Transient receptor potential ankyrin 1 channel expression on peripheral blood leukocytes from rheumatoid arthritic patients and correlation with pain and disability

Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H(2)O(2)) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14(+) cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14(+) cells. We suggest that the activation levels of CD14(+) cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function

Cuminaldehyde potentiates the antimicrobial actions of ciprofloxacin against Staphylococcus aureus and Escherichia coli.

Escherichia coli and Staphylococcus aureus are important agents of urinary tract infections that can often evolve to severe infections. The rise of antibiotic-resistant strains has driven the search for novel therapies to replace the use or act as adjuvants of antibiotics. In this context, plant-derived compounds have been widely investigated. Cuminaldehyde is suggested as the major antimicrobial compound of the cumin seed essential oil. However, this effect is not fully understood. Herein, we investigated the in silico and in vitro activities of cuminaldehyde, as well as its ability to potentiate ciprofloxacin effects against S. aureus and E. coli. In silico analyses were performed by using different computational tools. The PASS online and SwissADME programmes were used for the prediction of biological activities and oral bioavailability of cuminaldehyde. For analysis of the possible toxic effects and the theoretical pharmacokinetic parameters of the compound, the Osiris, SwissADME and PROTOX programmes were used. Estimations of cuminaldehyde gastrointestinal absorption, blood brain barrier permeability and skin permeation by using SwissADME; and drug likeness and score by using Osiris, were also evaluated The in vitro antimicrobial effects of cuminaldehyde were determined by using microdilution, biofilm formation and time-kill assays. In silico analysis indicated that cuminaldehyde may act as an antimicrobial and as a membrane permeability enhancer. It was suggested to be highly absorbable by the gastrointestinal tract and likely to cross the blood brain barrier. Also, irritative and harmful effects were predicted for cuminaldehyde if swallowed at its LD50. Good oral bioavailability and drug score were also found for this compound. Cuminaldehyde presented antimicrobial and anti-biofilm effects against S. aureus and E. coli.. When co-incubated with ciprofloxacin, it enhanced the antibiotic antimicrobial and anti-biofilm actions. We suggest that cuminaldehyde may be useful as an adjuvant therapy to ciprofloxacin in S. aureus and E. coli-induced infections

The Brazilian Global Atmospheric Model (BAM): Performance for Tropical Rainfall Forecasting and Sensitivity to Convective Scheme and Horizontal Resolution

Abstract This article describes the main features of the Brazilian Global Atmospheric Model (BAM), analyses of its performance for tropical rainfall forecasting, and its sensitivity to convective scheme and horizontal resolution. BAM is the new global atmospheric model of the Center for Weather Forecasting and Climate Research [Centro de Previsão de Tempo e Estudos Climáticos (CPTEC)], which includes a new dynamical core and state-of-the-art parameterization schemes. BAM’s dynamical core incorporates a monotonic two-time-level semi-Lagrangian scheme, which is carried out completely on the model grid for the tridimensional transport of moisture, microphysical prognostic variables, and tracers. The performance of the quantitative precipitation forecasts (QPFs) from two convective schemes, the Grell–Dévényi (GD) scheme and its modified version (GDM), and two different horizontal resolutions are evaluated against the daily TRMM Multisatellite Precipitation Analysis over different tropical regions. Three main results are 1) the QPF skill was improved substantially with GDM in comparison to GD; 2) the increase in the horizontal resolution without any ad hoc tuning improves the variance of precipitation over continents with complex orography, such as Africa and South America, whereas over oceans there are no significant differences; and 3) the systematic errors (dry or wet biases) remain virtually unchanged for 5-day forecasts. Despite improvements in the tropical precipitation forecasts, especially over southeastern Brazil, dry biases over the Amazon and La Plata remain in BAM. Improving the precipitation forecasts over these regions remains a challenge for the future development of the model to be used not only for numerical weather prediction over South America but also for global climate simulations