Reduction in 5-HT1A receptor density, 5-HT1A mRNA expression, and functional correlates for 5-HT1A receptors in genetically defined aggressive rats

The present experiments tested the hypothesis that one of the critical mechanisms underlying genetically defined aggressiveness involves brain serotonin 5-HT1A receptors. 5-HT1A receptor density, the receptor mRNA expression in brain structures, and functional correlates for 5-HT1A receptors identified as 8-OH-DPAT-induced hypothermia and lower lip retraction (LLR) were studied in Norway rats bred for 59 generations for the lack of aggressiveness and for high affective aggressiveness with respect to man. Considerable differences between the highly aggressive and the nonaggressive rats were shown in all three traits. A significant decrease in B(max) of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, hypothalamus, and amygdala and a reduction in 5-HT1A receptor mRNA expression in the midbrain of aggressive rats were found. 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p.) produced a distinct hypothermic reaction in nonaggressive rats and did not affect significantly the body temperature in aggressive rats. Similar differences were revealed in 8-OH-DPAT-induced LLR: LLR was expressed much more in nonaggressive than in aggressive animals. Additionally, 8-OH-DPAT (0.5 mg/kg i.p.) treatment significantly attenuated the aggressive response to man. The results demonstrated an association of aggressiveness with reduced 5-HT1A receptor expression and function, thereby providing support for the view favoring the idea that brain HT1A receptor contributes to the genetically defined individual differences in aggressiveness.     

An open-label study of amisulpride in the treatment of mania

BACKGROUND: Amisulpride is a selective D(2)-D(3) antagonist that has been reported to be effective in the treatment of schizophrenia and major depressive disorder. However, no prospective study to date has assessed the effectiveness and tolerability of this compound in mania. METHOD: Twenty DSM-IV-defined acutely ill manic bipolar patients with a Young Mania Rating Scale (YMRS) score of 20 or more entered this open, prospective, 6-week study. Assessments included the YMRS, the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions Scale for Bipolar Disorder, Modified (CGI-BP-M), and the systematic report of adverse events. Amisulpride was added to other medications, but other antipsychotics were not allowed. RESULTS: Fourteen patients (70%) completed the study. Using last-observation-carried-forward (LOCF) analyses, amisulpride produced significant improvements on the YMRS (p = .0001), the HAM-D (p < .0141), and the overall (p = .0003), mania (p = .0001), and depression (p = .0268) subscales of the CGI-BP-M. The most common side effect was sedation (N = 5, 25%), but there were also some extrapyramidal symptoms, galactorrhea, insomnia, and agitation. The mean amisulpride dose was 680 mg/day (LOCF) and 786 mg/day in completers. CONCLUSIONS: This first prospective study on amisulpride in the treatment of mania suggests that, despite the limitations of the open, observational design and small sample size, amisulpride may be effective and reasonably safe in the treatment of bipolar mania. D(2) and D(3) antagonism may be involved in the mechanisms of the therapeutic response to antipsychotics in mania.     

A comparison of the tolerability of two dilution volumes (0.5 mL and 1.0 mL) of a purified chick embryo cell rabies vaccine administered intramuscularly to healthy adult volunteers: A randomized, intraindividual, assessor-blind study

Background: The current recommendation of the manufacturer for administering purified chick embryo cell rabies vaccine (PCECV) is to reconstitute the contents with 1.0 mL of water for injection (WFI). However, it has been debated whether a lower volume of WFI (0.5 mL) is likely to cause less pain.Objectives: The aims of this study were to compare the tolerability of PCECV administered IM at a volume of 0.5 mL versus 1.0 mL of diluent and to determine the immunogenicity of the vaccine when administered according to the World Health Organization-recommended preexposure prophylaxis regimen for rabies immunization.Methods: This comparative, intraindividual, assessor-blind study was conducted at the Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital Mumbai, India). Healthy volunteers aged 18 to 50 years received, by randomized sequence, 3 IM injections of PCECV, diluted in 0.5 mL or 1.0 mL of WFI, on study days 0, 7, and 28. Tolerability was assessed at 30 minutes and 24 hours after injection and included assessments for local and systemic reactions. For immunogenicity assessment, rabies virus-neutralizing antibody 0RVNA) titers were assayed at baseline and on day 49 (ie, 3 weeks after the third injection).Results: Twenty-six subjects (24 men, 2 women; mean [SD] age, 22.4 [2.4] years; mean [SD] body weight, 59.0 [11.3] kg) entered the study. Twenty-five subjects were included in the tolerability assessment; 24 in the immunogenicity assessment. No statistically significant differences were found between dilutions in the frequency of local and systemic reactions. Most reactions were mild. All subjects developed RVNA titers >0.5 IU/mL (indicative of protection) by day 49.Conclusions: In this population of healthy volunteers, a full antigenic dose of PCECV in a dilution of 0.5 mL WFI is as well tolerated locally and systemically as in a dilution of 1.0 mL. All subjects developed levels of RVNA far exceeding 0.5 IU/mL, which is indicative of protection against rabies.     

Retrospective analysis of the morphological, cytochemical, cytogenetic, electron microscopic, and biochemical features of blast cells in acute promyelocytic leukemia

The paper presents a retrospective analysis of long-term follow-ups (from 1959 to 2000) of 86 patients with acute pro-myelocytic leukemia, a rare type of hemoblastoses. The specific features of this form of leukemia is that blast cells of the bone marrow and peripheral blood have a specific granularity that plays a decisive role in the development of the severe hemorrhagic syndrome leading to patients' death. The morphological, cytochemical, cytogenetic, electron microscopic, and biochemical features of blast cells in this disease and its pathogenesis, clinical presentation, and treatment are considered. An extract from the records of a female patient who has had a complete clinical and hematological remission for 22 years is given. The follow-up of such a prolonged remission has not been covered in the Russian literature.     

Hygienic aspects of urinary system developing pathology in children (review)

The paper deals with the impact of environmental factors of industrial cities and towns on children's health. Particular emphasis is laid on urinary tract pathology since the kidney is a xenobiotically exposed target organ. The main criteria for a risk of environment-induced diseases are ambient air pollution, low drinking water quality, soil heavy metal pollution, etc. The review covers the pathogenetic mechanisms and clinical features of the manifestation of renal diseases in children living in the regions with different heavy metal-loaded environment.