Azathioprine induction of tumors with microsatellite instability: Risk evaluation using a mouse model

Mismatch-repair (MMR)-deficient cells show increased in vitro tolerance to thiopurines because they escape apoptosis resulting from MMR-dependent signaling of drug-induced DNA damage. Prolonged treatment with immunosuppressants including azathioprine (Aza), a thiopurine prodrug, has been suggested as a risk factor for the development of late onset leukemias/lymphomas displaying a microsatellite instability (MSI) phenotype, the hallmark of a defective MMR system. We performed a dose effect study in mice to investigate the development of MSI lymphomas associated with long term Aza treatment. Over two years, Aza was administered to mice that were wild type, null or heterozygous for the MMR gene Msh2. Ciclosporin A, an immunosuppressant with an MMR-independent signaling, was also administered to Msh2^wt mice as controls. Survival, lymphoma incidence and MSI tumor phenotype were investigated. Msh2^+/− mice were found more tolerant than Msh2^wt mice to the cytotoxicity of Aza. In Msh2^+/− mice, Aza induced a high incidence of MSI lymphomas in a dose-dependent manner. In Msh2^wt mice, a substantial lifespan was only observed at the lowest Aza dose. It was associated with the development of lymphomas, one of which displayed the MSI phenotype, unlike the CsA-induced lymphomas. Our findings define Aza as a risk factor for an MSI-driven lymphomagenesis process.     

Antibacterial activity against Streptococcus mutans and diametrical tensile strength of an interim cement modified with zinc oxide nanoparticles and terpenes: An in vitro study

Statement of problem

Interim restorations are occasionally left in the mouth for extended periods and are susceptible to bacterial infiltration. Thus, dental interim cements with antibacterial properties are required.

Advanced hydrogels for treatment of diabetes

Diabetes mellitus is a chronic disease characterized by high levels of glucose in the blood, which leads to metabolic disorders with severe consequences. Today, there is no cure for diabetes. The current management for diabetes and derived medical conditions, such as hyperglycemia, cardiovascular diseases, or diabetic foot ulcer, includes life style changes and hypoglycemia‐based therapy, which do not fully restore euglycemia or the functionality of damaged tissues in patients. This encourages scientists to work outside their boundaries to develop routes that can potentially tackle such metabolic disorders. In this regard, acellular and cellular approaches have represented an alternative for diabetics, although such treatments still face shortcomings related to limited effectiveness and immunogenicity. The advent of biomaterials has brought significant improvements for such approaches, and three‐dimensional extracellular matrix analogs, such as hydrogels, have played a key role in this regard. Advanced hydrogels are being developed to monitor high blood glucose levels and release insulin, as well as serve as a therapeutic technology. Herein, the state of the art in advanced hydrogels for improving treatment of diabetes, from laboratory technology to commercial products approved by drug safety regulatory authorities, will be concisely summarized and discussed.     

Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation

Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.     

Thoracic paracoccidioidomycosis: radiographic and CT findings

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Latin America. Although most cases occur in developing countries, recent immigration patterns and an increase in travel have led to a growing number of PCM cases in the United States and Europe. PCM is caused by the dimorphic fungus Paracoccidioides brasiliensis, and the chronic form may progress to severe pulmonary involvement. Several radiologic patterns have been described for pulmonary PCM, including linear and reticular opacities, variable-sized nodules, patchy ill-defined opacities, airspace consolidation, and cavitary lesions. Fibrosis and paracicatricial emphysema are common associated findings. Chest computed tomography (CT) is the method of choice for evaluating pulmonary PCM, with the most common CT findings being ground-glass attenuation, consolidation, small or large nodules, masses, cavitations, interlobular septal thickening, emphysema, and fibrotic lesions. PCM is also an important cause of the "reversed halo" sign at high-resolution CT and should be considered in the differential diagnosis. Awareness of the multiple radiologic manifestations of PCM as well as its epidemiologic and clinical characteristics may permit early diagnosis and initiation of specific treatment, thereby reducing associated morbidity and mortality.