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At least 631 records · Page 35Linked to original sources
PubMed2003

Importance of hydroxyapatite particles characteristics on cytokines production by human monocytes in vitro.

Calcium phosphate bioceramics have been applied as bone substitutes for several decades. Aseptic loosening after total joint arthroplasty is a major problem in orthopaedic surgery. Hydroxyapatite particles from materials wear have been reported as the main cause of implant failure. For this reason, an investigation into possible wear particles from materials used in the implant may lead to longevity after arthroplasty. Monocytes are among the first cells to colonize the inflammatory site. In the present study, we have evaluated the inflammatory response after exposition to particles with different characteristics (size, sintering temperature and shape). Our data demonstrate that the most important characteristic was the shape and the size of the particles. The needle shaped particles induced the larger production of TNF-alpha, IL-6 and IL-10 by cells. To a less manner, the smallest particles induced an increase of the expression and production of the cytokines studied (TNF-alpha, IL-6 and IL-10). The sintering temperature appeared to be a less important characteristic even though it was involved in the dissolution/precipitation process.

Cells, Cultured↗
PubMedDate not supplied

Validation of the French version of the Fecal Incontinence Quality-of-Life (FIQL) scale.

INTRODUCTION: The aim of this multicenter study was to validate the French version of the fecal incontinence quality-of-life scale (FIQL scale) developed in the Unites States of America. PATIENTS AND METHODS: The FIQL scale has 29 items in four scales: lifestyle, coping/behavior, depression/self-perception and embarrassment. Each item is scored from 1 to 4, with poorest quality-of-life scored 1. An average is calculated for each scale. After linguistic validation of the questionnaire, the French version of the FIQL scale was tested twice, at day 0 and day 7, by 100 patients with fecal incontinence (FI). Construction validity, internal reliability, clinical validity and reproducibility were analysed. RESULTS: Analysis of convergent validity of the French version of the FIQL scale showed very good correlation between items and the corresponding scale for lifestyle (0.50-0.79) and depression/self-perception (0.44-0.74), good correlation for coping/behavior (0.31-0.70) and weak correlation for embarrassment (0.30-0.40). Valid discrimination was observed for 24 of the 29 items. Internal reliability was good for each scale (alpha Cronbach between 0.78 and 0.92). Scores determined with the FIQL scale were significantly correlated with Wexner FI scores, demonstrating the clinical validity of the instrument. Reproducibility, evaluated in patients whose FI was unchanged between day 0 and day 7, was good with intraclass correlation coefficients ranging from 0.80 (embarrassment) to 0.93 (lifestyle). CONCLUSIONS: The linguistic and psychometric evaluation demonstrated the validity of the French version of the FIQL scale. This standardized instrument is now available for clinical use in France for quality-of-life assessment in patients with FI.

Adult↗
PubMed2002

Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2.

Lipopolysaccharide (LPS) induces a delayed release (lag phase of 2-4 h) of arachidonic acid (AA) and prostaglandin (PG) D2 in rat liver macrophages. Group IV cytosolic phospholipase A2 (cPLA2) becomes phosphorylated within minutes after the addition of LPS. The phosphorylated form of cPLA2 shows an enhanced in vitro activity. The Ca2+ dependence of cPLA2 activity is not affected by phosphorylation of the enzyme. In addition, LPS induces an enhanced expression of cPLA2 mRNA (after 2-4 h) and an enhanced expression of cPLA2 protein (after 8 h). The cellular cPLA2 activity is enhanced about twofold 24 h after LPS treatment. Liver macrophages constitutively express mRNAs encoding Groups V and IIA secretory PLA2 (sPLA2). LPS has no effect on the levels of Groups V and IIA sPLA2 mRNA expression. Despite mRNA expression, Groups V and IIA sPLA2 protein and sPLA2 activity are not detectable in unstimulated or LPS-stimulated liver macrophages. Collectively, these and earlier [Mediators Inflammation 8 (1999) 295.] results suggest that in liver macrophages the LPS-induced delayed release of AA and prostanoids is mediated by phosphorylation and an enhanced expression of cPLA2, a de novo expression of cyclooxygenase (COX)-2, but not by the actions of Group V or Group IIA sPLA2.

Animals↗
PubMedDate not supplied

Differential regulation of TNF-alpha, IL-6 and IL-10 in UVB-irradiated human keratinocytes via cyclic AMP/protein kinase A pathway.

