The effect of beta-2 adrenergic receptor haplotype variations on the haemodynamic response following spinal anaesthesia for caesarean delivery.

We investigated whether genetic variations of the beta-2 adrenergic receptor (ADRB2) modulate the haemodynamic response following spinal anaesthesia for caesarean delivery. We focused on the effects of haplotypes formed by combinations of the Arg16Gly and Gln27Glu polymorphisms. Clinical data from 143 healthy parturients were collected. Only the ArgGln haplotype appeared to influence the risk of hypotension, most probably through a recessive mode of inheritance (p=0.027). Therefore, patients were grouped according to ArgGln homozygosity in two groups: presence of one or no copies of the haplotype (n=120) or two copies of the haplotype (n=23). Both groups presented similar baseline characteristics. Comparatively, patients homozygous for the ArgGln haplotype presented consistently higher blood pressure levels throughout the evaluation period (p=0.001 for systolic arterial pressure variation from baseline). In conclusion, our results demonstrate that haplotype variations of the the ADRB2 modulate the haemodynamic response following spinal anaesthesia for caesarean delivery.

Effects of a methanolic fraction of soybean seeds on the transcriptional activity of peroxisome proliferator-activated receptors (PPAR)

Since the anti-inflammatory, antidiabetic and hypolipidemic effects of soy isoflavones may be mediated by activation of peroxisome proliferator-activated receptors (PPAR), the present study investigated whether the methanolic fractions obtained from soybean seeds (E1) and soybean seed coats with hypocotyls (E2) could influence PPARα, PPARγ and PPARβ/δ transcriptional activity. The isoflavones from E1 and E2 were quantified by HPLC analysis. E1 and E2 were rich in isoflavones (daidzin, glycitin, genistin, malonyldaidzin, malonylglycitin, malonylgenistin, daidzein, glycitein, and genistein). Moreover, E1 and E2 showed no evidence of genetically modified material containing the gene CP4 EPSPS. To investigate PPAR transcriptional activity, human promonocytic U-937 cells were treated with E1 and E2 (200, 400, 800, and 1600 µg/mL), positive controls or vehicle. Data are reported as fold-activation of the luciferase reporter driven by the PPAR-responsive element. Dose-response analysis revealed that E1 and E2 induced the transcriptional activity of PPARα (P < 0.001), with activation comparable to that obtained with 0.1 mM bezafibrate (positive control) at 1600 µg/mL (4-fold) and 800 µg/mL (9-fold), respectively. In addition, dose-response analysis revealed that E1 and E2 activated PPARβ/δ (P < 0.05), and the activation at 800 µg/mL (4- and 9-fold, respectively) was comparable to that of 0.1 mM bezafibrate (positive control). However, no effect on PPARγ was observed. Activation of PPARα is consistent with the lipid-lowering activity of soy isoflavones in vivo, but further studies are needed to determine the physiological significance of PPARβ/δ activation.

Effects of a methanolic fraction of soybean seeds on the transcriptional activity of peroxisome proliferator-activated receptors (PPAR).

Since the anti-inflammatory, antidiabetic and hypolipidemic effects of soy isoflavones may be mediated by activation of peroxisome proliferator-activated receptors (PPAR), the present study investigated whether the methanolic fractions obtained from soybean seeds (E1) and soybean seed coats with hypocotyls (E2) could influence PPARalpha, PPARgamma and PPARbeta/delta transcriptional activity. The isoflavones from E1 and E2 were quantified by HPLC analysis. E1 and E2 were rich in isoflavones (daidzin, glycitin, genistin, malonyldaidzin, malonylglycitin, malonylgenistin, daidzein, glycitein, and genistein). Moreover, E1 and E2 showed no evidence of genetically modified material containing the gene CP4 EPSPS. To investigate PPAR transcriptional activity, human promonocytic U-937 cells were treated with E1 and E2 (200, 400, 800, and 1600 microg/mL), positive controls or vehicle. Data are reported as fold-activation of the luciferase reporter driven by the PPAR-responsive element. Dose-response analysis revealed that E1 and E2 induced the transcriptional activity of PPARalpha (P < 0.001), with activation comparable to that obtained with 0.1 mM bezafibrate (positive control) at 1600 microg/mL (4-fold) and 800 microg/mL (9-fold), respectively. In addition, dose-response analysis revealed that E1 and E2 activated PPARbeta/delta (P < 0.05), and the activation at 800 microg/mL (4- and 9-fold, respectively) was comparable to that of 0.1 mM bezafibrate (positive control). However, no effect on PPARgamma was observed. Activation of PPARalpha is consistent with the lipid-lowering activity of soy isoflavones in vivo, but further studies are needed to determine the physiological significance of PPARbeta/delta activation.

Crystallization and preliminary X-ray diffraction studies of isoform alpha1 of the human thyroid hormone receptor ligand-binding domain.

Thyroid hormone receptors (TR) play critical roles in virtually all tissues. The TR ligand-binding domain (LBD) participates in important activities, such as transcriptional activation and repression, through conformational changes induced by hormone binding. Two crystal forms of isoform alpha1 of the human thyroid hormone receptor LBD (hTRalpha1) in complex with the thyroid hormones T3 and Triac were obtained. The hTRalpha1-T3 complex was crystallized in a previously unobserved crystal form (space group P2(1)2(1)2(1), a = 59.98, b = 80.80, c = 102.21 A), with diffraction patterns extending to 1.90 A resolution on a rotating-anode X-ray source, and in space group C2 (a = 117.54, b = 80.66, c = 62.55 A, beta = 121.04 degrees), with data extending to 2.32 A resolution. The hTRalpha1-Triac complex was also crystallized in the new space group P2(1)2(1)2(1), with unit-cell parameters a = 60.01, b = 80.82, c = 102.39 A; its resolution limit extended to 2.20 A on a home source. Phasing was carried out by the molecular-replacement method and structural refinement is currently in progress. The refined structures may provide insight into the design of new thyromimetics.

Stress and hypertension: studies in three experimental models

The effects of three models of stress upon blood pressure and central responsiveness to angiotensin II (AII) and noradrenaline (NA) were assessed in rats. Considering general parameters of stress efficacy, all models were effective to induce stress but hypertension only occurred in animals submitted to rapid eye movement sleep deprivation (REM-sd) and electric shock (ES). An increased central pressor effect of AII and NA was observed in these groups. On the other hand, restriction (R) did not increase blood pressure or central responsiveness to AII or NA. Instead of hypertension, R induced gastric ulcers and testis atrophy. Thus, hypertension occurs only in some models of stress and may be due to increased central responsiveness to AII and NA.