RESUMO
Relatamos um caso de dano hepático em paciente idosa após uso de produtos naturais à base de Hypericum perforatum e copaíba (Copaifera langsdorffii Desf). A hepatotoxicidade do Hypericum perforatum é conhecida por relatos, mas a respeito da copaíba, largamente usada como anti-inflamatório, há apenas dados experimentais na literatura nacional. Essa apresentação visou chamar a atenção para possível efeito tóxico dessa associação, bem como para a recuperação clínica da paciente após interrupção de seu uso. Há uma tendência de suspeitar sobre a ação de medicamentos para justificar a lesão hepática aguda não viral, em razão do grande número de fármacos responsáveis por hepatotoxicidade. A literatura tem publicado experimentos e relatos clínicos em que produtos fitoterápicos, inclusive Hypericum perforatum, são o agente causador dessa agressão, considerados inócuos e utilizados livremente. É preciso lembrar que reações adversas ocorrem também com essas substâncias, merecendo sua investigação na obtenção da anamnese, pela possibilidade de promoverem quadros graves de falência hepática.
We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure.
Assuntos
Idoso , Feminino , Humanos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fabaceae/efeitos adversos , Fabaceae/toxicidade , Hypericum/efeitos adversos , Fitoterapia/efeitos adversos , Extratos Vegetais/efeitos adversosRESUMO
OBJECTIVES: Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated. METHODS: Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections. RESULTS: LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1ß and tumor necrosis factor-α), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase IIα and tubulin). CONCLUSION: The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.
Assuntos
Aterosclerose/tratamento farmacológico , Colesterol/administração & dosagem , Etoposídeo/farmacologia , Nanoestruturas/administração & dosagem , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Ingestão de Alimentos/efeitos dos fármacos , Emulsões/administração & dosagem , Emulsões/farmacologia , Emulsões/toxicidade , Eritrócitos/efeitos dos fármacos , Etoposídeo/toxicidade , Histocitoquímica , Leucócitos/efeitos dos fármacos , Lipoproteínas/sangue , Masculino , Nanoestruturas/toxicidade , Coelhos , Receptores de LDL/sangue , Testes de ToxicidadeRESUMO
OBJECTIVE: To verify whether the capacity of high-density lipoprotein (HDL) to simultaneously receive nonesterified cholesterol, triglycerides, cholesteryl esters, and phospholipids changes with aging and the presence of coronary artery disease. DESIGN: Cross-sectional study with biochemical analyses. SUBJECTS: Eleven elderly patients with coronary artery disease (74±5 years) were compared with the following groups of non-coronary artery disease subjects (referred to as "healthy"): 25 young (25±5 years), 25 middle-aged (42± years), and 25 elderly subjects (75±8 years). METHODS: Plasma samples were incubated with a nanoemulsion labeled with radioactive lipids; the transfer of the lipids from the nanoemulsion to the HDL was measured in chemically precipitated HDL. HDL size and paraoxonase-1 activity were also determined. RESULTS: The transfer of cholesteryl esters and phospholipids to high-density lipoprotein was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. Non-esterified cholesterol and triglyceride transfer was not different among these three groups. The HDL size was significantly greater (p<0.001) in healthy elderly subjects than in the middle-aged and younger subjects. The paraoxonase-1 activity was similar among the groups. Compared with healthy elderly subjects, coronary artery disease elderly subjects had significantly less (p<0.05) transfer of non-esterified cholesterol, triglycerides, and cholesteryl esters to the HDL and a significantly smaller (p<0.05) HDL size. CONCLUSION: Because lipid transfer is enhanced in healthy elderly subjects but not in those with coronary artery disease, increasing lipid transfer to HDL may be a protective mechanism against the disease.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envelhecimento/sangue , Ésteres do Colesterol/sangue , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Fosfolipídeos/sangue , Triglicerídeos/sangue , Arildialquilfosfatase/sangue , Emulsões , Métodos Epidemiológicos , Nanopartículas , Tamanho da PartículaRESUMO
Os fármacos hipolipemiantes, apesar de diminuírem a morbimortalidade por doença coronariana, não são destituídos de efeitos indesejáveis. Estes freqüentemente são transitórios, mas podem ocorrer alterações clínicas e laboratoriais que exigem especial atenção e diferentes condutas. Neste artigo, os autores relatam fundamentalmente como proceder diante do comprometimento muscular e hepático, considerados efeitos adversos mais relevantes dos hipolipemiantes. De modo sucinto, apontam os demais efeitos e a respectiva conduta.
Hypolipemic drugs improve coronary morbidity and mortality and appear to be safe; nevertheless appropriate monitoring is recommended. Adverse effects are reported that are frequently transitory. Severe adverse effects are infrequent, but clinicians must correctly screen them; symptoms and laboratory changes must be carefully interpreted. Often they call for special treatment and replacement of the hypolipemic drugs in use. This article emphasizes how to treat dyslipidemia if skeletal muscle and liver involvement are present. Briefly other adverse effects are also reported.
