Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Antigenic relationships between strains of influenza B virus.

An immunological relationship between strains of influenza B virus, considerably differing from one another in haemagglutination inhibition (HI) and virus neutralization (VN) tests, was established. The relationships were also evaluated based on the ability of influenza B viruses to replicate in the lungs of mice immunized with strains possessing antigenically distinct haemagglutinin. There was no substantial difference in the protection of animals immunized with homologous or heterologous strains. Studies on the character of the immunological response of men convalescent after influenza B infection or after vaccination showed an antibody increase to both the epidemic virus and chronologically remote viruses considerably differing in antigenic properties. The data obtained suggest that influenza B viruses isolated from 1940 to 1975 belong to one antigenic subtype.     

Effects of haloperidol on communicative and aggressive behavior in male mice with different experiences of aggression.

Effects of two doses of haloperidol (0.1 and 0.4 mg/kg, 30 min and 24 h, IP) on communicative and aggressive behavior in C57BL/6J male mice have been studied. Some of the mice were without prior experience of aggression ("recruits"); the others had been victorious in 20 daily aggressive confrontations ("experienced winners"). Communicative behavior was estimated as the behavioral reaction to a standard tester (loser) in the partition test. Haloperidol in either dose significantly reduced communicative behavior in the "recruits." but not in the "experienced winners." Significantly fewer attacks, less total attacking time, and total time of aggressive behavior (aggressive grooming + attacks) were demonstrated by the "experiences winners," than by the "recruits," while the latency of the first attack, the number, the total and average duration of aggressive grooming events were significantly higher. In the "recruits," haloperidol dose dependently increased the latency and decreased the number of attacks, the total attacking time, and the total time of aggressive behavior 30 min and 24 h after injection. However, haloperidol did not affect the average or total time of aggressive grooming. Neither dose significantly affected any measure of aggressive behavior in the "experienced winners." It has been concluded that repeated aggression experience reduces the pharmacological sensitivity of the dopamine receptors.     

Behavioral effects of novel enterosorbent Noolit on mice with mixed depression/anxiety-like state

The aim of this work was to examine the behavioral effects of a novel lithium-based enterosorbent, Noolit (665 mg/kg), on male mice with mixed depression/anxiety-like state evoked by exposure to repeated social defeats in daily agonistic confrontations. The lithium component allows Noolit to be used as a psychotropic drug. Two experiments are described, in which the therapeutic and preventative effects of chronic Noolit treatment were examined. Response to Noolit was assessed in the plus maze, open field, partition test, and Porsolt's test. In both experiments, Noolit produced obvious anxiolytic and antidepressant effects. Treatment with Noolit fully restored some behavioral parameters in the plus maze and open field in depressed mice and prevented depression that would otherwise have developed. It has been suggested that enterosorbent Noolit can be a potent drug for the treatment of mixed anxiety/depression pathologies and for prevention of mood disorders.     

Association between experience of aggression and anxiety in male mice

The sensory contact technique increases aggressiveness in male mice and allows an aggressive type of behavior to be formed as a result of repeated experience of social victories in daily agonistic confrontations. In the low aggressive and high emotional mice of CBA/Lac strain, repeated positive fighting experience leads to increased plus maze anxiety in the winners after 10 days of experience of victories and much more after 20 days. Behavioral reactivity to other conspecifics was significantly increased as revealed by the parameters of partition test, which measures aggressive motivation in the winners. Thus, anxiety as a consequence of repeated experience of aggression is associated with the increase of aggressive motivation in CBA/Lac mice. It is concluded, that: (1) Repeated experience of aggression provokes the development of anxiety in male mice. (2) The level of anxiety as well as its behavioral realization depends on the duration of aggressive experience and genetic strain. Genetically defined features of innate anxiety (trait or state) in individuals may determine the kind of association between aggressive experience, aggressive motivation and anxiety.     

Decrease of kappa-opioid receptor mRNA level in ventral tegmental area of male mice after repeated experience of aggression

Brain opioid systems have been implicated in the regulation of social interaction, including agonistic behaviour. kappa-Opioid receptor B and C mRNA levels were decreased in the ventral tegmental area but not in the nucleus accumbens in male mice with repeated experience of social victories (winners), but not in mice after social defeats (losers) after 10 but not 20 days of confrontations. mu-Opioid receptor mRNA levels were not changed.     

Relative role of plutonium excretion with urine and feces from human body

The ratio of plutonium content in 35 pairs of daily fecal and urine samples from 19 former MAYAK workers several decades after the end of occupational exposure was measured in clinical conditions. No dependence of the ratio Pu(feces)/Pu(urine) on plutonium aerosol transportability, sex, and age of workers was revealed in the late times after the end of occupational exposure. It was found that at the late times after the end of occupational exposure, the ratio of feces/urine is characterized by the lognormal distribution with the median value, 0.57, and error for this index characterized geometric deviation, sigmag = 1.12 Urinary and fecal excretions were analyzed after chronic exposure to inhaled plutonium compounds of different transportability for another group of 345 workers. During 500-16,000 d after the started chronic inhalation, plutonium biokinetic model ("Doses-2000") used in Southern Ural Biophysics Institute (SUBI) and based on the ICRP Publication 66 overestimated the feces/urine ratio by an order of magnitude as compared with the observed values. It indicates a necessity for further improvement of the biokinetic model used in SUBI.