Experimental Zika virus infection induces spinal cord injury and encephalitis in newborn Swiss mice

A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America, with neurological symptons including meningoencephalitis and Guillain-Barré syndrome in adults, besides an apparent increased incidence of microcephaly in infants born to infected mothers. It is becoming a necessity to have a trustworthy animal model to better understand ZIKV infection. In this study we used newborn white Swiss mice as a model to investigate the ZIKV strain recently isolated in Brazil. ZIKV was inoculated via intracerebral and subcutaneous routes and analysed through gross histopathology and immunohistochemistry. Here we demonstrated first that the intracerebral group (ICG) displayed severe cerebral lesions, with neuronal death, presence of apoptotic bodies, white matter degeneration and neutrophil perivascular cuffing. In the subcutaneous group (SCG), we observed moderate cerebral lesions, morphologically similar to that found in ICG and additional myelopathy, with architectural loss, marked by neuronal death and apoptotic bodies. Interestingly, we found an intense astrogliosis in brain of both groups, with increased immunoexpression of GFAP (glial fibrillary acidic protein) and presence of hypertrophic astrocytes. The spinal cord of subcutaneous group (SCG) exhibited reduction of astrocytes, but those positive for GFAP were hypertrophic and presented prolonged cellular processes. Finally significant lesions in the central nervous system (CNS) were present in newborn mice inoculated by both routes, but SCG method led to an important neurological manifestations (including myelopathy), during a longer period of time and appears for us to be a better model for ZIKV infection.     

Pre-Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain Associated with Disseminated Tuberculosis in a Pet Dog

Resistance to isoniazid, ethambutol, and streptomycin was detected in a Mycobacterium tuberculosis strain, belonging to the Beijing family lineage, isolated from two nodule exudates of a Yorkshire terrier with generalized tuberculosis. This report alerts medical practitioners to the risk of dissemination of pre-multidrug-resistant tuberculosis (preMDR-TB) through exposure to M. tuberculosis-shedding pets.     

Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology

Wound dressing biomaterials are increasingly being designed to incorporate bioactive molecules to promote healing, but the impact of matrix mechanical properties on the biology of resident cells orchestrating skin repair and regeneration remains to be fully understood. This study investigated whether tuning the stiffness of a model wound dressing biomaterial could control the behavior of dermal fibroblasts. Fully interpenetrating networks (IPNs) of collagen-I and alginate were fabricated to enable gel stiffness to be tuned independently of gel architecture, polymer concentration or adhesion ligand density. Three-dimensional cultures of dermal fibroblasts encapsulated within matrices of different stiffness were shown to promote dramatically different cell morphologies, and enhanced stiffness resulted in upregulation of key-mediators of inflammation such as IL-10 and COX-2. These findings suggest that simply modulating the matrix mechanical properties of a given wound dressing biomaterial deposited at the wound site could regulate the progression of wound healing.     

Molecular surveillance of Neisseria meningitidis capsular switching in Portugal, 2002-2006

Neisseria meningitidis capsular switching has been reported in several countries. In order to establish the genetic relationship within group B and C strains expressing subtypes 2a or 2b, and to evaluate whether C to B capsular switching occurred in Portugal, 64 meningococci (56 serogroup C and 8 serogroup B) isolated from invasive meningococcal disease were typed using molecular methods. The studied phenotypes, 2b:P1.5,2 and 2a:P1.5-1,10-8, were the most frequent among serogroup C, but were uncommon among serogroup B strains. The multi-locus sequence typing (MLST) allelic profile and the pulsed-field gel electrophoresis (PFGE) fingerprints showed that seven serogroup B strains were genotypically identical to C strains, suggesting that capsular switching occurred. Active laboratory surveillance to find evidence of capsule switching is a now priority as MenC was introduced in the Portuguese vaccination schedule in January 2006.     

Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

Registo Nacional de Eletrofisiologia Cardíaca 2017‐2018

IntroductionThe authors present the results of the national cardiac electrophysiology registry of the Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE) and the Portuguese Institute of Cardiac Rhythm (IPRC) for 2017 and 2018.MethodsThe registry is annual, voluntary, and observational. Data are collected retrospectively. Developments over the years and their implications are analyzed and discussed.ResultsIn the 22 electrophysiology centers, 3407 ablations were performed in 2017 and 3653 ablations in 2018. Atrial fibrillation (AF) ablation was the most frequently performed procedure: 1017 ablations in 2017 and 1222 procedures in 2018. Of the patients undergoing AF ablation, 63% were male, 60% were between 50 and 69 years old and 74% had paroxysmal AF. Clinically relevant complications were reported in 0.8% of the procedures. In 2017, 216 ventricular tachycardia (VT) ablation procedures were performed in 15 centers. In 2018, 19 centers performed 249 VT ablations. About 45% of VT ablations were performed in patients with structural heart disease. Complications were reported in 3.2% of the procedures, including one death (0.2%).ConclusionsThe national electrophysiology registry showed a sustained increase in the number of catheter ablations. In addition, procedural complexity increased and AF ablation assumed a dominant position among the procedures performed.     

Effects of the treatment with glibenclamide, an ATP-sensitive potassium channel blocker, on intestinal ischemia and reperfusion injury

Intestinal ischemia and reperfusion injury is dependent on the recruitment and activation of neutrophils. Glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker, has been shown to suppress neutrophil migration and chemotaxis during acute inflammatory responses by a mechanism dependent on its K(ATP) channel blocking activity. In the present study, we evaluated whether the treatment with glibenclamide prevented local, remote and systemic injury following reperfusion of the ischemic superior mesenteric artery in rats. The artery was made ischemic for a period of 30 or 120 min followed by 30 (mild I/R) or 120 (severe I/R) min of reperfusion, respectively. Glibenclamide (0.8 to 20 mg/kg) or vehicle was administered subcutaneously 40 min prior to the reperfusion. Glibenclamide dose-dependently inhibited the reperfusion-associated increase in vascular permeability and neutrophil accumulation in mild I/R. In the severe injury model, glibenclamide inhibited inflammatory parameters, as assessed by Evans blue extravasation, neutrophil influx and haemoglobin content, and the increase in TNF-alpha (tumor necrose factor-alpha) and IL (interleukin)-6 levels in the intestine and lung. The drug did not affect the increase in IL-1beta and IL-10 levels. TEA, a nonselective potassium channel blocker, also inhibited reperfusion injury in both intestine and lungs of animals submitted to mild and severe I/R. Our experiments suggest a role for K(ATP) channels in mediating neutrophil influx and consequent reperfusion-associated injury in rats. The lack of effect of these drugs on the reperfusion-associated hypotension and lethality may limit their usefulness after severe reperfusion injury.