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At least 217 records · Page 12Linked to original sources
PubMed2003

Cellular environment of metabolites and a metabonomic study of tamoxifen in endometrial cells using gradient high resolution magic angle spinning 1H NMR spectroscopy.

High resolution magic angle spinning (HRMAS) 1H NMR spectroscopy was used to metabolically characterise Ishikawa cells, a human cell line derived from endometrial adenocarcinoma. The spectra obtained had well-resolved resonances from the nucleotide derivatives of uridine and adenosine. Using a combination of diffusion- and relaxation-weighted spectroscopy, the cellular environment of key metabolites previously identified as related to cell growth was also investigated. As Ishikawa cells are hormone-responsive, the metabolic action of tamoxifen, a selective estrogen receptor modulator (SERM), was also investigated. Cells were exposed to 5, 1 and 0.1 microM tamoxifen. Using the statistical regression technique of prediction to latent structures by partial least squares, a predictive model was built modelling the metabolic profile of the cells against exposure to tamoxifen. These spectral changes were characterised by increased resonance intensities from ethanolamine (3.26 ppm), glucose (3.34-3.94 ppm), glutamate (2.14, 2.32 ppm), tyrosine (7.24 ppm), uridine (7.85 ppm) and adenosine (8.20 ppm), and a relative decrease in contributions from myo-inositol resonances (3.30, 3.62, 3.55 ppm). The nucleotide changes suggest that tamoxifen affects RNA transcription, while the changes in ethanolamine and myo-inositol concentrations are indicative of cell membrane turnover.

Adenocarcinoma↗
PubMed1999

A polycaprolactone nanoparticle formulation of cyclosporin-A improves the prediction of area under the curve using a limited sampling strategy.

Therapeutic monitoring of Cyclosporine (CyA) by using area under the curve (AUC) from abbreviated kinetic profiles is of recent trend in clinical practice due to the potential improvement in transplant and clinical outcome with costs reduction in mind. Several papers describe successful use of the limited sampling strategy to predict AUCs in different transplant populations when treated with Sandimmun or Sandimmun Neoral. However, the same predictive potential is achieved for the latter formulation with lesser effort. The present paper describes the application of the limited sampling strategies to demonstrate the advantages of using CyA incorporated in polymeric nanoparticles (CyA-NP) as compared to two reference Sandimmun formulations which consisted of an emulsion of the oily solution in milk (SIM-EM) and a microemulsion (SIM-Neoral) formerly tried on rats. Two independent data batches were used: group 1 which included 36, 31 and 10 animals receiving SIM-EM, CyA-NP and SIM-Neoral, respectively, and group 2 made of nine and eight rats treated with SIM-EM and CyA-NP. Several limited sampling equations were derived for each formulation from group 1 by stepwise multiple linear regression. Statistical analysis disclosed that CyA concentrations 8 and 32 h after dose administration vouched for 88 and 69% variability in AUC (0-48 h) for CyA-NP and SIM-EM, respectively. When summed up, these two concentrations revealed nearly 97% of AUC (0-48 h) variability. CyA concentrations 8 h post-treatment with SIM-Neoral explained 89% variability in AUC (0-48 h). This value raised to 98% when a second CyA concentration (24 h) was introduced. The equations derived from group 1 were then employed to predict AUCs in group 2. CyA blood levels at 8 h post-treatment confirmed AUC for CyA-NP (r(2)=0.98) to be very precise and unbiased (error=1. 46%, interval -16.2 to 21.33%), while the results for SIM-EM obtained with the CyA concentration at 32 h were r(2)=0.93 plus error=5.71%, interval -44.33 to 105.94%. Similar results were obtained when the study period was reduced to 24 h. The use of these limited sampling models manifested the coincidence between CyA-NP and SIM-Neoral as well as the advantages of both formulations over SIM-EM when it comes to CyA monitoring.

Animals↗
PubMed2003

Statistical analysis of impact parameters of soft nose bullet fired on windowpane.

Proper collection of glass evidence from crime spot is very important for its latter probative values. Glass evidence when properly collected and analyzed becomes a powerful witness and it can speak truth long after the crime. In criminal investigation glass evidence can tell what had happened and when it had happened. In the present study, a statistical regression analysis relationship between thickness of windowpane used as targets by soft nose bullet using.315"/8mm caliber sporting gun made in ordnance factory, India and various associated impact parameters were investigated. The relationship is found to be reasonably linear. The ballistics performance of windowpane has been found to correlate with the shear strength behavior above the elastic limit.

