Concomitant activation of Gi protein-coupled receptor and protein kinase C or phospholipase C is required for platelet aggregation

AbstractIt has recently been suggested that the concomitant activation of two distinct G protein-coupled receptors (Gi and Gq) is essential for platelet aggregation: in fact, the thromboxane A2 synthetic agonist, U46619, which causes the selective activation of Gq, is not able to elicit fibrinogen receptor exposure unless ADP or epinephrine is present. In the present study we demonstrate that a direct Gq activation is not required for platelet aggregation and that the activation of an enzyme downstream of Gq, such as phospholipase C (PLC) or protein-kinase C (PKC), is sufficient for such a process. In fact, platelet aggregation occurred in response to the snake venom toxin convulxin, which activates the PLC isoform PLCγ2 or to cytosolic PKC activator phorbol 12-myristate 13-acetate (PMA) provided a Gi protein-coupled receptor was activated by ADP or epinephrine. The evidence that the PKC inhibitor, Ro 31-8220 did not suppress platelet aggregation in response to convulxin plus ADP or epinephrine led us to conclude that PLC and PKC are both involved in platelet aggregation, although not concomitantly, provided a Gi protein-coupled receptor is activated

Theoretical calculations of the kinetics of the oh reaction with 2-methyl-2-propen-1-ol and its alkene analogue

In this work, the first and rate determining steps on the mechanism of the OH addition to 2-methyl-2-propen-1-ol (MPO221) and methylpropene (M2) have been studied at the DFT level, employing the BHandHLYP functional and the cc-pVDZ and aug-cc-pVDZ basis sets. The thermochemical properties of equilibrium (enthalpy, entropy and Gibbs free energies) have been determined within the conventional statistical thermodynamics relations and the rate coefficients have been determined on the basis of the variational transition state theory. The adoption of the microcanonical variational transition state theory was proved to be crucial for the description of the kinetics of OH addition to these unsaturated compounds. The rate coefficients obtained for the OH reactions with MPO221 and M2 at 298.15K deviate, respectively, 27% and 13% from the experimental rate coefficient available in the literature. A non-Arrhenius profile is observed for the rate coefficients. Moreover, the values of the rate coefficients for the MPO221 + OH reaction are greater than those for the M2 + OH reaction, suggesting that the substitution of the hydrogen atom in an alkene by the ?OH functional group, increases the reactivity in respect to the hydroxyl radical.Fil: Da Silva Barbosa, Thais. Departamento de Físico-química, Instituto de Química; BrasilFil: Nieto, Jorge Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; ArgentinaFil: Cometto, Pablo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; ArgentinaFil: Lane, Silvia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; ArgentinaFil: Bauerfeldt, Glauco Favilla. Universidade Federal Rural Do Rio de Janeiro; Brasil. Departamento de Química, Instituto de Ciencias Exatas; Brasi

Oral administration and intralesional injection of hyaluronic acid Versus intralesional injection alone in peyronie's disease: Results from a phase III study

Purpose: The aim of this study was to compare the effect of combined oral administration and intralesional injection of hyaluronic acid (HA) with intralesional injections alone, in patients with early onset of Peyronie's disease (PD). Materials and Methods: For this prospective, randomized phase III clinical trial we included patients with recent diagnosis of PD. Eighty-one patients were randomized into two groups. Group A consisted of 41 patients receiving oral administration of HA in combination with weekly intralesional injection of HA for 6 weeks. Group B consisted of 40 patients group B who received weekly intralesional injections of HA for 6 weeks, only. The main outcome measures were the changes from baseline to the end of therapy after three months in penile curvature (°) and changes in the international index of erectile function (IIEF-5) score and patient's global impressions of improvement (PGI-I) score. Results: Group A had a significantly larger reduction in penile curvature as compared with group B (Group A: -7.8°, Group B: -4.1° [p<0.001]). Group A also showed a higher improvement in IIEF-5 and PGI-I scores in comparison with Group B (Group A: +4 IIEF-5, Group B: +2 IIEF-5 [p<0.001]; Group A: 3 PGI-I, Group B: 1 PGI-I, [p<0.001]). At three months both groups had a significant reduction of penile curvature from baseline (p<0.001). Conclusions: Oral administration combined with intralesional treatment with HA shows greater efficacy to improve penile curvature and overall sexual satisfaction in comparison with intralesional HA treatment alone

