Longitudinal assessment of coping abilities at exacerbation and stabilization in schizophrenia

BACKGROUND: Coping strategies play an important role in one's ability to adapt to stressful life conditions such as schizophrenia. To better understand the nature of various coping mechanisms at various stages in schizophrenia, this study examined task-, emotion-, and avoidance-oriented coping strategies and explored associated clinical factors at exacerbation and stabilization phases of the illness. METHOD: Patients with schizophrenia were examined twice (at exacerbation phase, N = 237 and at stabilization phase, N = 148) with the Coping Inventory for Stressful Situations, and standardized measures of psychopathology and emotional distress severity, side effects, insight, self-constructs, social support, and quality of life. Multiple regression analysis was performed with coping strategies as dependent variables at exacerbation and stabilization including analysis of any change during the 16-month follow-up period. RESULTS: Analysis indicated that emotion coping strategies were used more at exacerbation than at stabilization phase. Regression analysis demonstrated emotional distress to be a strong predictor of emotion-oriented coping, with self-efficacy and social support being the best predictors of task and avoidance coping strategies, respectively. Individual changes in these variables also appear to be important predictors for fluctuations of these coping strategies over time. Severity of symptoms accounted for 3.5% and 5.5% to 9% of the total variance of emotion- and task-oriented coping strategies, respectively. CONCLUSIONS: Emotion, task, and avoidance coping strategies and their predictors are influenced and may vary over the course of schizophrenia illness. Experienced emotional distress, self-efficacy, and social support are the best predictors of coping strategies both at exacerbation and stabilization phases of illness.     

Model of nonalcoholic steatohepatitis

BACKGROUND: Obesity and diabetes are frequently associated with nonalcoholic steatohepatitis (NASH), but studies have been hampered by the absence of a suitable experimental model. OBJECTIVE: Our objective was to create a rat model of NASH. DESIGN: Sprague-Dawley rats were fed a high-fat, liquid diet (71% of energy from fat, 11% from carbohydrates, 18% from protein) or the standard Lieber-DeCarli diet (35% of energy from fat, 47% from carbohydrates, 18% from protein). The diets were given ad libitum or as two-thirds of the amount consumed ad libitum. RESULTS: Rats fed the high-fat diet ad libitum for 3 wk developed panlobular steatosis, whereas those fed the standard diet had few fat droplets. Accordingly, total lipid concentrations with the high-fat and standard diets were 129.9 +/- 9.1 ( +/- SEM) and 66.7 +/- 4.6 mg/g liver, respectively (P < 0.001). The high-fat diet caused abnormal mitochondria and mononuclear inflammation, which were accompanied by increased hepatic tumor necrosis factor alpha (TNF-alpha; P < 0.001), TNF-alpha messenger RNA (mRNA) (P < 0.001), collagen type 1, and alpha1(I) procollagen mRNA (P < 0.001). In addition, these rats had increased cytochrome P4502E1 (CYP2E1) mRNA (P < 0.001), which was accompanied by CYP2E1 induction (P < 0.001) and oxidative stress with increased 4-hydroxynonenal (P < 0.001). Plasma insulin was elevated, which reflected insulin resistance, a NASH pathogenic factor. Rats fed a restricted high-fat diet developed only mild steatosis with attenuated biochemical changes, whereas those given a restricted standard diet had normal livers. CONCLUSION: This rat model reproduces the key features of human NASH and provides a realistic experimental model for elucidating its treatment.     

Subjective response to antipsychotics of schizophrenia patients treated in routine clinical practice: a naturalistic comparative study

In routine practice, subjective response to antipsychotics is becoming a critical outcome measure among schizophrenia patients. This study sought to compare subjective response to atypical (risperidone and olanzapine) and typical antipsychotic drugs. Using a naturalistic cross-sectional design, we examined subjective response to antipsychotics (satisfaction with medication and subjective tolerability), psychopathology, side effects, emotional distress, and awareness in schizophrenia patients stabilized on atypical (n = 78) and typical (n = 55) drugs. Analysis of variance and multiple regression analysis were applied. We found that atypical drugs were superior to typical antipsychotics in both measures of subjective response, which were positively correlated (r = 0.52, P < 0.001). Poor subjective response was associated with severity of emotional distress, negative, and activation symptoms in the atypical group and with extrapyramidal side effects and positive symptoms in the typical group. Awareness of treatment is a positive factor that accounted for 20% and 34% of variation in the subjective responses to atypical and typical antipsychotic drugs, respectively. Demographic variables, age of onset, illness duration, and adjunctive drugs did not relate significantly to subjective response to antipsychotic drugs. Thus, atypical drugs are characterized by better subjective response compared with typical antipsychotics; their determinants differed considerably. Satisfaction with medication together with subjective tolerability needs to be considered in clinical trials.     

