitroprusside (an nitric oxide generator) or phorbol ester (PKC activator), all of which signal substantial reductions in cell-to-lumen FL-MTX transport. Fluo-cAMP transport was reduced by forskolin, and this reduction was blocked by the PKA inhibitor H-89. Finally, in membrane vesicles from Spodoptera frugiperda (Sf9) cells containing human MRP4, ATP-dependent and specific uptake of fluo-cAMP could be demonstrated. Thus, based on inhibitor specificity and regulatory signaling, cell-to-lumen transport of fluo-cAMP in killifish renal tubules is mediated by a transporter distinct from Mrp2, presumably a teleost form of Mrp4.
This comprehensive, quantitative assessment of how injury sustained by service members deployed to Iraq and Afghanistan affects their subsequent labor market earnings also explores the extent to ...which retirement and disability payments compensate for any resulting earnings losses. The analysis controls for a rich array of individual-level characteristics, including labor market outcomes prior to deployment.
Working
collaboratively, psychologist educators and trainers at the doctoral,
internship, and postdoctoral levels; credentialers; practitioners; and students
offer 8 proposals for psychologists to ...consider in recognizing, assessing, and
intervening with problems of professional competence in students and practicing
professionals. In the proposals, the authors address the following topics:
definitions and categories; preparing the system; self-assessment; remediation;
diversity; communication across various levels of the system; confidentiality;
and ethical, regulatory, and legal underpinnings. They also propose future
directions for the assessment of problems in professional competence in both
students and practicing psychologists.
Examines how the death of service members affects the subsequent labor market earnings of surviving spouses and the extent to which survivor benefits provided by the Department of Defense, the ...Department of Veterans Affairs, and the Social Security Administration compensate for lost household earnings. Also assesses the extent to which payments surviving spouses and children receive compensate for earnings losses attributable to combat death.
Scales as outcome measures for Alzheimer's disease Black, Ronald; Greenberg, Barry; Ryan, J. Michael ...
Alzheimer's & dementia,
July 2009, Letnik:
5, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Abstract The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimer's disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an ...increasing number of trials are focusing on potential disease-modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimer's Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross-cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo-treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics.
Trainees with problems of professional competence (i.e., trainees with difficulty acquiring or maintaining developmentally appropriate levels of skill, functioning, attitudes, and/or ethical, ...professional, or interpersonal behavior across 1 or more settings) have broad and significant impacts across psychology education and training (Elman & Forrest, 2007; Forrest, Elman, & Shen-Miller, 2008; Kaslow et al., 2007). Existing data are equivocal about whether trainees perceive the training environment as helpful or harmful in addressing peer trainees with problems of professional competence (TPPC), and no published studies have targeted trainees' decision-making about taking action with or the impact of TPPCs on relationships. We analyzed interviews with 12 trainees at various levels of training in professional psychology. Factors affecting relationships and decisions to take action included program characteristics, personal contexts, professional responsibilities (e.g., peer supervision) and expectations, boundary concerns, and fear of negative consequences. Program climate, trainer behaviors, and intersections with diversity provoked discomfort, frustration, conflict, withdrawal, loss of faith in peers and trainers, and negative relational outcomes. These factors also led to deepened relationships, action, and overall positive and negative learning experiences. Based on our results, we recommend integrating the competence constellation model (Johnson, Barnett, Elman, Forrest, & Kaslow, 2012, 2013) into training, building competence for intervening with peer TPPCs, and revising aspects of APA's Ethical Code of Conduct.
We used proximal tubules isolated from the killifish, Fundulus heteroclitus, to examine the effect of environmentally relevant, sublethal levels of arsenic on the function and expression of MRP2, an ...ABC transporter that transports xenobiotics into urine, including arsenic-glutathione conjugates. Exposure of fish to arsenic as sodium arsenite (4–14 days) increased both MRP2 expression in the apical membrane of proximal tubules and MRP2-mediated transport activity. The level of MRP2 mRNA was not affected, suggesting a posttranslational mechanism of action. Acute exposure of proximal tubules isolated from control fish to 75–375 ppb arsenic decreased mitochondrial function (inner membrane electrical potential). However, in tubules from fish that were preexposed to arsenic (4–14 days), no such effect on mitochondrial function was observed. Thus, chronic in vivo exposure to arsenic induces mechanisms that protect proximal tubules during subsequent arsenic exposure. Upregulation of MRP2 expression and activity is one likely contributing factor.
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