Modified Pediatric ASPECTS Correlates with Infarct Volume in Childhood Arterial Ischemic Stroke

Background and Purpose: Larger infarct volume as a percent of supratentorial brain volume (SBV) predicts poor outcome and hemorrhagic transformation in childhood arterial ischemic stroke (AIS). In perinatal AIS, higher scores on a modified pediatric version of the Alberta Stroke Program Early CT Score using acute MRI (modASPECTS) predict later seizure occurrence. The objectives were to establish the relationship of modASPECTS to infarct volume in perinatal and childhood AIS and to establish the interrater reliability of the score. Methods: We performed a cross sectional study of 31 neonates and 40 children identified from a tertiary care center stroke registry with supratentorial AIS and acute MRI with diffusion weighted imaging (DWI) and T2 axial sequences. Infarct volume was expressed as a percent of SBV using computer-assisted manual segmentation tracings. ModASPECTS was performed on DWI by three independent raters. The modASPECTS were compared among raters and to infarct volume as a percent of SBV. Results: ModASPECTS correlated well with infarct volume. Spearman rank correlation coefficients (ρ) for the perinatal and childhood groups were 0.76, p < 0.001 and 0.69, p < 0.001, respectively. Excluding one perinatal and two childhood subjects with multifocal punctate ischemia without large or medium sized vessel stroke, ρ for the perinatal and childhood groups were 0.87, p < 0.001 and 0.80, p < 0.001, respectively. The intraclass correlation coefficients for the three raters for the neonates and children were 0.93 [95% confidence interval (CI) 0.89–0.97, p < 0.001] and 0.94 (95% CI 0.91–0.97, p < 0.001), respectively. Conclusion: The modified pediatric ASPECTS on acute MRI can be used to estimate infarct volume as a percent of SBV with a high degree of validity and interrater reliability

Quantitative analysis of the thermal distortions in a 100 W CW Nd:YAG ceramic slab laser.

Making use of an interferometric diagnostic system, we analyze the thermo-mechanical distortions taking place in the slab shaped ceramic Nd:YAG active medium of a 100 W class laser. These distortions are collected in different pumping regimes, both in static situations and during transient warm-up, and compared to the results of computer simulations. This procedure enables us to determine the relevance of different stress causes and thus to increase the specific power extraction of the active slab module

Developmental language disorder: Early predictors, age for the diagnosis, and diagnostic tools. A scoping review

Background. Developmental Language Disorder (DLD) is frequent in childhood and may have long-term sequelae. By employing an evidence-based approach, this scoping review aims at identifying (a) early predictors of DLD; (b) the optimal age range for the use of screening and diagnostic tools; (c) effective diagnostic tools in preschool children. Methods. We considered systematic reviews, meta-analyses, and primary observational studies with control groups on predictive, sensitivity and specificity values of screening and diagnostic tools and psycholinguistic measures for the assessment of DLD in preschool children. We identified 37 studies, consisting of 10 systematic reviews and 27 primary studies. Results. Delay in gesture production, receptive and/or expressive vocabulary, syntactic comprehension, or word combination up to 30 months emerged as early predictors of DLD, a family history of DLD appeared to be a major risk factor, and low socioeconomic status and environmental input were reported as risk factors with lower predictive power. Optimal time for screening is suggested between age 2 and 3, for diagnosis around age 4. Because of the high variability of sensitivity and specificity values, joint use of standardized and psycholinguistic measures is suggested to increase diagnostic accuracy. Conclusions. Monitoring risk situations and employing caregivers\u2019 reports, clinical assessment and multiple linguistic measures are fundamental for an early identification of DLD and timely interventions