Quality of life outcomes of risperidone, olanzapine, and typical antipsychotics among schizophrenia patients treated in routine clinical practice: a naturalistic comparative study

Findings in previous studies investigating the beneficial effect of risperidone and olanzapine versus typical antipsychotics on quality of life (QOL) are controversial since they did not adjust for various factors contributing to QOL. To test this assumption in a naturalistic cross-sectional design, we evaluated general and domain-specific QOL scores for baseline data of schizophrenia outpatients stabilized on atypical (N = 78, risperidone or olanzapine) and typical (N = 55) agents. Self-report and observer-rated QOL outcomes of both risperidone and olanzapine with typical antipsychotic therapy were compared across demographic, illness-related, and treatment-related factors using analysis of variance, multivariate analysis of variance, and correlation analysis. No significant differences were found in QOL outcomes of risperidone-treated and olanzapine-treated patients. Both self-report and rater-observed QOL measures indicated superiority of atypical over typical antipsychotic agents after adjusting for daily doses, duration of treatment, subjective tolerability, and adjuvant antidepressants. Lower daily doses and longer antipsychotic treatment were associated with better QOL. Self-report and observer-rated QOL scores correlated positively (r = 0.64, P < 0.001). Gender, marital status, age, education, living arrangement and employment status, age of onset, illness duration, symptom severity, emotional distress, subtypes of schizophrenia, and side effects did not affect QOL outcomes in either group. Risperidone and olanzapine revealed an advantage over typical agents in terms of QOL. Findings suggest that when calculating the beneficial effects of atypical antipsychotic therapy on QOL outcomes, daily doses, duration of treatment, and subjective tolerability may be intervening variables and should be adjusted accordingly to clearly appreciate benefits of atypical antipsychotics.     

Enhanced therapeutic effects of doxorubicin and paclitaxel in combination with liposome-entrapped ends-modified raf antisense oligonucleotide against human prostate, lung and breast tumor models

Raf-1 protein kinase plays an important role in cell growth, proliferation and cell survival. We have previously described the use of liposome-entrapped antisense raf oligonucleotide (LErafAON) to inhibit Raf-1 expression resulting in tumor growth inhibition and radiosensitization. The present study was undertaken to evaluate the chemosensitization effects of LErafAON in combination with doxorubicin or paclitaxel on a panel of human tumor xenografts. LErafAON (25.0 mg/kg i.v. x 10) displayed significant antitumor activity (P<0.05) when administered as a single agent in prostate (PC-3), lung (A549) and breast (MDA-MB 231) carcinoma models. Doxorubicin (1.0-4.0 mg/kg i.v. per week x 3) and paclitaxel (1.0-4.0 mg/kg i.v. on alternate days x 3) were administered as single agents at non-toxic doses that led to only minimal to moderate antitumor activity. However, a combination of LErafAON with doxorubicin or paclitaxel led to significantly enhanced antitumor activity in all the tumor types tested (PC-3, P<0.03; A549, P<0.035; MDA-MB 231, P<0.045) as compared with LErafAON alone or chemotherapeutic agents alone treated groups. This effect of chemosensitization appeared to be sequence-specific because a mismatch control oligonucleotide continued to show significant tumor growth. Additionally, no inhibition in Raf-1 expression in MDA-MB 231 tumor tissue was observed with mismatch oligonucleotide treatment. On the other hand, LErafAON treatment led to >75% inhibition of Raf-1 expression in tumor tissue. These preclinical observations support the use of LErafAON in combination with chemotherapeutic agents to improve the treatment of human cancers.     

From PET detectors to PET scanners

This review describes the properties of available and emerging radiation detector and read-out technologies and discusses how they may affect PET scanner performance. After a general introduction, there is a section in which the physical properties of several different detector scintillators are compared. This is followed by a discussion of recent advances in read-out electronics. Finally, the physical performance of the several commercial PET scanners is summarized.     

