Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection.

BACKGROUND AND AIMS: Redox signaling is involved in the pathophysiology of aortic aneurysm/dissection. Protein Disulfide Isomerases and its prototype PDIA1 are thiol redox chaperones mainly from endoplasmic reticulum (ER), while PDIA1 cell surface pool redox-regulates thrombosis, cytoskeleton remodeling and integrin activation, which are mechanisms involved in aortic disease. Here we investigate the roles of PDIA1 in aortic dissection. METHODS: Initially, we assessed the outcome of aortic aneurysm/dissection in transgenic PDIA1-overexpressing FVB mice using a model of 28-day exposure to lysyl oxidase inhibitor BAPN plus angiotensin-II infusion. In a second protocol, we assessed the effects of PDIA1 inhibitor isoquercetin (IQ) against aortic dissection in C57BL/6 mice exposed to BAPN for 28 days. RESULTS: Transgenic PDIA1 overexpression associated with ca. 50% (p = 0.022) decrease (vs.wild-type) in mortality due to abdominal aortic rupture and protected against elastic fiber breaks in thoracic aorta. Conversely, exposure of mice to IQ increased thoracic aorta dissection-related mortality rates, from ca. 18%-50% within 28-days (p = 0.019); elastic fiber disruption and collagen deposition were also enhanced. The structurally-related compound diosmetin, which does not inhibit PDI, had negligible effects. In parallel, stretch-tension curves indicated that IQ amplified a ductile-type of biomechanical failure vs. control or BAPN-exposed mice aortas. IQ-induced effects seemed unassociated with nonspecific antioxidant effects or ER stress. In both models, echocardiographic analysis of surviving mice suggested that aortic rupture was dissociated from progressive dilatation. CONCLUSIONS: Our data indicate a protective role of PDIA1 against aortic dissection/rupture and potentially uncovers a novel integrative mechanism coupling redox and biomechanical homeostasis in vascular remodeling.

Avaliação acerca do conhecimento sobre a dengue em jovens em idade escolar / Evaluation about dengue knowledge of children at school age

INTRODUÇÃO: A dengue é uma arbovirose, transmitida para o homem através da picada do mosquito Aedes aegypti, e que acomete grande número de indivíduos no mundo. Nos últimos 50 anos, junto com o aumento da expansão geográfica, a incidência de dengue aumentou aproximadamente 30 vezes. Ao longo dos anos, diversas medidas de combate à dengue foram implementadas, a partir daí, no ano de 2004 foi possível evidenciar que houve redução de 290% nos casos de dengue em relação ao ano anterior. OBJETIVO: Descrever o conhecimento de escolares do Rio Grande do Sul sobre o tema dengue. MÉTODOS: Estudo com abordagem quantitativa do tipo descritiva realizado com jovens alunos da rede pública de educação da cidade de Tupãnciretã, por meio de um questionário estruturado. RESULTADOS: Evidenciou-se que a maioria dos alunos tinha conhecimento sobre como a dengue é transmitida, sendo que 35% acreditavam que a fêmea do mosquito transmite a doença e ainda, 58,8% afirmaram que conseguem reconhecer o mosquito. Uma parcela dos alunos acredita que o mosquito pica preferencialmente durante o dia, onde a principal forma de transmissão selecionada foi "O mosquito pica uma pessoa doente e transmite a doença à outra pessoa" e os principais sintomas assinalados foram febre, dor de cabeça e cansaço. CONCLUSÃO: O estudo demonstrou que boa parte dos jovens possuem conhecimentos sobre a dengue, entretanto, ainda há crianças e adolescentes que não conhecem o assunto, trazendo à tona a importância deste tema nas campanhas de saúde.

INTRODUCTION: Dengue is an arbovirus, transmitted to humans through the bite of the Aedes aegypti mosquito, and which affects a large number of individuals in the world. Over the past 50 years, along with increased geographic expansion, the incidence of dengue increased approximately 30-fold. Over the years, several measures to combat dengue have been implemented and due to this factor, in 2004, there was a 290% reduction in dengue cases in relation to the previous year. OBJECTIVE: To describe the knowledge of schoolchildren from Rio Grande do Sul on the subject of dengue. METHODS: A quantitative descriptive study carried out with young students of the public education system of the city of Tupãnciretã, through a structured questionnaire. RESULTS: It was evidenced that most of the students had knowledge about how dengue is transmitted, 35% believed that the mosquito female transmits the disease and 58.8% claim to be able to recognize the mosquito. A significant portion of the students believe that the mosquito bites preferentially during the day, where the main form of transmission selected was "The mosquito bites a sick person and transmits the disease to the other person" and the main symptoms were fever, headache and tiredness. CONCLUSION: The study showed that most of the young people have knowledge about dengue, however, there are still children and adolescents who do not know the subject, bringing to the fore the importance of this theme in health campaigns.