Force-Field Compensation in a Manual Tracking Task

This study addresses force/movement control in a dynamic “hybrid” task: the master sub-task is continuous manual tracking of a target moving along an eight-shaped Lissajous figure, with the tracking error as the primary performance index; the slave sub-task is compensation of a disturbing curl viscous field, compatibly with the primary performance index. The two sub-tasks are correlated because the lateral force the subject must exert on the eight-shape must be proportional to the longitudinal movement speed in order to perform a good tracking. The results confirm that visuo-manual tracking is characterized by an intermittent control mechanism, in agreement with previous work; the novel finding is that the overall control patterns are not altered by the presence of a large deviating force field, if compared with the undisturbed condition. It is also found that the control of interaction-forces is achieved by a combination of arm stiffness properties and direct force control, as suggested by the systematic lateral deviation of the trajectories from the nominal path and the comparison between perturbed trials and catch trials. The coordination of the two sub-tasks is quickly learnt after the activation of the deviating force field and is achieved by a combination of force and the stiffness components (about 80% vs. 20%), which is a function of the implicit accuracy of the tracking task

Parrots Eat Nutritious Foods despite Toxins

Generalist herbivores are challenged not only by the low nitrogen and high indigestibility of their plant foods, but also by physical and chemical defenses of plants. This study investigated the foods of wild parrots in the Peruvian Amazon and asked whether these foods contain dietary components that are limiting for generalist herbivores (protein, lipids, minerals) and in what quantity; whether parrots chose foods based on nutrient content; and whether parrots avoid plants that are chemically defended.We made 224 field observations of free-ranging parrots of 17 species in 8 genera foraging on 102 species of trees in an undisturbed tropical rainforest, in two dry seasons (July-August 1992-1993) and one wet season (January-February1994). We performed laboratory analyses of parts of plants eaten and not eaten by parrots and brine shrimp assays of toxicity as a proxy for vertebrates. Parrots ate seeds, fruits, flowers, leaves, bark, and insect larvae, but up to 70% of their diet comprised seeds of many species of tropical trees, in various stages of ripeness. Plant parts eaten by parrots were rich in protein, lipid, and essential minerals, as well as potentially toxic chemicals. Seeds were higher than other plant materials in protein and lipid and lower in fiber. Large macaws of three species ate foods higher in protein and lipids and lower in fiber compared to plant parts available but not eaten. Macaws ate foods that were lower in phenolic compounds than foods they avoided. Nevertheless, foods eaten by macaws contained measurable levels of toxicity. Macaws did not appear to make dietary selections based on mineral content.Parrots represent a remarkable example of a generalist herbivore that consumes seeds destructively despite plant chemical defenses. With the ability to eat toxic foods, rainforest-dwelling parrots exploited a diversity of nutritious foods, even in the dry season when food was scarce for other frugivores and granivores

Tailored treatment including radical prostatectomy and radiation therapy + androgen deprivation therapy versus exclusive radical prostatectomy in high-risk prostate cancer patients: results from a prospective study

Purpose To evaluate outcomes of patients with high risk prostate cancer (PCa) who underwent radical prostatectomy (RP) in a context of a multidisciplinary approach including adjuvant radiation (RT) + androgen deprivation therapy (ADT). Matherials and Methods 244 consecutive patients with high risk localized PCa underwent RP and bilateral extended pelvic lymph node dissection at our institution. Adjuvant RT + 24 months ADT was carried out in subjects with pathological stage ≥ T3N0 and/or positive surgical margins or in patients with local relapse. Results After a median follow-up was 54.17 months (range 5.4-117.16), 13 (5.3%) subjects had biochemical progression, 21 (8.6%) had clinical progression, 7 (2.9%) died due to prostate cancer and 15 (6.1%) died due to other causes. 136 (55.7%) patients did not receive any adjuvant treatment while 108 (44.3%) received respectively adjuvant or salvage RT+ADT. Multivariate Cox proportional hazard analysis showed that pre-operative PSA value at diagnosis is a significant predictive factor for BCR (HR: 1.04, p < 0.05) and that Gleason Score 8-10 (HR: 2.4; p<0.05) and PSMs (HR: 2.01; p < 0.01) were significant predictors for clinical progression. Radical prostatectomy group was associated with BPFS, CPFS, CSS and OS at 5-years of 97%, 90%, 95% and 86% respectively, while adjuvant radiation + androgen deprivation therapy group was associated with a BPFS, CPFS and CSS at 5-years of 91%, 83%, 95% and 88%, without any statistical difference. Conclusions Multimodality tailored treatment based on RP and adjuvant therapy with RT+ADT achieve similar results in terms of OS after 5-years of follow-up