Journal Article↗
PubMed2003

Transthoracic needle biopsy: factors effecting risk of pneumothorax.

OBJECTIVE: to evaluate the factors that could effect the risk of pneumothorax in patients undergoing transthoracic biopsy. MATERIAL AND METHODS: variables that could increase the risk of pneumothorax were evaluated in 453 CT-guided transthoracic biopsies. Factors were evaluated in two groups: (1) lesion related (presence of emphysema around the lesion, lesion depth, cavitation, presence of fissure/atelectasis and pleural tag in the needle trajectory); and (2) procedure related (biopsy type, needle size, number of passages, level of experience of the operator). All variables were analysed by chi2 test and multivariate logistic regression statistics. RESULTS: pneumothorax was developed in 85 (18.8%) out of 453 procedures. A chest tube was inserted in ten (11.7%) of them. Variables that were significantly associated with an increased risk of pneumothorax were depth of the lesion (P<0.001) and severity of the emphysema (P<0.01). CONCLUSION: the length of the lung parenchyma traversed during the biopsy is the predominant risk factor for pneumothorax in patients undergoing CT-guided transthoracic biopsy. The risk of pneumothorax was also increased with the severity of the emphysema around the lesion.

Adolescent↗
PubMed2001

Can antimicrobial susceptibility testing results for ciprofloxacin or levofloxacin predict susceptibility to a newer fluoroquinolone, gatifloxacin?: Report from The SENTRY Antimicrobial Surveillance Program (1997-99).

A serious problem confronting clinical laboratories and hospital formulary practices is the delayed availability of approved, commercially prepared susceptibility test reagents for newer antimicrobials. A current example is gatifloxacin, a new 8-methoxy fluoroquinolone with expanded potency against many Gram-positive pathogens. This study addresses the use of "surrogate marker" fluoroquinolones to predict susceptibility for gatifloxacin. Reference broth microdilution MIC results for 29,632 strains isolated in United States medical centers (SENTRY Antimicrobial Surveillance Program, 1997-99) were used: staphylococci (9,940 strains), enterococci (2,570), Streptococcus pneumoniae (3,784), Enterobacteriaceae (10,670) and Pseudomonas aeruginosa (2,668). Gatifloxacin interpretation categories were compared to those of ciprofloxacin and levofloxacin by regression statistics and error rate bounding analyses. For the Enterobacteriaceae, the absolute categorical agreement was 97.9 to 98.7% (false-susceptible or very-major error [VME], 0.03%-0.1%) for comparisons of both ciprofloxacin and levofloxacin with gatifloxacin. P. aeruginosa testing was more problematic (higher minor error rates), but acceptable at 0.6% to 1.1% VME and a 85.7% to 89.9% overall agreement. Ciprofloxacin results used to predict gatifloxacin in Gram-positive species was almost without VME (0.0%-0.2%) because gatifloxacin was significantly superior against these species, especially for S. pneumoniae, where gatifloxacin (MIC(90,) 0.5 microg/ml) was fourfold more potent than levofloxacin (MIC(90,) 2 microg/ml). The preferred gatifloxacin predictor drug was ciprofloxacin for all species except S. pneumoniae and P. aeruginosa, where levofloxacin results had a slightly greater predictive value. Susceptibility testing results for selected currently available fluoroquinolones can be used to predict susceptibility to gatifloxacin with high confidence. Many Gram-positive cocci, however, will be categorized as false-resistant by this interim method since gatifloxacin has a 11% to 34% wider spectrum of activity compared to ciprofloxacin when testing staphylococci and enterococci. Clinical laboratories can reliably use these suggested "surrogate markers" until reliable tests for gatifloxacin become available.

Anti-Infective Agents↗
PubMed1997

[Clinical data on the diagnosis of colic in infants. Survey in 2,773 infants aged 15-119 days. Groupment des pédiatres de la région de Lyon (GPRL), le Groupment lyonnais de recherche en pédiatrie ambulatoire (GLYRPA), l'association des pédiatres de la région stéphanoise (APRS) et la Formation pédiatrique grenobloise (FPG)].

