Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease

Toll-like receptors (TLRs) are involved in pathogen recognition by the innate immune system. Different TLRs and the adaptor molecule myeloid differentiation factor 88 (MyD88) were previously shown to mediate in vitro cell activation induced by group B streptococcus (GBS). The present study examined the potential in vivo roles of TLR2 and MyD88 during infection with GBS. When pups were infected locally with a low bacterial dose, none of the TLR2- or MyD88-deficient mice, but all of the wild-type ones, were able to prevent systemic spread of GBS from the initial focus. Bacterial burden was higher in MyD88- than in TLR2-deficient mice, indicating a more profound defect of host defense in the former animals. In contrast, a high bacterial dose induced high level bacteremia in both mutant and wild-type mice. Under these conditions, however, TLR2 or MyD88 deficiency significantly protected mice from lethality, concomitantly with decreased circulating levels of TNF-alpha and IL-6. Administration of anti-TNF-alpha Abs to wild-type mice could mimic the effects of TLR2 or MyD88 deficiency and was detrimental in the low dose model, but protective in the high dose model. In conclusion, these data highlight a dual role of TLR2 and MyD88 in the host defense against GBS sepsis and strongly suggest TNF-alpha as the molecular mediator of bacterial clearance and septic shock.     

Bacterium-bacterium inhibitory interactions among psychrotrophic bacteria isolated from Antarctic seawater (Terra Nova Bay, Ross Sea)

One hundred and forty bacteria isolated from Antarctic seawater samples were examined for their ability to inhibit the growth of indigenous isolates and their sensitivity to antibacterial activity expressed by one another. On the basis of 16S rRNA gene sequencing and analysis, bacterial isolates were assigned to five phylogenetically different taxa, Actinobacteria, alpha and gamma subclasses of Proteobacteria, Bacillaceae, and Bacteroidetes. Twenty-one isolates (15%), predominantly Actinobacteria, exhibited antagonistic properties against marine bacteria of Antarctic origin. Members of Bacteroidetes and Firmicutes did not show any inhibitory activity. Differences were observed among inhibition patterns of single isolates, suggesting that their activity was more likely strain-specific rather than dependent on phylogenetic affiliation. A novel analysis based on network theory confirmed these results, showing that the structure of this population is probably robust to perturbations, but also that it depends strongly on the most active strains. The determination of plasmid incidence in the bacterial strains investigated revealed that there was no correlation between their presence and the antagonistic activity. The data presented here provide evidence for the antagonistic interactions within bacterial strains inhabiting Antarctic seawater and suggest the potential exploitation of Antarctic bacteria as a novel source of antibiotics.     

Extracts of black and brown rice powders improve hepatic lipid accumulation via the activation of PPARα in obese and diabetic model mice

Rice powder extract (RPE) from black and brown rice (Oryza sativa L. indica) improves hepatic lipid accumulation in obese and diabetic model mice via peroxisomal fatty acid oxidation. RPE showed PPARα agonistic activity which did not differ between black and brown RPE despite a higher anthocyanin content in black RPE.     

Integrating mental health into primary care in Sverdlovsk

Introduction Mental disorders occur as frequently in Russia as elsewhere, but the common mental disorders, especially depression, have gone largely unrecognised and undiagnosed by policlinic staff and area doctors.Methods This paper describes the impact and sustainability of a multi-component programme to facilitate the integration of mental health into primary care, by situation appraisal, policy dialogue, development of educational materials, provision of a training programme and the publication of standards and good practice guidelines to improve the primary care of mental disorders in the Sverdlovsk region of the Russian Federation.Results The multi-component programme has resulted in sustainable training about common mental disorders, not only of family doctors but also of other cadres and levels of professionals, and it has been well integrated with Sverdlovsk's overall programme of health sector reforms.Conclusion It is possible to facilitate the sustainable integration of mental health into primary care within the Russian context. While careful adaptation will be needed, the approach adopted here may also hold useful lessons for policy makers seeking to integrate mental health within primary care in other contexts and settings.     

Nonisothermal bioreactors in the treatment of vegetation waters from olive oil: laccase versus syringic acid as bioremediation model

Laccase from Trametes versicolor was immobilized by diazotization on a nylon membrane grafted with glycidil methacrylate, using phenylenediamine as spacer and coupling agent. The behavior of these enzyme derivatives was studied under isothermal and nonisothermal conditions by using syringic acid as substrate, in view of the employment of these membranes in processes of detoxification of vegetation waters from olive oil mills. The pH and temperature dependence of catalytic activity under isothermal conditions has shown that these membranes can be usefully employed under extreme pH and temperatures. When employed under nonisothermal conditions, the membranes exhibited an increase of catalytic activity linearly proportional to the applied transmembrane temperature difference. Percentage activity increases ranging from 62% to 18% were found in the range of syringic acid concentration from 0.02 to 0.8 mM, when a difference of 1 degrees C was applied across the catalytic membrane. Because the percentage activity increase is strictly related to the reduction of the production times, the technology of nonisothermal bioreactors has been demonstrated to be an useful tool also in the treatment of vegetation waters from olive oil mills.     

An aminomethylpyrimidine DPP-IV inhibitor with improved properties

A recently identified DPP-IV inhibitor (1) was found to induce phospholipidosis and to inhibit CYP3A4. A small series of less lipophilic and less amphiphilic analogues was synthesized in an effort to overcome these issues. One compound from this series was equipotent to 1, did not induce phospholipidosis and showed a reduced CYP3A4 inhibition.