B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity

Neutralizing antibodies have been thought to be required for protection against acutely cytopathic viruses, such as the neurotropic vesicular stomatitis virus (VSV). Utilizing mice that possess B cells but lack antibodies, we show here that survival upon subcutaneous (s.c.) VSV challenge was independent of neutralizing antibody production or cell-mediated adaptive immunity. However, B cells were absolutely required to provide lymphotoxin (LT) α1β2, which maintained a protective subcapsular sinus (SCS) macrophage phenotype within virus draining lymph nodes (LNs). Macrophages within the SCS of B cell-deficient LNs, or of mice that lack LTα1β2 selectively in B cells, displayed an aberrant phenotype, failed to replicate VSV, and therefore did not produce type I interferons, which were required to prevent fatal VSV invasion of intranodal nerves. Thus, although B cells are essential for survival during VSV infection, their contribution involves the provision of innate differentiation and maintenance signals to macrophages, rather than adaptive immune mechanisms.     

Cross-national cognitive assessment in schizophrenia clinical trials: a feasibility study

Clinical trials for the treatment of schizophrenia now often include cognitive assessments in addition to clinical ratings of symptoms. Recently, these trials have included cross-national assessments. It is not clear if translated psychological tests produce consistent results across different languages. This paper presents the results of a study of the comparability of the results of cognitive assessments in different English-speaking countries and a number of countries where tests were translated into other languages. Performance on tests of executive functioning, verbal and visuo-spatial learning and memory, language skills, psychomotor speed, and vigilance was compared across the first episode patients with schizophrenia (n = 301) assessed in six different languages (English, French, Finnish, German, Hebrew, and Afrikaans), including two different countries where patients were assessed in English and other languages: Canada (French) and South Africa (Afrikaans). The variance in performance across the sites tested in English was as large as the variance between English and non-English speakers when all tests were considered. Performance differences across English and other languages were found only for executive functions, vigilance, and psychomotor speed, with executive functioning differences nonsignificant when education was considered. No differences were found between English and non-English speakers in Canada. These results suggest that the translation of tests of memory and verbal skills can lead to consistent results across translated versions of the tests. Differences between countries were greater than differences between languages, suggesting the need to consider representativeness of patient samples in terms of local educational attainment. In general, these data support the validity of cross-national neuropsychological assessments.     

In vitro amoebicidal activity of borage (Borago officinalis) extract on Entamoeba histolytica

Borage (Borago officinalis) is a plant with nutritional value that is also used in traditional medicine to treat gastrointestinal disease. This study investigated the amoebicidal activity of a methanol extract of borage. The 50% inhibitory concentration (IC??) of the extract for Entamoeba histolytica was 33 μg/mL. The 50% lethal dose of the extract for brine shrimp was greater than 1,000?μg/mL. The IC?? of the extract for Vero cells was 203.9?μg/mL. These results support the use of borage to prevent diseases associated with E. histolytica infection.     

Bioactive properties of Tynanthus panurensis (Bureau) Sanwith bark extract, the Amazonian "clavo huasca"

Tynanthus panurensis (Bureau) Sanwith (Bignoniaceae) is a liana vine used in traditional Amazonian medicine as a tonic and energizer as well as a treatment for rheumatism. These traditional indications prompted this study of the antioxidant and anti-inflammatory activities of T. panurensis bark extract (ETP). Phytochemical analysis of ETP showed the presence of saponins and a high concentration of phenols and flavonoids. A battery of in vitro tests revealed that the extract has free radical-scavenging antioxidant properties and reduces microsomal lipid peroxidation, uric acid synthesis, and tumor necrosis factor-α production. The anti-inflammatory properties of ETP were further confirmed in vivo in a rat carrageenan edema model, in which the extract exhibited a potent activity. These results support the idea that T. panurensis bark extract could be beneficial for treating inflammation and are in agreement with one of the main traditional uses of this plant.     

Evaluation of HPβCD-PEG microparticles for salmon calcitonin administration via pulmonary delivery

For therapeutic peptides, the lung represents an attractive, noninvasive route into the bloodstream. To achieve optimal bioavailability and control their fast rate of absorption, peptides can be protected by coprocessing with polymers such as polyethylene glycol (PEG). Here, we formulated and characterized salmon calcitonin (sCT)-loaded microparticles using linear or branched PEG (L-PEG or B-PEG) and hydroxypropyl-beta-cyclodextrin (HPβCD) for pulmonary administration. Mixtures of sCT, L-PEG or B-PEG and HPβCD were co-spray dried. Based on the particle properties, the best PEG:HPβCD ratio was 1:1 w:w for both PEGs. In the sCT-loaded particles, the L-PEG was more crystalline than B-PEG. Thus, L-PEG-based particles had lower surface free energy and better aerodynamic behavior than B-PEG-based particles. However, B-PEG-based particles provided better protection against chemical degradation of sCT. A decrease in sCT permeability, measured across Calu-3 bronchial epithelial monolayers, occurred when the PEG and HPβCD concentrations were both 1.6 wt %. This was attributed to an increase in buffer viscosity, caused by the two excipients. sCT pharmacokinetic profiles in Wistar rats were evaluated using a 2-compartment model after iv injection or lung insufflation. The maximal sCT plasma concentration was reached within 3 min following nebulization of sCT solution. L-PEG and B-PEG-based microparticles were able to increase T(max) to 20 ± 1 min and 18 ± 8 min, respectively. Furthermore, sCT absolute bioavailability after L-PEG-based microparticle aerosolization at 100 μg/kg was 2.3 times greater than for the nebulized sCT solution.     

Development of endocannabinoid-based chemical probes for the study of cannabinoid receptors

We report the synthesis of new chemical probes (1a,b, 2a-c, 3a-c) based on the structure of the main endocannabinoids for their use in biological systems directly or via click chemistry. As proof of concept, 2-arachidonyl glyceryl ether based biotinylated 3b enables direct visualization of CB(1) receptor in cells. These results represent the starting point for the development of advanced small molecule chemical probes able to generate valuable information about the cannabinoid receptors.