BACKGROUND: Crying is called "Infantile colic" when such cries are numerous, paroxystic, difficult to comfort, and without an obvious cause. METHODOLOGY: An information mailing on the study (named Encolie) and the associated methodology was distributed in April 1995 to 212 private practice pediatricians. They have included in the study all infants aged 15 to 119 days who were seen during consultation from June 12 to June 27. They filled out a two page, 32 item, epidemiological questionnaire. Question 31 asked; "following this consultation, would you call for an 'infantile colic' diagnosis for this child? Yes, no. if no, what is your diagnosis?" RESULTS: One hundred and sixty-nine private practice pediatricians out of 212 (79.7%) participated in the study, and have included 2,797 infants 2,773 infant files were analyzed. The 625 infants identified as "colic" (22.5% of all cases), differed from the 2,148 identified as "non-colic" by the following factors: average age (51.3 vs 61.3 days), birth weight (2,226 vs 3,307 g), being a first born (52.7 vs 45.1% of cases), and mother's anxiety (47.8 vs 29.1% of cases). Significant differences were observed concerning feeding behavior (slow or gluttonous feeding), digestive symptoms, and unexplained crying, always more frequent in the case of the infants identified as "colic". These infants received more drugs, and their parents were given more advice on diet and hygiene. The symptoms supporting the "infantile colic" diagnosis were derived using a statistical regression model. They included: frequent and/or unexplained crying at the time of the study, frequent and/or unexplained crying in the past, abdominal distention at the time of the clinical examination, and frequent gas emissions as indicated by parental questioning. Factors associated with this diagnosis were: young age of the child, drugs administered before the consultation, maternal anxiety, anomalies in feeding behavior, and to a lesser degree, low birth weight and mother or father atopy. CONCLUSION: Given the sample size and origin, and the rigor of both the study and the analysis, we believe that these data could be extrapolated to the usual pediatrician's patient population. This highlighting of differences between our two groups indicate the validity of this diagnosis.

Colic↗
PubMed2003

Green mussel Perna viridis L.: attachment behaviour and preparation of antifouling surfaces.

The green mussel Perna viridis LINNE can be kept in simulated seawater for more than 6 months in good condition. The mussel forms many threads by secreting an adhesive protein from the foot, and attaches with more than 50 byssal threads, which makes most mussels clump together. In order to investigate the preparation of the antifouling surfaces toward green mussels, the attachment of mussels was tested using glass surfaces modified with silane coupling agents, together with non-treated material surfaces such as glass and silicone. The correlation between the attachment percentage and the mean number of the secreted byssus was highly significant, indicating that the mussel selects a favorable surface prior to the secretion of byssus. The relationships between the mussel attachment and the surface chemical parameters (surface free energy (sfe) and its dispersion and polar components) were examined based on a working hypothesis, which we have previously reported. The result of statistical regression test indicated that a certain correlation was found between the dispersion component and the mussel attachment, while the polar component did not correlate to the mussel attachment. The present surface chemical approach provided an additional clue for the preparation of ecologically clean antifouling materials that takes into account the combination of the wettability of both the marine adhesive proteins (MAP) and the modified surfaces.

Animals↗
PubMed1982

Psychotropic drug use in Northern Ireland 1966-80: prescribing trends, inter- and intra-regional comparisons and relationship to demographic and socioeconomic variables.

A study of psychotropic drug prescribing, derived from the computerized pricing data in Northern Ireland from 1966, showed that the use of these drugs reached a peak in 1975, when about 12.5% of the adult population were estimated to have been receiving them, and declined in the following 5 years. Benzodioazepines accounted for three-quarters of all psychotropic drugs prescribed in 1980. Benzodiazepine tranquillizer prescribing was consistently 20-30% higher than in the rest of the United Kingdom, in contrast to hypnotic and antidepressant prescribing which has been consistently lower. The rate of increase in benzodiazepine tranquillizer prescribing was greater than in other European countries, but the level remains lower than in Iceland and Denmark. The influence of a number of demographic and socioeconomic variables was studied in an intra-regional analysis of the 1978 data for the 17 health districts in the province, using multivariate and multiple regression statistics. The prescribing of benzodiazepine hypnotics was almost entirely accounted for by the proportion of elderly (over 65 years) and women aged 45-59 years: neuroleptic prescribing was largely a function of factors associated with rural areas (overcrowding and unemployment) and the proportion of elderly; but neither tranquillizer, antidepressant, barbiturate hypnotic nor psychostimulant prescribing were satisfactorily explained by these variables.

Anti-Anxiety Agents↗
PubMed2004

Prediction of gas-phase reduced ion mobility constants (K0).

