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Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice‐daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV‐positive patients taking abacavir once daily and twice daily, respectively. Patients on once‐daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml(−1), P = 0.038 and 123 vs. 49 ng ml(−1), P = 0.038) but similar CSF‐to‐plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once‐daily treatment.

Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform and two pan-BRPF bromodomain inhibitors (OF-1, NI-57). The developed inhibitors displaced BRPF bromodomains from chromatin and did not inhibit cell growth and proliferation. Intriguingly, the inhibitors impaired RANKL-induced differentiation of primary murine bone marrow cells and human primary monocytes into bone resorbing osteoclasts by specifically repressing transcriptional programs required for osteoclastogenesis. The data suggest a key role of BRPF in regulating gene expression during osteoclastogenesis, and the excellent druggability of these bromodomains may lead to new treatment strategies for patients suffering from bone loss or osteolytic malignant bone lesions.

The aim of the present paper was to assess benefit of strategic anthelmintic treatments on milk production in six commercial dairy sheep farms, located in southern Italy, whose animals were naturally infected with gastrointestinal strongyles. On each farm, two similar groups were formed, one untreated control group and one treated group. In all the treated groups, the strategic anthelmintic schemes were based on: (i) only one treatment with moxidectin in the periparturient period (February, Farm No. 6), or; (ii) two treatments, i.e. the first with moxidectin performed in the periparturient period (February, Farms Nos. 1, 2, 3 and 4) or in the postparturient period (April, Farm No. 5), and the second with netobimin at the mid/end of lactation (June, Farms Nos. 1, 2, 3, 4 and 5). Faecal egg count reduction (FECR) tests were performed on each farm in order to asses the anthelmintic efficacy of the drugs used. In addition, milk yield measurements for each animal fortnightly in each farm for the lactation period were performed. In terms of FECR, both moxidectin and netobimin were effective in all the 6 studied farms. Regarding milk production, overall in the 6 study farms the mean daily milk productions of the treated groups were higher than those of the control group. However, there were important differences between the 6 farms, i.e. the increase of milk production in the treated groups versus the control groups was as follows: +18.9% (Farm 1), +30.4% (Farm 2), +4.0% (Farm 3), +37.0% (Farm 4), +5.5% (Farm 5) and +40.8% (Farm 6). The results of the study showed that the economic efficacy of an anthelmintic treatment is not a cause-effect issue, but is a multifactorial issue which depends upon the quali-quantitative parasitological status of the animals, the pathogenesis of the species of parasites, the virulence of the strains of parasites, the local epidemiology, the timing of treatment, the breed of animal in terms of genetics and production types, nutrient supply.

Objective: High-grade gliomas (HGG) are the most common brain tumors with an average survival of 14 months. A large number of highly methylated gene loci (G-CIMP) are associated with the proneural subgroup and better clinical outcome. Our aim was to identify and characterize putative transcription factors[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

The adrenal gland of the lizard Podarcis sicula is formed by a dorsal ribbon of chromaffin cells, generally defined as medullary tissue, arranged along a central part of steroidogenic cells considered as cortical tissue. These two tissues produce catecholamines and steroids as part of the hypothalamo-hypophyseal-adrenal gland axis. Recent studies have demonstrated that Podarcis sicula adrenal gland is not only under hypothalamo-hypophyseal axis control but that several peptides may influence the physiological activity of the gland; among these, vasoactive intestinal peptide is able to enhance strongly both catecholamine and steroid hormone production. The aim of the present study was to verify whether vasoactive intestinal peptide administration could become deleterious. For this reason, we monitored the pattern of expression of two members of the Bcl-2 family, Bcl-2 and Bax, in control and vasoactive intestinal peptide treated specimens. Furthermore, we also tested if peptide treatment induces apoptosis by TUNEL assay.