Adaptogenic effect of the vitamin D3 containing supplement "videchol" on glucose-6-phosphate dehydrogenase activity in erythrone of irradiated rats

Two fast migrating, major, multiple molecular forms (MMF) of glucose-6-phosphate dehydrogenase [EC:1.1.1.49]: G-6-PDH-1 and G-6-PDH-2, and two minor forms: G-6-PDH-3 and G-6-PDH-4 were revealed in the electrophoregrams of both erythrocytes haemolisates as well in the homogenates of bone marrow cellular lines of rats at control conditions. Daily 1 cGy irradiation of rats up to a cumulative dose of 20 cGy led to a drop of G-6-PDH total activity and it caused a redistribution of the MMF of the enzyme in bone marrow cellular populations. However, G-6-PDH activity in erythrocytes exceeded the control means in all the experimental terms. The calculation of the local redistribution coefficient (l(G-6-FDH-i)) showed that these changes are mainly determined by the increase of the activity of the isoform G-6-PDH-3. Vitamin D3 administration to rats generated a correction of G-6-PDH activity in all studied cellular populations. Meanwhile, the MMF profiles were characterized by multidirectional rearrangements in the bone marrow erythroid and granulocyte-monocyte cells and in erythrocytes. The specificity of changes in the distribution of the MMF of G-6-PDH in the three studied cellular populations depends on the particularities of their energetic metabolism at irradiation conditions and on the modifying action of the natural adaptogen 1,25-dihydroxicholecalciferol.     

Does asymmetric gene flow among matrilines maintain the evolutionary potential of the European eel?

Using evolutionary theory to predict the dynamics of populations is one of the aims of evolutionary conservation. In endangered species, with geographic range extending over continuous areas, the predictive capacity of evolutionary‐based conservation measures greatly depends on the accurate identification of reproductive units. The endangered European eel (Anguilla anguilla) is a highly migratory fish species with declining population due to a steep recruitment collapse in the beginning of the 1980s. Despite punctual observations of genetic structure, the population is viewed as a single panmictic reproductive unit. To understand the possible origin of the detected structure in this species, we used a combination of mitochondrial and nuclear loci to indirectly evaluate the possible existence of cryptic demes. For that, 403 glass eels from three successive cohorts arriving at a single location were screened for phenotypic and genetic diversity, while controlling for possible geographic variation. Over the 3 years of sampling, we consistently identified three major matrilines which we hypothesized to represent demes. Interestingly, not only we found that population genetic models support the existence of those matriline‐driven demes over a completely panmictic mode of reproduction, but also we found evidence for asymmetric gene flow amongst those demes. We uphold the suggestion that the detection of demes related to those matrilines reflect a fragmented spawning ground, a conceptually plausible consequence of the low abundance that the European eel has been experiencing for three decades. Furthermore, we suggest that this cryptic organization may contribute to the maintenance of the adaptive potential of the species.     

IL-4 induces differentiation and expansion of Th2 cytokine-producing eosinophils

Innate effector cells that produce Th2-type cytokines are critical in Th2 cell-mediated immune responses. However, it is not known how these cells acquire the ability to produce Th2 cytokines. IL-4 is a potent inducer that directs differentiation of naive CD4(+) T cells into CD4(+) Th2 effector cells. To determine whether IL-4 can induce differentiation and expansion of Th2 cytokine-producing innate cells, we used mice whose il-4 gene was replaced by a knock-in green fluorescence protein (gfp) gene. We found that, directly ex vivo, IL-4 increased the number of GFP(+) cells in the airway and the lung tissue in an Ag-specific manner. The majority of GFP(+) cells were eosinophils, suggesting that IL-4 plays a pivotal role in expanding IL-4-producing eosinophils in vivo. IL-4-producing eosinophils showed some unique features compared with IL-4-producing CD4(+) T cells. They exhibited biallelic expression of the il-4 gene when stimulated and were more dominant IL-4- and IL-5-producing cells. Furthermore, we show that IL-4 drove bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils in vitro. These results strongly suggest IL-4 is a potent factor in directing bone marrow progenitor cells to differentiate into Th2 cytokine-producing eosinophils.     

A novel conotoxin from Conus delessertii with posttranslationally modified lysine residues

A major peptide, de13a from the crude venom of Conus delessertii collected in the Yucatan Channel, Mexico, was purified. The peptide had a high content of posttranslationally modified amino acids, including 6-bromotryptophan and a nonstandard amino acid that proved to be 5-hydroxylysine. This is the first report of 5-hydroxylysine residues in conotoxins. The sequence analysis, together with cDNA cloning and a mass determination (monoisotopic mass of 3486.76 Da), established that the mature toxin has the sequence DCOTSCOTTCANGWECCKGYOCVNKACSGCTH, where O is 4-hydroxyproline, W 6-bromotryptophan, and K 5-hydroxylysine, the asterisk represents the amidated C-terminus, and the calculated monoisotopic mass is 3487.09 Da. The eight Cys residues are arranged in a pattern (C-C-C-CC-C-C-C) not described previously in conotoxins. This arrangement, for which we propose the designation of framework #13 or XIII, differs from the ones (C-C-CC-CC-C-C and C-C-C-C-CC-C-C) present in other conotoxins which also contain eight Cys residues. This peptide thus defines a novel class of conotoxins, with a new posttranslational modification not previously found in other Conus peptide families.     

