•Using additional datasets in parameter learning increased log-likelihood.•The increase correlated with the number of nodes estimated using additional data.•Additional datasets reduced the influence ...of heterogeneity.•A meta-analytic approach enables learning networks from diverse data sources.
Previous research suggested that using additional data sources could improve parameter learning in Bayesian networks. However, when additional datasets do not include all network variables, neither standard Bayesian network learning techniques nor standard missing data methods can be applied. In such situations, the use of a meta–analytic approach is proposed. The performance of one such meta–analytic approach was evaluated by simulating several study results on two real–life biomedical examples (one discrete and one Gaussian Bayesian network). Regardless of the network type, the meta–analytic approach showed higher mean log–likelihood values, less sensitive to the presence of heterogeneity, than a single dataset analysis. The difference between the two methods was most pronounced when sample sizes were small (N=100). For the meta–analytic approach, the increase in log–likelihood was in most cases positively related to the number of nodes estimated with additional data. However, as in the case of single dataset analysis, care is needed when estimating rare event probabilities from small datasets due to the problems with unidentifiability and increased bias.
In the present study, various procedures have been compared for the determination of lipophilicity, hydrophobicity, and plasma protein binding of curcuminoids, boswellic acids, andrographolides, and ...piperine as biologically active ingredients of botanicals used in IBD treatment. Our results have shown that IAM-HPLC assay is the most suitable one for lipophilicity determination of all analytes regardless of their class and botanical source. HSA-HPAC and AGP-HPAC assays revealed that all investigated compounds have a higher affinity for HSA which is the most abundant protein in human plasma. The high affinity of biologically active compounds to all biological structures (phospholipids and proteins) admonishes that their small portion is available for therapeutic effects in IBD patients. Our experimental research is complemented by various theoretical approaches based on different algorithms for pharmacokinetic properties prediction. The similarities between experimental and calculated values were evaluated using PCA and CA as a statistical tool. The statistical analysis implies that plasma protein binding is a complex process, and theoretical approaches still cannot fully replace experimental ones.
Since oxidative stress has been linked to several pathological conditions and diseases, drugs with additional antioxidant activity can be beneficial in the treatment of these diseases. Therefore, ...this study takes a new look at the antioxidant activity of frequently prescribed drugs using the HPLC-DPPH method. The antioxidative activity expressed as the TEAC value of 82 drugs was successfully determined and is discussed in this work. Using the obtained values, the QSAR model was developed to predict the TEAC based on the selected molecular descriptors. The results of QSAR modeling showed that four- and seven-variable models had the best potential for TEAC prediction. Looking at the statistical parameters of each model, the four-variable model was superior to seven-variable. The final model showed good predicting power (r = 0.927) considering the selected descriptors, implying that it can be used as a fast and economically acceptable evaluation of antioxidative activity. The advantage of such model is its ability to predict the antioxidative activity of a drug regardless of its structural diversity or therapeutic classification.
Etrasimod, a novel selective sphingosine-1-phosphate receptor modulator, was recently approved by the U.S. Food and Drug Administration and the European Medicinal Agency for the treatment of ...moderately to severely active ulcerative colitis in adults. In this research, the forced degradation study as an integral part of drug product and packaging development, which generates data on degradation mechanisms, is published. The development and validation of the stability-indicating method using a superior high-performance liquid chromatography technique coupled with a diode array detector and tandem mass spectrometer was performed to support the forced degradation study and monitor the formation of degradation products. Etrasimod demonstrated good stability under elevated temperature and basic stress conditions, while acidic hydrolysis, oxidative, and photolytic degradation produced eight degradation products. The knowledge of degradation products will be useful in the long-term stability study for establishing the acceptance criteria of etrasimod as a drug substance and dosage form during quality control and stability assessment. The eco-friendliness of the developed forced degradation procedure was evaluated using various greenness appraisal tools. The green metric tools showed that the forced degradation procedure obeys eco-friendly conditions.
•Development of stability-indicating method for etrasimod by HPLC/DAD/MS/MS.•Etrasimod demonstrated stability under elevated temperature and basic hydrolysis.•The stress conditions produced eight degradation products of etrasimod.•The eco-friendliness of the procedure was evaluated using 4 greenness appraisal tools.
Inflammatory bowel disease is a complex disorder characterized by chronic gastrointestinal inflammation. Thus, patients prefer to use herbal dietary supplements containing turmeric, Indian ...frankincense, green chiretta, and black pepper in an attempt to cope better with their chronic condition. The dietary supplements' dosage forms and herbal ingredients were assessed in terms of the products' physicochemical parameters (weight uniformity, friability, disintegration, rupture test, tablet's breaking force, and powder flowability) in view of the USP-NF requirements. In addition, contaminants such as organic solvents and ethylene oxide were evaluated using gas chromatography. Assessment of gluten via an Enzyme-Linked Immunosorbent Assay was also performed. Most of the products met USP requirements. The high average weight of one multicomponent tablet sample with a high breaking force value can explain the observed negative results of the disintegration test. A total of 26% of samples tested positive for gluten, but the most alarming fact is that the ethylene oxide levels found in two samples were up to 30 times higher than the EU limit. Accordingly, dietary supplement quality control is of fundamental importance.
