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Potential Interactions (potential + interaction)
Selected AbstractsPharmacoepidemiologic study of potential drug interactions in outpatients of a university hospital in ThailandJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2005B. Janchawee PhD Summary Background:, Drug,drug interaction is a potential cause of adverse drug reactions. The incidence of such drug interactions in university hospitals in Thailand is unknown. Purpose:, To estimate the rate of potential drug,drug interactions in outpatients of a typical Thai university hospital, and to identify risk factors for such interactions in Thai patients. Methods:, One-year outpatients' prescription data were retrieved from the hospital computer records. Potential drug interactions were identified using the existing drug-interaction database system. Potential interactions within a specific prescription and involving drugs prescribed 1-, 3- and 7-day earlier were searched for. Possible associations between occurrence of an interaction and a patient's age and gender and the number of items on the prescription were explored. Results:, The overall rate of potential drug interactions was 27·9% with a maximal value of 57·8% at the Department of Psychiatry. The rate of the most potentially significant interactions was 2·6%, being the highest in the Department of Medicine (6·0%), with isoniazid vs. rifampin as the most common interacting combination. The rate increased with the patient's age and prescription size (P = 0·000). The odd's ratio of having at least one potential drug interaction was 1·8 (64·2%) when age increased by 20 years (P = 0·000) and 2·8 (165·7%) when another drug was added (P = 0·000). The rate of potential drug interactions was the same for both genders. The rate of potential drug interactions detected across prescriptions was higher than within prescriptions and was dependent on the time interval between prescriptions. Conclusions:, Potential drug interactions were common in our sample of patients. The rate of such interactions increased with the number of drugs prescribed and the patient's age. [source] The role of guidelines in quality improvement for cancer surgeryJOURNAL OF SURGICAL ONCOLOGY, Issue 8 2009FRCPC, George P. Browman MD Abstract In February 2008, Cancer Surgery Alberta hosted a conference on surgical outcomes and quality. The objective here is to review the interactions between quality/outcomes and guidelines, highlighting surgeons' roles. Potential interactions between quality measurement and guidelines are discussed. We analyzed data from practitioner surveys about guidelines to determine surgeons' participation compared with other specialists. The response rate of surgeons in both community-based and academic practices to guideline development surveys was equivalent to other cancer disciplines. J. Surg. Oncol. 2009;99:467,469. © 2009 Wiley-Liss, Inc. [source] A role for ethylene in the phytochrome-mediated control of vegetative developmentTHE PLANT JOURNAL, Issue 6 2006Eloise Foo Summary Members of the phytochrome family of photoreceptors play key roles in vegetative plant development, including the regulation of stem elongation, leaf development and chlorophyll accumulation. Hormones have been implicated in the control of these processes in de-etiolating seedlings. However, the mechanisms by which the phytochromes regulate vegetative development in more mature plants are less well understood. Pea (Pisum sativum) mutant plants lacking phytochromes A and B, the two phytochromes present in this species, develop severe defects later in development, including short, thick, distorted internodes and reduced leaf expansion, chlorophyll content and CAB gene transcript level. Studies presented here indicate that many of these defects in phyA phyB mutant plants appear to be due to elevated ethylene production, and suggest that an important role of the phytochromes in pea is to restrict ethylene production to a level that does not inhibit vegetative growth. Mutant phyA phyB plants produce significantly more ethylene than WT plants, and application of an ethylene biosynthesis inhibitor rescued many aspects of the phyA phyB mutant phenotype. This deregulation of ethylene production in phy-deficient plants appears likely to be due, at least in part, to the elevated transcript levels of key ethylene-biosynthesis genes. The phytochrome A photoreceptor appears to play a prominent role in the regulation of ethylene production, as phyA, but not phyB, single-mutant plants also exhibit a phenotype consistent with elevated ethylene production. Potential interactions between ethylene and secondary plant hormones in the control of the phy-deficient mutant phenotype were explored, revealing that ethylene may inhibit stem elongation in part by reducing gibberellin levels. [source] Hydrocolloid Coating of Xenopus laevis EmbryosBIOTECHNOLOGY PROGRESS, Issue 3 2000N. Kampf A novel technology for coating single cells and embryos with thin hydrocolloid (water-soluble polymer) films has been invented and patented. Coating is different from entrapment and immobilization in that the coating around the cell is thinner, comprising only a small fraction of the cell or embryo's diameter. Xenopus laevis embryos were coated with thin films of low-methoxy pectin (LMP), alginate, and ,- and ,-carrageenans. These gums have different compositions and structures and as such created different coatings around the fertilized cells. All coated embryos appeared to develop normally, similar to noncoated embryos. Elemental detection by ICP-AES spectroscopy revealed that the embryo can control the diffusion of excess ions to which it is exposed during the coating process. The coatings delayed hatching by 18,24 h. Consequently, at hatch the embryos were at a more developed stage than their noncoated counterparts. The hydrocolloid coating reduced the thickness of the natural jelly coating (JC). With the ,-carrageenan coating, percent hatch was maximal, while with LMP it was minimal, as a result of the films' mechanical properties and thicknesses. LMP and alginate created smoother coatings than the carrageenans. Potential interactions between the coating and the natural JC are hypothesized. Overall, coatings appear to be a suitable tool for laboratories interested in performing longer-term experiments with embryos. [source] Consumer Control of Salt Marshes Driven by Human DisturbanceCONSERVATION BIOLOGY, Issue 3 2008MARK D. BERTNESS control de consumidor; impactos humanos; conservación de pantano de sal; cascadas de trophic Abstract:,Salt marsh ecosystems are widely considered to be controlled exclusively by bottom,up forces, but there is mounting evidence that human disturbances are triggering consumer control in western Atlantic salt marshes, often with catastrophic consequences. In other marine ecosystems, human disturbances routinely dampen (e.g., coral reefs, sea grass beds) and strengthen (e.g., kelps) consumer control, but current marsh theory predicts little potential interaction between humans and marsh consumers. Thus, human modification of top,down control in salt marshes was not anticipated and was even discounted in current marsh theory, despite loud warnings about the potential for cascading human impacts from work in other marine ecosystems. In spite of recent experiments that have challenged established marsh dogma and demonstrated consumer-driven die-off of salt marsh ecosystems, government agencies and nongovernmental organizations continue to manage marsh die-offs under the old theoretical framework and only consider bottom,up forces as causal agents. This intellectual dependency of many coastal ecologists and managers on system-specific theory (i.e., marsh bottom,up theory) has the potential to have grave repercussions for coastal ecosystem management and conservation in the face of increasing human threats. We stress that marine vascular plant communities (salt marshes, sea grass beds, mangroves) are likely more vulnerable to runaway grazing and consumer-driven collapse than is currently recognized by theory, particularly in low-diversity ecosystems like Atlantic salt marshes. Resumen:,Se ha considerado extensamente que los ecosistemas de marismas son controlados exclusivamente por dinámicas abajo-arriba, pero se ha acumulado evidencia de que las perturbaciones humanas están provocando el control por consumidores en marismas del Atlántico occidental, a menudo con consecuencias catastróficas. En otros ecosistemas marinos, las perturbaciones humanas rutinariamente disminuyen (e.g., arrecifes de coral, pastos marinos) y refuerzan (e.g., varec) el control por consumidores, pero la teoría de marismas actual predice una leve interacción potencial entre humanos y consumidores en las marismas. Por lo tanto, las modificaciones humanas al control arriba-abajo en las marismas no estaba anticipada y aun era descontada en la teoría de marismas actual, a pesar de advertencias sobre el potencial de impactos humanos en cascada en trabajos en otros ecosistemas marinos. No obstante los experimentos recientes que han desafiado el dogma de marismas establecido y que han demostrado la desaparición gradual de marismas conducida por consumidores, las agencias gubernamentales y las organizaciones no gubernamentales continúan manejando la disminución de marismas en el marco de la teoría vieja y sólo consideran como agentes causales a factores abajo-arriba. Esta dependencia intelectual en la teoría sistema-específico (i.e., teoría de marismas abajo-arriba) de muchos ecólogos y manejadores costeros tiene el potencial de tener repercusiones graves para el manejo y conservación de ecosistemas costeros frente a las crecientes amenazas humanas. Enfatizamos que las comunidades plantas vasculares marinas (marismas, pastos marinos, manglares) son potencialmente más vulnerables al pastoreo descontrolado y al colapso conducido por consumidores que lo que reconoce la teoría actualmente, particularmente en ecosistemas con baja diversidad como las marismas del Atlántico. [source] Characterization of interaction between doxycycline and human serum albumin by capillary electrophoresis-frontal analysisELECTROPHORESIS, Issue 11 2009Hanwen Sun Abstract The binding of doxycycline to HSA under simulated physiological conditions (pH 7.4, 67,mM phosphate, I=0.17, drug concentration 100,,M, HSA concentration up to 475,,M, 36.5°C) was studied by CE-frontal analysis. The number of primary binding sites, binding constant and physiological protein-binding percentage were 1.9, 1.51×103,M,1 and 59.80%, respectively. In addition, the thermodynamic parameters including enthalpy change (,H), entropy change (,S) and free energy change (,G) of the reaction were obtained in order to characterize the acting forces between doxycycline and HSA. Furthermore, to better understand the nature of doxycycline,HSA binding and to get information about potential interaction with other drugs, displacement experiments were performed. The results showed that doxycycline binds at site II of HSA. [source] Caveolin-1 influences P2X7 receptor expression and localization in mouse lung alveolar epithelial cellsFEBS JOURNAL, Issue 12 2007K. Barth The P2X7 receptor has recently been described as a marker for lung alveolar epithelial type I cells. Here, we demonstrate both the expression of P2X7 protein and its partition into lipid rafts in the mouse lung alveolar epithelial cell line E10. A significant degree of colocalization was observed between P2X7 and the raft marker protein Caveolin-1; also, P2X7 protein was associated with caveolae. A marked reduction in P2X7 immunoreactivity was observed in lung sections prepared from Caveolin-1-knockout mice, indicating that Caveolin-1 expression was required for full expression of P2X7 protein. Indeed, suppression of Caveolin-1 protein expression in E10 cells using short hairpin RNAs resulted in a large reduction in P2X7 protein expression. Our data demonstrate a potential interaction between P2X7 protein and Caveolin-1 in lipid rafts, and provide a basis for further functional and biochemical studies to probe the physiologic significance of this interaction. [source] Carriage of a tumor necrosis factor polymorphism amplifies the cytotoxic T-lymphocyte antigen 4 attributed risk of primary biliary cirrhosis: Evidence for a gene,gene interaction,HEPATOLOGY, Issue 1 2010Brian D. Juran Common genetic variants significantly influence complex diseases such as primary biliary cirrhosis (PBC). We recently reported an association between PBC and a single