Inhibition of the Casein-Kinase-1-Epsilon/Delta Prevents Relapse-Like Alcohol Drinking

During the past decade, it has been shown that circadian clock genes have more than a simple circadian time-keeping role. Clock genes also modulate motivational processes and have been implicated in the development of psychiatric disorders such as drug addiction. Recent studies indicate that casein-kinase 1ɛ/δ (CK1ɛ/δ)—one of the components of the circadian molecular clockwork—might be involved in the etiology of addictive behavior. The present study was initiated to study the specific role of CK1ɛ/δ in alcohol relapse-like drinking using the ‘Alcohol Deprivation Effect'' model. The effect of CK1ɛ/δ inhibition was tested on alcohol consumption in long-term alcohol-drinking rats upon re-exposure to alcohol after deprivation using a four-bottle free-choice paradigm with water, 5%, 10%, and 20% ethanol solutions, as well as on saccharin preference in alcohol-naive rats. The inhibition of CK1ɛ/δ with systemic PF-670462 (0, 10, and 30 mg/kg) injections dose-dependently decreased, and at a higher dosage prevented the alcohol deprivation effect, as compared with vehicle-treated rats. The impact of the treatment was further characterized using nonlinear regression analyses on the daily profiles of drinking and locomotor activity. We reveal that CK1ɛ/δ inhibition blunted the high daytime alcohol intake typically observed upon alcohol re-exposure, and induced a phase shift of locomotor activity toward daytime. Only the highest dose of PF-670462 shifted the saccharin intake daily rhythm toward daytime during treatment, and decreased saccharin preference after treatment. Our data suggest that CK1 inhibitors may be candidates for drug treatment development for alcoholism.     

The osteogenic differentiation of human osteoprogenitor cells on Anodic-Plasma-Chemical treated Ti6Al7Nb

Biological integration of an implant to surrounding bone is an important event for its clinical success and is driven by numerous factors, including the attraction of bone forming cells. The implant's surface properties influence the initial cell response at the cell/material interface, ultimately affecting the rate and quality of new tissue formation and the stability of the implant. As a consequence, various surface treatments have been developed to increase the clinical performance of titanium-based implants. Among them, the Anodic Plasma-Chemical (APC) technique allows for the combined chemical and morphological modification of titanium surfaces in a single process step. In the present study, we compared the potential of APC surface treatment of high-strength titanium alloys with vacuum plasma spray treatment and yellow gold anodization in supporting osteogenic differentiation of two different osteoprogenitor cell types. Both human fetal osteoblast cell line (hFOB1.19) and human mesenchymal stromal cells showed extensive cell spreading, faster cell growth and differentiation on APC surfaces compared to vacuum plasma spray treated and yellow gold anodized surfaces. Our findings showed that APC titanium-based surfaces provided an effective substrate for osteoprogenitor cells adhesion, proliferation and differentiation.     

Lycorine derivatives against Trichomonas vaginalis

Six lycorine derivatives were prepared, characterized, and evaluated for their in vitro anti‐Trichomonas vaginalis activity. Compounds bearing an acetyl ( 2 ), lauroyl ( 3 ), benzoyl ( 4 and 5 ), and p‐nitrobenzoyl ( 6 and 7 ) groups were synthesized. The best activity was achieved with lycorine esterified at C‐2 position with lauroyl group. Preliminary structure–activity relationship points that unprotected OH group at C‐1 and C‐2 is not necessary to the antiparasitic activity, and none of the derivative was less active than lycorine. The lycorine structural requisites required to kill this amitochondriate cell seem to be different in comparison with the derivatives most active against other parasites and tumor cell lines, both mitochondriated cells. This result is an important contribution with our ongoing studies regarding the mechanism of action of the Amaryllidaceae alkaloids on T. vaginalis cell death opening a new perspective to optimize this innovative pharmacological potential.     

Synthesis and antimalarial activity of dihydroperoxides and tetraoxanes conjugated with bis(benzyl)acetone derivatives

Dihydroperoxides and tetraoxanes derived from symmetrically substituted bis(arylmethyl)acetones were synthesized in modest to good yields using several methods. Three of these compounds exhibit an important in vitro antimalarial activity (1.0 μm ≤ IC₅₀ ≤ 5.0 μm ) against blood forms of the human malaria parasite Plasmodium falciparum.     

