Acute toxicity estimation by calculation--Tubifex assay and quantitative structure-activity relationships

A quantitative structure-activity relationship (QSAR) model dependent on log P(n - octanol/water), or log P(OW), was developed with acute toxicity index EC50, the median effective concentration measured as inhibition of movement of the oligochaeta Tubifex tubifex with 3 min exposure, EC50(Tt) (mol/L): log EC50(Tt) = -0.809 (+/-0.035) log P(OW) - 0.495 (+/-0.060), n=82, r=0.931, r2=0.867, residual standard deviation of the estimate 0.315. A learning series for the QSAR model with the oligochaete contained alkanols, alkenols, and alkynols; saturated and unsaturated aldehydes; aniline and chlorinated anilines; phenol and chlorinated phenols; and esters. Three cross-validation procedures proved the robustness and stability of QSAR models with respect to the chemical structure of compounds tested within a series of compounds used in the learning series. Predictive ability was described by q2 .801 (cross-validated r2; predicted variation estimated with cross-validation) in LSO (leave-a structurally series-out) cross-validation.     

Perceived health status as measured by the SF-36 in patients with multiple sclerosis: a review

This review of literature gives an overview of recent studies about perceived health status as measured by the Short-Form-36 (SF-36) Health Survey in patients with multiple sclerosis (MS). The SF-36 is one of the tools measuring health status in patients used in international research and clinical practice. It measures two main health concepts – physical and mental. The SF-36 represents a valid instrument able to detect differences in perceived health status in patients. A computer-aided search in Medline and PsycINFO resulted in 504 articles in English published from 1996 to August 2006. After the screening process on the basis of abstracts, eight articles consisting of empirical studies remained in which perceived health status was evaluated using the SF-36 Health Survey. Seven studies focused on disability and perceived health status in the SF-36. Two studies focused on the relationship between depression and perceived health status. These studies showed that MS patients with low disability and minor depression scored significantly better than patients with high disability and major depression in the SF-36 health dimensions. Gender seems to have no influence on perceived health status in MS patients. The longer the disease duration and the more severe the disease, the lower the patients scored in perceived health status. The more disabled, the more depressive and the older the patients, the poorer their perceived health status was. Health providers supporting appropriate treatment might pay more attention to more disabled and more depressive patients, with longer disease duration. Perceived health status can be a predictor of prognosis and intervention outcomes. The study shows the importance of measuring perceived health status in MS patients with implications for their quality of life and provision of care.     

Prevalence and characteristics of noncompliant behaviour and its risk factors in kidney transplant recipients

Noncompliance with therapy is one possible explanation for the observation that long-term graft survival is not sufficiently improved by the development in immunosuppression. The aim of the study was to explore the prevalence, characteristics and risk factors of noncompliance with immunosuppression. A total of 161 adult kidney transplant recipients were interviewed about their self-rated health, social support, education, stress from adverse effects and compliance with the immunosuppression. The prevalence of subclinical noncompliance was 54%. Noncompliant patients declared significantly worse self-rated health, less satisfaction with social support and higher stress from adverse effects. Male gender (OR 7.5, CI 2.4-23.39), high stress from adverse effects (OR 12.27, CI 2.44-61.88), fair self-rated health (OR 4.45, CI 1.04-19.55) and fair satisfaction with social support (OR 4.55, CI 1.08-19.24) were predictors of noncompliance. Standardized detection methods should be developed with the aim of identifying patients who are at risk of noncompliance in order to prevent graft loss.     

Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells

BackgroundPatient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation.MethodsNasal epithelial brushings from 14 individuals (CF=9; non-CF=5) were collected, then equally divided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free “dual-SMAD inhibition” (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult?-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRC^ALI and SMADi^ALI under basal and CFTR corrector treated (VX-809) conditions.ResultsNo significant difference in the structural morphology or baseline global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADi^ALI compare to their CRC^ALI counterparts.ConclusionAlteration of cellular physiological function in vitro were more prominent than structural and differentiation potential in airway ALI. Since initial expansion culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.     

The impact of pain on psychological well-being in rheumatoid arthritis: the mediating effects of self-esteem and adjustment to disease

The aim of this study was to determine whether self-esteem and adjustment to disease can mediate the association between pain and psychological well-being in patients with Rheumatoid Arthritis (RA). Coefficients of correlation, multiple linear regressions and Structural Equation Model (SEM) were employed in order to examine the direct and indirect relationships between pain, self-esteem, adjustment to disease and psychological well-being in a sample of 160 recently-diagnosed RA-patients. The outcomes of the analyses indicate that self-esteem and adjustment to disease are important links between pain and psychological well-being. Moreover, the results suggest the increasing importance of personality variables in mediating the relationship between pain and psychological well-being as the disease advances. The findings provide evidence for considerations that psychosocial interventions, focused on increasing the self-esteem and improving the adjustment to disease, may reduce the impact of pain on patients' psychological well-being and quality of life in general.     

Bradykinin preconditioning affects the number of degenerated neurons and the level of antioxidant enzymes in spinal cord ischemia in rabbits

Bradykinin preconditioning has been used for acquisition of tolerance after spinal cord ischemia. Rabbits were preconditioned intraperitoneally with bradykinin 48 h prior to 20 min of abdominal aorta ligation followed by 24 and 48 h of reperfusion. The activities of SOD and catalase were measured and Fluoro Jade B (FJB)-positive degenerated neurons were evaluated. The outcomes of Tarlov scoring system used to assess neurological functions showed significant improvement in bradykinin groups compared to the ischemic group. The number of FJB-positive degenerated neurons was decreased in ventral horns of both bradykinin groups. Significantly decreased activities of total SOD and mitochondrial Mn-SOD were also detected in both bradykinin groups versus ischemic group while CuZn-SOD and catalase activities were significantly decreased only in the bradykinin group after 24 h of reperfusion versus ischemic group. These findings suggest that one of the possibilities of the neuroprotective effect of delayed bradykinin preconditioning against spinal cord ischemic injury could be realized by mitochondrial protection and decreased synthesis of Mn-SOD as well as by promotion of neuronal survival.     

Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease

BackgroundFibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population.MethodsA total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay.ResultsHigher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times.ConclusionFibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.