Genome sequences of poa semilatent and lychnis ringspot hordeiviruses

The nucleotide sequences of the genomic RNAs of two hordeiviruses, poa semilatent virus (PSLV) and lychnis ringspot virus (LRSV), were determined. The genome organization of both viruses is similar to that of the type hordeivirus, barley stripe mosaic virus (BSMV). Comparisons of the amino acid sequences of the hordeivirus replicase components revealed a high level of sequence similarity to those of soil-borne wheat mosaic virus (SBWMV), peanut clump virus (PCV), and Indian peanut clump virus. The cysteine-rich gamma b proteins of hordeiviruses are similar to those of SBWMV, PCV, and tobraviruses. Analysis of cis-acting elements in the genomes of the three hordeiviruses revealed conservation of putative core elements of subgenomic RNA promoters. Complex patterns of conservation were also found in the 5'-untranslated regions of hordeivirus genomic RNAs alpha, beta, and gamma.     

The sequelae of the intraspecific isolation of adult rats (right-handed, left-handed and ambidextrous animals)

We studied the influence of social isolation at the age of 2 months on zoosocial behaviour of mixed-bred male rats with different paw preference. Paw preference was determined in the test of reaching for food in the horizontal tube. The level of aggression but not sociability was found to increase significantly in dextral and ambidextrous late isolants. In sinistrals the increase of sociability but not aggression was observed. Analysis of probabilistic ethological structure of aggressive behaviour showed its validity and revealed the appearance of pathological aggression as a result of isolation in all groups of animals. Being connected with a disfunction of the regulating role of the right brain hemisphere this feature of aggressive behaviour is most pronounced in dextrals and ambidextrals.     

On the recording of sample times and parameter estimation from repeated measures pharmacokinetic data

A pharmacokinetic screen has been advocated for the characterization of the population pharmacokinetics of drugs during Phase 3 clinical trials. A common perception encountered in the collection of such data is that the accuracy of sampling times relative to dose is inadequate. A prospective simulation study was carried out to evaluate the effect of error in the recording of sampling times on the accuracy and precision of population parameter estimates from repeated measures pharmacokinetic data. A two-compartment model with intravenous bolus input(s) (single and multiple doses) was assumed. Random and systematic error in sampling times ranging from 5-50% using profile (block) randomized design were introduced. Sampling times were simulated in EXCEL while concentration data simulation and analysis were done in NONMEM. The effect of error in sampling times was studied at levels of variability ranging from 15-45% for a drug assumed to be dosed at its elimination half-life. One hundred replicate data sets of 100 subjects each were simulated for each case. Although estimates of clearance (CL) and variability in clearance were robust for most of the sampling time errors, there was an increase in bias and imprecision in overall parameter estimation as intersubject variability was increased. If there is interest in parameters other than CL, then the design of prospective population studies should include procedures for minimizing the error in the recording of sample times relative to dosing history.     

Comparative characteristics of steroidogenesis and its biorhythm in the hyperfunctioning adrenal cortex

The paper summarizes the results od several studies of the daily rhythms of steroid hormones in patients with ACTH-dependent Itsenko-Cushing's disease (CD) and congenital adrenal hyperplasia (late-onset forms) (CAH). Normal daily rhythms of adrenal C21- and C19-steroids and ACTH were observed in 23.5% of CD patients. CAH patients had the marked daily rhythms of adrenal androgens and testosterone which were typical of those of cortisole. The ratios of steroid hormones to its precursors provide evidence for enhanced activities of 17-, 11 beta- and 18-hydroxylases in CD patients and normal enzymatic activities in CAH patients, whereas 21-hydroxylase being an exception.