Prednisolone Targets Claudins in Mouse Brain Blood Vessels

Endothelial cells in brain capillaries are crucial for the function of the blood–brain barrier (BBB), and members of the tight junction protein family of claudins are regarded to be primarily responsible for barrier properties. Thus, the analysis of bioactive substances that can affect the BBB’s permeability is of great importance and may be useful for the development of new therapeutic strategies for brain pathologies. In our study, we tested the hypothesis that the application of the glucocorticoid prednisolone affects the murine blood–brain barrier in vivo. Isolated brain tissue of control and prednisolone-injected mice was examined by employing immunoblotting and confocal laser scanning immunofluorescence microscopy, and the physiological and behavioral effects were analyzed. The control tissue samples revealed the expression of barrier-forming tight junction proteins claudin-1, -3, and -5 and of the paracellular cation and water-channel-forming protein claudin-2. Prednisolone administration for 7 days at doses of 70 mg/kg caused physiological and behavioral effects and downregulated claudin-1 and -3 and the channel-forming claudin-2 without altering their localization in cerebral blood vessels. Changes in the expression of these claudins might have effects on the ionic and acid–base balance in brain tissue, suggesting the relevance of our findings for therapeutic options in disorders such as cerebral edema and psychiatric failure

The Use of Mesenchymal Stem Cells in the Complex Treatment of Kidney Tuberculosis (Experimental Study)

In recent years, the application of mesenchymal stem cells (MSCs) has been recognized as a promising method for treatment of different diseases associated with inflammation and sclerosis, which include nephrotuberculosis. The aim of our study is to investigate the effectiveness of MSCs in the complex therapy of experimental rabbit kidney tuberculosis and to evaluate the effect of cell therapy on the reparative processes. Methods: To simulate kidney tuberculosis, a suspension of the standard strain Mycobacterium tuberculosis H37Rv (106 CFU) was used, which was injected into the cortical layer of the lower pole parenchyma of the left kidney under ultrasound control in rabbits. Anti-tuberculosis therapy (aTBT) was started on the 18th day after infection. MSCs (5 × 107 cells) were transplanted intravenously after the start of aTBT. Results: 2.5 months after infection, all animals showed renal failure. Conducted aTBT significantly reduced the level of albumin, ceruloplasmin, elastase and the severity of disorders in the proteinase/inhibitor system and increased the productive nature of inflammation. A month after MSC transplantation, the level of inflammatory reaction activity proteins decreased, the area of specific and destructive inflammation in kidneys decreased and the formation of mature connective tissue was noted, which indicates the reparative reaction activation

Culture-Independent Survey of Thermophilic Microbial Communities of the North Caucasus

The Greater Caucasus is a part of seismically active Alpine–Himalayan orogenic belt and has been a center of significant volcanic activity during the Quaternary period. That led to the formation of the number of hydrothermal habitats, including subterranean thermal aquifers and surface hot springs. However, there are only a limited number of scientific works reporting on the microbial communities of these habitats. Moreover, all these reports concern only studies of specific microbial taxa, carried out using classical cultivation approaches. In this work, we present first culture-independent study of hydrotherms in the Republic of North Ossetia-Alania, located in the southern part of the North Caucasus. Using 16S metabarcoding, we analyzed the composition of the microbial communities of two subterranean thermal aquifers and terrestrial hot springs of the Karmadon valley. Analysis of correlations between the chemical composition of water and the representation of key taxa allowed us to identify the key factors determining the formation of microbial communities. In addition, we were able to identify a significant number of highly abundant deep phylogenetic lineages. Our study represents a first glance on the thermophilic microbial communities of the North Caucasus and may serve as a basis for further microbiological studies of the extreme habitats of this region

Climate Change and the Rise and Fall of the Oxus Civilization in Southern Central Asia

International audienc

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. Methods: The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6–118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. Results: A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. Conclusion: This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment

HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences