Rosiglitazone in the assistance of metabolic control during olanzapine administration in schizophrenia: a pilot double-blind, placebo-controlled, 12-week trial.

INTRODUCTION: Excessive body weight gain (BWG), hyperglycemia and dyslipidemia are important side effects of olanzapine. We assessed the effects of rosiglitazone on BWG, the insulin resistance index (HOMA-IR), lipids, glycated hemoglobin and fibrinogen in olanzapine-treated schizophrenia patients. METHODS: Thirty patients taking olanzapine (10-20 mg daily for 8 months) were randomly allocated to rosiglitazone (n=15; 4 to 8 mg daily) or placebo (n=15) in a 12-week double-blind protocol. Anthropometric and biochemical variables were evaluated at baseline, weeks 6 and 12. RESULTS: The rosiglitazone and placebo groups gained 3.2+/-4.5 and 2.2+/-2.3 kg, respectively (p=0.65). Insulin and the HOMA-IR significantly decreased after rosiglitazone (p<0.05). Rosiglitazone did not improve the lipid profile, fibrinogen and Hb1c levels. DISCUSSION: The positive impact of rosiglitazone was limited to improved glycemic control. It cannot be recommended for metabolic control during olanzapine treatment.

Molecular epidemiology of rabies virus strains isolated from wild canids in Northeastern Brazil

Rabies in wild canids in Northeastern Brazil is frequent and has been reported for some time, with episodes of rabies transmission from these animals to humans also reported. In this study, we analyzed the antigenic and genetic profiles of the rabies virus nucleoprotein gene, isolated from 20 samples taken from domestic animals and wild canids located in the Northeastern region of Brazil. All viruses isolated from domestic animals (dogs and cats) belonged to the antigenic variant 2 (AgV2). Among the wild animal samples, only four were AgV2, and nine showed a divergent antigenic profile. Phylogenetic analysis revealed two Brazilian clusters. Cluster 1 (Brazilian domestic carnivore-related strains) showed two subclusters, called 1A and 1B, and cluster 2 (Brazilian wild canid-related strains) also showed two subclusters, called 2A and 2B. The majority of the samples with divergent antigenic strains segregated into subcluster 2A. The intracluster identity of cluster 1 was 95.6% and that of cluster 2, 92.4%. When clusters 1 and 2 were compared, an identity of 88.6% was found. The genetic analysis of wild canid samples performed in this study indicates that there are two distinct rabies cycles among canids in Brazil, one represented by domestic canids and the other by wild canids. This study shows that the virus samples isolated in Northeastern Brazil are region and species-specific.

QTL mapping and introgression of yield-related traits from Oryza glumaepatula to cultivated rice ( Oryza sativa) using microsatellite markers.

Rice ( Oryza sativa) cultivar development currently faces the task of overcoming yield plateaus, which is difficult due to the narrow genetic base of breeding programs. Oryza glumaepatula is a diploid wild relative of cultivated rice, native to Central and South America, and is therefore a potential source of alleles of agronomic importance to rice breeding programs. We studied 11 agronomic traits in BC(2)F(2) families of the interspecific cross Oryza sativa x O. glumaepatula. Transgressive lines which are almost isogenic to the elite recurrent O. sativa parent were identified for most of these traits. Quantitative trait locus (QTL) analysis was performed by single-point and interval mapping using a molecular map based on 157 microsatellite and STS markers. Marker regions accounting for 14.5 to 72.9% of a phenotypic variation trait were identified in 9 of the 12 rice chromosomes. Positive QTL effects from O. glumaepatula were observed in chromosomal regions associated with tillering and panicle-number traits.

Comparison of the binding activities of some drugs on alpha 2A, alpha 2B and alpha 2C-adrenoceptors and non-adrenergic imidazoline sites in the guinea pig.