Tijekom posljednja tri desetljeća mikroekstrakcija čvrstom fazom donijela je značajan napredak u bioanalitičkim istraživanjima. Razlog tome su brojne modifikacije tehnike koje su omogućile njezinu ...primjenjivost za raznovrsne i složene biološke uzorke, ali i ekološku prihvatljivost. Tehnika se primjenjuje u kombinaciji s različitim analitičkim instrumentima među kojima se posebno ističu tekućinska i plinska kromatografija. Ovo pregledno istraživanje usmjereno je na najnovija dostignuća i načine primjene mikroekstrakcije čvrstom fazom. Nadalje, posebno su istaknuta nova, inovativna rješenja koja trenutačno nemaju komercijalnu primjenu.
This study evaluates the interaction of toxic elements cadmium (Cd) and lead (Pb) due to exposure from cigarette smoking, essential elements, and steroidogenesis in the maternal–placental–fetal unit. ...In a cohort of 155 healthy, postpartum women with vaginal term deliveries in clinical hospitals in Zagreb, Croatia, samples of maternal blood/serum and urine, placental tissue, and umbilical cord blood/serum were collected at childbirth. The biomarkers determined were concentrations of Cd, Pb, iron (Fe), zinc (Zn), copper (Cu), and selenium (Se), and steroid hormones progesterone and estradiol in maternal and umbilical cord blood and the placenta. Three study groups were designated based on self-reported data on cigarette smoking habits and confirmed by urine cotinine levels: never smokers (n = 71), former smokers (n = 48), and active smokers (n = 36). Metal(loid)s, steroid hormones, urine cotinine, and creatinine levels were analyzed by ICP–MS, ELISA, GC–MS, and spectrophotometry. Cigarette smoking during pregnancy was associated with increased Cd levels in maternal, placental, and fetal compartments, Pb in the placenta, and with decreased Fe in the placenta. In active smokers, decreased progesterone and estradiol concentrations in cord blood serum were found, while sex steroid hormones did not change in either maternal serum or placenta. This study provides further evidence regarding toxic and essential metal(loid) interactions during prenatal life, and new data on sex steroid disruption in cord serum related to cigarette smoking. The results indicate that umbilical cord sex steroid levels may be a putative early marker of developmental origins of the future burden of disease related to harmful prenatal exposure to cigarette smoke.
The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se ...and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking.
This pilot study aimed to estimate annual occupational ultraviolet radiation (UVR) exposures based on 5 consecutive months of dosimetry measurements in Croatian construction workers and assess its ...relationship with the environmental data collected during the same period.
Four male construction industry workers from the vicinity of Zagreb (lat. 45.8° N, alt. 128 m) participated in the study. The study was a part of the GENESIS-UV project, attempting to collect long-term dosimetry data for outdoor occupations across Europe. Workers wore personal dosimeters (model X2012–10, Gigahertz, Tuerkenfeld, Germany) on the left upper arm during working hours in the period from June to October 2017. Median exposure assessment period was 57 working days.
Estimates of annual occupational UVR exposure ranged from 76 SED to 976 SED per worker, reflecting large differences in patterns of workers' exposure. Daily UVR doses received by the workers were comparable to the values of other studies at similar latitudes, reaching up to 12 SED in summer months. Measurements of workers with high exposure values (estimated >600 SED/year) showed moderate to high associations with environmental UVR and insolation data (Spearman's correlation coefficient ranging from 0.57 to 0.73).
The results confirmed high occupational exposure of tested Croatian construction workers to solar UVR. However, more data are needed to explain the between-worker variability and develop prediction models with respect to specific work tasks. The use of environmental UVR for predicting long-term exposure should be considered, especially for high exposure tasks.
•Data confirmed high exposure of tested Croatian construction workers to solar UVR.•Annual occupational exposure estimates ranged from 76 SED to 976 SED per worker.•High between-worker variability was observed.•Dosimetry data was well predicted by the environmental UVR for highly exposed workers.
Size exclusion chromatography (SEC) has become a powerful tool for analysing size variants of biologic drugs in their native form. Modern SEC can be defined by the use of chromatographic columns ...packed with sub-3 µm particles, allowing an increase in method throughput compared to that of conventional SEC.
We performed the forced degradation study of adalimumab, the first genetically engineered fully humanised immunoglobulin G1 monoclonal antibody, and evaluated tha possibilities of an advanced SEC column packed with sub-3 µm particles for elucidation of the degradation pathway. Our results revealed the main adalimumab degradation products to be antibody fragments. Acidic and basic conditions had the most intensive effect on the degradation of the adalimumab while the drug exhibits relative stability under thermal and photolytic stress conditions.
The AGREE and AGREEprep calculators were used for the evaluation of the environmental performance of the forced degradation procedure. The results of the green score evaluation are presented as round pictograms with a circle in the centre that shows the overall score of 0.81 and 0.61, respectively. Both pictograms are highlighted in green, indicating the eco-friendly conditions.
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