nucleotide polymorphism (rs231725) of the immunoreceptor gene cytotoxic T-lymphocyte antigen 4 (CTLA4). We hypothesized that PBC risk attributed to this polymorphism might be increased by propensity to an overly robust inflammatory response. Thus, we examined its potential interaction with the commonly studied ,308AG promoter polymorphism (rs1800629) of the tumor necrosis factor (TNF) gene for which the variant TNF2A allele causes increased TNF production. The polymorphisms were genotyped in 866 PBC patients and 761 controls from independent US and Canadian registries; the effects of individual single nucleotide polymorphisms (SNPs) and their interaction on PBC risk was assessed by logistic regression. The reported association of PBC with the CTLA4 "A/A" genotype was replicated in the Canadian cohort and significant for PBC risk in the combined data (odds ratio [OR], 1.68; P = 0.0005). TNF2A allele frequency was elevated in PBC patients, but only reached borderline significance using the combined data (OR, 1.21; P = 0.042). Analysis showed that TNF2A carriage was significantly increased in CTLA4 "A/A" PBC patients compared with CTLA4 "A/A" controls (39.7% versus 16.5%, P = 0.0004); no apparent increase of TNF2A carriage was noted in CTLA4 "A/G" or "G/G" individuals. Finally, interaction under a logistic model was highly significant, as TNF2A carriage in combination with the CTLA4 "A/A" genotype was present in 6.5% of PBC patients, compared with 1.7% of controls (OR, 3.98; P < 0.0001). Conclusion: TNF2A amplifies the CTLA4 rs231725 "A/A" genotype risk for PBC. Although the mechanisms remain unclear, the premise that deficiency in T-cell regulation resulting in an increased risk of PBC is amplified by overexpression of an important proinflammatory cytokine provides a basis for future functional studies. HEPATOLOGY 2010 [source] The Appropriateness of Drug Use in an Older Nondemented and Demented PopulationJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2001Maria Stella T. Giron MD OBJECTIVE: To assess the extent of inappropriateness of drug use in an older nondemented and demented population. DESIGN: Descriptive analysis based on data from a sample of older subjects age 81 years and older. Data were collected from the second follow-up conducted in 1994,1996. SETTING: A population-based study of the Kungsholmen project in Stockholm, Sweden. PARTICIPANTS: Drug information was obtained from 681 subjects with a mean age of 86.9 years. The subjects were predominantly women (78%). Thirteen percent resided in institutions and 27.6% were diagnosed with dementia. MEASUREMENTS: Dementia diagnosis based on DSM III-R. Criteria for inappropriateness of drug use: use of drugs with potent anticholinergic properties, drug duplication, potential drug-drug and drug-disease interactions, and inappropriate drug dosage. RESULTS: The mean number of drugs used was 4.6: 4.5 drugs for nondemented and 4.8 for demented subjects. Nondemented subjects more commonly used cardiovascular-system drugs and demented subjects used nervous-system drugs. Demented subjects were more commonly exposed to drug duplication and to drugs with potent anticholinergic properties, both involving the use of psychotropic drugs. Nondemented subjects were more commonly exposed to potential drug-disease interactions, mostly with the use of cardiovascular drugs. The most common drug combination leading to a potential interaction was the use of digoxin with furosemide, occurring more frequently among nondemented subjects. The most common drug-disease interaction was the use of beta-blockers and calcium antagonists in subjects with congestive heart failure. The doses of drugs taken by both nondemented and demented subjects were mostly lower than the defined daily dose. CONCLUSION: There was substantial exposure to presumptive inappropriateness of drug use in this very old nondemented and demented population. The exposure of demented subjects to psychotropic drugs and nondemented subjects to cardiovascular drugs reflect the high frequency of prescribing these drugs in this population. [source] Mapping the evolutionary twilight zone: molecular markers, populations and geographyJOURNAL OF BIOGEOGRAPHY, Issue 5 2008José Alexandre Felizola Diniz-Filho Abstract Since evolutionary processes, such as dispersal, adaptation and drift, occur in a geographical context, at multiple hierarchical levels, biogeography provides a central and important unifying framework for understanding the patterns of distribution of life on Earth. However, the advent of molecular markers has allowed a clearer evaluation of the relationships between microevolutionary processes and patterns of genetic divergence among populations in geographical space, triggering the rapid development of many research programmes. Here we provide an overview of the interpretation of patterns of genetic diversity in geographical and ecological space, using both implicit and explicit spatial approaches. We discuss the actual or potential interaction of phylogeography, molecular ecology, ecological genetics, geographical genetics, landscape genetics and conservation genetics with biogeography, identifying their respective roles and their ability to deal with ecological and evolutionary processes at different levels of the biological hierarchy. We also discuss how each of these research programmes can improve strategies for biodiversity conservation. A unification of these research programmes is needed to better achieve their goals, and to do this it is important to develop cross-disciplinary communication and collaborations among geneticists, ecologists, biogeographers and spatial statisticians. [source] Exogenous PTH and Endogenous 1,25-Dihydroxyvitamin D Are Complementary in Inducing an Anabolic Effect on Bone,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2008Rana Samadfam Abstract PTH and 1,25(OH)2D each exert dual anabolic and catabolic skeletal effects. We assessed the potential interaction of PTH and 1,25(OH)2D in promoting skeletal anabolism by comparing the capacity of exogenous, intermittently injected PTH(1-34) to produce bone accrual in mice homozygous for the 1,(OH)ase-null allele [1,(OH)ase,/, mice] and in wildtype mice. In initial studies, 3-mo-old wildtype mice were either injected once daily (40 ,g/kg) or infused continuously (120 ,g/kg/d) with PTH(1,34) for up to 1 mo. Infused PTH reduced BMD, increased the bone resorption marker TRACP-5b, and raised serum calcium but did not increase serum 1,25(OH)2D. Injected PTH increased serum 1,25(OH)2D and BMD, raised the bone formation marker osteocalcin more than did infused PTH, and did not produce sustained hypercalcemia as did PTH infusion. In subsequent studies, 3-mo-old 1,(OH)ase,/, mice, raised on a rescue diet, and wildtype littermates were injected with PTH(1,34) (40 ,g/kg) either once daily or three times daily for 1 mo. In 1,(OH)ase,/, mice, baseline bone volume (BV/TV) and bone formation (BFR/BS) were lower than in wildtype mice. PTH administered intermittently increased BV/TV and BFR/BS in a dose-dependent manner, but the increases were always less than in wildtype mice. These studies show that exogenous PTH administered continuously resorbs bone without raising endogenous 1,25(OH)2D. Intermittently administered PTH can increase bone accrual in the absence of 1,25(OH)2D, but 1,25(OH)2D complements this PTH action. An increase in endogenous 1,25(OH)2D may therefore facilitate an optimal skeletal anabolic response to PTH and may be relevant to the development of improved therapeutics for enhancing skeletal anabolism. [source] Src is a major signaling component for CTGF induction by TGF-,1 in osteoblasts,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010X. Zhang Connective tissue growth factor (CTGF/CCN2) is induced by transforming growth factor ,1 (TGF-,1) where it acts as a downstream mediator of TGF-,1 induced matrix production in osteoblasts. We have shown the requirement of Src, Erk, and Smad signaling for CTGF induction by TGF-,1 in osteoblasts; however, the potential interaction among these signaling pathways remains undetermined. In this study we demonstrate that TGF-,1 activates Src kinase in ROS17/2.8 cells and that treatment with the Src family kinase inhibitor PP2 prevents Src activation and CTGF induction by TGF-,1. Additionally, inhibiting Src activation prevented Erk activation, Smads 2 and 3 activation and nuclear translocation by TGF-,1, demonstrating that Src is an essential upstream signaling partner of both Erk and Smads in osteoblasts. MAPKs such as Erk can modulate the Smad pathway directly by mediating the phosphorylation of Smads or indirectly through activation/inactivation of required nuclear co-activators that mediate Smad DNA binding. When we treated cells with the Erk inhibitor, PD98059, it inhibited TGF-,1-induced CTGF protein expression but had no effect on Src activation, Smad activation or Smad nuclear translocation. However PD98059 impaired transcriptional complex formation on the Smad binding element (SBE) of the CTGF promoter, demonstrating that Erk activation was required for SBE transactivation. These data demonstrate that Src is an essential upstream signaling transducer of Erk and Smad signaling with respect to TGF-,1 in osteoblasts and that Smads and Erk function independently but are both essential for forming a transcriptionally active complex on the CTGF promoter in osteoblasts. J. Cell. Physiol. 224: 691,701, 2010. © 2010 Wiley-Liss, Inc. [source] Advances in the management of irritable bowel syndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2002John E Kellow Abstract Recent advances in different aspects of irritable bowel syndrome have led to a need to reassess the overall management of this common, complex disorder. Important areas include: first, the heterogeneity of symptom patterns and the role of specific diagnostic symptom criteria for use in both clinical practice and in clinical research; second, the growing interest in the potential interaction between ,peripheral' and ,central' pathophysiological mechanisms; and third, the development of novel and effective drugs designed to target specific receptor systems in the enteric nervous system. This review covers each of these aspects and emphasizes an approach to management of patients based on pathophysiological considerations. © 2002 Blackwell Publishing Asia Pty Ltd [source] Grapefruit juice,drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cellsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Whocely Victor de Castro Abstract To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, bergamottin, 6,,7,-dihydroxybergamottin, 6,,7,-epoxybergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6,,7,-epoxybergamottin, was the most potent inhibitor (IC50,=,0.7 µM), followed by 6,,7,-dihydroxybergamottin (IC50,=,34 µM) and bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808,2817, 2007 [source] Body mass index, chronic atrophic gastritis and heartburn: a population-based study among 8936 older adults from GermanyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010L. Gao Aliment Pharmacol Ther 2010; 32: 296,302 Summary Background, Obesity and overweight have been positively related to gastro-oesophageal reflux disease (GERD). It has been suggested that this relationship is as a consequence of an increased gastric acid reflux, which is caused by an enhanced intra-abdominal pressure. Aim, To assess potential interaction of the association between body mass index (BMI) and GERD by chronic atrophic gastritis, which goes along with decreased acid production. Methods, In the baseline examination of ESTHER, a study conducted in 9953 older adults in Saarland, information on frequency of heartburn, potential risk factors and medical history was obtained by self-administered standardized questionnaire. Serological measurements of pepsinogen I and II were taken for definition of chronic atrophic gastritis. Results, In total, 2565 (28.7%) of the included subjects experienced heartburn within the previous 4 weeks. A pronounced dose-response relationship was observed between BMI and heartburn occurrence (P < 0.001) among people without chronic atrophic gastritis, but not among people with chronic atrophic gastritis (P -value for interaction = 0.018). Obese/overweight people with chronic atrophic gastritis had a much lower risk of heartburn compared with obese/overweight people without chronic atrophic gastritis (OR = 0.31, 95% CI = 0.24,0.40). Conclusion, Our results are consistent with the hypothesis that BMI is related positively to GERD