A method of predicting reduced ion mobility values, K0, for use in ion mobility spectrometry is described. While the method is very similar to a previously reported method based on a neural network, the method described in this paper uses a purely statistical regression approach. Furthermore, it has been applied to a wider class of compounds, including chemical agents. Various molecular parameters were evaluated in the predictive model to determine the qualitative dynamics that have the greatest effect on K0. An R2 value of 80.1% was obtained when calculated K0 values were plotted against measured K0 values for 162 compounds for which experimental K0 values were available. However, when chloroacetophenone and 3-xylyl bromide (3-methylbenzyl bromide) were removed from the set due to their large residual values, the predictability increased to an R2 value of 87.4%. This compares well with the value of 88.7%, which was obtained in a regression step of a previous neural network study for a less diverse set of 168 compounds.

Journal Article↗
PubMed1999

Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.

Several statistical regression models and artificial neural networks were used to predict the hepatic drug clearance in humans from in vitro (hepatocyte) and in vivo pharmacokinetic data and to identify the most predictive models for this purpose. Cross-validation was performed to assess prediction accuracy. It turned out that human hepatocyte data was the best predictor, followed by rat hepatocyte data. Dog hepatocyte data and dog and rat in vivo data appear to be uncorrelated with human in vivo clearance and did not significantly contribute to the prediction models. Considering the present evaluation, the most cost-effective and most accurate approach to achieve satisfactory predictions in human is a combination of in vitro clearances on human and rat hepatocytes. Such information is of considerable value to speed up drug discovery. This study also showed some of the limitations of the approach related to the size of the database used in the present evaluation.

Animals↗
PubMedDate not supplied

A cell-based molecular transport simulator for pharmacokinetic prediction and cheminformatic exploration.

In the body, cell monolayers serve as permeability barriers, determining transport of molecules from one organ or tissue compartment to another. After oral drug administration, for example, transport across the epithelial cell monolayer lining the lumen of the intestine determines the fraction of drug in the gut that is absorbed by the body. By modeling passive transcellular transport properties in the presence of an apical to basolateral concentration gradient, we demonstrate how a computational, cell-based molecular transport simulator can be used to define a physicochemical property space occupied by molecules with desirable permeability and intracellular retention characteristics. Considering extracellular domains of cell surface receptors located on the opposite side of a cell monolayer as a drug's desired site of action, simulation of transcellular transport can be used to define the physicochemical properties of molecules with maximal transcellular permeability but minimal intracellular retention. Arguably, these molecules would possess very desirable features: least likely to exhibit nonspecific toxicity, metabolism, and side effects associated with high (undesirable) intracellular accumulation; and most likely to exhibit favorable bioavailability and efficacy associated with maximal rates of transport across cells and minimal intracellular retention, resulting in (desirable) accumulation at the extracellular site of action. Simulated permeability values showed good correlations with PAMPA, Caco-2, and intestinal permeability measurements, without "training" the model and without resorting to statistical regression techniques to "fit" the data. Therefore, cell-based molecular transport simulators could be useful in silico screening tools for chemical genomics and drug discovery.

Biological Availability↗
PubMed2005

Phenotypic anchoring of global gene expression profiles induced by N-hydroxy-4-acetylaminobiphenyl and benzo[a]pyrene diol epoxide reveals correlations between expression profiles and mechanism of toxicity.

The goal of this study was to compare changes in gene expression induced by exposure to different carcinogens and to anchor these changes to the induced levels of toxicity and mutagenesis. The human TK6 lymphoblastoid cell line was used as an in vitro model system, and reactive metabolites of two human carcinogens, benzo[a]pyrene and 4-aminobiphenyl, were used as model compounds. We first determined the toxicity of the model compounds N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and benzo[a]pyrene diol epoxide (BPDE) in TK6 cells. BPDE was about 1000-fold more toxic and mutagenic than N-OH-AABP in TK6 cells on a molar basis. We next treated cells with three doses of each compound that resulted in low, medium, and high toxicities (5, 15, and 40%) and harvested cells at different times after exposure. Using comparable levels of toxicity as the phenotypic anchor, we compared the patterns of gene expression induced by each reactive metabolite using printed cDNA microarrays comprising approximately 18,000 human gene/EST sequences. The microarray data from the N-OH-AABP and BPDE treatment groups were compared using self-organizing map clustering algorithms, as well as a statistical regression modeling approach. While subsets of genes indicative of a generalized stress response [Hsp 40 homologue (DNAJ), Hsp70, Hsp105, and Hsp 125] were detected after exposure to both compounds at all concentrations, there were also many differentially regulated genes, including phase I xenobiotic metabolism [e.g., glutathione transferase omega (GSTTLp28) and antioxidant enzymes (Apxl)]. Other differentially regulated genes included those encoding proteins involved in all major DNA repair pathways, including excision repair (e.g., ERCC5), mismatch repair (e.g., MLH3), damage specific DNA binding protein (e.g., DDB2), and cisplatin resistance-associated overexpressed protein (LUC7A, CRA). Differences in the transcriptional response of TK6 cells to N-OH-AABP or BPDE exposure may explain the dramatic differences in the toxicity and mutagenicity of these human carcinogens.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Evaluation of a Pitot type spirometer in helium/oxygen mixtures.