Inhibitory effect of Campomanesia xanthocarpa in platelet aggregation: Comparison and synergism with acetylsalicylic acid.

BACKGROUND AND AIMS: Cardiovascular diseases of thrombotic origin are related to high mortality and standard therapeutic agent used in this case is acetylsalicylic acid (ASA), but serious adverse events may occur. However, recent data has suggested the plant Campomanesia xanthocarpa has antiplatelet activity and could be a viable alternative. In this study we investigated the effects of the encapsulated powder of this plant in human platelet aggregation. METHODS: 23 healthy subjects were randomly divided into three groups: (1) ASA (100mg), (2) C. xanthocarpa (1000mg) or (3) synergism (500mg of C. xanthocarpa plush 50mg of ASA); daily for five days. Antiplatelet activity was determined by turbidimetric method using ADP or arachidonic acid (AA) agonists before, 5 and 8days after treatments. RESULTS: Treatment with C. xanthocarpa and synergism caused a reduction of 8±13.5% and 12.5±5% in platelet aggregation induced by ADP after 5days of treatment, respectively, returning to basal levels after 8days. For AA agonist, 5days of treatment with C. xanthocarpa, ASA or synergism caused a reduction of 46±15%, 36±12% and 69.3±6% in platelet aggregation, respectively, and first two groups returned to baseline values 8days after treatment ended. Synergism group prolonged antiplatelet effect maintaining aggregation reduction after 8days the end of treatment. CONCLUSION: C. xanthocarpa showed antiplatelet action when stimulated by agonist AA, and contributed to the antiplatelet effect when associated with ASA for both agonists, allowing dose reduction to 50mg.

Natural Products with Antiplatelet Action.

BACKGROUND: Complex hemostatic mechanisms are involved in the pathophysiology of various diseases, including cardiovascular diseases. Among them, dysregulation of platelet activity is linked to the progression of atherosclerosis and mainly involves platelet aggregation and a decrease in blood flow in the vascular endothelium. The major platelet activation pathways mediated by agonists involve the arachidonic acid pathway, adenosine diphosphate pathway, serotonin pathway, nitric oxide pathway, and action of free radicals on molecules involved in platelet aggregation. These mechanisms have been widely studied and discussed because they are inhibited by the use of medicinal plants in complementary and alternative medicine, thus reducing platelet aggregation. RESULTS: Of the main plants discussed in this review, which have antiplatelet activity, some include saffron, garlic, green tea, St. John's wort, ginger, ginkgo biloba, ginseng, and guavirova. These herbal medicines have phytochemical components, which are directly related to the antiplatelet activity of the plant, such as flavonoids, curcumins, catechins, terpenoids, polyphenols, and saponins. While the majority of the medicinal plants mentioned here were native to the Asian continents, some are distributed worldwide, and found to a smaller extent throughout the American continent, European continent, Mediterranean, African continent, and the Middle East. CONCLUSION: This review showed that several plants and/or compounds exhibit anti-platelet activity, and are therefore potential research targets for developing drugs to treat diseases related to aggregation disorders.

Study of oxidative and inflammatory parameters in LDLr-KO mice treated with a hypercholesterolemic diet: Comparison between the use of Campomanesia xanthocarpa and acetylsalicylic acid.

