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Biomedical subjects

D Coomans

Publications and source records attributed to D Coomans.

At least 19 recordsLinked to original sources
PubMed2006

Exploration of linear modelling techniques and their combination with multivariate adaptive regression splines to predict gastro-intestinal absorption of drugs.

In general, linear modelling techniques such as multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS), are used to model QSAR data. This type of data can be very complex and linear modelling techniques often model only a limited part of the information captured in the data. In this study, it was tried to combine linear techniques with the flexible non-linear technique multivariate adaptive regression splines (MARS). Models were built using an MLR model, combined with either a stepwise procedure or a genetic algorithm for variable selection, a PCR model or a PLS model as starting points for the MARS algorithm. The descriptive and predictive power of the models was evaluated in a QSAR context and compared to the performances of the individual linear models and the single MARS model. In general, the combined methods resulted in significant improvements compared to the linear models and can be considered valuable techniques in modelling complex QSAR data. For the used data set the best model was obtained using a combination of PLS and MARS. This combination resulted in a model with a Pearson correlation coefficient of 0.90 and a cross-validation error, evaluated with 10-fold cross-validation of 9.9%, pointing at good descriptive and high predictive properties.

Algorithms↗
PubMed2005

Selection of orthogonal reversed-phase HPLC systems by univariate and auto-associative multivariate regression trees.

In order to select chromatographic starting conditions to be optimized during further method development of the separation of a given mixture, so-called generic orthogonal chromatographic systems could be explored in parallel. In this paper the use of univariate and multivariate regression trees (MRT) was studied to define the most orthogonal subset from a given set of chromatographic systems. Two data sets were considered, which contain the retention data of 68 structurally diversive drugs on sets of 32 and 38 chromatographic systems, respectively. For both the univariate and multivariate approaches no other data but the measured retention factors are needed to build the decision trees. Since multivariate regression trees are used in an unsupervised way, they are called auto-associative multivariate regression trees (AAMRT). For all decision trees used, a variable importance list of the predictor variables can be derived. It was concluded that based on these ranked lists, both for univariate and multivariate regression trees, a selection of the most orthogonal systems from a given set of systems can be obtained in a user-friendly and fast way.

Chromatography, High Pressure Liquid↗
PubMed2005

Classification of drugs in absorption classes using the classification and regression trees (CART) methodology.

Classification and regression trees (CART) were evaluated for their potential use in a quantitative structure-activity relationship (QSAR) context. Models were build using the published absorption values for 141 drug-like molecules as response variable and over 1400 molecular descriptors as potential explanatory variables. Both the role of two- and three-dimensional descriptors and their relative importance were evaluated. For the used dataset, CART models showed high descriptive and predictive abilities. The predictive abilities were evaluated based on both cross-validation and an external test set. Application of the variable ranking method to the models showed high importances for the n-octanol/water partition coefficient (logP) and polar surface area (PSA). This shows that CART is capable of selecting the most important descriptors, as known from the literature, for the absorption process in the intestinal tract.

Intestinal Mucosa↗
PubMed2005

Prediction of gastro-intestinal absorption using multivariate adaptive regression splines.

Multivariate adaptive regression splines (MARS) and a derived method two-step MARS (TMARS) were used for modelling the gastro-intestinal absorption of 140 drug-like molecules. The published absorption values for these molecules were used as response variable and calculated molecular descriptors as potential explanatory variables. Both methods were compared and their potential use in quantitative structure-activity relationship (QSAR) context evaluated. The predictive abilities of the models were studied using different sequences of Monte Carlo cross validation (MCCV). It was shown that both types of models had good predictive abilities and that for the data used, MARS gave better results than TMARS. It could be concluded that both methods could be valuable for QSAR modelling.

Algorithms↗
PubMed2003

Classification and regression tree analysis for molecular descriptor selection and retention prediction in chromatographic quantitative structure-retention relationship studies.

