Callipeltin A, a cyclic depsipeptide inhibitor of the cardiac sodium-calcium exchanger and positive inotropic agent

Callipeltin A, a cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp., is a macrocyclic lactone containing four amino acids in the L configuration, Ala, Leu, Thr (2 residues); one (Arg) in the D configuration; two N-methyl amino acids, N-MeAla and N-MeGln; a methoxy tyrosine, a 3, 4-dimethyl-l-glutamine; and a 4-amino-7-guanidino-2,3 dihydroxypentanoic acid (AGDHE), formally derived from L-Arg. In cardiac sarcolemmal vesicles Callipeltin A induces a powerful (IC(50) = 0.85 microM) and selective inhibition of the Na(+)/Ca(2+) exchanger. In electrically driven guinea-pig atria, at concentrations ranging between 0.7 and 2.5 microM, Callipeltin A induces a positive inotropic effect, which at the highest concentrations is accompanied by a rise in resting tension. It is suggested that the positive inotropic effect is linked to the inhibition of the Na(+)/Ca(2+) exchanger and that Callipeltin A may be an useful tool to study the role of the cardiac Na(+)/Ca(2+) exchanger in physiological and pathological conditions. (I.F.= 2.836

Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance. In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 x 10(-10); OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Delta2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease

Correspondence to 'Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort'.

We read with interest the clinical study entitled ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’ by Pouletty et al.1 In this series, the authors suggest that paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS) may represent a new inflammatory syndrome, different from classical Kawasaki disease (KD) as it occurs at an older age, and with a higher frequency of severe myocarditis.1 Likewise to this study, our Pediatric Tuscany Network (PTN)—16 paediatric units serving a region of 593 606 people aged less than 18 years—worked out the COVASAKI survey to detect the incidence of PMIS-TS cases and the eventual rise of KD in Tuscany during COVID-19 pandemic. Between 1 February 2000 and 30 June 2020, we tracked children with PMIS-TS and KD, aiming to compare the number of KD cases in the same 5 months of the previous 5 years and overall with the total number in the last 5 years. No PMIS-TS cases were reported in our region. Ten KD children were diagnosed in 5 units (incidence two per month). Demographics, clinical and imaging findings, treatment and outcome of patients are reported in table 1. No specific intensive support was required. No coronary involvement was reported. Nasopharyngeal swabs (performed in 7/10) and serological test (available in 6/10) for SARS CoV-2 resulted negative

Small animal models

Animal assays represent an important stage between in vitro studies and human clinical applications. These models are crucial for biomedical research and regenerative medicine studies, as these offer precious information for systematically assessing the efficacy and risks of recently created biomaterials, medical devices, drugs, and therapeutic modalities prior to initiation of human clinical trials. Therefore, selecting a suitable experimental model for tissue engineering purposes is essential to establish valid conclusions. However, it remains important to be conscious of the advantages and limitations of the various small and large animal models frequently used for biomedical research as well as the different challenges encountered in extrapolating data obtained from animal studies and the risks of misinterpretation. This chapter discusses the various small animal model strategies used for osteochondral defect repair. Particular emphasis will be placed on analyzing the materials and strategies used in each model.FCT -Fundação para a Ciência e a Tecnologia(IF/00423/2012)info:eu-repo/semantics/publishedVersio