Pro-inflammatory cytokines are important mediators of cutaneous cellular activities during many skin diseases. In the present study, we investigated the production of tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-10 by UVB-irradiated human keratinocytes NCTC 2544 cell line in the presence of cAMP-elevating agents and we attempted to determine the implication of cyclic AMP/PKA pathway in the regulation of cytokine gene expression. Cytokine mRNA expression levels and cytokine concentrations were investigated by reverse transcription polymerase chain reaction and by ELISA method, respectively. Treatment of UVB-irradiated NCTC 2544 cells with drugs known to enhance cAMP concentration [dibutyryl cAMP, PGE(2) and cholera toxin] results in a significant decrease of TNF-alpha mRNA expression whereas IL-6 and IL-10 mRNAs were enhanced. In the same experimental conditions, treatment of irradiated keratinocytes with PKA inhibitors [H89 and PKA inhibitor (PKAi)] induced a significant inhibition of mRNA expression for all tested cytokines. Except for IL-10, the pharmacological effect of cAMP-elevating agents or PKA inhibitors on radiation-induced TNF-alpha and IL-6 mRNA expression was associated with a concomitant regulation of cytokine release. Taken together our results showed: (i) a differential regulation of TNF-alpha, IL-6 and IL-10 in UVB-irradiated human keratinocytes via cyclic AMP/protein kinase A pathway, and (ii) a possible reduction of deleterious inflammatory effects of cytokine following UVB-irradiation by using pharmacological agents that regulate both the intracellular cAMP levels and the cellular PKA activity.

Blotting, Northern↗
PubMed2006

Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study.

BACKGROUND: The Common Terminology Criteria for Adverse Events (CTCAE) are used as standard practice in trials of cancer treatments by clinicians to elicit and report toxic effects. Alternatively, patients could report this information directly as patient-reported outcomes, but the accuracy of these reports compared with clinician reports remains unclear. We aimed to compare the reporting of symptom severity reported by patients and clinicians. METHODS: Between March and May, 2005, a questionnaire with 11 common CTCAE symptoms was given to consecutive outpatients and their clinicians (physicians and nurses) in lung and genitourinary cancer clinics in the Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Patients completed a version that used language adapted from the CTCAE for patient self-reporting. The results from the questionnaire were compared with clinician reporting of the same symptoms. FINDINGS: Of 435 patients and their clinicians asked to take part in the study, 400 paired surveys were completed. For most symptoms, agreement between patient and clinician was high, and most discrepancies were within a grade difference of one point. Agreement was higher for symptoms that could be observable directly, such as vomiting and diarrhoea, than for more subjective symptoms, such as fatigue and dyspnoea. Differences in symptom reporting rarely would have changed treatment decisions or dosing, and patients assigned greater severity to symptoms more than did clinicians. No significant differences were recorded between the results when the questionnaire was completed by the patient before or after the clinician. INTERPRETATION: Patient reporting of symptoms could add to the current approach to symptom monitoring in cancer treatment trials. Future research should assess the effect of self reporting on clinical outcomes and efficiency, and the use of real-time collection of patient-reported outcomes for early detection of potentially serious adverse events.

Adult↗
PubMed2007

Temporal processing deficits in letter-by-letter reading.

Theories of the cognitive impairment underlying letter-by-letter reading vary widely, including prelexical and lexical level deficits. One prominent prelexical account proposes that the disorder results from difficulty in processing multiple letters simultaneously. We investigated whether this deficit extends to letters presented in rapid temporal succession. A letter-by-letter reader, G.M., was administered a rapid serial visual presentation task that has been used widely to study the temporal processing characteristics of the normal visual system. Comparisons were made to a control group of 6 brain-damaged individuals without reading deficits. Two target letters were embedded at varying temporal positions in a stream of rapidly presented single digits. After each stream, the identities of the two letters were reported. G.M. required an extended period of time after he had processed one letter before he was able to reliably identify a second letter, relative to the controls. In addition, G.M.'s report of the second letter was most impaired when it immediately followed the first letter, a pattern not seen in the controls, indicating that G.M. had difficulty processing the two items together. These data suggest that a letter-by-letter reading strategy may be adopted to help compensate for a deficit in the temporal processing of letters.

Adult↗
PubMed2005

Experimental validation of the docking orientation of Cdc25 with its Cdk2-CycA protein substrate.

