Control of hemopoiesis in mice by sensitized L3T4+ Lyt2-lymphocytes during infection with bacillus Calmette-Guérin.

When injected intravenously with bacillus Calmette-Guérin (BCG; 10(7) viable units), C57BL/6 mice rapidly develop a transient anemia associated with an increased number of granulocytes and monocytes, whereas C3H/He mice do not. Because these two features are lacking in C57BL/6 nude mice we postulated that T lymphocytes can regulate hemopoiesis during infection. To assess further the role in hemopoiesis of T lymphocytes present in bone marrow of C57BL/6 and C3H/He mice, the frequency of BCG-specific T lymphocytes and their surface marker phenotype were determined by limiting dilution analysis and use of monoclonal antibodies. The number of BCG-specific T lymphocytes was estimated to be 50- to 100-fold higher in bone marrow of C57BL/6 than in that of C3H/He mice. Although L3T4+ Lyt2-and L3T4- Lyt2+ BCG-specific T lymphocytes were generated in mice of both strains, in C57BL/6 mice L3T4+ cells were induced preferentially from day 1 through day 5 after infection in correlation with hemopoietic changes. The relation between T-cell immune response and hemopoietic changes was substantiated by results obtained after in vivo treatment with monoclonal antibodies. Selective depletion of L3T4+ T cells by in vivo injection of anti-L3T4 monoclonal antibodies (GK 1-5) inhibited the development of the anemia and the related increased production of phagocytes in C57BL/6 mice receiving BCG.     

A retrospective study of immunotherapy using the cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guérin (BCG-CWS) for cervical cancer

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has the potential to promote adaptive immunity. We sought to examine the synergistic effect of BCG-CWS vaccination on cervical cancer patients undergoing standard treatments including surgery, chemotherapy, and/or radiation. We retrospectively analyzed 103 patients (13 cases administered with BCG-CWS vaccine and 90 controls without BCG-CWS) who underwent a standard treatment for cervical cancer from 2005 to 2021. The BCG-CWS group underwent repeated intradermal injections of the BCG-CWS vaccine before or immediately after the standard therapy start from 2011 to 2018. The vaccination was repeated weekly for 1 month, and then every 4 weeks thereafter. The effectiveness of the BCG-CWS vaccination on cervical cancer treatment was evaluated by determining the hazard ratios of overall survival between the BCG-CWS group and the control group with multivariate analysis using the Cox model. Hazard ratios between 2 groups were determined after adjustment by clinical parameters including surgery, chemotherapy, radiation, age, clinical stage, presence of human papillomavirus, and pathology. Long-term follow-up revealed a significantly better prognosis (hazard ratio: 0.2108, P = .008 by the Cox model) for patients with cervical cancer in the BCG-CWS group compared to patients in the control group. Among patients with advanced cancer worse than stage IB2, some completely cleared the disease, whereas the others showed long-term survival with recurrence. BCG-CWS therapy appears to be an effective immune adjuvant therapy for cervical cancer, although randomized control studies are needed to confirm this. We also need to clarify the underlying mechanisms slowing the progression of cervical cancer in those receiving this vaccination. This study sheds light on the potential of immunostimulatory drugs such as BCG-CWS and suggests the important role of immunity for cancer elimination in combination therapy.     

Familial giant hypertrophic gastritis (Ménétrier's disease).

Familial giant hypertrophic gastritis involving three generations is reported. A review of the literature, where approximately 200 cases are described, showed only few cases of familial occurrence of this disease, and only in siblings. Our findings suggest dominant heredity, but considering the sparsity of familial occurrence reported earlier, heredity seems to be of only minor pathogenetic significance.     