Mycalosides B-I,eight new spermostatic steroid oligoglycosides from the sponge Mycale laxissima

New steroidal oligoglycosides mycalosides B-I (2-9) have been isolated from the polar extract of the Caribbean sponge Mycale laxissima, and their structures have been elucidated by 1D and 2D NMR ((1)H, (13)C, DEPT, COSY-45, COSY-RCT, HSQC, HMBC, and NOESY spectra) and MALDI-TOF mass spectrometry. Mycalosides B (2) and C (3) were shown to be 27- and 28-nor derivatives of the previously known tetraoside mycaloside A (1). Mycaloside D (4) differs from 1 only in the presence of an additional acetyl group in the carbohydrate moiety. Mycaloside E (5) was structurally identified as a 28-nor-4-dehydroxy derivative of 1. Mycalosides F-H (6-8), differing from each other by the structures of their side chains and nonacetylated (7, 8) or acetylated (6) tetrasaccharide carbohydrate moieties, have new 5(6)-unsaturated 3 beta,4 beta,21-trihydroxy-15-keto-steroidal aglycons. Mycaloside I (9) is a tetraoside of a new 7,24(28)-diunsaturated 3beta,15 beta,29-trihydroxystigmastane aglycon. It was established that the total fraction of the mycalosides as well as mycalosides A (1) and G (7) inhibit the fertilization of eggs by sperm of the sea urchin Strongylocentrotus nudus preincubated with these compounds.     

Free radicals potentiate the negative dromotropic effect of adenosine in guinea pig isolated heart

OBJECTIVE: Adenosine is released during myocardial ischaemia and delays atrioventricular nodal (AV) conduction. We hypothesized that free radicals present during reperfusion potentiate the negative dromotropic effect of adenosine on the AV node. METHODS AND RESULTS: Guinea pig hearts were prepared using the Langendorff technique, paced (200 beats/min), and instrumented to measure the atrium-to-His bundle (A-H) interval, an index of AV nodal conduction time. Adenosine (2 microM) prolonged the A-H interval by 5.7 +/- 0.5 ms from a control value of 35.7 +/- 1.3 ms. (n = 10, P < 0.05). In the absence of adenosine, the superoxide (O2-) generator pyrogallol (20 microM) did not affect the A-H interval (0.7 +/- 0.2 ms prolongation, n = 10). However, concurrent infusion of adenosine (2 microM) and pyrogallol (20 microM) lengthened the A-H interval by 11.0 +/- 0.8 ms from control (n = 10, P < 0.001). This A-H interval prolongation was reversed by cyclopentyl-1,3-dipropylxanthine (100 nM), a selective A1-adenosine receptor antagonist (P<0.001, n = 5). Similarly, A-H interval prolongation was decreased to 4.3 +/- 0.4 ms when NG-methyl-L-arginine (100 microM), a nitric oxide (NO) synthase inhibitor, was infused (n = 4). The superoxide scavenger superoxide dismutase (200 U/ml) also diminished the A-H interval prolongation to 7.1 +/- 0.6 ms (n = 4, P < 0.001). Ba2+ ( 100 microM), a blocker of the adenosine-induced inward potassium current (I(K,ADO)), did not significantly affect this potentiation (13.0 +/- 0.8 and 10.8 +/- 0.7 ms greater than control A-H interval in the absence and presence of Ba2+, respectively, n = 4). CONCLUSIONS: Superoxides and adenosine delay AV nodal conduction in a synergistic manner via a NO-dependent mechanism involving an I(K,ADO)-independent component. This phenomenon may contribute to the genesis of reperfusion arrhythmias.     

The influence of anticonvulsant and antioxidant drugs on nitric oxide level and lipid peroxidation in the rat brain during penthylenetetrazole-induced epileptiform model seizures

Nitric oxide (NO) generation in the brain cortex of Wistar rats was measured by direct method of electron paramagnetic resonance (EPR) spectroscopy. Dramatic (fivefold) elevation of NO production was found during penthylenetetrazole (PTZ)-induced epileptiform seizures. The level of secondary products of lipid peroxidation (LPO; thiobarbituric acid reactive substances, TBARS) was also significantly increased in the cerebral cortex of rats with PTZ-evoked seizures. The effects of anticonvulsant drugs phenobarbital, lamotrigine, phenazepam, as well as antioxidant substances alpha-tocopherol and novel original Russian synthetic drug mexidol (2-ethyl-6-methyl-3-oxypiridine succinate), were investigated. All the substances studied significantly decreased seizure manifestations and partially prevented both enhancement of NO generation and increase in TBARS formation. Mexidol and phenobarbital were found to be the most effective in the preventing of PTZ-induced seizures among all the substances studied. The data obtained support our speculation that neuroprotective action of mexidol may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also NO generation. While the molecular mechanism underlying action of mexidol and phenobarbital still remains unclear, it is likely that the effect of these drugs on NO production is contributing to their neuroprotective action. It might be concluded that both the suppression of seizure-induced NO generation and LPO enhancement may be involved in the mechanism of action of antiepileptic drugs.