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Characterization of anti-inflammatory compounds using transcriptomics, proteomics, and metabolomics in combination with multivariate data analysis.

The discovery of new anti-inflammatory drugs is often based on an interaction with a specific target, although other pathways often play a primary or secondary role. Anti-inflammatory drugs can be categorized into classes, based on their mechanism of action. In this article we investigate the possibility to characterize novel anti-inflammatory compounds by three holistic methods. For this purpose, we make use of macrophage-like U937 cells which are stimulated with LPS in the absence or presence of an anti-inflammatory compound. Using micro-arrays, 2-D gel electrophoresis and a LC-MS method for lipids the effects on the transcriptome, proteome and metabolome of the exposed cells is investigated. The expression patterns are subsequently analyzed using in-house developed pattern recognition tools. Using the methods described above, we have examined the effects of six anti-inflammatory compounds. Our results demonstrate that different classes of anti-inflammatory compounds show distinct and characteristic mRNA, protein, and lipid expression patterns, which can be used to categorise known molecules and to discover and classify new leads. The potential of our approach is illustrated by the analysis of several beta (2)-adrenergic agonists (beta2-agonists). In addition to their primary pharmacological target, beta2-agonists posses certain anti-inflammatory properties. We were able to show that zilpaterol, a poorly characterized beta2-agonist, gives rise to an almost identical expression pattern as the beta2-agonists clenbuterol and salbutamol. Furthermore we have identified specific mRNA, protein and lipid markers for the anti-inflammatory compounds investigated in this study.

Adrenergic beta-2 Receptor Agonists↗

Potentially protective factors associated with healthful body mass index in adolescents with obese and nonobese parents: a secondary data analysis of the third national health and nutrition examination survey, 1988-1994.

OBJECTIVE: To identify factors potentially protective against obesity in 12- to 16-year-olds with one or two obese parents, and those with no obese parents. DESIGN: A secondary analysis of the Third National Health and Nutrition Examination Survey, 1988-1994. SUBJECTS/SETTING: A nationally representative sample of healthful weight, at-risk, or overweight adolescents with measured heights and weights (n=1,890). Subsamples with any obese parent (body mass index > or =30) and no obese parents (both with body mass index <25) were analyzed. STATISTICAL ANALYSES PERFORMED: Bivariate analyses examined the association of predictor variables (demographics, nutrient intake, and physical activity) on the outcome. Logistic regressions examined the likelihood of being healthful weight. SUDAAN software (release 7.5, 1997, Research Triangle Institute, Research Triangle Park, NC) was used to account for the sample design. RESULTS: Overall, 71% of subjects had a healthful weight, 29% were at risk or overweight. Factors associated with healthful weight included having two nonobese parents (odds ratio [OR]=5.4), only father obese (OR=4.9), only mother obese (OR=3.3), higher reading scores (OR=1.02), lower water consumption (OR=1.8), more exercise programs (OR=2.8), and higher energy intake (OR=2.0). For adolescents with any obese parent, factors potentially protective against obesity included being female (OR=2.2), higher household education (OR=1.1), lower water consumption (OR=2.0), and eating breakfast some days (OR=3.1) or everyday (OR=4.0). For adolescents with no obese parents, potentially protective factors included older age (OR=1.2), not having asthma (OR=2.6), more exercise programs (OR=6.1), and higher energy intake (OR=2.9). All P<.05. CONCLUSIONS: Interventions targeted at adolescents who are at risk because they have parents with obesity should employ a family approach focused on regular breakfast consumption.

Adolescent↗

Insurance status and race represent independent predictors of undergoing laparoscopic surgery for appendicitis: secondary data analysis of 145,546 patients.

BACKGROUND: Studies have shown that racial and socioeconomic differences lead to inequality in access to health care. It is unknown whether insurance status and race affect the choice of surgical treatment for patients presenting with appendicitis. STUDY DESIGN: Patients with primary ICD-9 procedure codes for laparoscopic and open appendectomy were selected from the 1998, 1999, and 2000 Nationwide (US) Inpatient Samples. The primary predictor variables were insurance status (private, Medicare, Medicaid, other) and race (Caucasian, African American, Hispanic, other). Multiple logistic regression models were used to assess whether insurance status and race are associated with the choice of surgical procedure for patients presenting with appendicitis. RESULTS: Discharge abstracts of 145,546 patients were used for our analyses. There were 32,407 patients (22.3%) who underwent laparoscopic appendectomy and 113,139 patients (77.7%) who had open appendectomy. Although 24.2% of privately insured patients underwent laparoscopic appendectomy, only 16.9% of Medicare patients, 17.4% of Medicaid patients, and 19.6% of patients in the "other" insurance category were treated using the laparoscopic procedure (p < 0.001). Caucasian patients underwent laparoscopic surgery in 24.8%, African Americans in 18.6%, Hispanics in 19.6%, and other ethnicities in 18.8% of patients (p < 0.001). Compared with the Medicaid subset, and after adjusting for potential confounders such as age, gender, race, patient comorbidity, median ZIP code income, hospital location and teaching status, and presence of abscess or perforation, privately insured patients (odds ratio [OR] = 1.26, 95% [CI [1.20, 1.33], p < 0.001) and Medicare patients (OR = 1.17, 95% CI [1.05, 1.30], p = 0.004) were significantly more likely to undergo laparoscopic surgery. Caucasian patients (OR = 1.42, 95% CI [1.33, 1.51], p < 0.001) and Hispanics (OR = 1.12, 95% CI [1.04, 1.20], p = 0.002) were significantly more likely to have laparoscopic appendectomy, compared with African Americans, even after adjusting for the previously mentioned confounders and insurance status. CONCLUSIONS: Even after adjusting for potential confounders, insurance status and race are marked independent predictors of having laparoscopic surgery in patients treated for appendicitis in this sample.