Associação entre Ácido Úrico Sérico e Pré-Hipertensão e Hipertensão entre Adultos Chineses

BackgroundUric acid (UA), the end product of purine nucleotide metabolism, participates in the processes of metabolic and cardiovascular diseases. Experimental evidence suggests it is an important mediator in the physiological response to blood pressure increase.ObjectiveTo evaluate the association between serum UA levels and pre-hypertension and hypertension in a Chinese population.MethodsA cross-sectional study was conducted from March to September 2017, and 1,138 participants aged 35 to 75 were enrolled in this study, where 223 normotensive, 316 pre-hypertensive, and 599 hypertensive subjects were selected to evaluate the association between serum UA levels and hypertension. A p-value <0.05 was considered statistically significant.ResultsSerum UA levels were significantly higher in the pre-hypertension and hypertension group compared to the control group in the entire population (p<0.05 for all). Quantitative trait analysis indicated that serum UA levels were (2.92±0.81, 3.06±0.85, 3.22±0.98 mg/d) linearly increased in normotensive, pre-hypertensive and hypertensive females, with a p value of 0.008. Serum UA levels in the quartiles were positively correlated with DBP (p<0.05), particularly in females. After adjusting for age, gender, body mass index (BMI), glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-hypertension from the lowest (referent) to the highest levels of serum UA were 1.718 (1.028–2.872), 1.018 (0.627–1.654) and 1.738 (1.003–3.010). Additionally, the second quartile of serum UA levels were significantly associated with hypertension, with an OR (95% CI) of 2.036 (1.256–3.298).ConclusionsThis study suggests that higher serum UA levels are positively associated with pre-hypertension and hypertension among Chinese adults.     

Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca

BackgroundPharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible.ObjectivesThis study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined.MethodsPatients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05.ResultsElderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients.ConclusionPharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.     

Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL)

Background:Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies.Objective:We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization).Methods:Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05.Results:Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22).Conclusion:Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.     

Perfil de IL-6 e TNF na Formação de Células Espumosas: Um Método Aprimorado Usando a Sonda de Isotiocianato de Fluoresceína (FITC)

BackgroundThe formation of foam cells occurs due to the increase in low-density plasma lipoprotein (LDL) and dysregulation of inflammation, which is important for the development of atherosclerosis.ObjectiveTo evaluate the profile of tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) in the existing foam cell formation method, optimizing this protocol.MethodsThe LDL was isolated, oxidized, and labeled with a Fluorescein isothiocyanate (FITC) probe. Foam cells were generated from THP-1 human monocyte-derived cells and incubated in the absence (control) or presence of FITC-ox-LDL (10, 50, 100, 150, or 200 μg/mL), for 12, 24, 48, or 72 hours. The accumulated FITC-ox-LDL in the cell was quantified by microscopy. The enzyme-linked immunosorbent assay was evaluated to quantify the IL-6 and TNF-α, with p < 0.05 considered significant.ResultsAll the FITC-ox-LDL concentrations tested showed a higher fluorescence when compared to the control, showing a greater accumulation of lipoprotein in cells. The higher the concentration of FITC-ox-LDL, the greater the production of TNF-α and IL-6. The production of IL-6 by foam cells was detected up to the value of 150 µg/mL of the maximum stimulus for LDL. Concentrations above 50 μg/mL LDL stimulated greater release of TNF-α compared to control.ConclusionsOur model contributes to the understanding of the release of IL-6 and TNF-α in response to different concentrations of ox-LDL, using an optimized method for the formation of foam cells.     

