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Biomedical subjects

E Adams

Publications and source records attributed to E Adams.

At least 37 records · Page 2Linked to original sources

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↗

Analysis of a formulation containing lincomycin and spectinomycin by liquid chromatography with pulsed electrochemical detection.

A reversed phase ion-pair liquid chromatographic method using a base deactivated column and pulsed electrochemical detection on a gold electrode is described. It allows the separation of a mixture of spectinomycin sulfate, lincomycin hydrochloride and their related substances. A step gradient was necessary to obtain a good separation together with a reasonable analysis time of 40 min. The mobile phases consisted of an aqueous solution of 3.3 or 0.55 g/l pentanesulfonic acid, 10 mM acetic acid and 20 ml/l tetrahydrofuran. Both mobile phases were adjusted to pH 4.0 with diluted sodium hydroxide. The influence of the different chromatographic parameters on the separation was investigated. Two commercial samples were analyzed using the described method. In total 12 components could be separated.

Anti-Bacterial Agents↗

Analysis of spectinomycin by liquid chromatography with pulsed electrochemical detection.

Until now, no LC method is described to determine the purity and content of spectinomycin without prior derivatization. A reversed-phase ion-pair LC method using a base deactivated column and pulsed electrochemical detection is described. The mobile phase consisted of an aqueous solution containing 5.8 g/l pentafluoropropionic acid, 1.25 g/l potassium dihydrogen phosphate and 5.5 ml/l tetrahydrofuran. The pH was adjusted to 6.25 using dilute NaOH solution. An experimental design was used to optimize the chromatographic parameters and to check the robustness. The quality of separation was investigated on different stationary phases. The method allows the separation of spectinomycin from its related substances as well as some other components of unknown identity. The total time of analysis is 65 min. A number of commercial samples were examined using this method.

Anti-Bacterial Agents↗

Principal component analysis of dissolution data with missing elements.

The use of principal component analysis (PCA) for incomplete dissolution data sets is examined. The PC space is constructed using a reference set and the test set is projected in that space. Several cases such as a reference set with missing data, an incomplete test set and both sets measured at different time points, are discussed using two examples: one simulation and one obtained from the pharmaceutical practice. From the many possibilities to deal with missing data, the expectation-maximization algorithm in combination with PCA was chosen. The influence on the similarity or f2 factor is examined too. The sampling with replacement or bootstrap technique, which can be used to obtain confidence limits, can also be used when missing data are present in one of the data sets.

Algorithms↗

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↗

Evaluation of dissolution profiles using principal component analysis.

The performance of principal component analysis (PCA) for the evaluation of dissolution profiles is examined and compared with other methods such as the similarity factor and the calculation of the area under the curve. Both simulated and real data from the pharmaceutical industry are used. The PCA scores plots of the dissolution curves provide information about the between- and within-batch variations. Differences in level or shape can be observed in the first two principal components (PCs). Irrelevant irregularities, which have a strong influence on the similarity factor, are neglected in PC1/PC2. To detect outliers in a set of dissolution curves, PCA was preferred above Hotelling's T2 test. In general, PCA is found to be a useful technique to examine dissolution data visually, but however, it does not contain criteria to decide if batches are similar or not. This can be done by combining PCA with the resampling with replacement or bootstrap method to construct confidence limits.

Solubility↗

Therapeutic aspects of tolerance.

The immune system is naturally unresponsive to 'self' antigens. Improved knowledge of mechanisms underlying self tolerance is giving rise to a new generation of immunosuppressive agents, that can exploit these mechanisms and so reduce the nature and level of medication that needs to be given long-term to control diseases where the immune system does harm.

Animals↗

Disparities in reported prenatal care advice from health care providers among women of Mexican origin in California.

Poorer birth outcomes have been documented among U.S.-born women of Mexican descent when compared with Mexican immigrant women. Behavioral changes that are associated with acculturation may contribute to these deteriorating outcomes. Prenatal health promotion advice can alter prenatal risk behaviors. The growing diversity of the U.S. population during the 1990s heightens the importance of examining the cultural relevance of current health promotion practices. This study examines disparities in the reported receipt of health behavior advice during pregnancy among U.S.-born women of Mexican origin and Mexican immigrant women in California. Data for the analysis are from the 1994-95 California Pregnancy Risk Assessment Monitoring System. The study sample includes 1,423 women of Mexican descent. All participants had a live birth in California between January 1994 and December 1995. Women were interviewed about the prenatal counseling they received related to diet, smoking, and alcohol use. Logistic regression was used to analyze the likelihood of reporting advice after controlling for sociodemographic and health system characteristics. Immigrant women were more likely than the U.S.-born to report receipt of prenatal advice on smoking, alcohol, and diet (OR = 1.83, p < .05) despite evidence of the lower prevalence of related health risks among Mexican-born women. Culturally appropriate prenatal counseling would emphasize the maintenance of traditional protective behaviors among less acculturated foreign-born women, and the prevention or cessation of those risk behaviors among the more acculturated women.

