Effects of beta-adrenoceptors blocking eye drops in patients with chronic bronchitis.

Beta-blocker eyedrops used on asthmatic patients are known to enhance asthma which is, as chronic bronchitis, an obstructive disease of the lung, and an authentic bronchoconstriction is always possible. A single blind parallel trial in 3 groups of 10 patients with grade II and III chronic bronchitis, was conducted to evaluate the cardiovascular and bronchial tolerance of 3 beta-blocker eyedrops: timolol, betaxolol and carteolol compared to placebo. The following parameters were measured during a 90 minutes period: heart rate, systolic and diastolic blood pressure, forced expiratory volume in one second, vital capacity. It appeared that only heart rate lowers significantly under the influence of the beta-blocker eyedrop, the other parameters did not change and no difference was noticed between the three eyedrops. However, comparison of individual values showed a significant decrease of forced expiratory volume in one second in certain subjects and this, although betaxolol is a beta 1 selective beta-blocker. Caution should be taken each time beta-blocker eyedrops are prescribed for glaucoma to patients with chronic bronchitis.     

Alterations of the cerebral cortex in sporadic small vessel disease: A systematic review of in?vivo MRI data

Cerebral small vessel diseases of the brain are a major determinant of cognitive impairment in the elderly. In small vessel diseases, the most easily identifiable lesions, both at post-mortem evaluation and magnetic resonance imaging, lie in subcortical areas. However, recent results obtained post-mortem, particularly in severe cases, have highlighted the burden of cortex lesions such as microinfarcts and diffuse neuronal loss. The recent development of image post-processing methods allows now assessing in vivo multiple aspects of the cerebral cortex. This systematic review aimed to analyze in vivo magnetic resonance imaging studies evaluating cortex alterations at different stages of small vessel diseases. Studies assessing the relationships between small vessel disease magnetic resonance imaging markers obtained at the subcortical level and cortex estimates were reviewed both in community-dwelling elderly and in patients with symptomatic small vessel diseases. Thereafter, studies analyzing cortex estimates in small vessel disease patients compared with healthy subjects were evaluated. The results support that important cortex alterations develop along the course of small vessel diseases independently of concomitant neurodegenerative processes. Easy detection and quantification of cortex changes in small vessel diseases as well as understanding their underlying mechanisms are challenging tasks for better understanding cognitive decline in small vessel diseases.     

In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs

Idiosyncratic adverse drug reactions (IADRs) in humans can result in a broad range of clinically significant toxicities leading to attrition during drug development as well as postlicensing withdrawal or labeling. IADRs arise from both drug and patient related mechanisms and risk factors. Drug related risk factors, resulting from parent compound or metabolites, may involve multiple contributory mechanisms including organelle toxicity, effects related to compound disposition, and/or immune activation. In the current study, we evaluate an in vitro approach, which explored both cellular effects and covalent binding (CVB) to assess IADR risks for drug candidates using 36 drugs which caused different patterns and severities of IADRs in humans. The cellular effects were tested in an in vitro Panel of five assays which quantified (1) toxicity to THLE cells (SV40 T-antigen-immortalized human liver epithelial cells), which do not express P450s, (2) toxicity to a THLE cell line which selectively expresses P450 3A4, (3) cytotoxicity in HepG2 cells in glucose and galactose media, which is indicative of mitochondrial injury, (4) inhibition of the human bile salt export pump, BSEP, and (5) inhibition of the rat multidrug resistance associated protein 2, Mrp2. In addition, the CVB Burden was estimated by determining the CVB of radiolabeled compound to human hepatocytes and factoring in both the maximum prescribed daily dose and the fraction of metabolism leading to CVB. Combining the aggregated results from the in vitro Panel assays with the CVB Burden data discriminated, with high specificity (78%) and sensitivity (100%), between 27 drugs, which had severe or marked IADR concern, and 9 drugs, which had low IADR concern, we propose that this integrated approach has the potential to enable selection of drug candidates with reduced propensity to cause IADRs in humans.     

Phenotypic characterization and functional analysis of human tumor immune infiltration after mechanical and enzymatic disaggregation

Multi-parametric flow cytometry analysis is a reliable method for phenotypic and functional characterization of tumor infiltrating immune cells (TIIC). The isolation of infiltrating leukocytes from solid tumors can be achieved through various methods which can be both enzymatic and mechanical; however, these methods may alter cell biology. The aim of this study was to compare the effects of three tissue disaggregation techniques on TIIC biology in breast, kidney and lung tumor specimens. We therefore compared two enzymatic treatments using either collagenase type IA alone or in combination with collagenase type IV and DNase I type II, and one mechanical system (Medimachine?). We evaluated the impact of treatments on cell viability, surface marker integrity and proliferative capacity. We show that cell viability was not significantly altered by treatments. However, enzymatic treatments decreased cell proliferation; specifically collagenases and DNase provoked a significant decrease in detection of surface markers such as CD4, CD8, CD45RA and CD14, indicating that results of phenotypic studies employing these techniques could be affected. In conclusion, mechanical tissue disaggregation by Medimachine? appears to be optimal to maintain phenotypic and functional TIIC features.     

Characteristics of voluntary participants versus nonparticipants in a psychoeducation program for euthymic patients with bipolar disorder

We aimed to assess the participation rate and predictive factors of participation in psychoeducation programs for euthymic outpatients with bipolar disorder. Ninety-five consecutive euthymic outpatients with bipolar disorder treated with lithium were recruited in a university department of psychiatry. The participants and nonparticipants in a program of psychoeducation were compared for sociodemographic, clinical, and psychological characteristics. According to univariate statistics, a younger age, a higher education level, a shorter duration of illness, a better initial knowledge about lithium, and a less external locus of control were predictive of participation in the program. A binary logistic regression model showed that an external locus of control was an independent predictor of participation. Among bipolar patients, the older, the less educated, those who have less knowledge about their treatment, and those with a more external locus of control were less likely to participate in hospital-based psychoeducation programs.