symptoms by its impact on acid reflux. [source] Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants on eczema riskALLERGY, Issue 7 2010J. M. Mahachie John To cite this article: Mahachie John JM, Baurecht H, Rodríguez E, Naumann A, Wagenpfeil S, Klopp N, Mempel M, Novak N, Bieber T, Wichmann H-E, Ring J, Illig T, Cattaert T, Van Steen K, Weidinger S. Analysis of the high affinity IgE receptor genes reveals epistatic effects of FCER1A variants eczema risk. Allergy 2010; 65: 875,882. Abstract Background:, High levels of total and allergen-specific IgE levels are a key feature in allergic diseases. The high-affinity receptor for IgE, which is composed of one alpha (FCER1A), one beta (FCER1B), and two gamma (FCER1G) subunits, represents the central receptor of IgE-induced reactions. In a genome-wide association scan, we recently identified associations between functional FCER1A variants and total serum IgE levels. Previous studies had reported linkage and association of FCER1B variants with IgE and atopic traits. The FCER1G gene has not yet been investigated with regard to atopy. Filaggrin (FLG) is the strongest known risk gene for eczema, in particular the allergic subtype of eczema. Methods:, We investigated the association of FCER1A, FCER1B, and FCER1G variants with IgE in a large population-based cohort (n = 4261) and tested for epistatic effects using the model-based multifactor dimensionality reduction (MB-MDR) method. In addition, we investigated a potential interaction between FLG and FCER1A variants in a large collection of eczema cases (n = 1018) and population controls. Results:, Three strongly correlated FCER1A polymorphisms were significantly associated with total and specific IgE levels as well as allergic sensitization. No associations were seen for FCER1B and FCER1G. After adjustment for FLG effects, a significant epistatic effect of the FCER1A variants rs10489854 and rs2511211 on eczema risk was detected. Conclusions:, These results suggest that FCER1A variants by themselves and in combination influence IgE levels and act synergistically to influence eczema risk. [source] Consideration of magnetically-induced and conservative electric fields within a loaded gradient coilMAGNETIC RESONANCE IN MEDICINE, Issue 6 2006Weihua Mao Abstract We present a method to calculate the electric (E)-fields within and surrounding a human body in a gradient coil, including E-fields induced by the changing magnetic fields and "conservative" E-fields originating with the scalar electrical potential in the coil windings. In agreement with previous numerical calculations, it is shown that magnetically-induced E-fields within the human body show no real concentration near the surface of the body, where nerve stimulation most often occurs. Both the magnetically-induced and conservative E-fields are shown to be considerably stronger just outside the human body than inside it, and under some circumstances the conservative E-fields just outside the body can be much larger than the magnetically-induced E-fields there. The order of gradient winding and the presence of conductive RF shield can greatly affect the conservative E-field distribution in these cases. Though the E-fields against the outer surface of the body are not commonly considered, understanding gradient E-fields may be important for reasons other than peripheral nerve stimulation (PNS), such as potential interaction with electrical equipment. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] A Mediterranean diet rich in virgin olive oil may reverse the effects of the -174G/C IL6 gene variant on 3-year body weight changeMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue S1 2010Cristina Razquin Abstract Only a few studies have analyzed the effects of the potential interaction between the -174G/C polymorphism of IL6 gene and the adherence to the Mediterranean diet (MD) on adiposity indexes. Our aim was to investigate the interplay between the -174G/C polymorphism of the IL6 gene and a Mediterranean-style diet on body weight changes after 3 years of nutritional intervention in a high cardiovascular risk population. A total of 737 participants, aged 55,80 years were assigned to a low-fat diet or to a Mediterranean-style diet group with high intake of virgin olive oil (VOO) or nuts. Anthropometric measurements were taken at baseline and after 3-year follow-up. The -174G/C polymorphism of the IL6 gene was genotyped. Minor allele frequency (C) was 0.39. At baseline, the CC genotype was associated with higher measures of adiposity. After 3 years, a significant interaction (p=0.028) was found between the polymorphism (GG+GC versus CC) and the nutritional intervention: CC subjects following the MD+VOO had the lowest body weight gain. In conclusion, at baseline, CC subjects for the -174G/C polymorphism of IL6 had the highest body weight and BMI. However, after 3 years of nutritional intervention with MD+VOO, these subjects were predicted to have the greatest reduction in body weight. [source] Selenium nutrition of hybrid striped bass (Morone chrysops × M. saxatilis) bioavailability, toxicity and interaction with vitamin EAQUACULTURE NUTRITION, Issue 2 2009F. JARAMILLO JR Abstract Two concurrent 12-week feeding trials were conducted to evaluate the bioavailability of inorganic sodium selenite and organic seleno-DL-methionine and to investigate the potential interaction between selenium and vitamin E in juvenile hybrid striped bass. In experiment 1, purified diets utilizing casein, gelatin and an amino acid premix as protein sources with a basal selenium concentration of 0.11 mg Se kg,1 were supplemented with either Na2SeO3 to provide selenium concentrations of 1.19, 2.00, 5.17 and 21.23 mg Se kg,1 or with seleno-DL-methionine to provide 0.90, 1.26 and 2.55 mg Se kg,1 and fed to juvenile hybrid striped bass in aquaria. A second experiment evaluated potential interactions by feeding these purified diets with or without supplemental vitamin E or sodium selenite, singularly or in combination. No overt selenium deficiency signs were exhibited by fish in either of the experiments; however, signs of selenium toxicity including retarded weight gain (WG), reduced feed intake and feed efficiency ratio (FER) as well as increased mortality, were observed in fish fed the diet containing more than 20 mg Se kg,1. Whole-body selenium and whole-body selenium retention were linearly influenced by sodium selenite and selenomethionine. However, there was no significant effect of dietary selenium, vitamin E or their interaction on WG, FER and survival. Slope-ratio analysis showed that bioavailability of seleno-DL-methionine as a selenium source for juvenile hybrid striped bass was significantly (P < 0.01) higher (3.3-fold) than sodium selenite. [source] Interaction of dexloxiglumide, a cholecystokinin type-1 receptor antagonist, with human cytochromes P450BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2004Michael Hall Abstract Dexloxiglumide (DEX) is a cholecystokinin type-1 receptor antagonist under development for the treatment of constipation-predominant irritable bowel syndrome. Studies of the potential interaction of DEX with human cytochromes P450 (CYPs) were conducted in vitro. DEX (300µM), both with and without a 15-min pre-incubation, was incubated with pooled human liver microsomes and substrates selective for each of eight CYPs. This resulted in >30% inhibition of tolbutamide 4-methyl-hydroxylase (CYP2C9/10) and lauric acid 11-hydroxylase (CYP2E1) activities. Mean Ki (SD) for CYP2C9/10 and CYP2E1 were 69.0 (24.3) and 426 (60)µM, respectively. Incubations of [14C]DEX with pooled human liver microsomes produced one major phase I metabolic fraction, with Vmax=131 pmol/min/mg protein and Km=23.7µM. Further incubations with (i) liver microsomes from 16 individual donors (correlation analysis), (ii) SupersomesÔ and (iii) selective chemical inhibitors, implicated CYP3A4/5, CYP2B6 and CYP2C9 in the formation of this component. Thus, DEX interacts with CYP2C9 both as inhibitor (Ki=69.0µM) and as substrate in vitro. However, based on the maximum concentration (27µM) after repeated oral doses of 200mg t.i.d. and the unbound fraction (0.03) of DEX in human plasma, no clinically relevant metabolic interactions with other CYP substrates are predicted. Copyright © 2004 John Wiley & Sons, Ltd. [source] Local environmental influences on uveal melanomaCANCER, Issue 8 2008Vitreous humor promotes uveal melanoma invasion, whereas the aqueous can be inhibitory Abstract BACKGROUND Uveal melanomas of the choroid and ciliary body are aggressive tumors causing the death of approximately 50% of patients. In contrast, iris melanomas only infrequently metastasize; why these differences exist is not known. The local environment can regulate cancer growth and development, and it is probable the aqueous and vitreous humors have an important role in regulating uveal melanoma behavior. METHODS To explore this possibility cultures of uveal melanoma were exposed to aqueous and vitreous and the effects investigated using invasion and proliferation assays. ChemiArrays (Chemicon International, Temecula, Calif) were performed to determine which regulatory factors might influence the process. RESULTS The vitreous universally promoted uveal melanoma invasion, whereas the aqueous mainly had no effect or was inhibitory. Tumor location, and the baseline invasion of the melanoma, affected the ability of aqueous and vitreous from different patients to regulate invasive behavior. Proliferation was not significantly altered as a result of exposure to the aqueous or vitreous. The ability of the humors to regulate uveal melanomas may involve TIMP-2, TIMP-3, and TGF-,2, as high expression was found by ChemiArray analysis and there were differences in the levels of the regulators in the aqueous compared with the vitreous. CONCLUSIONS The findings suggest that in situ uveal melanoma development reflects an interaction between the tumor and the environment of the eye. Exposure to the aqueous would therefore contribute to the benign nature of iris melanomas, whereas potential interaction with the vitreous appears to promote the aggressive behavior of posterior uveal melanomas. Cancer 2008. © 2008 American Cancer Society. [source] Use of poly(vinyl alcohol)-coated capillaries for separation of amino-terminated polyamidoamine dendrimersELECTROPHORESIS, Issue 3 2007Britton Carter Abstract Characterization of amino-terminated polyamidoamine dendrimers by CE suffers from a lack of resolution for higher generations and poor between-day reproducibility of retention times. Under optimal conditions of temperature, voltage, and sample amount, 0,5,generations of dendrimers could be resolved with a bare fused-silica capillary. However, reproducibility was poor due to potential interactions of the polycationic dendrimers with the uncoated quartz capillary wall. Use of a poly(vinyl alcohol)-coated capillary significantly decreased the migration times of the nanomolecules without compromising resolution. Dendrimer mixtures containing generations,0,5 are separated as discrete, nonoverlapping peaks in about 15,min. In addition, the between-day precision of retention times was dramatically improved without the need for internal standards or data normalization. Dendrimers of various generations and cores run on different days showed an RSD of retention times of less than 4%. The poly(vinyl alcohol) coating was very stable as shown by the excellent precision of migration times obtained on a capillary used for a month with more than 100,injections. Similar to PAGE, separation of polyamidoamine dendrimers on a bare fused-silica and poly(vinyl alcohol)-coated capillary showed an exponential relationship between migration times and calculated charge density of the nanomolecules. [source] Dose-dependent Induction of Cytochrome P450 (CYP) 3A4 and Activation of Pregnane X Receptor by TopiramateEPILEPSIA, Issue 12 2003Srikanth C. Nallani Summary:,Purpose: In clinical studies, topiramate (TPM) was shown to cause a dose-dependent increase in the clearance of ethinyl estradiol. We hypothesized that this interaction results from induction of hepatic cytochrome P450 (CYP) 3A4 by TPM. Accordingly, we investigated whether TPM induces CYP3A4 in primary human hepatocytes and activates the human pregnane X receptor (hPXR), a nuclear receptor that serves as a regulator of CYP3A4 transcription. Methods: Human hepatocytes were treated for 72 h with TPM (10, 25, 50, 100, 250, and 500 ,M) and known inducers, phenobarbital (PB; 2 mM), and rifampicin (10 ,M). The rate of testosterone 6,-hydroxylation by hepatocytes served as a marker for CYP3A4 activity. The CYP3A4-specific protein and mRNA levels were determined by using Western and Northern blot analyses, respectively. The hPXR activation was assessed with cell-based reporter gene assay. Results: Compared with controls, TPM (50,500 ,M),treated hepatocytes exhibited a considerable increase in the CYP3A4 activity (1. 