Simultaneous computer modelling of control and guanfacine-masked [3H]-MK 912 saturation curves as well as guanfacine competition curves revealed that both alpha 2A- and alpha 2C-adrenoceptor subtypes were present in the guinea pig cerebral cortex. The Kd value of [3H]-MK 912 determined for the alpha 2A-subtype was 403 pM and for the alpha 2C-subtype 79.8 pM; the receptor sites showing capacities 172 and 19.5 fmol/mg protein, respectively. The Kds of guanfacine were 20 and 880 nM for the alpha 2A- and alpha 2C-adrenoceptor, respectively. In the guinea pig kidney [3H]-MK 912 bound to a single saturable site with Kd 8.34 nM and capacity 285 fmol/mg protein, the site showing pharmacological properties like an alpha 2B-adrenoceptor. Binding constants of 22 compounds for the three guinea pig alpha 2-adrenoceptor subtypes were determined by computer modelling competition curves using for the cerebral cortex a "3-curve assay", for the kidney an "1-curve assay", and using [3H]-MK 912 as labelled ligand. Of the tested drugs guanfacine and BRL 44408 were found to be clearly alpha 2A-selective, Spiroxatrine, yohimbine, rauwolscine and WB 4101, as well as [3H]-MK 912 itself, were found to be alpha 2C-selective. The most selective compounds for alpha 2B-adrenoceptors, when compared to alpha 2A-adrenoceptors, were ARC 239 and prazosin. In the guinea pig kidney [3H]-p-aminoclonidine bound to alpha as well as to non-adrenergic imidazoline sites. The alpha 2-adrenoceptors could be completely blocked using 10 microM (-)-adrenaline without the non-adrenergic sites being affected. During these conditions the analysis of combined saturation and competition studies using labelled and unlabelled p-aminoclonidine with computer modelling revealed that the ligand labelled two different sites with Kds of 310 and 47,000 nM, respectively. Competition curves of 16 compounds for the non-adrenergic [3H]-p-aminoclonidine sites were shallow and resolved into two-site fits. For the high affinity [3H]-p-aminoclonidine site the highest affinities were shown by 1-medetomidine, UK-14,304, guanabenz and detomidine; the Kds of these drugs ranging 26-72 nM. All drugs tested showed low but varying affinities for the low affinity [3H]-p-aminoclonidine site. These data indicated that the [3H]-p-aminoclonidine binding sites of the guinea pig kidney are grossly different from the [3H]-idazoxan binding I2-receptors previously demonstrated also to be present in the guinea pig kidney.

Detomidine binding to guinea pig liver imidazoline receptors (I-receptors) shows marked positive cooperativity.

The binding of [3H]-idazoxan to guinea pig liver membranes was measured in the presence of 3 microM rauwolscine, which prevented the binding [3H]-idazoxan to alpha 2-adrenergic receptors. Under these conditions the radioligand bound to saturable imidazoline receptors (I-receptors) with a Kd of 18 nM and a Bmax of 665 fmol mg-1 protein. Six drugs which were used to compete for [3H]-idazoxan in the liver caused competition curves of widely varying steepness. Fitting the competition curves to the standard four parameter logistic function showed that the Hill coefficients (nH) varied from 2.02 (detomidine) to 0.43 (UK-14,304), The nH's obtained in liver for the six compounds correlated strongly (r = 0.99; P < 0.001) with the corresponding nH's obtained in a previous study on the guinea pig kidney where the drugs were also tested in competition with [3H]-idazoxan (Wikberg et al. 1992). Good correlation was also found for the Log(Ki) values of drugs determined in the two tissues (r = 0.96; P < 0.005). Whereas the standard logistic function accurately described the competition curves of the 5 drugs tested in the liver for which the competition curve Hill coefficients varied between 0.43 to 1.41 (UK-14,304, rilmenidine, histamine and d- and l-medetomidine), it did not accurately fit the detomidine competition curves. Instead the detomidine competition curves could be more accurately described by a model composed of the sum of two independent logistic functions.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR.

We here describe the cloning of an additional gene, called alpha 2-1.8, which is similar to the previously cloned human alpha 2-adrenergic receptor located on chromosome 4. The alpha 2-1.8 gene was identified by using the polymerase chain reaction with primers specific for sequences in transmembrane regions 2 and 5 of the previously isolated human alpha 2-C4 and alpha 2-C10 adrenoceptor genes, which are localized on chromosomes 4 and 10, respectively. The new gene was identified by amplifying the 1.8 kb size fractionated region of PstI restriction cut human genomic DNA. The previously cloned alpha 2-C10 and alpha 2-C4 genes were recovered at their expected locations, 0.96 and 5.9 kb, respectively. We have identified 387 bases of the new alpha 2-1.8 gene, and its sequence is identical to the previously described alpha 2-C4 gene, but it is distinct from the alpha 2-C10 and alpha 2-C2 genes. Our results demonstrate that the alpha 2-C4 adrenergic receptor exists in more than one copy in the human genome.