Adult↗

Low temperature solid-state NMR experiments of half-integer quadrupolar nuclides: caveats and data analysis.

Solid-state NMR spectroscopy of half-integer quadrupolar nuclides has received a lot of interest recently with the advent of new methodologies and higher magnetic fields. We present here the extension of our previous low temperature method to an 18.8T system. This new probe entailed a total redesign including a cross coil and variable capacitors that are operational at cryogenic temperatures. The limitations to sensitivity are also discussed; including a new diode network, the utilization of a cryogenic band pass filter, and the consequences of the RF profiles of the coil. Further, details of the spectroscopy of quadrupolar nuclei in a protein are discussed, such as the observation of the outer transitions and how to distinguish them from the desired +/-1/2 transition.

Journal Article↗

AFLP fingerprinting of Colombian Clostridium spp strains, multivariate data analysis and its taxonomical implications.

Amplified Fragment Length Polymorphism (AFLP) analysis was used for characterising 13 native Colombian Clostridium spp strains. The DNA extraction method was optimised and the use of cetyl trimethyl ammonium bromide (CTAB) and sodium chloride (NaCl) was incorporated. All strains could be typed in these conditions. The AFLP profiles obtained were submitted to multivariate analysis and compared with previous pulsed field gel electrophoresis (PFGE) results. The results suggested that the set of native strains could correspond to two new species different to those having been described to date. It is proposed that DNA-DNA hybridisation analysis should be done to produce complementary information for describing the new species.

Classification↗

Fracture treatment in children--data analysis and follow-up results of a prospective study.

The versatile Orthofix modular system can be used to treat long-bone fractures in children from the 2nd year of life. It allows definitive fracture management over a short period of time without traumatizing the soft tissues. The possible early mobilization and full weight-bearing mean that the children are able to return early to school or kindergarten. The method enables the stabilization of open fractures with or without excessive soft tissue injury as well as secondary callus distraction. There is no need for a second surgical intervention and no prolonged period of physiotherapy. This fracture treatment suits children's needs and maintains their quality of life.

Adolescent↗

Model discrimination and estimation of the intraparticle mass transfer parameters for the adsorption of bovine serum albumin onto porous adsorbent particles by the use of experimental frontal analysis data.

Experimental data from a chromatographic system involving the adsorption of bovine serum albumin (BSA) onto porous anion-exchange adsorbent particles packed in a column are presented. The parameters that characterize the mass transfer mechanisms of intraparticle diffusion and convection are estimated by fitting the predictions of dynamic mathematical models describing adsorption in column systems having spherical perfusive and purely diffusive adsorbent particles to the experimental breakthrough data obtained from the column adsorption system. Both linear and nonlinear expressions for the equilibrium isotherm are considered. The values of the transport parameters are estimated in the time domain for the nonlinear adsorption models and in the Laplace transform domain for the linear adsorption models. The capabilities of the different models to describe satisfactorily the dynamic behavior of the adsorption system are compared. The dynamic nonlinear adsorption model for purely diffusive particles is found to describe most appropriately the dynamic behavior of the experimental chromatographic system studied in this work.

Adsorption↗

Bone mineral content: data analysis.

We reviewed the literature related to intrauterine bone mineral content (BMC) curves and the expression of BMC measurements in infants. From this review, it appears that the curves developed by Greer and by Minton for the radius are extremely similar and that both should be used as the reference curve. It also appears that expression of assessment results in terms of BMC and bone width (BW) permits an evaluation of growth of bone mass versus growth of size of the bone scanned. Although the BMC/BW ratio might be a useful but unproved conceptual adjunct, expression of photon absorptiometry results in terms of the BMC/BW ratio alone does not confer any specific advantage and theoretically could mask important specific information about bone mass and size.

Bone Development↗