The use of the classification and regression tree (CART) methodology was studied in a quantitative structure-retention relationship (QSRR) context on a data set consisting of the retentions of 83 structurally diverse drugs on a Unisphere PBD column, using isocratic elutions at pH 11.7. The response (dependent variable) in the tree models consisted of the predicted rention factor (log kw) of the solutes, while a set of 266 molecular descriptors was used as explanatory variables in the tree building. Molecular descriptors related to the hydrophobicity (log P and Hy) and the size (TPC) of the molecules were selected out of these 266 descriptors in order to describe and predict retention. Besides the above mentioned, CART was also able to select hydrogen-bonding and molecular complexity descriptors. Since these variables are expected from QSRR knowledge, it demonstrates the potential of CART as a methodology to understand retention in chromatographic systems. The potential of CART to predict retention and thus occasionally to select an appropriate system for a given mixture was also evaluated. Reasonably good prediction, i.e. only 9% serious misclassification, was observed. Moreover, some of the misclassifications probably are inherent to the data set applied.

Chromatography↗
PubMed2002

Non-linear mixed effects models for the evaluation of dissolution profiles.

The use of non-linear mixed effects models to describe dissolution data has been evaluated. A theoretical part is included to introduce this approach to scientists who are not familiar with this type of statistics. The standard settings of the statistical software package (S-plus) are used as much as possible. Several mathematical functions like the Weibull, logistic, first-order and Gompertz are employed as basis for the non-linear mixed effects models. Examples are given using dissolution data of immediate and extended release tablets. The results are compared with those obtained using linear mixed effects models.

Linear Models↗
PubMed2001

Application of linear mixed effects models to the evaluation of dissolution profiles.

The performance of linear mixed effects models for the comparison of dissolution profiles is examined. This type of model is frequently used by statisticians, but is rather unknown to people that work in dissolution laboratories. Hence, an extensive theoretical part was introduced to make the methodology more accessible. Firstly, repeated measures ANOVA is discussed, followed by the "real" linear mixed effects models. The theory is applied to two types of dissolution data: one corresponding to an immediate and another to a slow release formulation. We tried to use as much as possible the standard settings of the statistical software (S-plus). Suggestions are given to solve problems encountered during model fitting. It was found that the statistical limits are much more discriminative than the similarity factor.

Analysis of Variance↗
PubMed1993

Rehardening of surface softened and surface etched enamel in vitro and by intraoral exposure.

The rehardening of surface-softened and surface-etched enamel was investigated in vitro and by intraoral exposure. Surface-softened enamel was obtained by treatment with 0.1 M acetic acid buffer solution (pH = 5.5) for 3 h. Surface-etched enamel was obtained by the acid etch procedure used in clinical situations (37% phosphoric acid gel, 30 s). The enamel lesions were treated in vitro, with calcifying solutions for 8 h or were carried for 48 h in an intraoral appliance. Changes at the enamel surfaces were investigated by surface microhardness measurements. Following the treatment with calcifying solutions a significantly greater indentation length was observed in surface-etched than in surface-softened enamel. No significant difference in indentation length between both types of enamel lesions was observed following intraoral exposure. It was concluded that the initial rate of rehardening between both types of enamel lesions is comparable. At his stage remineralization occurs in microspaces created in the slightly destroyed enamel structures. The influence of the etch pits on the indentation length becomes dominating when remineralization continues. An obliteration of etch pits was observed in enamel samples treated with the calcifying solution with the highest degree of saturation. It was suggested that freshly prepared highly supersaturated calcifying solutions can be used to enhance mineral appositions in accidental etch pits.

Acetates↗
PubMed1993

[In vivo evaluation of the level of lead in human superficial enamel using a double biopsy].

Two successive acid etch biopsies were performed on the permanent maxillary right central incisors of two age groups of children resident in an urban area in Belgium. Lead was determined in the biopsy solutions and the concentrations were related to etch depths, which were calculated from the calcium and phosphorus concentrations in the biopsy solutions. The mean lead concentration in the first enamel biopsy layer was five times higher than in the second biopsy. A strong correlation was observed between the two biopsies. It was shown that calibration of the lead values with respect to etch depths and Ca/P ratio was desirable and that a robust regression analysis approach was needed instead of classical more reliable calibration. In this study no age related increase in the surface enamel lead concentration could be demonstrated. Therefore, it was concluded that for these children the presence of lead in surface enamel had to be attributed primarily to pre-eruptive uptake.