Hábito Alimentar de Idosos Diabéticos e não Diabéticos: Vigitel,Brasil, 2016

BackgroundA healthy diet is a protection factor against type 2 diabetes and plays an important role in the treatment of the disease, as well as associated comorbidities.ObjectiveCharacterize the eating habits of older adults (≥ 65 years) with and without diabetes residing in capital cities and the Federal District of Brazil.MethodsA cross-sectional study was conducted using data from the Surveillance of Risk and Protection Factors for Chronic Diseases Through a Telephone Survey (Vigitel, 2016). The prevalence of diabetes mellitus was estimated according to sociodemographic variables, physical inactivity level, self-rated health status and body mass index. Dietary habits were assessed based on the frequency (weekly and daily) of consumption of healthy and unhealthy foods and the replacement of food by snacks. Differences were determined using Pearson’s chi-square test (Rao-Scott), with the significance level set at 5%.ResultsA total of 13,649 older adults were interviewed. The prevalence of self-reported diabetes was 27.2% (95% CI: 25.5; 29.0). Compared to non-diabetics, diabetic individuals had a higher consumption of raw vegetables (32.1% vs. 26.5%/3-4 days/week) and lower consumption of chicken (3.8% vs. 6.4%/hardly ever/never), fruit juice (24.0% vs. 29.6%) and sweets (6.8% vs. 16.2%) ≥ 5 days/week. Compared to non-diabetics, diabetic individuals consumed more skim milk (51.5% vs. 44.6%) and diet soda (60.0% vs. 17.3%) ≥ 5 days/week, raw vegetables (9.1% vs. 2.5%/at dinner) and sweets (37.7% vs. 20.5%/twice/day) 3-4 days/week.ConclusionThe observed differences emphasize the need for healthy eating interventions for all older adults, as well as specific counseling for those with diabetes.     

Fístulas da Artéria Coronária

Coronary artery fistula is a rare anatomic abnormality of the coronary arteries that affects 0.002% of the general population and represents 14% of all anomalies of coronary arteries. Its clinical relevance focuses mainly on the mechanism of the coronary steal phenomenon, causing myocardial functional ischemia, even in the absence of stenosis; therefore, angina and effort dyspnea are common symptoms. The suggested diagnostic approach is driven by patients’ symptoms, and it consists of a number of instrumental examinations like ECG, treadmill test, echocardiography, computed tomography scan, cardiac magnetic resonance, and coronary angiography. If it is not an incidental finding, coronary angiography is required in view of optimal therapeutic planning. Small fistulae are usually asymptomatic, and prognosis is excellent if they are managed medically with clinical follow-up and echocardiography every 2 to 5 years. Large/giant, symptomatic fistulae, on the contrary, should undergo invasive closure, via either transcatheter approach or surgical ligation, whose results are equivalent at long-term follow-up. Antibiotic prophylaxis for prevention of bacterial endocarditis is recommended in all patients with coronary artery fistulae who undergo dental, gastrointestinal, or urological procedures. Life-long follow-up is always essential to ensure that the patient does not undergo progression of the disease or further cardiac complications.     

Avaliação da Senescência de Células Sanguíneas Mononucleares Periféricas e na Disfunção Endotelial entre Adultos com Alto Risco Cardiovascular

BackgroundCardiovascular diseases (CVD) are one of the leading causes of mortality and morbidity worldwide. Biological aging has been associated with the occurrence of adverse cardiovascular outcomes; however, the underlying mechanism of this process remains unknown.ObjectivesThis study sought to evaluate if peripheral blood mononuclear cell (PBMC) senescence and endothelial biomarkers could influence cardiovascular (CV) risk and be suitable markers for the early detection of cardiovascular diseases in adults.MethodsIn this cross-sectional study patients free of CVD were classified as lower (n=32) and higher Interheart Risk (IHR) scores (n=28). PBMC senescence was assessed by estimating the telomerase activity (TA) and detecting the presence of senescent cells and endothelial dysfunction by estimating the concentration of nitrite and nitrate and of total antioxidant capacity (TAC). Statistical analysis was performed with SPSS version 16.0 (SPSS Inc., Chicago, IL). All p-values <0.05 were considered statistically significant.ResultsPBMC senescence 0.95 [p-value = 0.0001; 95% CI (0.874-1.026)] was a significant predictor of patients with higher IHR scores with a cut-off value of 21.65 with a sensitivity and specificity of 92% and 88% respectively. PBMC senescence, nitrite and nitrate and TA were found to be independently associated with high IHR scores.ConclusionPBMC senescence, TA and nitrite, and nitrate status are suitable measures to predict high cardiovascular risk in adults with CV risk. Nevertheless, long-term follow-up studies are needed to confirm these findings. (Arq Bras Cardiol. 2021; 116(1):37-47)