Risk and predictors of sudden death in cardiac sarcoidosis: A systematic review and meta-analysis.

Background: To evaluate the risk for ventricular arrhythmia (VA) and sudden cardiac death (SCD) in patients with cardiac sarcoidosis (CS) and determine the prognostic factors.

Methods And Results: PUBMED, EMBASE and SCOPUS were searched up to 14th April 2020. Studies reporting the incidence of SCD, appropriate ICD therapy in CS patients, or relevant prognostic information in patients having undergone MRI, PET, or programmed electrical stimulation (PES) were included.

Stemistry: the control of stem cells in situ using chemistry.

A new paradigm for drug research has emerged, namely the deliberate search for molecules able to selectively affect the proliferation, differentiation, and migration of adult stem cells within the tissues in which they exist. Recently, there has been significant interest in medicinal chemistry toward the discovery and design of low molecular weight molecules that affect stem cells and thus have novel therapeutic activity. We believe that a successful agent from such a discover program would have profound effects on the treatment of many long-term degenerative disorders.

Technology evaluation: ISIS-104838, OraSense.

OraSense Ltd (a joint venture between Isis Pharmaceuticals Inc and Elan Corp) is developing ISIS-104838, an antisense oligonucleotide specific for TNF alpha mRNA, as an inhibitor of TNF alpha synthesis. The compound is being developed for the potential treatment of inflammatory diseases such as rheumatoid arthritis, Crohn's disease and psoriasis. This antisense oligonucleotide is currently undergoing phase II clinical trials for RA and Crohn's disease.

Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles.

4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured.

Studies on the absorption, distribution and elimination of 6-o-chlorophenyl-2,4-dihydro-2(N-methyl-piperazin-1-yl)-methylene-8-nitro-1H-imidazo[1,2-a] [1,4]benzodiazepin-1-one methanesulphonate in the male rat and rabbit.

The fate of a novel imidazo-benzodiazepine (I) was studied in male rats and rabbits using 14C and 3H-labelled I. In both species the compound was rapidly and widely absorbed after an oral dose of 5 mg/kg to give peak tissue and plasma levels after 1 hour in the rat and 4 hours in the rabbit. The highest concentrations of radioactivity were present in the liver (rat) and liver, kidney and subcutaneous fat (rabbit).