Dexamethasone and RU24858 induce survival and growth factor receptor bound protein 2, leukotriene B4 receptor 1 and annexin-1 expression in primary human neutrophils

Glucocorticoids are widely used anti-inflammatory medication in diseases like asthma and chronic obstructive pulmonary disease. Glucocorticoids can either activate (transactivation) or inhibit (transrepression) transcription. RU24858 was introduced as a dissociated glucocorticoid and it has been reported to transrepress but not to transactivate. The aim of this study was to compare the effects of RU24858 and dexamethasone in human neutrophils. RU24858 delayed spontaneous neutrophil apoptosis and further enhanced GM-CSF- induced neutrophil survival to a similar extent as dexamethasone. Like dexamethasone RU24858 also reduced CXCL8 and MIP-1α. Unexpectedly however, RU24858 increased the expression of the glucocorticoid-inducible genes BLT-1, Annexin-1 and Grb-2 in neutrophils to a similar level as seen with dexamethasone. We have shown here that dexamethasone and RU24858 both increase Grb-2, BLT1 and Annexin-1 expression and inhibit CXCL8 and MIP-1α production. This suggests that RU24858 was not able to dissociate between transactivation and transrepression in human neutrophils but enhanced neutrophil survival. © the author(s), publisher and licensee Libertas Academica Ltd

Pyrazine-Fused Triterpenoids Block the TRPA1 Ion Channel in Vitro and Inhibit TRPA1-Mediated Acute Inflammation in Vivo

TRPA1 is a nonselective cation channel, most famously expressed in nonmyelinated nociceptors. In addition to being an important chemical and mechanical pain sensor, TRPA1 has more recently appeared to have a role also in inflammation. Triterpenoids are natural products with anti-inflammatory and anticancer effects in experimental models. In this paper, 13 novel triterpenoids were created by synthetically modifying betulin, an abundant triterpenoid of the genus Betula L., and their TRPA1-modulating properties were examined. The Fluo 3-AM protocol was used in the initial screening, in which six of the 14 tested triterpenoids inhibited TRPA1 in a statistically significant manner. In subsequent whole-cell patch clamp recordings, the two most effective compounds (pyrazine-fused triterpenoids 8 and 9) displayed a reversible and dose- and voltage-dependent effect to block the TRPA1 ion channel at submicromolar concentrations. Interestingly, the TRPA1 blocking action was also evident in vivo, as compounds 8 and 9 both alleviated TRPA1 agonist-induced acute paw inflammation in mice. The results introduce betulin-derived pyrazine-fused triterpenoids as promising novel antagonists of TRPA1 that are potentially useful in treating diseases with a TRPA1-mediated adverse component

Spatial characteristics of species distributions as drivers in conservation prioritization

Peer reviewe

Revisiting the minimum set cover, the maximal coverage problems and a maximum benefit area selection problem to make climate‐change‐concerned conservation plans effective

1. Informed decisions for the selection of protected areas (PAs) are grounded in two general problems in Operations Research: the minimum set covering problem (minCost), where a set of ecological constraints are established as conservation targets and the minimum cost PAs are found, and the maximal coverage problem (maxCoverage) where the constraint is uniquely economic (i.e., a fixed budget) and the goal is to maximize the number of species having conservation targets adequately covered. 2. We adjust minCost and maxCoverage to accommodate the dynamic effects of climate change on species’ ranges. The selection of sites is replaced by the selection of time-ordered sequences of sites (climate change corridors), and an estimate of the persistence of each species in corridors is calculated according to the expected suitability of each site in the respective time period and the capacity of species to disperse between consecutive sites along corridors. In these problems, conservation targets are expressed as desired (and attainable) species persistence levels. We also introduce a novel problem (minShortfall) that combines minCost and maxCoverage. Unlike these two problems, minShortfall allows persistence targets to be missed and minimizes the sum of those gaps (i.e., target shortfalls), subject to a limited budget. 3. We illustrate the three problems with a case study using climatic suitability estimates for ten mammal species in the Iberian Peninsula under a climate change scenario until 2080. We compare solutions of the three problems with respect to species persistence and PA costs, under distinct settings of persistence targets, number of target-fulfilled species, and budgets. The solutions from different problems differed with regard to the areas to prioritize, their timings and the species whose persistence targets were fulfilled. This analysis also allowed identifying groups of species sharing corridors in optimal solutions, thus allowing important financial savings in site protection. 4. We suggest that enhancing species persistence is an adequate approach to cope with habitat shifts due to climate change. We trust the three problems discussed can provide complementary and valuable support for planners to anticipate decisions in order that the negative effects of climate change on species’ persistence are minimized

