A PET imaging study of 5-HT(1A) receptors in cat brain after acute and chronic fluoxetine treatment

Immuno-electron microscopic and beta-microprobe studies have demonstrated that the internalization of serotonin 5-HT(1A) autoreceptors, after acute treatment with the selective 5-HT(1A) receptor agonist 8-OH-DPAT or with the specific serotonin reuptake inhibitor (SSRI) fluoxetine, is associated with a marked decrease in the in vivo binding of [(18)F]MPPF in the nucleus raphe dorsalis (NRD) of rat. To determine whether this event might be amenable to brain imaging, the present [(18)F]MPPF positron emission tomographic (PET) study was carried out in anesthetized cats given or not a single dose (5 mg/kg, i.v.) or chronically treated with fluoxetine (5 mg/kg, s.c. for 21 days). Compared to control, [(18)F]MPPF binding potential was considerably (and visibly) decreased in the cat NRD after acute fluoxetine treatment, while it remained unchanged in other brain regions. Unexpectedly, after chronic fluoxetine treatment, [(18)F]MPPF binding potential was not affected in any brain region. In parallel immuno-electron microscopic experiments carried out in rat, the density of 5-HT(1A) autoreceptors on the plasma membrane of NRD dendrites was comparable to control after chronic fluoxetine treatment. If the decrease in [(18)F]MPPF binding at the onset of SSRI treatment was detectable by PET imaging, it could potentially serve as a biological index of efficacy.     

The vector competence of Phlebotomus perniciosus for Leishmania infantum zymodemes of Tunisia

Parasitology Research - Experimental infections of Phlebotomus (L.) perniciosus from a colony established in Madrid (Spain) carried out with the Leishmania (L.) infantum zymodemes MON-1, MON-24,...     

Essential role of RSK2 in c-Fos-dependent osteosarcoma development

Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.     

Modelling,Analysis, and Optimization of the Effects of Pulsed Electrophoretic Deposition Parameters on TiO2 Films Properties Using Desirability Optimization Methodology

Titanium dioxide thin films immobilized over treated stainless steel were prepared using the pulsed electrophoretic deposition technique. The effects of process parameters (deposition time, applied voltage, initial concentration, and duty cycle) on photocatalytic efficiency and adhesion properties were investigated. To optimize the multiple properties of the thin film, a response surface methodology was combined with a desirability optimization methodology. Additionally, a quadratic model was established based on response surface analysis. The precision of the models was defined based on the analysis of variance (ANOVA), R², and the normal plot of residuals. Then, a desirability function was used to optimize the multiple responses of the TiO₂ thin film. The optimum values of applied voltage, catalyst concentration, duty cycle, and deposition time were 4 V, 16.34 g/L, 90% DC, and 150 s, respectively. Under these conditions, the decolorization efficiency of tested dye solution reached 82.75%. The values of critical charges L_C1, L_C2, and L_C3 were 5.9 N, 12.5 N, and 16.7 N, respectively.     

Timescales of developmental toxicity impacting on research and needs for intervention

Much progress has happened in understanding developmental vulnerability to preventable environmental hazards. Along with the improved insight, the perspective has widened, and developmental toxicity now involves latent effects that can result in delayed adverse effects in adults or at old age and additional effects that can be transgenerationally transferred to future generations. Although epidemiology and toxicology to an increasing degree are exploring the adverse effects from developmental exposures in human beings, the improved documentation has resulted in little progress in protection, and few environmental chemicals are currently regulated to protect against developmental toxicity, whether it be neurotoxicity, endocrine disruption or other adverse outcome. The desire to obtain a high degree of certainty and verification of the evidence used for decision‐making must be weighed against the costs and necessary duration of research, as well as the long‐term costs to human health because of delayed protection of vulnerable early‐life stages of human development and, possibly, future generations. Although two‐generation toxicology tests may be useful for initial test purposes, other rapidly emerging tools need to be seriously considered from computational chemistry and metabolomics to CLARITY‐BPA‐type designs, big data and population record linkage approaches that will allow efficient generation of new insight; epigenetic mechanisms may necessitate a set of additional regulatory tests to reveal such effects. As reflected by the Prenatal Programming and Toxicity (PPTOX) VI conference, the current scientific understanding and the timescales involved require an intensified approach to protect against preventable adverse health effects that can harm the next generation and generations to come. While further research is needed, the main emphasis should be on research translation and timely public health intervention to avoid serious, irreversible and perhaps transgenerational harm.