Journal Article↗

Racial and ethnic disparities in the discordance between women's assessment of the timing of their prenatal care entry and the first trimester standard.

OBJECTIVE: The purpose of this study was to investigate whether the discordance between women's assessment of the adequacy of the timing of their prenatal care entry and the standard of first trimester initiation was associated with maternal race or ethnicity. METHODS: A population-based surveillance system, the California Pregnancy Risk Assessment Monitoring System, provided data on a stratified random sample of 4,987 women. The women delivered live-born infants from 1994-95 in three perinatal regions. Respondents completed an in-hospital, self-administered questionnaire. Weighted data were analyzed with multiple logistic regression. RESULTS: Twenty-two percent of the women in the sample initiated prenatal care after the first trimester of pregnancy (n = 1,097). Among the women with untimely care, 57% (n = 591) were satisfied with the time of care initiation. Discordance between the women's perception of the adequacy of the time of care initiation and the public health standard of first trimester initiation was associated with maternal ethnicity. After controlling for potential confounders, Mexican-born women with untimely care were more likely to report being satisfied with the time of initiation than were white non-Latina women with untimely care (OR = 4.03, CI = 2.46, 6.59). CONCLUSIONS: The design of public health interventions to increase the timeliness of prenatal care initiation will require a greater understanding of pregnant women's own perceptions of their needs for prenatal care, and the differences in perceptions across ethnic groups.

Adolescent↗

The role of CD4+ T-cell subsets in determining transplantation rejection or tolerance.

Peripheral tolerance to allogeneic organ grafts can be induced in rodents by treating with non-depleting CD4 and CD8 monoclonal antibodies. This tolerance is maintained by CD4+ T cells with a potent capacity to induce tolerance in further cohorts of T cells (i.e. infectious tolerance). We have cloned CD4+ T-cell subsets against the male transplantation antigen in vitro and find, in contrast to Th1 or Th2 clones that elicit rejection, that there is a distinct population of CD4+ T cells that suppress rejection by adoptive transfer (here called Treg). In order to identify molecular markers associated with tolerance and gain insights into the mechanisms of action of Treg cells, we carried out serial analysis of gene expression. We identified genes overexpressed in Treg compared to Th1 and Th2 cultures and found that some of these correlated in vivo with CD4-induced transplantation tolerance rather than rejection. The genes overexpressed in Treg cultures and within tolerated skin grafts were primarily expressed by mast cells (e.g. tryptophan hydroxylase and FcepsilonR1alpha), suggesting that regulatory cell activity and this form of tolerance may be associated with a localised but non-destructive form of Th2-like activation and a recruitment of mast cells.

Animals↗

Estrogen promotes growth of human thyroid tumor cells by different molecular mechanisms.

Thyroid tumors are about 3 times more frequent in females than in males. Epidemiological studies suggest that the use of estrogens may contribute to the pathogenesis of thyroid tumors. In a very recent study a direct growth stimulatory effect of 17beta-estradiol was demonstrated in FRTL-5 rat thyroid cells. In this work the presence of estrogen receptors alpha and beta in thyroid cells derived from human goiter nodules and in human thyroid carcinoma cell line HTC-TSHr was demonstrated. There was no difference between the expression levels of estrogen receptor alpha in males and females, but there was a significant increase in expression levels in response to 17beta-estradiol. Stimulation of benign and malignant thyroid cells with 17beta-estradiol resulted in an increased proliferation rate and an enhanced expression of cyclin D1 protein, which plays a key role in the regulation of G(1)/S transition in the cell cycle. In malignant tumor cells maximal cyclin D1 expression was observed after 3 h, whereas in benign cells the effect of 17beta-estradiol was delayed. ICI 182780, a pure estrogen antagonist, prevented the effects of 17beta-estradiol. In addition, 17beta-estradiol was found to modulate activation of mitogen-activated protein (MAP) kinase, whose activity is mainly regulated by growth factors in thyroid carcinoma cells. In response to 17beta-estradiol, both MAP kinase isozymes, extracellular signal-regulated protein kinases 1 and 2, were strongly phosphorylated in benign and malignant thyroid cells. Treatment of the cells with 17beta-estradiol and MAP kinase kinase 1 inhibitor, PD 098059, prevented the accumulation of cyclin D1 and estrogen-mediated mitogenesis. Our data indicate that 17beta-estradiol is a potent mitogen for benign and malignant thyroid tumor cells and that it exerts a growth-promoting effect not only by binding to nuclear estrogen receptors, but also by activation of the MAP kinase pathway.