Response to antipsychotic drugs in treatment-resistant schizophrenia : Conclusions based on systematic review

Peer reviewe

Influence of FADS Polymorphisms on Tracking of Serum Glycerophospholipid Fatty Acid Concentrations and Percentage Composition in Children

Tracking of fatty acid (FA) contribution to plasma or serum lipids over time was shown in children and adults. However, the potential role of FADS gene variants has not been investigated. Serum GP FA composition of 331 children aged 2 and 6 years, participating in an ongoing birth cohort study, was analyzed. Correlation coefficients were estimated to describe FA tracking over 4 years and to assess the influence of FADS variants on tracking. We found low to moderate tracking (r = 0.12-0.49) of FA compositions and concentration between 2 and 6 years. Concentration changes of total monounsaturated FA and total saturated FA over time correlated closely (r = 0.79) but percentage values were unrelated (r = -0.02). Tracking for n-6 long chain polyunsaturated fatty acid (LC-PUFA) concentrations was lower in subjects homozygous for the major allele of FADS variants and higher in carriers of at least one minor allele, whereas for total n-3 LC-PUFA concentrations and compositions this was vice versa. For individual n-3 PUFA inconsistent results were found. Serum GP FA composition shows low to moderate tracking over 4 years with a higher tracking for LC-PUFA metabolites than for their precursor FA. Serum PUFA levels and their tracking seem to be more influenced by lipid and lipoprotein metabolism than by FA specific pathways

Influence of FADS Polymorphisms on Tracking of Serum Glycerophospholipid Fatty Acid Concentrations and Percentage Composition in Children

BACKGROUND: Tracking of fatty acid (FA) contribution to plasma or serum lipids over time was shown in children and adults. However, the potential role of FADS gene variants has not been investigated. METHODS AND PRINCIPAL FINDINGS: Serum GP FA composition of 331 children aged 2 and 6 years, participating in an ongoing birth cohort study, was analyzed. Correlation coefficients were estimated to describe FA tracking over 4 years and to assess the influence of FADS variants on tracking. We found low to moderate tracking (r = 0.12-0.49) of FA compositions and concentration between 2 and 6 years. Concentration changes of total monounsaturated FA and total saturated FA over time correlated closely (r = 0.79) but percentage values were unrelated (r = -0.02). Tracking for n-6 long chain polyunsaturated fatty acid (LC-PUFA) concentrations was lower in subjects homozygous for the major allele of FADS variants and higher in carriers of at least one minor allele, whereas for total n-3 LC-PUFA concentrations and compositions this was vice versa. For individual n-3 PUFA inconsistent results were found. CONCLUSIONS AND SIGNIFICANCE: Serum GP FA composition shows low to moderate tracking over 4 years with a higher tracking for LC-PUFA metabolites than for their precursor FA. Serum PUFA levels and their tracking seem to be more influenced by lipid and lipoprotein metabolism than by FA specific pathways

AUTOEVALUACIÓN DEL PROGRAMA DE MEDICINA VETERINARIA Y ZOOTECNIA CON FINES DE ACREDITACIÓN DE CALIDAD

Las Facultades de Medicina Veterinaria y Zootecnia y Agronomía se crearon en la ciudad de Montería como dependencias de la Universidad Nacional de Colombia según la Ley 103 del Congreso Nacional, de fecha 29 de Diciembre de 1962, pero dicha Ley no tuvo cumplimiento. Ante el anhelo frustrado de no contar con una Universidad seccional, pretendida con la Ley 103, el Gobierno Departamental dictó el Decreto 0319 de 1964 por el cual se le otorgó personería jurídica a la Universidad de Córdoba. En el año 1966 el Congreso de República expidió la Ley 37 por medio de la cual se crea la Universidad de Córdoba como una entidad autónoma y descentralizada que se acogía al Decreto-Ley 0277 de 1958 que regía para las universidades departamentales. Sólo hasta el año de 1970, mediante una sentencia de Estado, se enmienda el error y se le da el carácter nacional a la Institución por haber sido creada mediante Ley de la República

Translation of clinical problems in osteoarthritis into pathophysiological research goals

Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives