A critical role for microglia in maintaining vascular integrity in the hypoxic spinal cord.

Hypoxic preconditioning reduces disease severity in a mouse model of multiple sclerosis (MS), in part by enhancing the barrier properties of spinal cord blood vessels. Because other studies have shown that similar levels of hypoxia transiently increase permeability of central nervous system (CNS) blood vessels, the goal of this study was to define the impact of chronic mild hypoxia (CMH, 8% O2) on the integrity of spinal cord blood vessels and the responses of neighboring glial cells. Using extravascular fibrinogen as a marker of vascular disruption, we found that CMH triggered transient vascular leak in spinal cord blood vessels, particularly in white matter, which was associated with clustering and activation of Mac-1-positive microglia around disrupted vessels. Microglial depletion with the colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX5622, while having no effect under normoxic conditions, profoundly increased vascular leak in both white and gray matter during CMH, and this was associated with disruption of astrocyte-vascular coupling and enhanced loss of tight junction proteins. Microglial repair of leaky blood vessels was blocked by a peptide that inhibits the interaction between fibrinogen and its Mac-1 integrin receptor. These findings highlight an important role for microglia in maintaining vascular integrity in the hypoxic spinal cord and suggest that a fibrinogen-Mac-1 interaction underpins this response. As relative hypoxia is experienced in many situations including high altitude, lung disease, obstructive sleep apnea, and age-related CNS ischemia/hypoxia, our findings have important implications regarding the critical role of microglia in maintaining vascular integrity in the CNS.

An Electrophilic Natural Product Provides a Safe and Robust Odor Neutralization Approach To Counteract Malodorous Organosulfur Metabolites Encountered in Skunk Spray.

The anal secretions of skunks comprise several types of malodorous organosulfur compounds. The pungent metabolites are used defensively by skunks to repel threats posed by predators, and in many parts of the world, those perceived threats include humans and their pets. The extremely low thresholds for detection of the organosulfur metabolites make efforts to "de-skunk" people, animals, and clothing a process fraught with many challenges. The fungal-derived metabolite pericosine A (4) is a promiscuous yet stabile electrophilic compound that we propose is used by some fungi as a novel form of chemical defense. Our investigations have indicated that pericosine A readily reacts with skunk-spray secretions to transform them into odorless products. Mechanistic and computational studies suggested that pericosine A and its synthetic analogues react via SN2'-type mechanisms with thiols and thioacetates under aqueous conditions to generate stable thioethers. Testing revealed that pericosine A did not cause skin or eye irritation and was highly effective at deodorizing skunk anal gland secretions when formulated to include adjunctive cosmetic ingredients.

Recent progress of sample stacking in capillary electrophoresis (2014-2016).

The term "sample stacking" comprises a relatively broad spectrum of techniques that already form an almost inherent part of the methodology of CZE. Their principles are different but the effect is the same: concentration of a diluted analyte into a narrow zone and considerable increase of the method sensitivity. This review brings a survey of papers on electrophoretic sample stacking published approximately since the second quarter of 2014 till the first quarter of 2016. It is organized according to the principles of the stacking methods and includes chapters aimed at the concentration adjustment principle (Kohlrausch stacking), techniques based on pH changes, micellar methods, and other stacking techniques. Not reviewed are papers on transient ITP that are covered by another review in this issue.

Tratamento de compostos orgânicos odoríferos tóxicos por biorreatores / Treatment of odorous toxic organic compounds by bioreactor

Introdução É importante o desenvolvimento de sistemas de controle de poluição do ar que sejam eficientes, além de aplicáveis à condição nacional e pra proteção da saúde humana, uma vez que os compostos do grupo BTEX são tóxicos. Objetivo - Avaliar o desempenho de sistema de tratamento biológico para vapores de BTEX e investigar as melhores condições de operação para os critérios de projeto adotados. Métodos. Trata-se de trabalho experimental com utilização de unidade piloto constituída de coluna de vidro (diâmetro interno de 80 mm e altura total de 1,2 m) tendo no seu interior um meio filtrante composto vegetal e anéis de Pall - que serviram de suporte para os microrganismos e onde se realizou a biodegradação. Foram monitorados parâmetros como temperatura, perda de carga, vazão, concentração dos gases na entrada e na saída, que constituíram a base para desenvolver intervenções e melhorar seu desempenho. A análise dos gases foi feita por fotoionização (PID) em aparelho portátil. Conclusões - Conclui-se que é viável o tratamento biológico para remoção do BTEX de efluentes gasosos, nas condições operacionais adotadas, com eficiência máxima de remoção em torno de 90 por cento . A máxima eficiência foi obtida para tempo de retenção de 2,4 min., carga superficial do gás de 11,9 m3/m2xh, carga mássica no leito de 67 g/m3xh e capacidade de eliminação de 4 g/m3xh. O uso de anéis de Pall misturados ao composto evitou que valores elevados de perda de carga. Foi relevante a participação da adsorção. A utilização de composto mostrou-se viável como alternativa para a biodegradação do BTEX, fortalecendo seu uso com essa prática ambiental.

Oxidative damage of biomolecules in mouse liver induced by morphine and protected by antioxidants.

This study investigates the oxidative damage of biomolecules in livers of mice treated with morphine intraperitoneally. The oxidative damage of DNA as measured by single cell electrophoresis and high-performance liquid chromatography equipped with electrochemical and UV detection, the protein carbonyl content was measured by 2,4-dinitrophenylhydrazine method, and the malondialdehyde content was measured by the HPLC method. The activities of antioxidative enzymes, superoxide dismutase, catalase and glutathione peroxidase, and the activity of alanine aminotransferase were assayed by spectrophotometer method. Glutathione and oxidized glutathione were detected by fluorescence spectrophotometer method. All the indexes of oxidative damage, such as 8-OHdG, protein carbonyl group and malondialdehyde content, and the activity of alanine aminotransferase (n=27) increased significantly compared to those of control (n=27) (P<0.01) in livers of morphine-administered alone mice, while the indexes related with the in vivo antioxidative capacity, such as the ratio of glutathione and oxidized glutathione, activities of superoxide dismutase, catalase and glutathione peroxidase significantly decreased (P<0.01). When mice were treated with morphine combined with exogenous antioxidants, glutathione and ascorbic acid, all the indexes of oxidative damage and the activity of alanine aminotransferase showed no changes as compared to those of control (P>0.05), i.e., both glutathione and ascorbic acid completely abolished the damage of morphine on the hepatocyte. These results implied that morphine caused a seriously oxidative stress in mice livers and hence caused hepatotoxicity, while exogenous antioxidants were able to prevent the oxidative damage of biomolecules and hepatotoxicity caused by morphine. Thus, blocking oxidative damage may be a useful strategy for the development of a new therapy for opiate abuse.

Adsorbent materials commonly used in air analysis for adsorptive enrichment and thermal desorption of volatile organic compounds.

A review is given dealing with commonly used adsorbent materials in ambient air analysis of volatile organic compounds (VOCs). The adsorbents covered in the paper are selected in consideration of their compatibility with thermal desorption. Initially, we discuss the requirements that an adsorbent should fulfill, and useful parameters for the selection and evaluation of an appropriate material. Then, the most important materials are presented considering their properties, advantages, and drawbacks. A few applications are given, but a complete review of sampling techniques and applications dealing with adsorptive enrichment and thermal desorption is beyond the scope of this paper.