Bial

About: Bial is a company organization based out in Porto, Portugal. It is known for research contribution in the topics: Eslicarbazepine acetate & Catechol-O-methyl transferase. The organization has 321 authors who have published 591 publications receiving 30583 citations.

Search of the Orion spur for continuous gravitational waves using a loosely coherent algorithm on data from LIGO interferometers

Abstract: We report results of a wideband search for periodic gravitational waves from isolated neutron stars within the Orion spur towards both the inner and outer regions of our Galaxy. As gravitational waves interact very weakly with matter, the search is unimpeded by dust and concentrations of stars. One search disk (A) is 6.87° in diameter and centered on 20^h10^m54.71^s+33°33′25.29′′, and the other (B) is 7.45° in diameter and centered on 8^h35^m20.61^s−46°49′25.151′′. We explored the frequency range of 50–1500 Hz and frequency derivative from 0 to −5×10^(−9) Hz/s. A multistage, loosely coherent search program allowed probing more deeply than before in these two regions, while increasing coherence length with every stage. Rigorous follow-up parameters have winnowed the initial coincidence set to only 70 candidates, to be examined manually. None of those 70 candidates proved to be consistent with an isolated gravitational-wave emitter, and 95% confidence level upper limits were placed on continuous-wave strain amplitudes. Near 169 Hz we achieve our lowest 95% C.L. upper limit on the worst-case linearly polarized strain amplitude h_0 of 6.3×10^(−25), while at the high end of our frequency range we achieve a worst-case upper limit of 3.4×10^(−24) for all polarizations and sky locations.

Quantification assay for the major allergen of cupressus sempervirens pollen, cup s 1, by sandwich elisa

Abstract: Background: The Cupressaceae are an important cause of pollinosis, particularly in Mediterranean countries. Cypress pollen allergenic extracts are difficult to produce since they have a low protein and a high carbohydrate content and consequently accurate standardization of these extracts is essential for diagnosis and immunotherapy. Method: Natural Cup s 1 was purified by a combination of hydrophobic interaction, gel filtration and ion exchange chromatographies and its enzymatic activity was analyzed. The allergen was used as reference material in the ELISA standard curve. The assay was based on a specific monoclonal antibody (3D2) immobilized on ELISA plates and used to capture Cup s 1. Bound proteins were detected by a combination of biotinylated specific antiserum and peroxidase-conjugated streptavidin. Results: Purified Cup s 1 is a functional pectate lyase enzyme with a specific activity of 750 U/mg protein. The developed ELISA measured Cup s 1 concentrations ranging from 31.25 to 250 ng/ml in the lineal portion of the standard curve. The intra-assay and inter-assay variation coefficients in the working range were less than 8.1 % and 16 %, respectively. The assay was highly sensitive, with a detection limit of 3.8 ng/ml. The dose-response curves obtained with C. sempervirens pollen extracts and extracts belonging to other species from the Cupressaceae family showed a good parallelism compared with those obtained using the purified allergen, indicating that the same protein was measured. Conclusions: The assay described is sensitive, specific and reproducible for the quantification of Cup s 1 in C. sempervirens pollen extracts for clinical use. This ELISA could also be useful for other Cupressaceae-related pollen extracts.

Hepatic UDP-Glucuronosyltransferase Is Responsible for Eslicarbazepine Glucuronidation

Abstract: Eslicarbazepine acetate (ESL) is a once-daily novel antiepileptic drug approved in Europe for use as adjunctive therapy for refractory partial-onset seizures with or without secondary generalization. Metabolism of ESL consists primarily of hydrolysis to eslicarbazepine, which is then subject to glucuronidation followed by renal excretion. In this study, we have identified that human liver microsomes (HLM) enriched with uridine 5'-diphosphoglucuronic acid give origin to a single Escherichia coli β-glucuronidase-sensitive eslicarbazepine glucuronide (most likely the O-glucuronide). The kinetics of eslicarbazepine glucuronidation in HLM was investigated in the presence and absence of bovine serum albumin (BSA). The apparent K(m) were 412.2 ± 63.8 and 349.7 ± 74.3 μM in the presence and absence of BSA, respectively. Incubations with recombinant human UDP glucuronosyltransferases (UGTs) indicated that UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17 appear to be involved in eslicarbazepine conjugation. The UGT with the highest affinity for conjugation was UGT2B4 (K(m) = 157.0 ± 31.2 and 28.7 ± 10.1 μM, in the absence and presence of BSA, respectively). There was a significant correlation between eslicarbazepine glucuronidation and trifluoperazine glucuronidation, a typical UGT1A4 substrate; however, no correlation was found with typical substrates for UGT1A1 and UGT1A9. Diclofenac inhibited eslicarbazepine glucuronidation in HLM with an IC(50) value of 17 μM. In conclusion, glucuronidation of eslicarbazepine results from the contribution of UGT1A4, UGT1A9, UGT2B4, UGT2B7, and UGT2B17, but the high-affinity component of the UGT2B4 isozyme may play a major role at therapeutic plasma concentrations of unbound eslicarbazepine.

Blood pressure decrease in spontaneously hypertensive rats folowing renal denervation or dopamine β-hydroxylase inhibition with etamicastat

Abstract: Overactivity of the sympathetic nervous system has an important role in the development and progression of arterial hypertension Catheter-based renal nerve ablation for the treatment of drug-resistant hypertension has recently been developed An alternative strategy for the modulation of sympathetic nerve function is to reduce the biosynthesis of noradrenaline (NA) by inhibiting dopamine β-hydroxylase (DβH), the enzyme that catalyzes the conversion of dopamine (DA) to NA in the sympathetic nerves Renal denervation (RDN) surgery was performed in spontaneously hypertensive rats (SHR) to evaluate the effect of RDN on the DA and NA levels and on blood pressure over a 28-day period The selective peripheral DβH inhibitor etamicastat (30 mg kg (-1)day(-1)) was administered to another cohort of SHR RDN and etamicastat treatment had no effect on the renal function, as assessed by measuring the water balance response, renal function and urinary electrolyte levels RDN significantly decreased the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) A gradual return of the SBP and the DBP to the high baseline levels was observed over time Conversely, treatment with etamicastat resulted in a significant decrease in the SBP and the DBP at all time points On the last day of the assessment, NA levels in renal tissue were significantly decreased in both RDN and etamicastat-treated groups In contrast, the NA levels in the left ventricle were decreased only in the etamicastat-treated group Thus, RDN produces transitory decreases in blood pressure, whereas prolonged downregulation of sympathetic drive with the DβH inhibitor etamicastat results in a sustained decrease in the SBP and the DBP