Cdc25 phosphatases are key activators of the eukaryotic cell cycle and compelling anticancer targets because their overexpression has been associated with numerous cancers. However, drug discovery targeting these phosphatases has been hampered by the lack of structural information about how Cdc25s interact with their native protein substrates, the cyclin-dependent kinases. Herein, we predict a docked orientation for Cdc25B with its Cdk2-pTpY-CycA protein substrate by a rigid-body docking method and refine the docked models with full-scale molecular dynamics simulations and minimization. We validate the stable ensemble structure experimentally by a variety of in vitro and in vivo techniques. Specifically, we compare our model with a crystal structure of the substrate-trapping mutant of Cdc25B. We identify and validate in vivo a novel hot-spot residue on Cdc25B (Arg492) that plays a central role in protein substrate recognition. We identify a hot-spot residue on the substrate Cdk2 (Asp206) and confirm its interaction with hot-spot residues on Cdc25 using hot-spot swapping and double mutant cycles to derive interaction energies. Our experimentally validated model is consistent with previous studies of Cdk2 and its interaction partners and initiates the opportunity for drug discovery of inhibitors that target the remote binding sites of this protein-protein interaction.

Binding Sites↗
PubMed1998

Critical Evaluation of Metal Complex Molecular Mechanics. Part 1. Cobalt(III) Hexaamines.

The ability of available molecular mechanics programs to calculate structures and relative energies of metal complexes is examined via a comparative study of five different force fields: Molmec, Momec91(H), Momec91(C), Xnviron, and Spartan. The method used for assessing the validity of the force fields showed that four of the force fields were able to reproduce successfully the structures of various Co(III) hexaamine cations determined by X-ray analysis, even when these structures were considerably distorted. In certain cases, the calculated relative steric energies were not reliable. Small variations in force fields parameters sometimes led to large changes in the calculated steric energies, and in some instances, in the order of steric strain for different isomers. The most notable changes occurred when metal-dependent parameters were altered.

Journal Article↗
PubMed2006

Fermented pigeon pea (Cajanus cajan) ingredients in pasta products.

Pigeon pea (Cajanus cajan var. aroíto) seeds were fermented in order to remove antinutritional factors and to obtain functional legume flour to be used as pasta ingredients. Fermentation brought about a drastic reduction of alpha-galactosides (82%), phytic acid (48%), and trypsin inhibitor activity (39%). Fermented legume flours presented a notable increase of fat and total soluble available carbohydrates, a slight decrease of protein, dietary fiber, calcium, vitamin B2, vitamin E, and total antioxidant capacity, and a decrease of soluble dietary fiber, Na, K, Mg, and Zn contents. No changes were observed in the level of starch and tannins as a consequence of fermentation. The fermented flour was used as an ingredient to make pasta products in a proportion of 5, 10, and 12%. The supplemented pasta products obtained had longer cooking times, higher cooking water absorptions, higher cooking loss, and higher protein loss in water than control pasta (100% semolina). From sensory evaluations, fortified pasta with 5 and 10% fermented pigeon pea flour had an acceptability score similar to control pasta. Pasta supplemented with 10% fermented pigeon pea flour presented higher levels of protein, fat, dietary fiber, mineral, vitamin E, and Trolox equivalent antioxidant capacity than 100% semolina pasta and similar vitamins B1 and B2 contents. Protein efficiency ratios and true protein digestibility improved (73 and 6%, respectively) after supplementation with 10% fermented pigeon pea flour; therefore, the nutritional value was enhanced.

Cajanus↗
PubMed2003

Inhibition of Cdc25 phosphatases by indolyldihydroxyquinones.

Overexpression of the Cdc25A and Cdc25B dual-specificity phosphatases correlates with a wide variety of cancers, making the Cdc25s attractive drug targets for anticancer therapies. However, the search for good lead molecules has been hampered by the reactivity of the active site thiolate anion and the flat solvent-exposed active site region. We describe here the indolyldihydroxyquinones, a new class of inhibitors of Cdc25 that bind reversibly to the active site with submicromolar potency. Structure-activity relationships in the 50 derivatives of the lead molecule 2,5-dihydroxy-3-(1H-indol-3-yl)[1,4]benzoquinone show interesting and consistent trends identifying features required for inhibition of all three isoforms of Cdc25. The compounds do not show time-dependent inhibition, indicating that they form neither covalent adducts with nor oxidize the active site thiol. Our best compounds, 2,5-dihydroxy-3-(7-farnesyl-1H-indol-3-yl)[1,4]benzoquinone and 2,5-dihydroxy-3-(4,6-dichloro-7-farnesyl-1H-indol-3-yl)[1,4]benzoquinone, are competitive with substrate for the active site and yield K(i)s of 640 and 470 nM, respectively. Binding of the indolylhydroxyquinones is diminished by three, but not by six other, specific mutations in the active site region. Additionally, the flexible C-terminal tail required for binding of protein substrate is also required for binding derivatives with hydrophobic modifications at the 7-position. The indolyldihydroxyquinones compete effectively with the protein substrate for Cdc25 in vitro and lead to rapid cell death in vivo. Thus, the indolyldihydroxyquinones will serve as useful lead molecules for drug discovery and further cell-based studies on the role of Cdc25s in cell cycle control.