6- to 8.2-fold), protein levels (4.6- to 17.3-fold), and mRNA levels (1.9- to 13.3-fold). Comparatively, rifampicin (10 ,M) effected 14.5-, 25.3-, and a 20.3-fold increase in CYP3A4 activity, immunoreactive protein levels, and mRNA levels, respectively. TPM (50,500 ,M) caused 1.3- to 3-fold activation of the hPXR, whereas rifampicin (10 ,M) caused a 6-fold activation. Conclusions: The observed induction of CYP3A4 by TPM, especially at the higher concentrations, provides a potential mechanistic explanation of the reported increase in the ethinyl estradiol clearance by TPM. It also is suggestive of other potential interactions when high-dose TPM therapy is used. [source] What shields some can shackle others: the approach-related consequences of threat categorisations vary by agreeablenessEUROPEAN JOURNAL OF PERSONALITY, Issue 7 2005Michael D. Robinson It is common to think that threat categorisation tendencies (TCTs) should undermine a person's subjective well-being. However, recent research has suggested that the hedonic impact of such tendencies varies considerably according to a person's traits. The present research seeks to extend such a perspective by considering potential interactions between TCTs and the trait of agreeableness. TCTs were measured through the use of choice reaction time tasks contrasting the threat and non-threat categories. As expected, TCTs were not correlated with the trait of agreeableness, but interacted with this trait in predicting the dependent measures. Within three studies involving 184 undergraduates, TCTs were associated with the higher levels of approach-related behaviour and positive emotion among disagreeable individuals, but lower levels of these same variables among agreeable individuals. The authors suggest that threat categorisation tendencies psychologically protect or burden the individual, depending on the levels of agreeableness. Copyright © 2005 John Wiley & Sons, Ltd. [source] SEXUAL SELECTION AND INTERACTING PHENOTYPES IN EXPERIMENTAL EVOLUTION: A STUDY OF DROSOPHILA PSEUDOOBSCURA MATING BEHAVIOREVOLUTION, Issue 7 2008Leonardo D. Bacigalupe Sexual selection requires social interactions, particularly between the sexes. When trait expression is influenced by social interactions, such traits are called interacting phenotypes and only recently have the evolutionary consequences of interacting phenotypes been considered. Here we investigated how variation in relative fitness, or the opportunity for sexual selection, affected the evolutionary trajectories of interacting phenotypes. We used experimentally evolved populations of the naturally promiscuous Drosophila pseudoobscura, in which the numbers of potential interactions between the sexes, and therefore relative fitness, were manipulated by altering natural levels of female promiscuity. We considered two different mating interactions between the sexes: mating speed and copulation duration. We investigated the evolutionary trajectories of means and (co)variances (P) and also the influence of genetic drift on the evolutionary response of these interactions. Our sexual selection treatments did not affect the means of either mating speed or copulation duration, but they did affect P. We found that the means of both traits differed among replicates within each selection treatment whereas the Ps did not. Changes as a consequence of genetic drift were excluded. Our results show that although variable potential strengths of sexual interactions influence the evolution of interacting phenotypes, the influence may be nonlinear. [source] Interannual spatial variability of krill (Euphausia superba) influences seabird foraging behavior near Elephant Island, AntarcticaFISHERIES OCEANOGRAPHY, Issue 1 2009JARROD A. SANTORA Abstract We investigate the influence of krill (principally Euphausia superba) patchiness on the foraging distributions of seabirds to understand how variation in krill influences patch dynamics between krill and birds. At sea-surveys were conducted near Elephant Island, Antarctica, for 3 yr (2004,2006) during the annual U.S. Antarctic Marine Living Resources (AMLR) program. Standardized strip-transect surveys were used to map seabirds, and a combination of acoustic and net surveys was used to map krill. We measured patch size of krill and seabirds and elucidated how krill patch dynamics influence foraging seabirds. The spatial association between krill and predators was influenced by the size and arrangement of krill patches. We found a negative relationship between abundance and patchiness of krill and predators, indicating that when krill is less abundant, its predators are less abundant and concentrated. We conclude that annual patch dynamics of krill strongly influences the local abundance and distribution of seabirds. Such information should be used to interpret potential interactions between seabirds and krill fisheries operating near Elephant Island. [source] Effects of ultraviolet radiation on litter decomposition depend on precipitation and litter chemistry in a shortgrass steppe ecosystemGLOBAL CHANGE BIOLOGY, Issue 10 2007LESLIE A. BRANDT Abstract We examined the effect of altered levels of ultraviolet (UV) radiation (280,400 nm) and different amounts of precipitation on the decomposition rates of litter of contrasting carbon to nitrogen ratio (C : N) in a 3-year field experiment in a shortgrass steppe (SGS) ecosystem. UV radiation was either blocked or passed under clear plastic tents where precipitation was applied to simulate a very dry or very wet year. These treatments minimized or maximized the abiotic component (UV) or the biotic component (biological activity of decomposer organisms) of decomposition to assess potential interactions between the two. Initial litter chemistry varied in response to having been grown under ambient or elevated atmospheric CO2 concentrations. While precipitation and litter