OBJECTIVE: Mixtures of helium and oxygen are regaining a place in the treatment of obstruction of the upper and lower respiratory tract. The parenchymal changes during the course of IRDS or ARDS may also benefit from the reintroduction of helium/oxygen. In order to monitor and document the effect of low-density gas mixtures, we evaluated the Datex AS/3 Side Stream Spirometry module with D-lite (Datex-Engstrom Instrumentarium Corporation, Finland) against two golden standards. METHODS: Under conditions simulating controlled and spontaneous ventilation with gas mixtures of He (approx. 80, 50, and 20%)/O2 or N2(approx. 21 and 79%)/02, simultaneous measurements using Biotek Ventilator Tester (Bio-Tek Instr., Vermont, USA) or body plethysmograph (SensorMedics System, Anaheim, USA) were correlated with data from the spirometry module. Data were analyzed according to a statistical regression model resulting in a best-fit equation based on density, voltage, and volume measurements. RESULTS: As expected, the D-lite (a modified Pitot tube) showed density-dependent behaviour. Regression equations and percentage deviation of estimated versus measured values were calculated. CONCLUSION: Measurements with the D-lite using low-density gases are satisfactorily contained in best-fit equations with a standard deviation of less than 5% during all ventilatory modes and mixtures.

Airway Obstruction↗
PubMed2004

Investigating tendon fascicle structure-function relationships in a transgenic-age mouse model using multiple regression models.

Proper replacement or repair of damaged tendons or ligaments requires functionally engineered tissue that mimics their native mechanical properties. While tendon structure-function relationships are generally assumed, there exists little quantitative evidence of the roles of distinct tendon components in tendon function. Previous work has used linear correlations to assess the independent, univariate effects of one structural or one biochemical variable on mechanics. The current study's objective was to simultaneously and rigorously evaluate the relative contributions of seven different structural and compositional variables in predicting tissue mechanical properties through the use of multiple regression statistical models. Structural, biochemical, and mechanical analysis were all performed on tail tendon fascicles from different groups of transgenic mice, which provide a reproducible, noninvasive, in vivo model of changes in tendon structure and composition. Interestingly, glycosaminoglycan (GAG) content was observed to be the strongest predictor of mechanical properties. GAG content was also well correlated with collagen content and mean collagen fibril diameter. Collagen fibril area fraction was a significant predictor only of material properties. Therefore, in a large multivariate model, GAG content was the largest predictor of mechanical properties, perhaps both through direct influence and indirectly through its correlation with collagen content and fibril structure.

Animals↗
PubMed2004

Spatial analysis and indicator building for metal accumulation in mosses.

Mosses are used as passive accumulation monitors for metal accumulation in terrestrial ecosystems. Under leadership of the Federal Agency for Environmental Protection Germany took part in the previous European-wide moss monitoring campaigns 1990, 1995 and 2000. The investigations accomplished thereby cannot be presented completely in this article. The remarks rather concentrate on methodical aspects of the statistical data analysis. In Chapter 2 the design of data collection is summarized. Chapter 3 treats the geostatistical analysis and transformation of point data to areal information. Chapter 4 describes the aggregation of the element-specific metal concentrations in mosses to a spatially and temporally differentiated indicator of metal accumulation by means of descriptive and multivariate statistics. The work presented is only a small part of geostatistics and multivariate statistics which fit for analysis of moss monitoring data. Taking the results presented here as a basis, the following steps would further be of great importance: cluster-analytic evaluation of the results of the Moss Monitoring 1990 and 1995, detailing the cluster results using additional empirical and location describing information (e.g. moss species, ecoregions, site and species specific variability of metal accumulation) as well as optimizing the indicator buildung by testing of multivariate statistical regression models (e.g. Classification and Regression Trees).

Bryophyta↗