Binding Sites↗
PubMed2002

Air pollution in Athens basin and health risk assessment.

An inventory of air pollution sources within the Athens basin is carried out for the years 1989, 1992 and 1998 and the results are inputted in a climatological model for predicting ambient concentrations. Despite of the significant growth in the number of road vehicles and the deteriorating traffic, the emissions and ambient concentrations of fine particulates, CO, NOx and VOC appear to remain reasonably constant over for the period 1989 to 1998, while these of SO2 and Pb are reduced, mainly due to the renewal of vehicle fleet, the use of catalytic technologies and the improved quality of the used fuel. The results further indicate that for CO, NOx and VOC the major source is road traffic, while for PM2.5 and SO2 both space heating and traffic share responsibility. The air pollutant concentrations monitored by the network of 11 stations are reviewed and statistics related to air quality guidelines are presented. As fine particulate levels are not monitored, approximate PM2.5 and PM10 concentrations are derived from black smoke ones on basis of experimentally determined conversion factors. The computed and monitored air pollution levels are compared and found in reasonable agreement. The results of the above analysis show that the levels of all 'classical' pollutants, with the exception of SO2 and Pb, exceed significantly the WHO guidelines and are thus expected to exert a significant health impact. The latter could be quantified in relation to the PM2.5 or PM10 levels on the basis of risk assessment information developed by the World Health Organization (WHO). The results show that the existing levels of fine particle concentrations in Athens increase significantly the mortality and morbidity, and reduce the average longevity of the entire population from 1.3 to 1.7 years.

Adolescent↗
PubMed2003

Oxcarbazepine: clinical experience with hospitalized psychiatric patients.

BACKGROUND: Oxcarbazepine (10-keto-carbamazepine) appears to be better tolerated and simpler to use than carbamazepine. It has antimanic effects but, as its potential clinical usefulness and tolerability in broad samples of psychiatric patients remain to be tested, we reviewed both the pharmacology of oxcarbazepine and our early experience with this new agent among psychiatric inpatients. METHODS: We reviewed medical records of all inpatients given oxcarbazepine in the first 15 months of its use at McLean Hospital. Data analyzed included dosing, presenting illnesses, other medications, clinical changes, and adverse effects. RESULTS: Oxcarbazepine was given to 56 inpatients (1.3% of admissions; 31 women, 25 men) presenting with depression (n = 23), mania (n = 19), or psychosis (n = 14). The discharge daily dose for the 43 patients (76%) taking oxcarbazepine was 831 mg/day, 34% higher in men than women, and fell by 9 mg/year-of-age. Oxcarbazepine was the only putative mood-stabilizing agent given at discharge in 19 of 43 cases (44%). It was discontinued in 20% of patients for apparent inefficacy, and 4% for adverse effects. Changes in CGI and GAF scores were similarly high across illnesses, and unrelated to days of use of oxcarbazepine or its dose. CONCLUSIONS: Oxcarbazepine was well tolerated and simpler to use clinically than its precursor carbamazepine. This agent should be studied in controlled trials to test its efficacy in specific types of major psychiatric disorders, and particularly for long-term maintenance treatment in bipolar disorder.

Age Factors↗
PubMed2006

Recruitment and selection of couples for intervention research: achieving developmental homogeneity at the cost of demographic diversity.

Demographic and relationship quality data were collected from 704 individuals recruited to participate in a randomized study of relationship enhancing interventions. Recruiting at bridal shows produced partners who were more satisfied, earlier in their relationships, and less likely to be parents, with a marginally higher proportion of Latino couples. Radio and television coverage produced more established couples with higher levels of relationship discord. Self-selection effects revealed that couples from demographic groups at greater risk for divorce (those who had not completed high school, those with children at marriage, and African American couples) were more likely to agree to participate. In contrast, imposing a set of common selection criteria served to exclude couples from demographic risk groups and selected for couples with higher marital quality. Implications for recruiting couples to participate in preventive interventions are outlined.

Adult↗
PubMed2003

Universal sex differences in the desire for sexual variety: tests from 52 nations, 6 continents, and 13 islands.

