Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Concentration of lactoferrin and immunoglobulin G in cows milk in relation to health status of the udder, lactation and season

The aim of this study was to analyze an effect of udder health status, somatic cell count (SCC), stage and number of lactations, and different seasons on the concentration of lactoferrin (LF) and immunoglobulin G (IgG) in quarter milk samples (n=120) from crossbreed (Lithuanian Black-and-White & Holstein) dairy cows. Quarter health status was based on SCC and microbiological analysis. The highest mean value of LF and IgG were observed in quarters with subclinical mastitis 0.1 ± 0.02 mg/ml and 0.41 ± 0.06 mg/ml, respectively. Grouping the data according to SCC revealed increased LF (0.07 ± 0.01 mg/ml as against 0.06 ± 0.01 mg/ml) and IgG values (0.27 ± 0.05 mg/ml as against 0.23 ± 0.02 mg/ml) in DQ (SCC from 201,000 ≥ 401,000 cells/ml) compared to HQ (SCC up to 200,000 cells/ml). The milk LF and IgG levels were effected by stage of lactation (p0.05) had no effect on these immunity components

Effects of long-term construction noise on health of adult female Wistar rats

The aim of this study was to investigate the influence of long-term building construction noise from refurbishment, which including vibration, on some physiological parameters and histopathological changes of organs of Wistar rats. Twenty 12 month old female rats were divided into two groups: rats group I (n = 10) were exposed to long-term construction noise and rats group II (n = 10) were kept under normal noise level. Study results revealed that long-term construction noise from building refurbishment has an influence on body weight, haematological and some serum biochemical parameters affects caecal microbiota, and causes histopathological changes in the organs of adult female Wistar rats. It was noticed that rats in group I exihibited significantly higher mean values for total protein, albumin and lower values for glucose, AST, ALT, blood urea nitrogen, haematological and caecal microbiota parameters than rats in group II. The most common pathologies were determined in the kidney, liver and lungs. Other observed pathologies were lymphadenopathy, catarrhal inflammation of the intestines, spleen hyperplasia and mammary gland adenofibroma. Single cases were subcutaneous fibroma in the thoracic region, abortus with uterine inflammation and thymus hyperplasia with formation of cysts were found