Acid Etching, Dental↗
PubMed1992

Load dependency and reliability of microhardness measurements on acid-etched enamel surfaces.

The load dependency of hardness measurements was investigated on sound and demineralized enamel samples. For all samples investigated, the Knoop hardness number (KHN) varied as a function of the applied load. Higher loads enhanced indenter penetration into the test surface. The variation in KHN values observed in demineralized enamel, both surface-softened and surface-etched, was explained by a decrease in porosity as a function of depth. The reading error for indentations made on surface enamel etched with 37% phosphoric acid gel for 30 s was found to be slightly elevated compared to indentations made on a polished sound enamel surface. It was concluded that the surface microhardness technique can be used for the longitudinal investigation of etched surface enamel.

Acid Etching, Dental↗
PubMed1992

Comparison of salivary fluoride concentrations after administration of a bioadhesive slow-release tablet and a conventional fluoride tablet.

The in-vitro and in-vivo fluoride release of bioadhesive, slow-release tablets prepared from a mixture of polyethylene glycol polymers, containing 0.1 mg of fluoride as NaF was studied, and their ability to sustain fluoride levels in saliva were compared with conventional fluoride tablets with the same fluoride content. In-vitro release experiments showed that the bioadhesive tablets needed 8 h to release all their fluoride compared with less than 1 h for the conventional fluoride tablets. In-vivo, the bioadhesive tablets had a retention period of 6 h and could sustain a salivary fluoride level of more than 10 microM above the baseline for 7 h. The conventional fluoride tablets achieved a peak concentration of 0.5 mM directly after dissolution in the mouth, but the fluoride level could not be sustained for longer than 1 h. A good agreement was found between the in-vitro swelling behaviour of the bioadhesive tablets and their in-vitro and in-vivo release characteristics and their in-vivo retention time.

Adult↗
PubMed1992

Influence of bovine somatotropin on the composition and manufacturing properties of milk.

Three studies (84, 140, and 200 d) were performed to examine the effect of injecting dairy cows with various doses (0, 320, 640, or 960 mg/28 d; 0 or 640 mg/28 d; 0, 320 mg/14 d, or 320 or 640 mg/28 d) of bST on milk production, composition, and manufacturing properties. Mean bST response among studies on milk production varied from 0 (trial 1) to 7.3% (trial 2) and from 8.5 to 14.2% (trial 3) in relation to feeding conditions. Neither milk fat nor protein percentages in milk at time of maximum response were affected by the use of bST. Distribution of casein and protein in the whey was not affected by the treatments at any time. The nature of fatty acids varied more with time after injection than with bST doses. Neither coagulation time, standard curd firmness, nor soft or pressed cheese yields were affected by the treatments.

Animals↗
PubMed1991

A comparative study of the lead and cadmium content of surface enamel of Belgian and Kenyan children.

Acid etch surface enamel microbiopsies were performed on teeth from 378 children aged 6-12 years; 318 of the children lived in Belgium, an industrialized country, and 60 lived in a rural part of Kenya. In addition to lead and cadmium, calcium and phosphorus were also quantitatively determined in the etch solutions. Calcium was chosen as an internal reference for the expression of the lead and cadmium concentrations and for the assessment of the etch depth. The mean lead level in surface enamel of the Belgian children was approximately eight times higher than that of the Kenyan children. The cadmium levels were not significantly higher. An appropriate regression model taking into account differences in etch depth showed that a significant decrease of lead and cadmium with etch depth occurred and that a significant correlation between lead and cadmium in surface enamel existed for the Belgian cohort. Moreover, the same mean calcium/phosphorus ratios were obtained for the Belgian and Kenyan surface enamel samples, and were found not to play a significant role in the calibration of the lead and cadmium levels.

Belgium↗
PubMed1991

Acid-etched enamel surfaces after 24 h exposure to calcifying media in vitro and in vivo.