chemistry were the most important drivers in decomposition in this system, UV radiation increased decomposition rates under dry conditions in litter with higher C : N ratios. Exposure to UV radiation slightly increased the amount of holocellulose that was lost from the litter. UV exposure did not affect the decomposition of the lignin fraction. Increased decomposition with UV radiation was accompanied by a decrease in N immobilization over the summer months. These results suggest that the effects of UV radiation on decomposition rates may be primarily abiotic, caused by direct photochemical degradation of the litter. Our results demonstrate that the role of UV radiation in litter decomposition in semiarid systems depends on the aridity of the system and the chemistry of the litter. [source] Trends and methodological impacts in soil CO2 efflux partitioning: A metaanalytical reviewGLOBAL CHANGE BIOLOGY, Issue 6 2006JENS-ARNE SUBKE Abstract Partitioning soil carbon dioxide (CO2) efflux (RS) into autotrophic (RA; including plant roots and closely associated organisms) and heterotrophic (RH) components has received considerable attention, as differential responses of these components to environmental change have profound implications for the soil and ecosystem C balance. The increasing number of partitioning studies allows a more detailed analysis of experimental constraints than was previously possible. We present results of an exhaustive literature search of partitioning studies and analyse global trends in flux partitioning between biomes and ecosystem types by means of a metaanalysis. Across all data, an overall decline in the RH/RS ratio for increasing annual RS fluxes emerged. For forest ecosystems, boreal coniferous sites showed significantly higher (P<0.05) RH/RS ratios than temperate sites, while both temperate or tropical deciduous forests did not differ in ratios from any of the other forest types. While chronosequence studies report consistent declines in the RH/RS ratio with age, no difference could be detected for different age groups in the global data set. Different methodologies showed generally good agreement if the range of RS under which they had been measured was considered, with the exception of studies estimating RH by means of root mass regressions against RS, which resulted in consistently lower RH/RS estimates out of all methods included. Additionally, the time step over which fluxes were partitioned did not affect RH/RS ratios consistently. To put results into context, we review the most common techniques and point out the likely sources of errors associated with them. In order to improve soil CO2 efflux partitioning in future experiments, we include methodological recommendations, and also highlight the potential interactions between soil components that may be overlooked as a consequence of the partitioning process itself. [source] Synergistic effects associated with climate change and the development of rocky shore molluscsGLOBAL CHANGE BIOLOGY, Issue 3 2005R. Przeslawski Abstract Global climate change and ozone layer thinning will simultaneously expose organisms to increasingly stressful conditions. Early life stages of marine organisms, particularly eggs and larvae, are considered most vulnerable to environmental extremes. Here, we exposed encapsulated embryos of three common rocky shore gastropods to simultaneous combinations of ecologically realistic levels of ultraviolet radiation (UVR), water temperature stress and salinity stress to identify potential interactions and associated impacts of climate change. We detected synergistic effects with increases in mortality and retardation in development associated with the most physiologically stressful conditions. The effects of UVR were particularly marked, with mortality increasing up to 12-fold under stressful conditions. Importantly, the complex outcomes observed on applying multiple stressors could not have been predicted from examining environmental variables in isolation. Hence, we are probably dramatically underestimating the ecological impacts of climate change by failing to consider the complex interplay of combinations of environmental variables with organisms. [source] Synergistic premalignant effects of chronic ethanol exposure and insulin receptor substrate-1 overexpression in liverHEPATOLOGY RESEARCH, Issue 9 2008Lisa Longato Aim:, Insulin receptor substrate, type 1 (IRS-1) transmits growth and survival signals, and is overexpressed in more than 90% of hepatocellular carcinomas (HCCs). However, experimental overexpression of IRS-1 in the liver was found not to be sufficient to cause HCC. Since chronic alcohol abuse is a risk factor for HCC, we evaluated potential interactions between IRS-1 overexpression and chronic ethanol exposure by assessing premalignant alterations in gene expression. Methods:, Wild-type (wt) or IRS-1 transgenic (Tg) mice, constitutively overexpressing the human (h) transgene in the liver, were pair-fed isocaloric liquid diets containing 0% or 24% ethanol for 8 weeks. The livers were used for histopathologic study and gene expression analysis, focusing on insulin, insulin-like growth factor (IGF) and wingless (WNT),Frizzled (FZD) pathways, given their known roles in HCC. Results:, In wt mice, chronic ethanol exposure caused hepatocellular microsteatosis with focal chronic inflammation, reduced expression of proliferating cell nuclear antigen (PCNA) and increased expression of IGF-I and IGF-I receptor. In hIRS-1 Tg mice, chronic ethanol exposure caused hepatic micro- and macrosteatosis, focal chronic inflammation, apoptosis and disordered lobular architecture. These effects of ethanol in hIRS-1 Tg mice were associated with significantly increased expression of IGF-II, insulin, IRS-4, aspartyl,asparaginyl , hydroxylase (AAH), WNT-1 and FZD 7, as occurs in HCC. Conclusion:, In otherwise normal liver, chronic ethanol exposure mainly causes liver injury and inflammation with impaired DNA synthesis. In contrast, in the context of hIRS-1 overexpression, chronic ethanol exposure may serve as a cofactor in the pathogenesis of HCC by promoting expression of growth factors, receptors and signaling molecules known to be associated with hepatocellular transformation. [source] | |||||||||||||||||||||||||||||||||||||