BACKGROUND: Atherosclerosis is an inflammatory disease that affects the arterial wall leading to myocardial, cerebral, and peripheral ischemic syndromes. The use of low doses of aspirin inhibits platelet aggregation and inflammation and prevents cardiovascular mortality. However, ASA may produce hemorrhagic events. Thus, several studies have sought new natural compounds to suppress platelet aggregation without causing serious adverse effects. PURPOSE: In this sense, this study aims to compare the effects of Campomanesia xanthocarpa plant extract with those of acetylsalicylic acid (ASA) on inflammatory parameters observed in homozygous mice knockout for the low-density lipoprotein receptor (LDLr-KO) treated with a hypercholesterolemic diet. MATERIAL AND METHODS: In this study, 28 male LDLr-KO mice were divided into three groups and fed a hypercholesterolemic diet for 4 weeks. Thereafter, the animals that received the hypercholesterolemic diet were treated for 5 days with (1) distilled water, (2) C. xanthocarpa extract, or (3) acetylsalicylic acid. The levels of inflammatory markers were assessed in the blood samples. The gastric tolerability of the animals after oral administration of the treatments was assessed through quantification of the lesions in the gastric mucosa. RESULTS: The levels of proinflammatory cytokines IL-1, IL-6, TNF-α, and INF-γ were reduced to 19.2 ± 3%, 20.4 + 1.3%, 24.7 ± 1.2%, and 20.8 ± 1.7%, respectively, in the group treated with C. xanthocarpa, when compared to control group. Furthermore, treatment with plant extract significantly increased the levels of the anti-inflammatory cytokine IL-10 by 27.3 ± 5.9%, but ASA showed no significant effect on the same cytokines when compared to the control group, with the exception of IL-10, which presented an increase of 8.6 ± 3.5%. Treatments with C. xanthocarpa and ASA also caused significant reductions of 26.4 ± 3% and 38.4± 6% in the serum levels of oxLDL, respectively. However, only treatment with C. xanthocarpa reduced the levels of anti-oxLDL antibodies when compared with the control (25.8 ± 6%). In addition, the analyzed extract did not induce ulcerogenic activity, while ASA induced the formation of lesions. CONCLUSION: In conclusion, treatment with C. xanthocarpa causes anti-inflammatory activity in hypercholesterolemic animals, with results superior to those obtained with the use of ASA.

Biomarkers of Subclinical Atherosclerosis and Natural Products as Complementary Alternative Medicine.

Cardiovascular diseases (CVD) are considered the leading cause of morbidity and mortality from chronic diseases in the world. In addition, about 20% of first and recurrent acute myocardial infarctions (MI) are silent. In this context, subclinical atherosclerosis culminates in evident CVD, through the evolution of early risk factors such as hypercholesterolemia, hypertriglyceridemia and others. The main problem in CVD is related to the long-time between the start of the subclinical atherosclerosis and the manifestation of the disease. The identification of subjects at risk of such events is obviously substantial, since identification leads to implementation and compliance with effective preventive measures that reduce such risk. In this sense, this review demonstrates biomarkers as an alternative to early detection of subclinical atherosclerosis. One of the proposed biomarkers is the Ischemia-modified albumin (IMA), being considered a promising biochemical biomarker for atherosclerotic conditions. Another marker that is gaining strength and is associated with the IMA are the advanced oxidation protein products (AOPP), its measurement provides information on the level of exposure to potentially harmful changes to proteins and metabolic control. And last but not least we have nitric oxide as an early marker mainly related to endothelial dysfunction. In this review also is evidenced the use of the Campomanesia xanthocarpa, a plant native to southern region from Brazil extensively used as complementary and alternative medicine, and natural products to reduce protein oxidation and improve the availability of nitric oxide and consequently vascular function, reducing the risk for development of CVD.

Association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals.

BACKGROUND: Although hypercholesterolemia is a well-established risk factor for coronary heart disease, evidence suggests that increased triglyceride (TG) concentrations are also an independent risk factor. TG concentrations >150mg/dl are observed nearly twice as often in subjects with atherosclerosis. We assessed the association between hypertriglyceridemia and protein oxidation and proinflammatory markers in normocholesterolemic and hypercholesterolemic individuals. METHODS: We included 127 volunteers enrolled in Cruz Alta, RS, Brazil. The patients were stratified based on total cholesterol and TG concentrations for analysis of associations with inflammation (high-sensitivity C-reactive protein - hs-CRP), endothelial dysfunction (nitric oxide - NOx) and oxidative stress (advanced oxidation protein products - AOPPs; ischemia-modified albumin - IMA). Correlations between variables were determined and multiple regression analysis was employed to investigate whether some variables correlate with TG concentrations. RESULTS: Hypertriglyceridemia was related to oxidative stress and proinflammatory markers in individuals independent of total cholesterol concentrations. Moreover, the results indicate a stronger association of tested biomarkers with TG concentrations than with total cholesterol. The results indicate a positive correlation between oxidative stress and TG concentrations in the sera of hypercholesterolemia subjects. AOPPs and IMA concentrations were associated with the presence of hypertriglyceridemia in a manner that was independent of age, gender, hypertension and diabetes mellitus disease, smoking habits, sedentary lifestyle, BMI, waist circumference, LDL, HDL and total cholesterol concentrations. CONCLUSIONS: We speculate that TG concentrations can reflect the enhancement of protein oxidation and proinflammation.