Impact of Immunosuppressive Drugs on Fibroblasts:: An In Vitro Study

Background: The aim of this study was to compare the direct impact of different agents for immunosuppressive therapy on mouse fibroblasts as a possible cause of drug-induced gingival overgrowth (DIGO). Methods: 3T3 mouse fibroblasts were cultivated in cell-specific media (2 × 104 cells/mL) and treated for 6, 24, 48 and 72 h with one of three immunosuppressive drugs (IsDs): cyclosporin a (CsA), tacrolimus (TaC) and sirolimus (SiR). Different concentrations (10–750 ng/mL) were used to mimic serum levels under active immunosuppressive therapy conditions. Cell population characteristics (cell number, viability and morphology) were assessed using computer-assisted cell analysis. Expression of pro-collagen type I carboxy-terminal propeptide (PICP) was identified using an ELISA assay. Results: The influence of IsDs on the biological status of 3T3 fibroblasts was time- and dose-dependent. Comparing CsA and TaC, the total cell amount was enhanced using concentrations in the range of 10–150 ng/mL (p > 0.05). In contrast, treatment with SiR resulted in a decrease in the average cell number (p 0.05). Conclusions: Our results revealed time-dependent effects of IsDs, with distinct influences on cell number. The cell morphology and the PICP balance of the investigated fibroblast cell line remained unaffected. Hence, the potential role of IsDs is not a unilateral mechanism of action but rather a multifactorial process

Observation of e+e−→π+π−π0χbJe^+e^- \to \pi^+ \pi^- \pi^0 \chi_{bJ} and search for Xb→ωΥ(1S)X_b \to \omega \Upsilon(1S) at s∼10.867\sqrt{s}\sim 10.867 GeV

The $e^+e^- \to \pi^+ \pi^- \pi^0 \chi_{bJ}$ ($J=0,~1,~2$) processes are studied using a 118~fb$^{-1}$ data sample collected at a center-of-mass energy of 10.867 GeV, in the $\Upsilon(10860)$ energy range, with the Belle detector. The $\pi^+ \pi^- \pi^0 \chi_{b1}$, $\pi^+\pi^-\pi^0\chi_{b2}$, $\omega\chi_{b1}$ signals and the evidence of $\omega\chi_{b2}$ are observed for the first time and the cross sections are measured. No significant $\pi^+\pi^-\pi^0\chi_{b0}$ or $\omega\chi_{b0}$ signal is observed and 90\% confidence level upper limits on the cross sections for these two processes are obtained. In the $\pi^+\pi^-\pi^0$ invariant mass spectrum, significant non-$\omega$ signals are also observed. We search for the $X(3872)$-like state with a hidden $b\bar{b}$ component (named $X_b$) decaying into $\omega \Upsilon(1S)$; no significant signal is observed with a mass between $10.55$ and $10.65$ GeV/$c^2$.Comment: 7 pages, 3 figures, accepted for publication as a Letter in Physical Review Letter

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement.

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking