Antisense mqsR-PNA as a putative target to the eradication of Pseudomonas aeruginosa persisters.

Chemotherapy is frequently unsuccessful in fully eradicating bacterial biofilm infections. Persisters are a main cause for the failure of antibiotic therapies and are assumed to significantly impact the increased multidrug tolerance and unsuccessful elimination of chronic biofilm infections. Pseudomonas aeruginosa infections are frequently linked to high rates of drug-tolerant persisters, triggering a major challenge to human health. It is crucial to classify persisters to develop novel useful therapeutic strategies to fight infectious diseases. In this study, the mqsR gene was selected as a novel antimicrobial target, and silencing was with antisense peptide nucleic acid (PNA) assay to eradicate the P. aeruginosa persisters. First, they were analysed by experimental procedures. Functionality was assessed by stress conditions. We found that the expression of mqsR (as the toxin) compared with mqsA (as antitoxin) was increased under stress conditions. We demonstrated that when mqsR was targeted and treated with different concentrations of mqsR-PNA after 24 hours; the formation of P. aeruginosa persisters was eradicated. Antisense mqsR-PNA in concentrations of 35 µM or more could eradicate persister cell formation in P. aeruginosa. It was suggested that other toxin-antitoxin loci in P. aeruginosa are examined by antisense PNA to detect their functionality. However, considering the importance of persisters in human infections, ex vivo, in vivo, preclinical and clinical settings should be highlighted.

[Cannabinoids for symptomatic therapy of multiple sclerosis]. / Cannabinoide zur symptomatischen Therapie der Multiplen Sklerose.

Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany. The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS.

[4-Aminopyridine (Fampridine). A new attempt for the symptomatic treatment of multiple sclerosis]. / 4-Aminopyridin (Fampridin). Ein neuer Ansatz zur symptomatischen Therapie der Multiplen Sklerose.

Mobility limitation is a frequent clinical symptom of multiple sclerosis (MS) that poses a therapeutic challenge. For years results of animal experiments and clinical experience have indicated that the potassium channel blocker 4-aminopyridine improves axonal excitatory circuits and thus muscular strength in demyelinating diseases. A recently conducted randomized, placebo-controlled, multicenter phase 3 clinical trial in MS patients was able to show that an oral sustained-release formulation of 4-aminopyridine (Fampridine-SR) represents a suitable agent for treatment of walking disability in MS patients.This overview presents the study data and discusses the value of 4-aminopyridine for the symptomatic treatment of MS as a neurofunctional modifier of this disabling disease.