3,4-Diarylpiperidines as potent renin inhibitors

The discovery and SAR of a series of potent renin inhibitors possessing a novel 3,4-diarylpiperidine scaffold are described herein. The resulting compound 38 exhibit low nanomolar plasma renin IC(50), had a clean CYP 3A4 profile and displayed micromolar affinity for the hERG channel. Furthermore, it was found to be efficacious in the double transgenic rat hypertension model and show good to moderate oral bioavailability in two animal species.     

Morningness: protective factor for sleep-related and emotional problems in childhood and adolescence?

The relationship between morningness/eveningness, sleep, and psychological problems is well documented in adults as well as in adolescents. However, research on the circadian orientation and its concomitants in younger children is scarce. The authors investigated the distribution of morningness/eveningness and its connection to sleeping and psychological problems in 91 children and 151 adolescents in Austria. The authors found that morning (M) types had less sleep-related and psychological problems than intermediate (I) and evening (E) types, respectively. Among children, M-types suffered less from daytime sleepiness (females: χ(2)((2))?= 8.1, p =?.017; males: χ(2)((2))?= 14.8, p =?.001). Among adolescents, M-types showed fewer sleep-wake problems (females: χ(2)((2))?= 17.5, p 相似文献   

Isolation and characterization of a new hydrogen-utilizing bacterium from the rumen

Abstract A new H2 CO2-utilizing acetogenic bacterium was isolated from the rumen of a mature deer. This is the first report of a spore-forming Gram-negative bacterial species from the rumen. The organism was a strictly anaerobic, motile rod and was able to grow autotrophically on hydrogen and carbon dioxide. Acetate was the major product detected. Glucose, fructose and lactate were also fermented heterotrophically. The optimum pH for growth was 7.0–7.5, and the optimum temperature was 37–42 °C. Yeast extract was required for growth and rumen fluid was highly stimulatory. The DNA base ratio was 52.9 ± 0.5 mol% G + C. On the basis of these characteristics and fermentation products, the isolate was considered to be different from acetogenic bacteria described previously.     

Assessment of genetic stability of two micropropagated wild olive species using flow cytometry and microsatellite markers

Micropropagated plants from two wild-olive species, Olea maderensis and O. europaea ssp. europaea var. sylvestris were screened for genetic stability. O. maderensis shoots were elongated/multiplied on OMG medium with zeatin (9.12 μM), and rooted on 1/2 OMG with NAA (3.22 μM). O. europaea var. sylvestris shoots were elongated/multiplied on OM medium with zeatin, and rooting was optimal after a hormonal shock (IBA 100 μM) followed by transfer to the same medium without growth regulators. In both species, acclimatization was successful and plants looked normal and morphologically identical to the donor field trees. Genetic variability was assessed at several stages of the micropropagation process using flow cytometry (FCM) and nuclear microsatellites (SSR). No changes in ploidy level were found among micropropagated plants, though small deviations, putatively due to the negative effects of cytosolic compounds on propidium iodide staining, between these and field plants were observed. In SSRs analyses, ten SSR markers were able to distinguish between genotypes. No mutations were found in these tested SSR loci among the donor tree and micropropagated plants, suggesting, for the tested markers, genetic uniformity throughout the process. The FCM and SSR results obtained do not exclude the occurrence of other changes in the nuclear genome but, considering the morphological stability of micropropagated plants, indicate that both protocols are suitable and efficient for large scale, true-to-type micropropagation of these two wild olive species.     

Muscular Weakness in Individuals with HIV Associated with a Disorganization of the Cortico-Spinal Tract: A Multi-Modal MRI Investigation

Motor impairment is highly prevalent in HIV-infected patients. Here, we assess associations between peripheral muscular deficits as evaluated by the 5 sit-to-stand test (5STS) and structural integrity of the motor system at a central level. Eighty-six HIV-infected patients receiving combination antiretroviral therapy and with no major cerebral events, underwent an MRI scan and the 5STS. Out of 86 participants, forty presented a score greater than two standard deviations above mean normative scores calculated for the 5STS and were therefore considered as motor-impaired. MRI-structural cerebral parameters were compared to the unimpaired participants. Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD), reflecting microstructural integrity, were extracted from Diffusion-Tensor MRI. Global and regional cerebral volumes or thicknesses were extracted from 3D-T1 morphological MRI. Whereas the two groups did not differ for any HIV variables, voxel-wise analysis revealed that motor-impaired participants present low FA values in various cortico-motor tracts and low AD in left cortico-spinal tract. However, they did not present reduced volumes or thicknesses of the precentral cortices compared to unimpaired participants. The absence of alterations in cortical regions holding motor-neurons might argue against neurodegenerative process as an explanation of White Matter (WM) disorganization.     

