Evaluation of oxidative stress in an experimental model of Crohn's disease treated with hyperbaric oxygen therapy

Abstract Introduction: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD. Methods: Sixty male BALBc mice were divided into six groups. Group 1 was colitis-induced with trinitrobenzene sulfonic acid (TNBS) + ethanol, group 2 received TNBS + ethanol plus HBO, group 3 received only ethanol, group 4 received ethanol plus HBO, group 5 received saline solution, and group 6 received saline solution plus HBO. HBO was performed for four days, subsequently, the mice were evaluated daily. At the end of the study, samples from the intestine were collected for histological analysis as well as for measurement of antioxidant enzymes and cytokine levels. Results: HBO significantly improved the clinical and histological status of the animals. Treatment with HBO increased the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in all of the groups; moreover, the difference was only significant between the TNBS and TNBS + HBO groups and treatments promoted a reduction in the proinflammatory cytokines IFN-γ, IL-12, IL-17 and TNF-α and increased the anti-inflammatory cytokines IL-4 and IL-10, with no changes in IL-13. Conclusion: HBO effectively treats TNBS-induced colitis by increasing the activity of antioxidant enzymes and modulating cytokine profiles.

Relationship between lipoprotein (a) and subclinical carotid atherosclerosis in asymptomatic individuals

Abstract Background: This study aimed to evaluate the associations between Lipoprotein (a) ‒ Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. Methods: A total of 317 healthy normolipidemic subjects (20‒77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. Results: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. Conclusion: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.

Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration

Abstract Objectives Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). Method The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. Results PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. Conclusions The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.

Monocyte-to-HDL ratio and non-HDL cholesterol were predictors of septic shock in newborns

Abstract Background The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis. Methods This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admission (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry. Results Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL cholesterol on D0 were risk factors for septic shock (OR = 0.70, 0.49‒0.99; OR = 0.96, 0.92‒0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93‒0.99), VLDLc (OR = 0.91, 0.85‒0.98), and non-HDL cholesterol (OR = 0.92, 0.87‒0.98) were also predictors of septic shock. Conclusions Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis.

Development of a clinical laboratory data base of hyper and hypo alpha lipoproteins in Campinas-SP and neighboring region / Construção de um banco de dados clínico laboratorial de hiper e hipoalfalipoproteinêmicos em Campinas-SP e região

INTRODUCTION: The development of research for diagnosis, prevention and treatment of atherosclerotic cardiovascular disease is of utmost importance due to the fact that it is the main cause of morbidity and mortality in Brazil. OBJECTIVE: To demonstrate the phases of the selection process for candidates with the aim to develop a clinical-laboratorial database of hyper alpha lipoproteinemic patients (hyper A) - high density lipoprotein cholesterol (HDL-C) ≥ 68 mg/dl) and hypo alpha lipoproteinemic patients (hypo A) - HDL-C < 39 mg/dl. MATERIAL AND METHODS: The volunteers were contacted after selection of lipid profiles from individuals treated at the Sistema Único de Saúde (SUS), Campinas-SP and neighboring area. Afterwards, the selected patients went through blood collection, clinical examinations and answered questionnaires on dietary frequency and physical activity. After this preliminary evaluation, some individuals were convened to another blood collection and, subsequently, were submitted to an ultrasonographic exam of the carotid arteries. RESULTS: Only 0.6% and 0.3% from 598,288 lipid profiles were selected for hyper A and hypo A groups, respectively, including gender disparity. Lack of effective questionnaires (75%), missing calls (60%) and non-inclusion were the major hindrances in the construction of this database. DISCUSSION: The difficulties to obtain eligible candidates were also due to the low prevalence of both groups hypo A and hyper A and the high prevalence of pathologies that contribute to non-genetic variations of HDL-C. CONCLUSION: In spite of the obstacles in the development of this database, this study brought about several scientific publications. Furthermore, the development of molecular analyzes and functionality will shortly generate other findings, contributing to the diagnosis and follow-up of HDL dyslipidemias.

INTRODUÇÃO: O desenvolvimento de pesquisa para diagnóstico e prevenção da doença aterosclerótica cardiovascular no Brasil é de grande importância por esta ser a principal causa de morbimortalidade no país. OBJETIVO: Demonstrar as etapas do processo de seleção de voluntários para a construção de um banco de dados clínico-laboratorial de indivíduos hiperalfalipoproteinêmicos (hiper A) - colesterol da lipoproteína de alta densidade (HDL-C) ≥ 68 mg/dl - e hipoalfalipoproteinêmicos (hipo A) - HDL-C < 39 mg/dl. MATERIAL E MÉTODOS: Os voluntários são contatados a partir de resultados de perfis lipídicos de indivíduos atendidos pelo Sistema Único de Saúde (SUS) de Campinas-SP e região e, se selecionados, são convidados para coleta de sangue, exames clínicos e responder a questionários de atividade física e de frequência alimentar. Após essa avaliação, os indivíduos podem ser convocados para nova coleta de sangue e, posteriormente, para a ultrassonografia de carótidas. RESULTADOS: Entre 598.288 perfis lipídicos recebidos das redes públicas, apenas 0,6% e 0,3% compuseram os nossos grupos hiper A e hipo A, com disparidade entre os gêneros. A falta de questionários efetivos (75%), das chamadas não atendidas (60%) e a não inclusão foram os pontos mais difíceis na construção do banco de dados. DISCUSSÃO: A dificuldade de obtenção de voluntários elegíveis também se deve à baixa prevalência de hipo A e hiper A e à alta prevalência de patologias que contribuem para variações não genéticas do HDL-C. CONCLUSÃO: Apesar das dificuldades na criação da base de dados, este estudo gerou várias publicações e, com o desenvolvimento das análises moleculares e da funcionalidade, muitas outras seguirão em curto período, fatos contribuintes para o diagnóstico e o acompanhamento das dislipidemias envolvendo a HDL.