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BACKGROUND: Splenic artery aneurysms (SAAs) are rare but seem to have higher incidence in patients with portal hypertension (PH). The present article aims to analyze the interference of PH in the natural history of these aneurysms. METHODS: This was a retrospective study of data recorded prospectively. Between January 2000 and December 2019, all SAAs patients in follow-up at a tertiary institution were selected for analysis. Primary end point was to analyze the presentation and evolution of SAAs in patients with PH, and secondary was to identify cumulative rates of freedom from rupture, interventions, and survival in this group, during a 10-year follow-up. RESULTS: In total, 96 patients were identified with SAAs, 79 (82.29%) did not have PH and 17 (17.7%) had this comorbidity. Among the demographic characteristics, the patients with SAAs and PH were significantly younger (52 years [standard deviation {SD} 13.3] versus 61.9 years [SD 12.2] [P = 0.05]) and had lower number of pregnancies (1.1 pregnancies [SD 1.2] versus 3.37 pregnancies [SD 2.3] [P = 0.03]). Patients with PH had a higher cumulative rate of surgical intervention throughout follow-up (up to 75.6% in 10 years) when compared to patients without PH, with 36.9% intervention rate in 10 years of follow-up. Patients with PH had larger diameter at diagnosis (35 mm, SD 27.3) compared to patients without PH (22.6 mm, SD 16.1), P = 0.008. However, there were no statistical differences in the relative growth rate, in aneurysmal rupture rate throughout follow-up, as well as in survival over the years, between the groups. CONCLUSIONS: The patients with SAAs and PH are significantly younger, have larger SAA diameters at diagnosis and have a higher cumulative rate of surgical intervention throughout follow-up in 10 years, despite the relative growth rate being similar to that of patients without PH.
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Leprosy reactions are an acute and systemic manifestation, which occurs suddenly, can be severe and lead leprosy patients to disability. Reactional episodes are observed among half of the multibacillary patients, mainly in borderline lepromatous and lepromatous forms. They may begin at any time during multidrug therapy, and even before the treatment. Physical disabilities, which are the source of extreme suffering and pain for patients, occur in progression of the cellular immune response associated with a reaction and are still poorly understood. Thus, this work aimed to phenotypically and functionally characterize CD4+ and CD8+ Treg cells ex vivo and in response to Mycobacterium leprae (ML). We studied 52 individuals, including 18 newly diagnosed and untreated multibacillary leprosy patients, 19 reactional multibacillary patients (Type I or Type II episodes) and 15 healthy volunteers, included as controls, all residents of the city of Rio de Janeiro. The functional activity and frequencies of these cells were evaluated through multiparametric flow cytometry. In addition, the production of cytokines in supernatant from peripheral blood mononuclear cell cultures was also investigated against ML by enzyme-linked immunosorbent assay. Our results showed a decrease in CD4+TGF-ß+ Treg and CD8+ TGF-ß+ Treg in leprosy multibacillary patients during both types of reactional episodes. Alterations in the cytokine profile was also observed in Type II reactions, along with upregulation of IL-17 and IL-6 in supernatant. Thus, our study suggests that downregulation of Treg cells is related with both classes of reactional episodes, improving our understanding of immune hyporesponsiveness in multibacillary patients and hyperesponsiveness in both reactions.
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Chemical fixation of CO2 to produce cyclic carbonates can be a green and atomic efficient process. In this work, a series of porphyrazines (Pzs) containing electron-withdrawing groups and central MII ions (where M = Mg, Zn, Cu, and Co) were synthesized and investigated as catalysts for the cycloaddition of CO2 to epoxides. Then, the efficiency of the Pzs was tested by varying cocatalyst type and concentration, epoxide, temperature, and pressure. MgIIPz bearing trifluoromethyl groups (1) showed the best conversion, producing, selectively, 78% of propylene cyclic carbonate (PCC), indicating that a harder and stronger Lewis acid is more effective for epoxide activation. Moreover, cocatalyst variation showed a notable effect on the reaction yields. Spectrophotometric titrations, MALDI-TOF mass spectra, and theoretical calculations suggest poisoning of the catalyst when tetrabutylammonium chloride (TBAC) and large amounts of tetrabutylammonium bromide (TBAB) were used in the system. The same was not observed for tetrabutylammonium iodide (TBAI), indicating that the metal-cocatalyst interaction may govern the reaction rate. In addition, two rare examples of crystalline structures were obtained, proving the distorted square pyramidal geometry with water molecule as axial ligand. This is one of the first studies reporting Pzs as catalysts for the chemical fixation of CO2, and we believe that the intricate balance between cocatalyst concentration and conversion efficiency shown here may aid future studies in the area.
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BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.
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Hansenostáticos/uso terapêutico , Hanseníase/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Aldeídos , Antioxidantes , Carga Bacteriana , Brasil , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae , Estresse Oxidativo , Carbonilação Proteica , Pele/metabolismo , Pele/patologiaRESUMO
Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.
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Linfócitos T CD8-Positivos/imunologia , Senescência Celular/imunologia , Memória Imunológica , Imunossenescência/imunologia , Hanseníase/imunologia , Mycobacterium leprae , Dermatopatias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Antígenos CD/genética , Estudos de Casos e Controles , Citomegalovirus/imunologia , Feminino , Expressão Gênica , Humanos , Imunoglobulina G/sangue , Hanseníase/sangue , Hanseníase/microbiologia , Hanseníase/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Pele/imunologia , Pele/patologia , Dermatopatias/sangue , Dermatopatias/microbiologia , Dermatopatias/patologia , Adulto Jovem , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
OBJETIVO: O objetivo deste trabalho é a descrição dos ramos lateral, diagonal e ântero-superior, no tecido adiposo epicárdico do ventrículo esquerdo, e a análise da freqüência e do diâmetro destes, conforme o tipo de circulação coronariana. O conhecimento preciso desses ramos tem aplicabilidade na abordagem cirúrgica para a sua revascularização ou durante a injeção de substâncias cardioplégicas nos mesmos. MÉTODO: Dissecados 50 corações obtidos de necropsias de adultos, fixados em solução de formol e o ventrículo esquerdo dividido em três terços: superior, médio e inferior. O ramo lateral originou-se do ramo circunflexo; o ramo diagonal, do ponto de divisão da artéria coronária esquerda e o ramo ântero-superior, do ramo interventricular anterior no terço superior do ventrículo esquerdo. Para cada ramo foram medidos o comprimento no epicárdio e o diâmetro, além disso foi relacionado o fluxo sangüíneo com o tipo de circulação coronariana. RESULTADOS: O diâmetro do ramo lateral, presente em 88 por cento dos casos, variou de 0,6 a 4,5 mm (média 2,1 ± 0,7mm). O diâmetro do ramo diagonal, presente em 50 por cento dos casos, variou de 1,0 a 3,8 mm (média 2,2 ± 0,7 mm). O diâmetro do ramo ântero-superior, presente em 84 por cento dos casos, variou de 1,0 a 4,1 mm (média 2,5 ± 0,8 mm). Foram encontrados: 30/50 (60 por cento) casos de dominância da artéria coronária direita, 14/50 (28 por cento) casos de tipo balanceado e 6/12 (12 por cento) casos de dominância da artéria coronária esquerda. A média do fluxo sangüíneo do ramo ântero-superior apresentou valor decrescente nos tipos: dominância da artéria coronária direita, balanceado e dominância da artéria coronária esquerda. Inversamente, o ramo lateral mostrou valor crescente, enquanto o ramo diagonal apresentou maior fluxo no tipo balanceado. CONCLUSAO: Os resultados demonstraram a complementaridade entre os ramos lateral, diagonal e ântero-superior, bem como a correlação entre a distribuição dos mesmos e os tipos de circulação coronariana.
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Humanos , Adulto , Circulação Coronária/fisiologia , Coração/anatomia & histologia , Ventrículos do Coração/fisiologiaRESUMO
A fibrilação atrial e o "flutter" são as arritmias mais comuns na prática diária. O manuseio adequado dessas arritmias é de grande importância e o clínico necessitasaber quais drogas podem ser usadas, considerando as doenças do paciente. Diante da necessidade de saber qual o melhor tratamento para essas arritmias, sumarizamos, neste artigo, as indicações apropriadas das drogas.