The remineralization of acid-etched enamel lesions is investigated in this study both in vitro and in vivo over periods of 24 h. In an initial study, samples of etched bovine enamel were subjected in vitro to treatment with synthetic calcifying solutions, or were exposed to saliva by means of an intraoral appliance. Alterations in hardness of the enamel surface were measured by indentation techniques. In a second study the suitability of an impression technique for investigating the surface relief induced by an acid-etch procedure was investigated. Extracted human incisors were used to make SEM observations of eteched areas and corresponding sections of impressions. Subsequently, six subjects were selected for a clinical evaluation of the impression technique. Although a significant decrease in indentation length (increase in hardness) was observed for etched enamel lesions treated with calcifying solutions in vitro, no evidence for any such change was observed in samples exposed to the influence of saliva when investigated by the indentation and impression techniques.

Acid Etching, Dental↗
PubMed1991

Model for assessment of lead content in human surface enamel.

Acid etch surface enamel microbiopsies were taken in vitro and in vivo and analyzed for lead using electrothermal atomic absorption spectrometry. The in vitro samples were obtained from subjects resident in an urbanized region in Belgium or from a region close to a nonferrometal industrial plant. The smaller set of in vivo samples were all from subjects resident in an urbanized region. Using a regression tree approach it was possible to identify in a stepwise manner factors that contributed to the variation of lead in the samples. For the in vitro as well as in vivo samples, the etch depth, tooth type, and age of the subjects were identified as significant factors but sex and dental arch quadrant were not. The residual lead levels obtained after regression with the significant factors were better distributed with much lesser variance. Moreover, a significant higher lead concentration could be demonstrated in the in vitro samples from the region close to the nonferrometal industrial plant.

Dental Enamel↗
PubMed1991

Study of lead and cadmium content of surface enamel of schoolchildren from an industrial area in Belgium.

The amount of lead and cadmium was determined in surface enamel from permanent teeth of schoolchildren by means of an acid etch surface enamel microbiopsy method. Lead and cadmium levels were calculated on the amount of etched enamel. A comparison of the concentrations of these heavy metals was made between children (7 and 11 yr) from a school close to a non-ferrous metal plant and children from the same age group from a school situated nearby the same plant but in a zone polluted to a lesser degree. The lead concentrations in enamel biopsies from the first group were significantly higher than those from the second group. Cadmium shows the same trend but on a much lower level. A significant correlation between lead and cadmium was also found in both groups.

Acid Etching, Dental↗
PubMed1991

Development and testing of bioadhesive, fluoride-containing slow-release tablets for oral use.

The bioadhesive characteristics of tablets for oral use made from modified starch, polyacrylic acid (PAA), polyethylene glycol (PEG) and sodium carboxymethylcellulose (CMC) were investigated. Adhesion force and energy were determined in-vitro and maximal adhesion time was evaluated in-vivo in human subjects. In-vitro, PAA showed the best bioadhesive properties, followed by modified maize starch and PEG with a mol. wt of 300,000-400,000 daltons. The presence of 0.1 mg of fluoride as NaF did not lead to significant differences in adhesion force and energy for the same formulation. The in-vivo bioadhesion was not strongly correlated to the in-vitro data. PAA, despite its excellent adhesion, proved to be irritating to the mucosa. PEG with a mol, wt of 200,000 daltons was subject to erosion. CMC showed good bioadhesive properties but the mechanical strength of the tablets was low. Modified maize starch tablets containing 5% (w/w) PAA and PEG with a mol. wt of 300,000 daltons proved to be the most suitable formulations for a fluoride-slow-release tablet with bioadhesive properties. In-vitro, the tablets released all of the fluoride within the 8 h period, with a high initial release. The release rate was related to the water absorption rate of the tablets. The PAA-containing formulations and the CMC formulations had the fastest release. In-vivo, fluoride levels with a minimum of 150 and a maximum of 1000 micrograms mL-1 were maintained for 8 h in the oral cavity. These fluoride levels were sustained significantly longer than those obtained with the administration of fourfold the amount of fluoride in the form of a fluoride-containing toothpaste. The release characteristics in-vivo exhibited a high variation. The use of bioadhesive polymers in oral pharmacotherapy seems promising.

Acrylates↗