Polymorphisms in the serotonin transporter and monoamine oxidase A genes and their relationship to personality traits measured by the Temperament and Character Inventory and NEO Five-Factor Inventory in healthy volunteers

The associations between 5-HTT-linked polymorphic region (5-HTT-LPR), monoamine oxidase A (MAOA)-LPR and the dimensions of temperament evaluated using the Temperament and Character Inventory (TCI) and NEO Five-Factor Inventory (NEO-FFI) were studied. One hundred healthy volunteers (without psychiatric disorders) were recruited to represent a cross-section of the population of Szczecin (Poland) in terms of sex, age and education. No associations between 5-HTT-LPR and the TCI harm avoidance dimension and between 5-HTT-LPR and the NEO-FFI neuroticism dimension were found. Males carrying the 3-VNTR MAOA gene variant (209 bp) had significantly lower values on the NEO-FFI openness dimension (p = 0.039) and obtained higher scores on the subdimension 3 of the TCI reward dependence (RD3), i.e. attachment vs. detachment (p = 0.005). Individuals carrying the 'short' variant of 5-HTT-LPR had lower values on the reward dependence dimension and the RD4 subdimension (dependence vs. independence) than individuals not carrying the 'short' variant (p = 0.039 and p = 0.011, respectively). Females carrying the 'short' variant had lower values on NS1 (exploratory excitability vs. stoic rigidity) and RD4 (dependence vs. independence) than those not carrying the variant (p = 0.042 and 0.043, respectively). The obtained level of significance with respect to the observed associations between 5-HTT-LPR and the reward dependence scales and subscales and between 5-HTT-LPR and the NS1 subscale are too weak for further interpretation. Our results do not confirm the hypothesis that there is a simple correlation between single gene polymorphisms and a personality trait measured by the TCI and NEO-FFI scales.     

Rat anterodorsal thalamic head direction neurons depend upon dynamic visual signals to select anchoring landmark cues

Head direction cells, which are functionally coupled to 'place' cells of the hippocampus, a structure critically involved in spatial cognition, are likely neural substrates for the sense of direction. Here we studied the mechanism by which head direction cells are principally anchored to background visual cues [M.B. Zugaro et al. (2001) J. Neurosci., 21, RC154,1-5]. Anterodorsal thalamic head direction cells were recorded while the rat foraged on a small elevated platform in a 3-m diameter cylindrical enclosure. A large card was placed in the background, near the curtain, and a smaller card was placed in the foreground, near the platform. The cards were identically marked, proportionally dimensioned, subtended the same visual angles from the central vantage point and separated by 90 degrees. The rat was then disoriented in darkness, the cards were rotated by 90 degrees in opposite directions about the center and the rat was returned. Preferred directions followed either the background card, foreground card or midpoint between the two cards. In continuous lighting, preferred directions shifted to follow the background cue in most cases (30 of the 53 experiments, Batschelet V-test, P < 0.01). Stroboscopic illumination, which perturbs dynamic visual signals (e.g. motion parallax), blocked this selectivity. Head direction cells remained equally anchored to the background card, foreground card or configuration of the two cards (Watson test, P > 0.1). This shows that dynamic visual signals are critical in distinguishing typically more stable background cues which govern spatial neuronal responses and orientation behaviors.     

Hypoxia induces caspase-9 and caspase-3 activation without neuronal death in gerbil brains

To investigate the in vivo apoptotic machinery in oxygen deprived brain, we examined the expression of caspase-9 and caspase-3 in the hippocampus of Mongolian gerbils subjected to either transient hypoxia (4% O2 for 6 min) or forebrain ischemia (10 min bilateral carotid artery occlusion) followed by 8 h to 7 days of reoxygenation or blood recirculation. Apoptotic death was characterized by isolating hippocampal genomic DNA and analysing DNA fragmentation as well as histological studies including TUNEL assay and toluidine blue staining of brain sections. The results showed that both hypoxic and ischemic gerbil brains exhibited an increase in caspase-9 and caspase-3 gene expression. However, no cell damage was detectable following hypoxia, while marked DNA fragmentation and extensive cell death was observed following ischemia. Moreover, although hypoxia did not lead to cell death, both hypoxia and ischemia were associated with cleavage of procaspase-9 and procaspase-3 and increases in their activities as well as cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a major caspase-3 substrate. These results indicate that, in vivo, even late apoptotic events such as caspase activation and PARP-1 cleavage in hypoxic brains do not necessarily induce an irreversible commitment to apoptotic neuronal death.     

Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension

Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.     

Premature coronary artery disease shows no evidence of linkage to loci encoding for tissue inhibitors of matrix metalloproteinases

Tissue inhibitors of metalloproteinases (TIMP1, TIMP2, TIMP3) are naturally occurring inhibitors of matrix metalloproteinases (MMPs). It has been proposed that MMPs have a role in weakening the fibrous cap and subsequent plaque rupture. We hypothesized that TIMP polymorphisms could predispose to premature coronary artery disease. As a first step, we examined the relevant loci using a linkage approach. Sibling pairs recruited for the British Heart Foundation (BHF) Family Heart Study with premature coronary artery disease were examined. Two to three microsatellite markers were examined per TIMP gene. These markers were either intragenic or very close to the locus encoding for the gene. Products were analyzed by capillary gel electrophoresis. Single and multipoint linkage analysis based on the likelihood ratio test was performed using SPLINK and Mapmaker/Sibs software; 417 families were genotyped consisting of 385 sibling pairs, 27 trios, and five sets of four siblings. We were unable to detect linkage of premature coronary artery disease to loci encoding for TIMP1-3. Polymorphisms of the tissue inhibitors of MMP genes do not predispose to premature coronary artery disease in an epidemiologically significant way.     

Internal injuries of larynx in children. Case reports

The authors present larynx injuries among children especially with regard to iatrogenic internal injuries based on personally observed cases: dislocation of arytenoid cartilage in 11 year-old girl and post intubation granuloma in 8 year-old girl.     

Risperidone,but not olanzapine,decreases bone mineral density in female premenopausal schizophrenia patients

BACKGROUND: The hyperprolactinemia induced by conventional antipsychotics often leads to osteoporosis. The commonly used atypical antipsychotics risperidone and olanzapine vary in their hyperprolactinemic properties. Therefore, we compared hormone profiles and bone properties in female premenopausal schizophrenia patients treated with either risperidone or olanzapine. METHOD: In a cross-sectional study, consecutive premenopausal, female, DSM-IV schizophrenia patients who were treated with either risperidone (N = 12) or olanzapine (N = 14) for at least 2 years were included. Dual energy X-ray absorptiometry evaluated bone mineral density, and multisite quantitative ultrasound measured bone speed of sound. In addition, profiles of urinary excretion of deoxypyridinoline and circulating levels of hormones and lipids were assessed. RESULTS: Serum prolactin levels were higher in the risperidone-treated group as compared with the olanzapine subjects (123 +/- 144 and 25.9 +/- 25.7, p <.05). Whereas bone mineral density was similar in the treatment groups, bone speed of sound was lower in the risperidone group as compared with the olanzapine-treated group. Expressed as age-adjusted Z score, bone speed of sound at the radius was -0.31 and 0.58, respectively, p <.05, and at the phalanx, -1.41 and 0.04, respectively, p <.05. The bone speed of sound in the risperidone-treated patients inversely correlated with urinary deoxypyridinoline excretion (r = 0.73, p <.05). CONCLUSION: Risperidone treatment, as opposed to olanzapine, for female premenopausal schizophrenia results in hyperprolactinemia and clinically relevant decrease in bone mineral density. The calculated relative risk for fragility fracture of women treated with risperidone as compared to those treated with olanzapine is 1.78 when bone speed of sound was measured at the phalanx and 1.23 when measured at the radius.