Evolutionary psychologists have hypothesized that men and women possess both long-term and short-term mating strategies, with men's short-term strategy differentially rooted in the desire for sexual variety. In this article, findings from a cross-cultural survey of 16,288 people across 10 major world regions (including North America, South America, Western Europe, Eastern Europe, Southern Europe, Middle East, Africa, Oceania, South/Southeast Asia, and East Asia) demonstrate that sex differences in the desire for sexual variety are culturally universal throughout these world regions. Sex differences were evident regardless of whether mean, median, distributional, or categorical indexes of sexual differentiation were evaluated. Sex differences were evident regardless of the measures used to evaluate them. Among contemporary theories of human mating, pluralistic approaches that hypothesize sex differences in the evolved design of short-term mating provide the most compelling account of these robust empirical findings.

Adult↗
PubMed2004

Patterns and universals of mate poaching across 53 nations: the effects of sex, culture, and personality on romantically attracting another person's partner.

As part of the International Sexuality Description Project, 16,954 participants from 53 nations were administered an anonymous survey about experiences with romantic attraction. Mate poaching--romantically attracting someone who is already in a relationship--was most common in Southern Europe, South America, Western Europe, and Eastern Europe and was relatively infrequent in Africa, South/Southeast Asia, and East Asia. Evolutionary and social-role hypotheses received empirical support. Men were more likely than women to report having made and succumbed to short-term poaching across all regions, but differences between men and women were often smaller in more gender-egalitarian regions. People who try to steal another's mate possess similar personality traits across all regions, as do those who frequently receive and succumb to the poaching attempts by others. The authors conclude that human mate-poaching experiences are universally linked to sex, culture, and the robust influence of personal dispositions.

Adult↗
PubMed2004

What does a pigeon (Columba livia) brain look like during homing? selective examination of ZENK expression.

Lesion studies have shown that the avian hippocampus plays a crucial role in homing pigeon (Columba livia) navigation. Using the expression of the immediate early gene protein ZENK in intact pigeons, the authors found regional variation in hippocampal activation as a consequence of homing and, necessarily, the behavior and internal states that accompany it. Specifically, pigeons that homed displayed a significant increase in the number of ZENK-labeled cells in the lateral hippocampal formation compared with pigeons that did not home, whereas no difference was seen in the medial hippocampus. Significant changes in ZENK expression were also found in the medial striatum, which resembles the mammalian ventral striatum. The results identify portions of the hippocampal formation and the medial striatum as sites of plasticity associated with homing.

Animals↗
PubMed2006

Aging and implementation of encoding strategies in the generation of rhymes: the role of executive functions.

This experiment examines whether the age-related decrease in the generation effect of rhymes is mediated by executive functioning. Young and elderly adults read and generated pairs of rhyming words for subsequent recall. Participants were also administered neuropsychological tests (executive and mnemonic functions). Results showed that elderly adults performed less well on the neuropsychological tests and benefited less than the younger participants from the generation effect. Hierarchical regression analyses revealed that the executive functions composite score was correlated with the generation effect and that it accounted for a large proportion of the age-related variance of the size of this measure. This finding supports the view that the age-related decrement in strategic encoding implementation is due to a decrease of executive functioning.

Adult↗
PubMed2003

Effects of a longitudinal training program on responses to exercise in overweight men.

OBJECTIVE: The aim of this study was to determine how training modifies metabolic responses and lipid oxidation in overweight young male subjects. RESEARCH METHODS AND PROCEDURES: Eleven overweight subjects were selected for a 4-month endurance training program. Before and after the training period, they cycled for 60 minutes at 50% of their VO(2)max after an overnight fast or 3 hours after eating a standardized meal. Various metabolic and endocrine parameters, and respiratory exchange ratio values were evaluated. RESULTS: Exercise-induced plasma norepinephrine concentration increases were similar before and after training in fasted or fed conditions. After food intake, exercise promoted a decrease in plasma glucose and a higher increase in epinephrine than in fasting conditions. The increase in epinephrine after the meal was more marked after training (264 +/- 32 vs. 195 +/- 35 pg/mL). Training lowered the resting plasma nonesterified fatty acids. During exercise, changes in glycerol were similar to those found before training. Lipid oxidation during exercise was higher in fasting than in fed conditions (15.5 +/- 1.4 vs. 22.3 +/- 1.7 g/h). Training did not significantly increase fat oxidation when exercise was performed in fed conditions, but it did in fasting conditions (18.6 +/- 1.4 vs. 27.2 +/- 1.8 g/h). DISCUSSION: Endurance training decreased plasma nonesterified fatty acids, cholesterol, and insulin concentrations. Training increased lipid oxidation during exercise, in fasting conditions, and not when exercise was performed after the meal. During exercise in overweight subjects, the fasting condition seems more suited to oxidizing fat and maintaining glucose homeostasis than a 3-hour wait after a standard meal.

Adult↗