Um caso de pericardite constritiva e aneurisma da aorta torácica: abordagem terapêutica híbrida

The authors describe the case of a 59-year-old man, a former smoker, with hypertension, chronic renal failure undergoing hemodialysis, and a history of stent grafting for repair of an abdominal aortic aneurysm and miliary tuberculosis, who was diagnosed with constrictive pericarditis and a thoracic aortic aneurysm. In a patient with such a complex medical history, there were several etiologies to consider. The treatment consisted of pericardiectomy and a hybrid technique of supra-aortic debranching and subsequent endovascular stent-graft repair.     

Expression and functionality of histone H2A variants in cancer

Regulation of gene expression includes the replacement of canonical histones for non-allelic histone variants, as well as their multiple targeting by postranslational modifications. H2A variants are highly conserved between species suggesting they execute important functions that cannot be accomplished by canonical histones. Altered expression of many H2A variants is associated to cancer. MacroH2A variants are enriched in heterocromatic foci and are necessary for chromatin condensation. MacroH2A1.1 and macroH2A1.2 are two mutually exclusive isoforms. MacroH2A1.1 and macroH2A2 inhibit proliferation and are associated with better cancer prognosis; while macroH2A1.2 is associated to cancer progression. H2AX variant functions as a sensor of DNA damage and defines the cellular response towards DNA repair or apoptosis; therefore, screening approaches and therapeutic options targeting H2AX have been proposed. H2A.Z is enriched in euchromatin, acting as a proto-oncogene with established roles in hormone responsive cancers and overexpressed in endocrine-resistant disease. Other H2A family members have also been found altered in cancer, but their function remains unknown. Substantial progress has been made to understand histone H2A variants, their contribution to normal cellular function and to cancer development and progression. Yet, implementation of high resolution mass spectrometry is needed to further our knowledge on highly homologous H2A variants expression and function.     

Intestinal clear cell sarcoma with melanocytic differentiation and EWS [corrected] rearrangement: report of a case

A clear cell sarcoma-like tumor with osteoclast-like giant cells of the gastrointestinal tract without immunoexpression of CD117 was recently proposed as a new tumor entity. In this article, a case of a 37-year-old man with a neoplasm of the jejunum composed of polygonal cells with clear to eosinophilic cytoplasm forming nests and fascicles is reported. Giant cells were not identified. Immunohistochemically, the tumor cells expressed strongly S100 protein, human melanoma black 45, platelet-derived growth factor receptor alpha, B-cell lymphoma 2, p53, and to a lesser extent vimentin, neuron-specific enolase, and epithelial membrane antigen. Mindbomb homolog-1 index was 35%. Immunoreactivity for CD34 and CD117 was negative. The fluorescence in situ hybridization analysis showed a translocation involving chromosome 22q12, the diagnostic hallmark of clear cell sarcoma of soft tissues. This case indicates a close histogenetic relationship with the recently reported clear cell sarcoma with osteoclast-like giant cells of the gastrointestinal tract, as well as with the clear cell sarcoma of soft tissues.     

Role of Capsaicin-Sensitive Primary Afferent Neurons and Non-protein Sulphydryl Groups on Gastroprotective Effect of Amifostine Against Ethanol-Induced Gastric Damage in Rats

Background

Amifostine has been widely tested as a cytoprotective agent against a number of aggressors in different organs. Recently, a gastroprotective effect was observed for this drug in a model of indomethacin-induced gastric injury. Our objective was to investigate the effect of amifostine on ethanol-induced gastric injury and the role played in this mechanism by afferent sensory neurons, non-protein sulfhydryl groups, nitric oxide, ATP-sensitive potassium channels, and cyclooxygenase-2.

Methods

Rats were treated with amifostine (22.5, 45, 90, or 180 mg/kg, PO or SC). After 30 min, the rats received absolute ethanol (5 ml kg^?1, PO). One hour later, gastric damage was quantified with a planimeter. Samples from the stomach were also taken for histopathological assessment and for assays of non-protein sulfhydryl groups. The other groups were pretreated with L-NAME (10 mg kg^?1, IP), glibenclamide (10 mg kg^?1, PO), or celecoxib (10 mg kg^?1, PO). After 30 min, the animals were given amifostine (90 mg kg^?1, PO or SC), followed 30 min later by gavage with absolute ethanol (5 ml kg^?1). Other rats were desensitized with capsaicin (125 mg kg^?1, SC) 8 days prior to amifostine treatment.

Results

Amifostine administration PO and SC significantly and dose-dependently reduced ethanol-induced macroscopic and microscopic gastric damage by restoring glutathione levels in the stomach mucosa. Amifostine-promoted gastroprotection against ethanol-induced stomach injury was reversed by pretreatment with neurotoxic doses of capsaicin, but not by L-NAME, glibenclamide, or celecoxib.

Conclusions

Amifostine protects against ethanol-induced gastric injury by increasing glutathione levels and stimulating the afferent sensory neurons in the stomach.     

Impaired virulence and in vivo fitness of colistin-resistant Acinetobacter baumannii

Acinetobacter baumannii (American Type Culture Collection strain 19606) acquires mutations in the pmrB gene during the in vitro development of resistance to colistin. The colistin-resistant strain has lower affinity for colistin, reduced in vivo fitness (competition index, .016), and decreased virulence, both in terms of mortality (0% lethal dose, 6.9 vs 4.9 log colony-forming units) and survival in a mouse model of peritoneal sepsis. These results may explain the low incidence and dissemination of colistin resistance in A. baumannii in clinical settings.     

Rapidly evolving techniques for structural heart disease interventions

Structural heart disease interventions are the transcatheter techniques used for treating non-coronary heart disease. In recent years, these techniques have generated considerable interest even though they still comprise only a small percentage of the total volume of interventions performed in interventional cardiology departments. The level of interest in these techniques is high probably because their application is characterized by a number of special features: a) the need for multidisciplinary teams; b) the need for specialized education and training; c) the requirement for special skills developed through education and experience, and d) the limited number of referral centers at present. This article describes four specific techniques: a) percutaneous closure of perivalvular leaks; b) percutaneous left atrial appendage obliteration; c) percutaneous treatment of mitral regurgitation, and d) transcatheter implantation of prosthetic aortic valves. We explore the rationale for using the technique, the specific procedures involved and the results obtained.     

Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii

Acinetobacter baumannii produces different types of infections including pneumonia, meningitis, and bloodstream infections. The optimal treatment of these infections has been complicated by the global emergence of multidrug resistant strains, requiring the development of novel approaches for treatment and prevention. Outer membrane vesicles are outpouchings of the bacterial outer membrane that are secreted from numerous pathogenic Gram-negative bacteria. In the present study, we describe the isolation of outer membrane vesicles from A. baumannii and their use as a vaccine in a mouse model of disseminated sepsis. Immunization produced a robust antibody response against multiple bacterial antigens which consisted of antigen-specific IgG and IgM. In addition, both IgG1 and IgG2c subtypes were produced by immunization. Immunized mice had lower tissue bacterial loads and lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1β post-infection compared to control mice. Importantly, vaccination protected mice from challenge with the ATCC 19606 strain and provided protection against two clinical isolates, including a pan-resistant strain. These results indicate that vaccination with outer membrane vesicles may be a viable strategy for preventing A. baumannii infection.