Adenocarcinoma↗

Liquid chromatographic analysis of streptomycin sulfate.

The analysis of streptomycin sulfate using a column packed with base deactivated reversed phase silica gel and ultraviolet (UV) detection at 205 nm is described. The mobile phase consists of an aqueous solution containing 14 g/l of sodium sulfate, 1.5 g/l of sodium octanesulfonate, 50 ml/l of acetonitrile and 50 ml/l of a 0.2 M phosphate buffer at pH 3.0. The method allows separating streptidine, streptomycin B, streptomycin and dihydrostreptomycin, as well as several other components, which were not yet identified. The total time of analysis is 50 min. The effects of the different chromatographic parameters on the separation were investigated. A number of commercial samples were analyzed using this method.

Anti-Bacterial Agents↗

Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance.

Nondepleting anti-CD154 (CD40 ligand) mAbs have proven effective in inducing transplantation tolerance in rodents and primates. In the induction phase, anti-CD154 Ab therapy is known to enhance apoptosis of Ag reactive T cells. However, this may not be the sole explanation for tolerance, as we show in this study that tolerance is maintained through a dominant regulatory mechanism which, like tolerance induced with CD4 Abs, manifests as infectious tolerance. Therefore, tolerance induced with anti-CD154 Abs involves not only the deletion of potentially aggressive T cells, but also a contagious spread of tolerance to new cohorts of graft-reactive T cells as they arise.

Adoptive Transfer↗

Analysis of tobramycin by liquid chromatography with pulsed electrochemical detection.

The determination of tobramycin by liquid chromatography using a column packed with poly(styrene-divinylbenzene) and pulsed electrochemical detection on a gold electrode is described. The mobile phase consisted of an aqueous solution containing 52 g/l of sodium sulfate, 1.5 g/l of sodium octanesulfonate and 50 ml/l of a 0.2 M phosphate buffer pH 3.0. The total time of analysis was not more than 30 min. The effects of the different chromatographic parameters on the separation were also investigated. When a number of commercial samples of tobramycin was analyzed using this method, nine different components were separated, five of which are of unknown identity.

Anti-Bacterial Agents↗

Expression of murine IL-12 is regulated by translational control of the p35 subunit.

IL-12 is a heterodimer of two subunits, p35 and p40, encoded by separate genes that are regulated independently. To investigate the mechanisms underlying the regulation of the p35 gene, we characterized murine p35 expression in the B cell lymphoma line A20 and in bone marrow-derived dendritic cells. Multiple transcription start sites were identified in both cell types, resulting in four p35 mRNA isoforms (types I-IV) that differ in the number and position of upstream ATGs in their 5' untranslated regions. In nonstimulated cells, the predominant forms of p35 message (types II and IV) contained an additional upstream ATG, whose presence was shown to inhibit the downstream translation of the p35 subunit. After LPS stimulation, however, transcription initiated from alternate positions, so that the proportion of transcripts not containing this upstream ATG (types I and III) was significantly increased in the population of p35 mRNA. These type I and type III transcripts readily supported translation of the p35 subunit and its incorporation into bioactive IL-12. Furthermore, p35 mRNA levels were substantially up-regulated after LPS stimulation in both cell types. Thus, our results show that p35 gene expression is highly regulated by both transcriptional and translational mechanisms.

5' Untranslated Regions↗

Effects of the novel GH secretogogue, hexarelin on GH secretion and phosphatidylinositol hydrolysis by human pituitary somatotrophinomas in cell culture.

The effects of the novel GH-releasing hexapeptide, Hexarelin, on cultured human pituitary somatotrophinomas were investigated. Hexarelin (0.01-100 nmol/L) dose-dependently stimulated GH secretion up to 4.6-fold. Maximal effects occurred with 10 nmol/L. These effects were very similar to those observed with GHRP-6. The effects of Hexarelin were reduced by phloretin, an inhibitor of protein kinase C (PKC). The rate of phosphatidylinositol (PI) hydrolysis was markedly increased by Hexarelin in a dose-dependent manner. These results demonstrated that Hexarelin could directly stimulate GH secretion by human pituitary somatotrophs in a PKC-dependent manner, probably via activation of the PI transduction system.

Adenoma↗