Interaction between quinolones antibiotics and bacterial outer membrane porin OmpF

In these work, we try to establish a relation between the hydrophobicity of some quinolones and their interaction with OmpF. In order to do that, the values of the binding constant of some quinolones of different "generations" with OmpF were determined by UV-visible spectrophotometry and by fluorimetry. Our results show that there is a strong interaction between all the drugs and the protein and that it becomes larger for the last "generation" fluoroquinolones. These results were compared with previous ones obtained for the interaction of these drugs with simpler biomembrane models (liposomes) and it is possible to conclude that some of the quinolones associate preferably with the protein than with these models. This suggests that an interaction drug/porin is, probably, the preferentially used for the latest fluoroquinolones what makes reasonable to believe that a strong affinity for OmpF means a better capacity to transpose the barrier formed by the outer membrane.     

Photoprotection mechanisms in European beech (Fagus sylvatica L.) seedlings from diverse climatic origins

This study shows that beech leaves adapt to their light environment by inducing dramatic changes to antioxidant systems and pigment composition. Thus, ascorbate, tocopherol, glutathione, β-carotene and xanthophyll cycle pigments are much more concentrated in sun leaves, while α-carotene is much less concentrated than in shade leaves. These characteristics were used to identify the inherent potential of beech cotyledons from three contrasting climatic origins to tolerate light stress. The antioxidant content was initially different in the three provenances tested, but these initial differences tended to reduce with leaf ageing. The higher antioxidant and de-epoxidized xanthophyll content found in developing cotyledons indicated a superior potential for tolerance to photo-oxidative damage in those plants collected from the stressful climate of the Pyrenees. Nevertheless under an experimental high irradiation treatment no differences in light stress tolerance were observed between provenances. Received: 31 May 1999 / Accepted: 16 November 1999     

Photoprotective Responses to Winter Stress in Evergreen Mediterranean Ecosystems

Abstract: The role of antioxidants and regulation of photosynthesis as photoprotective adaptations of Mediterranean vegetation to winter stress have been studied. These mechanisms are influenced by the degree of environmental stress (studied at different altitudes) and the taxonomic origin of each species. Thus, antioxidant composition was species-dependent, but not apparently affected by altitude; while the reductions in photochemical efficiency, associated with the presence of zeaxanthin and a lower chlorophyll content, were common among species with increasing altitude. Three different strategies to cope with winter stress were observed in Mediterranean evergreens. First, in Buxus sempervirens antioxidant concentration was very high and the photochemical efficiency was much reduced, with a large accumulation of zeaxanthin. Second, in other Mediterranean sclerophylls, reversible reductions of PSII efficiency related to activity of the xanthophyll cycle allowed day to day adaptation of photosynthetic rates. Third, the summer semideciduous Cistus species maintained a high photochemical efficiency and accumulated little antioxidant, and this strategy could be justified by the occurrence two leaf populations with different physiological tolerances to environmental stress.     

Perioperative Care and the Importance of Continuous Quality Improvement—A Controlled Intervention Study in Three Tanzanian Hospitals

IntroductionSurgical services are increasingly seen to reduce death and disability in Sub-Saharan Africa, where hospital-based mortality remains alarmingly high. This study explores two implementation approaches to improve the quality of perioperative care in a Tanzanian hospital. Effects were compared to a control group of two other hospitals in the region without intervention.MethodsAll hospitals conducted quality assessments with a Hospital Performance Assessment Tool. Changes in immediate outcome indicators after one and two years were compared to final outcome indicators such as Anaesthetic Complication Rate and Surgical Case Fatality Rate.ResultsImmediate outcome indicators for Preoperative Care in the intervention hospital improved (52.5% in 2009; 84.2% in 2011, p<0.001). Postoperative Inpatient Care initially improved to then decline again (63.3% in 2009; 70% in 2010; 58.6% in 2011). In the control group, preoperative care declined from 50.8% (2009) to 32.8% (2011, p <0.001), while postoperative care did not significantly change. Anaesthetic Complication Rate in the intervention hospital declined (1.89% before intervention; 0.96% after intervention, p = 0.006). Surgical Case Fatality Rate in the intervention hospital declined from 5.67% before intervention to 2.93% after intervention (p<0.0010). Surgical Case Fatality Rate in the control group was 4% before intervention and 3.8% after intervention (p = 0.411). Anaesthetic Complication Rate in the control group was not available.DiscussionImmediate outcome indicators initially improved, while at the same time final outcome declined (Surgical Case Fatality, Anaesthetic Complication Rate). Compared to the control group, final outcome improved more in the intervention hospital, although the effect was not significant over the whole study period. Documentation of final outcome indicators seemed inconsistent. Immediate outcome indicators seem more helpful to steer the Continuous Quality Improvement program.ConclusionSpecific interventions as part of Continuous Quality Improvement might lead to sustainable improvement of the quality of care, if embedded in a multi-faceted approach.     

An in silico modeling approach to understanding the dynamics of sarcoidosis

Background

Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis.

Methodology/Results

Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNFα, IFNγ) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and “sarcoidosis-like” (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships.

Conclusions/Significance

Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials.