Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy.
Methods
We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY.
Results
We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-related – most of the latter involved in proinflammatory cytokine production. Significantly, incubation with IFN-γ on a human cardiomyocyte line treated with an inhibitor of dihydroorotate dehydrogenase brequinar (enzyme showing a loss-of-function variant in one family) markedly reduced mitochondrial membrane potential (ΔψM), indicating mitochondrial dysfunction.
Conclusion
Mitochondrial dysfunction and inflammation may be genetically determined in CCC, driven by rare genetic variants. We hypothesize that CCC-linked genetic variants increase mitochondrial susceptibility to IFN-γ-induced damage in the myocardium, leading to the cardiomyopathy phenotype in Chagas disease. This mechanism may also be operative in other inflammatory cardiomyopathies.
IntroductionThis study investigated the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on serum inflammatory mediators of rats with pulp exposure–induced apical periodontitis.MethodsForty male Wistar rats were divided into the following groups: control, untreated rats (C); control rats treated with ω-3 PUFAs (C-O); rats with pulp exposure–induced apical periodontitis (AP); and rats with pulp exposure–induced apical periodontitis treated with ω-3 PUFAs (AP-O). ω-3 PUFAs were administered orally once a day for 15 days before pulp exposure and continued for 30 days after pulp exposure. The rats were sacrificed, and then blood and jaw samples were collected. Blood analysis was conducted to determine the total number of leukocytes including neutrophils, monocytes, and lymphocytes. Proinflammatory cytokines tumor necrosis factor alpha, interleukin (IL) 6, and IL-17 were quantified by enzyme-linked immunosorbent assay. Histologic analysis was performed to confirm the development of apical periodontitis. The data were statistically evaluated using analysis of variance and the Tukey posttest. The significance level was set at 5%.ResultsThe development of apical periodontitis was confirmed in all infected groups. Bone destruction was larger in the AP group compared with the AP-O group (P < .05). Blood analysis showed that the AP and AP-O groups showed higher numbers of lymphocytes, leukocytes, monocytes, eosinophils, and expressions of tumor necrosis factor alpha and IL-6 compared with the C and C-O groups (P < .05). In contrast, the presence of leukocytes, lymphocytes, and the expression of IL-6 decreased in the AP-O group compared with the AP group (P < .05).Conclusionsω-3 PUFA supplementation influences the systemic effects caused by apical periodontitis, decreasing the number of leukocytes, lymphocytes, and IL-6 in rat blood. 相似文献
This study was a systematic review with meta-analysis to evaluate the influence of hyperbaric oxygen therapy (HBOT) on the survival of dental implants placed in patients who had had radiotherapy for cancer of the head and neck. A systematic literature search was conducted using the PubMed/Medline, Science Direct, Embase and the Cochrane Library, between January 1985 and July 2018. The study observed the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) declaration and norms, and the systematic review was duly recorded in the PROSPERO (International prospective register of systematic reviews) database. Inclusion and exclusion criteria were applied, and all articles were selected on the basis of PICO questions. The process of eligibility and quality evaluation yielded three studies for statistical analysis. Based on the survival rates, there was no evidence that the risk of an implant failing was different between the patients who received HBOT and those who did not. Moreover, the risk of an implant failing did not depend on the anatomical site. HBOT exerted no beneficial influence on the survival rates of implants placed in irradiated patients, and the risk of an implant failing did not depend on its location. 相似文献
Clinical Oral Investigations - This a cross-sectional study to evaluate the association between oral health findings and ventilator-associated pneumonia (VAP) among critically ill patients in... 相似文献
Whooping cough remains a health problem despite high vaccination coverage. It has been recommended that development of new strategies provide long-lasting immunity. The aim of this work was to evaluate the potential of proteoliposomes (PL) extracted from Bordetella pertussis as a vaccine candidate against whooping cough. The size of the B. pertussis PL was estimated to be 96.7±50.9 nm by Scanning Correlation Spectroscopy and the polydispersity index was 0.268. Western blots using monoclonal antibodies revealed the presence of pertussis toxin, pertactin, and fimbriae 3. The Limulus Amebocyte Lisate (LAL) assay showed endotoxin levels lower than those reported for whole cell pertussis licensed vaccines, while the Pyrogen Test indicated 75 ng/mL/Kg. The PL showed high protection capacity in mouse challenge models. There was 89.7% survival in the intracerebral challenge and total reduction of the number of CFU in the intranasal challenge. No significant differences (p>0.05) were observed between mice immunized with B. pertussis PL and the Cuban DTwP vaccine, whichever challenge model used. These results encouraged us to continue the development of the B. pertussis PL as a component of a new combined vaccine formulated with tetanus and diphtheria toxoids or as a booster dose for adolescents and adults. 相似文献
Clinical Oral Investigations - To assess whether salivary urea and creatinine levels accurately reflect their serum levels in blood samples of adults to detect chronic kidney disease. A systematic... 相似文献
Clinical Oral Investigations - To compare the microbial load and composition and to determine the lipopolysaccharides (LPS) and lipoteichoic acid (LTA) concentrations found in primary apical... 相似文献
Background The monocrotaline (MCT)-induced pulmonary arterial hypertension model is one of the most reproduced today, presenting as a limitation the absence of plexiform lesions, typical manifestations of the severe disease in humans.Objective To evaluate the severity of MCT-induced pulmonary arteriopathy by pathological findings of lung and heart tissue samples, clinical course and 37-day survival.Methods Fifty male Wistar rats were divided into one of the four groups – control (CG) (n = 10) and three intervention (MCT) groups. The MCT groups received intraperitoneal injection (60 mg/kg) of MCT and remained exposed to the substance for 15 days (G15, n = 10), 30 days (G30, n = 10) and 37 days (G37, n = 20). At the end of each period, the animals were sacrificed, and pulmonary and cardiac tissues were collected for anatomopathological and morphometric analysis. The Kruskal-Wallis test was used, considering a level of significance of 5%.Results In the lungs of MCT animals, lesions related to pulmonary arteriopathy were found, including muscularization of the arterioles, hypertrophy of the middle layer and concentric neointimal lesions. Complex lesions were observed in MCT groups, described as plexiform and plexiform-like lesions. Right ventricular hypertrophy was evidenced by increased thickness and diameter of the cardiomyocytes and a significant increase in the right ventricular wall thickness (p <0.0000).Conclusion The MCT model was able to generate moderate-severe pulmonary arteriopathy associated with secondary right ventricular hypertrophy. The 37-day survival rate was 50%. To our knowledge, this study was the first to note the presence of complex vascular lesions, similar to those observed in patients with severe pulmonary arterial hypertension, in an isolated MCT model. (Arq Bras Cardiol. 2020; 115(3):480-490) 相似文献
To evaluate the influence of pulmonary hypertension in the ultra-fast-track
anesthesia technique in adult cardiac surgery.
Methods
A retrospective study. They were included 40 patients divided into two
groups: GI (without pulmonary hypertension) and GII (with pulmonary
hypertension). Based on data obtained by transthoracic echocardiography. We
considered as the absence of pulmonary hypertension: a pulmonary artery
systolic pressure (sPAP) <36 mmHg, with tricuspid regurgitation velocity
<2.8 m/s and no additional echocardiographic signs of PH, and PH as
presence: a sPAP >40 mmHg associated with additional echocardiographic
signs of PH. It was established as influence of pulmonary hypertension: the
impossibility of extubation in the operating room, the increase in the time
interval for extubation and reintubation the first 24 hours postoperatively.
Univariate and multivariate analyzes were performed when necessary.
Considered significant a P value <0.05.
Results
The GI was composed of 21 patients and GII for 19. All patients (100%) were
extubated in the operating room in a medium time interval of 17.58±8.06 min
with a median of 18 min in GII and 17 min in GI. PH did not increase the
time interval for extubation (P=0.397). It required
reintubation of 2 patients in GII (5% of the total), without statistically
significant as compared to GI (P=0.488).
Conclusion
In this study, pulmonary hypertension did not influence on ultra-fast-track
anesthesia in adult cardiac surgery. 相似文献