The contribution of nurses in integrated primary cares for chronic obstructive pulmonary disease outpatient: first results from an ongoing trial in a health district in northern Italy

The study assesses the role and impact of nursing in an ongoing trial of integrated primary cares, carried out in a health district in northern Italy, started in 2004. The goals were to establish a joint collaboration with general practitioners (GP), in order to improve the follow-up of chronic patients. As a first stage, the trial focuses on COPD (chronic obstructive pulmonary disease), diabetes mellitus, hypertension, cardiovascular failure and patients following anticoagulant therapy. The district??s project covers up to 60,000 patients treated by the team of GPs and nurses. Benefits for users are represented by easier access to cares, dedicated projects for chronic disease, follow-up, health education and multidisciplinary work. This first reports presents the questionnaire data according to patients?? satisfaction and the results achieved so far on COPD patients: 101.6% of COPD patients followed by teams have had at least 1 spirometry/year (vs. 43.2% of all the COPD affected??regional data) Hospital admissions are lower according to people attending a COPD integrated program and it is getting lower in time (health district??s rate: 0.125% in 2005?C0.115% in 2007; regional data).     

Immunolocalization of G protein α subunits in the olfactory system of Polypterus senegalus (Cladistia, Actinopterygii)

In vertebrates, the receptor neurons of the olfactory/vomeronasal systems express different receptor gene families and related G-protein types (in particular the G protein alpha subunit). There are no data in the literature about the molecular features of the olfactory/vomeronasal systems of Cladistia thus, in this work, the presence and distribution of different types of G protein alpha subunits were investigated in the olfactory organs of the bichir Polypterus senegalus, using immunohistochemistry. Gαo-like immunoreactivity was detected in the microvillous receptor neurons, with the cell body in the basal zone of the sensory epithelium, and in the crypt neurons. Gαo-like ir glomeruli were mainly localized in the anterior part of the olfactory bulb. Gαolf-like immunoreactivity in the sensory epithelium was detected in the ciliated receptor neurons, while the immunoreactive glomeruli in the olfactory bulb were mainly localized in the ventral-posterior part. No Gαq nor Gαi3 immunoreactivity was detected. These data are partially in agreement with studies that show the distribution of G protein alpha subunits in teleosts, allowing to hypothesize a common organization of the olfactory/vomeronasal systems in the group of Actinopterigians.     

French Guiana Amerindian demographic history as revealed by autosomal and Y-chromosome STRs

Background: Previous investigations of French Guiana Amerindians performed by this group included blood group and protein genetic markers, mitochondrial DNA and Y-chromosome investigations. Molecular autosomal data and more extensive Y-chromosome determinations were lacking. Subjects and methods: The genetic variability of 15 autosome (ASTRs) and 17 Y-chromosome (YSTRs) microsatellite loci was studied in four French Guiana (Emerillon, Palikur, Wayampi, Kali'na) and one Brazilian (Apalai) Amerindian populations. A sixth group, the Peruvian Matsiguenga of the Maipurean linguistic family, was included in the data analysis since they could provide information about the past migration of people from that linguistic stock into northeastern Amazonia. Results: Marked ASTR and YSTR variability was found, with 96% of the YSTR haplotypes being found in one population only. There was excellent agreement between the present and previous autosomal or uniparental results. Multidimensional scaling based on F(ST) genetic distances and population structure analysis revealed heterogeneity in gene distribution, with a clear difference between the Matsiguenga and Emerillon and the other groups. In the latter, Wilcoxon sign-rank test between observed and expected heterozygosity and the mode of allele frequency distribution revealed clues of a significant past genetic bottleneck. The Wayampi stand genetically closer to the Apalai, Palikur and Kali'na when examined for the autosome but not the Y-chromosome panel of markers, suggesting preferential female gene flow. Conclusion: The new data provided additional important information about the biological history of people from a remote South American region, indicating how gene diversity analyses can be used to increase understanding of human microevolutionary processes.