Effectiveness of the sperm quality analyzer (SQA-Vp) for porcine semen analysis

The Sperm Quality Analyzer (SQA-Vp) was evaluated for assessing concentration and motility of porcine semen. Both fresh and diluted semen from 50 different boars from a commercial artificial insemination (AI) centre were investigated. For the fresh ejaculate, the concentration obtained with SQA-Vp was compared with a photometer and a haemocytometer. For the diluted samples, the concentration and motility were compared with computer assisted semen analysis (CASA) and visual sperm analysis. The agreement between methods was studied with Bland-Altman plots and the repeatability with coefficient of variation (CV) as well as Bland-Altman plots. The sperm concentration (x10⁶/ml) obtained with SQA-Vp (379.3 ± 134.9) for fresh ejaculates agreed well with concentration by the photometer (447.2 ± 154.2; difference= -67.9 x 10⁶/ml; difference + 2SD = 55.3 x 10⁶/ml; difference - 2SD = -191.1 x 10⁶/ml) and with the haemocytometer (332.8 ± 141.11; d = 92.8; d + 2SD = 448.6; d - 2SD = -263). For diluted semen, the agreement between the concentration (x10⁶/ml) assessed with SQA-Vp (20.4 ± 4.3) was good with CASA (23.2 ± 5.8; d = -2.8; d + 2SD = 6.2; d - 2 SD = -11.8) but poor with the haemocytometer (18.8 ± 5.0; d = 1.6; d+ 2SD = 12.2; d - 2SD = -9). The % motile spermatozoa assessed by SQA-Vp (65.8 ± 10.0) in diluted semen agreed well with CASA (72.2 ± 13.7; d = -6.4; d+ 2SD = 20; d - 2SD = -32.8) and with visual assessment (64.1 ± 11.6; d = 1.7; d+ 2SD = 30.9; d - 2SD = -27.5). The SQA-Vp showed a good repeatability (CV; repeatability coefficient) for measuring the concentration of both fresh (3.9%; d = 10.7; d + 2SD = 30.9; d - 2SD = -9.5) and diluted semen (2.6%; d = 1.0; d + 2SD = 2.38; d - 2SD = -0.42) and for motility (3.2%; d = 0.9; d + 2SD = 8.5; d - 2SD = -6.7). The mean SQA-Vp values fell between the other methods′ results for both fresh and diluted semen. Moreover the repeatability was acceptable. Therefore SQA-Vp can be used as a valid device for sperm quality analysis in pigs.     

Quantitative determination of dehydroepiandrosterone fatty acyl esters in human female adipose tissue and serum using mass spectrometric methods

Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) are naturally occurring water-insoluble metabolites of DHEA, which are transported in plasma exclusively by lipoproteins. To find out whether DHEA, like estradiol, might be stored in adipose tissue in FAE form, we set up a mass spectrometric method to quantify DHEA-FAE and free DHEA in human adipose tissue and serum. The method consists of chromatographic purification steps and final determination of hydrolyzed DHEA-FAE and free DHEA, which was carried out by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our results showed that no detectable amounts of DHEA-FAE could be found in adipose tissue although 32-178 pmol/g of free DHEA were determined by GC-MS and LC-MS/MS. The DHEA-FAE concentrations in serum quantified by GC-MS were 1.4±0.7 pmol/ml in premenopausal women (n=7), and 0.9±0.4 pmol/ml in postmenopausal women (n=5). Correspondingly, the free DHEA concentrations were 15.2±6.3 pmol/ml and 6.8±3.0 pmol/ml. In addition, the mean proportions of DHEA-FAE of total DHEA (DHEA-FAE+free DHEA) in serum were 8.6% and 11.2% in pre- and postmenopausal women, respectively. Serum DHEA-FAE concentration was below quantification limit for LC-MS/MS (signal-to-noise ratio, S/N=10), while free DHEA concentrations varied between 5.8 and 23.2 pmol/ml. In conclusion, the proportion of DHEA-FAE of total DHEA in serum was approximately 9%. However, in contrast to our previous findings for estradiol fatty acid esters in adipose tissue which constituted about 80% of total estradiol (esterified+free), the proportion of DHEA-FAE of total DHEA was below 5%. Four to ten times higher concentrations of free DHEA were quantified in adipose tissue compared to those in serum.