Weight loss dynamics during combined fluoxetine and olanzapine treatment

BACKGROUND: Fluoxetine and olanzapine combination therapy is rapidly becoming an effective strategy for managing symptoms of treatment-resistant depression. Determining drug-drug interactions, drug metabolism and pharmacokinetics is of particular interest for revealing potential liabilities associated with drug augmentation in special patient populations. In the current studies, we chronically administered fluoxetine and olanzapine in non-stressed rats to extend our previous findings regarding body weight dynamics. RESULTS: Chronic fluoxetine (10 mg/kg) and olanzapine (5 mg/kg and 0.5 mg/kg) treatment decreased weight gain irrespective of olanzapine dosing. At the 10 mg/kg and 5 mg/kg dose, respectively, fluoxetine and olanzapine also significantly reduced food and water consumption. This pharmacodynamic event-related effect, however, was not observed at the 10 mg/kg and 0.5 mg/kg dosing paradigm suggesting differences in tolerability rates as a function of olanzapine dose. The decrease in weight gain was not associated with apparent changes in glucose metabolism as vehicle- and drug-treated rats showed undistinguishable serum glucose levels. The combination of fluoxetine and olanzapine in rats yielded drug plasma concentrations that fell within an expected therapeutic range for these drugs in psychiatric patients. CONCLUSIONS: These data suggest that fluoxetine and olanzapine treatment decreases weight gain in rats; a pharmacodynamic event-related effect that differs considerably from what is observed in the clinical condition. The possibility of mismatched models regarding body weight changes during drug augmentation therapy should be seriously considered

Use of a Prescribed Ephedrine/Caffeine Combination and the Risk of Serious Cardiovascular Events: A Registry-based Case-Crossover Study

Ephedrine and herbal ephedra preparations have been shown to induce a small-to-moderate weight loss. Owing to reports on serious cardiovascular events, they were banned from the US market in 2004. There have been no large controlled studies on the possible association between prescribed ephedrine/caffeine and cardiovascular events in general. The authors linked data from four different sources within Statistics Denmark, using data on 257,364 users of prescribed ephedrine/caffeine for the period 1995–2002. The data were analyzed using a case-crossover technique with a composite endpoint: death outside of a hospital, myocardial infarction, or stroke. To account for effects of chronic exposure and effects in naïve users, the authors performed a secondary case-control study nested within the cohort of ephedrine/caffeine ever users. Among 2,316 case subjects, 282 (12.2%) were current users of ephedrine/caffeine. The case-crossover analysis yielded an odds ratio of 0.84 (95% confidence interval: 0.71, 1.00); after adjustment for trends in ephedrine/caffeine use, it was 0.95 (95% confidence interval: 0.79, 1.16). Subgroup analyses revealed no strata with significantly elevated risk. In the case-control substudy, there was no increased risk among naïve users or users with large cumulative doses. Prescribed ephedrine/caffeine was not associated with a substantially increased risk of adverse cardiovascular outcomes in this study

Developing Retina and PNS Segments for Transplantation Into the Adult Host Eye: Reconstruction of the Mammalian Visual System. 1. Methodology

Various techniques have been explored to determine the uses and limitations of techniques that enable the adult CNS to regenerate, but relatively little attention has been given to the consideration of a "reconstructed" visual system. Using this approach, one can design experiments to study the uses of exogenous tissues in reestablishing neuronal circuits that have been damaged. Toward this end, experiments were designed to determine whether embryonic retinal ganglion cells can project axons into a grafted PNS "bridge", and enter adult host targets that were partially deafferented. Embryonic eyes of E11, E14, E18 and E21 rats were sutured to peripheral nerve segments which served as bridges between the host eye and frontal cortex. Projections between the developing retina and the host brain could then be evaluated using HRP tracing techniques. From a methodological standpoint, the preparations are 65% effective; i.e., a viable bridge results between the embryonic eye and the host forebrain. The results presented in the accompanying paper demonstrate that the technique can yield results indicative of embryonic retinal development and axonal projection through the graft and into the host brain. This partial reconstruction of the visual system may prove a useful tool in understanding the uses and limitations of grafting in the CNS

Undergraduate Neuroscience Education in the U.S.: An Analysis using Data from the National Center for Education Statistics

Despite an apparent increase in undergraduate neuroscience programs offered by colleges and universities, there has been little effort to document this growth. In the present report we describe our analysis of the expansion of undergraduate neuroscience programs of study over more than 20 years and detail a number of institutional characteristics of colleges and universities that offer undergraduate neuroscience programs. These data reveal more than 100 institutions with undergraduate neuroscience programs as well as over 2000 college graduates that majored in neuroscience in 2008–2009. Understanding the current number as well as growth trends of undergraduate neuroscience programs found in U.S. colleges and universities has implications for neuroscience educators as well as for the funding of neuroscience research and educational activities

Anomalous metamagnetism in the low carrier density Kondo lattice YbRh3Si7

We report complex metamagnetic transitions in single crystals of the new low carrier Kondo antiferromagnet YbRh3Si7. Electrical transport, magnetization, and specific heat measurements reveal antiferromagnetic order at T_N = 7.5 K. Neutron diffraction measurements show that the magnetic ground state of YbRh3Si7 is a collinear antiferromagnet where the moments are aligned in the ab plane. With such an ordered state, no metamagnetic transitions are expected when a magnetic field is applied along the c axis. It is therefore surprising that high field magnetization, torque, and resistivity measurements with H||c reveal two metamagnetic transitions at mu_0H_1 = 6.7 T and mu_0H_2 = 21 T. When the field is tilted away from the c axis, towards the ab plane, both metamagnetic transitions are shifted to higher fields. The first metamagnetic transition leads to an abrupt increase in the electrical resistivity, while the second transition is accompanied by a dramatic reduction in the electrical resistivity. Thus, the magnetic and electronic degrees of freedom in YbRh3Si7 are strongly coupled. We discuss the origin of the anomalous metamagnetism and conclude that it is related to competition between crystal electric field anisotropy and anisotropic exchange interactions.Comment: 23 pages and 4 figures in the main text. 7 pages and 5 figures in the supplementary materia