Assuntos
Humanos , Hipolipemiantes/efeitos adversos , Hepatopatias/induzido quimicamente , Doenças Musculares/induzido quimicamente , Ensaios Clínicos como Assunto , Enzimas/efeitos dos fármacosRESUMO
Variants in leptin gene (LEP) have been implicated in the pathogenesis of obesity. The relationship between LEP G-2548A polymorphism and obesity-related traits was evaluated in a sample of Brazilian women (n = 228) who were randomly selected from two clinical centers in Sao Paulo city. Blood samples were collected for DNA extraction, plasma leptin and serum lipids measurements. LEP G-2548A genotypes were identified by a PCR- RFLP strategy using the endonuclease Alw44I. LEP G-2548A was associated with obesity after adjustment for covariates (age, hypertension, coronary artery disease, smoking and physical activity). Women carrying G allele had a four times higher risk of obesity than the A allele carriers (OR: 4.11, CI95%: 1.06-15.90, p = 0.041). G allele was also related to increased plasma leptin (p = 0.024) and body mass index (p = 0.027). Hypertension, hyperglycemia, dyslipidemia and coronary artery disease were associated with obesity. However LEP G-2548A polymorphism was not related to these variables. All together these data suggest that LEP G-2548A polymorphism has an important role in regulating plasma leptin levels and body mass index in women.
Assuntos
Leptina/sangue , Leptina/genética , Obesidade/sangue , Obesidade/genética , Regiões Promotoras Genéticas/genética , Índice de Massa Corporal , Brasil , DNA/análise , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Polimorfismo de Fragmento de RestriçãoRESUMO
Variants in leptin gene (LEP) have been implicated in the pathogenesis of obesity. The relationship between LEP G-2548A polymorphism and obesity-related traits was evaluated in a sample of Brazilian women (n = 228) who were randomly selected from two clinical centers in Sao Paulo city. Blood samples were collected for DNA extraction, plasma leptin and serum lipids measurements. LEP G-2548A genotypes were identified by a PCR- RFLP strategy using the endonuclease Alw44I. LEP G-2548A was associated with obesity after adjustment for covariates (age, hypertension, coronary artery disease, smoking and physical activity). Women carrying G allele had a four times higher risk of obesity than the A allele carriers (OR: 4.11, CI95 percent: 1.06-15.90, p = 0.041). G allele was also related to increased plasma leptin (p = 0.024) and body mass index (p = 0.027). Hypertension, hyperglycemia, dyslipidemia and coronary artery disease were associated with obesity. However LEP G-2548A polymorphism was not related to these variables. All together these data suggest that LEP G-2548A polymorphism has an important role in regulating plasma leptin levels and body mass index in women.
Variantes no gene da leptina (LEP) foram implicados na patogênese da obesidade. A relação entre o polimorfismo LEP G-2548A e as características relacionadas com a obesidade foram avaliadas em mulheres brasileiras (n = 228), que foram selecionadas randomicamente de dois centros de pesquisa clínica na cidade de São Paulo. As amostras de sangue foram coletadas para extração de DNA e determinações de leptina plasmática e lipídeos séricos. Os genótipos do LEP G-2548A foram identificados pela estratégia de PCR-RFLP, empregando a endonuclease Alw44I. O polimorfismo LEP G-2548A foi associado com obesidade, após ajuste para as covariáveis: idade, hipertensão, doença arterial coronariana, tabagismo e atividade física. Mulheres com alelo G tiveram quatro vezes maior risco de obesidade que as portadoras do alelo A (OR: 4,11, CI95 por cento: 1,06-15,90; p = 0,041). O alelo G também foi relacionado com leptina plasmática (p = 0,024) e o índice de massa corporal (p = 0,027) aumentado. A hipertensão, a hiperglicemia, a dislipidemia e a doença arterial coronariana foram associadas com obesidade. Entretanto, o polimorfismo LEP G-2548A não foi relacionado com essas variáveis. Os resultados deste estudo são sugestivos de que o polimorfismo LEP G-2548A tem papel importante na regulação da leptina plasmática e no índice de massa corporal em mulheres.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Leptina/sangue , Leptina/genética , Obesidade/sangue , Obesidade/genética , Regiões Promotoras Genéticas/genética , Índice de Massa Corporal , Brasil , DNA , Frequência do Gene , Genótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo Genético/genéticaRESUMO
OBJECTIVES: To evaluate the effectiveness of and tolerability to sustained-release bupropion, in smokers with cardiovascular diseases treated in a smoking cessation service, as well as to investigate variables predictive of success or failure in smoking cessation. METHODS: Sustained-release bupropion was prescribed to 100 current smokers with cardiovascular disease for 12 weeks. Patients were followed for 52 week. The variables studied were gender, age, number of cigarettes, exhaled carbon monoxide, nicotine dependence (Fagerstrom Tolerance Questionnaire), depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), alcohol consumption (Alcohol Use Disorders Identification Test), number of diagnoses other than smoking, adverse events, and use of medications concomitantly with sustained-release bupropion. RESULTS: Abstinence rate was 50% at week 12 and 25% at week 52. The logistic regression analysis showed that ageing was positively associated with success, whereas the worsening of the condition, as verified by the presence of a higher number of other health conditions associated with smoking, was negatively associated with success. CONCLUSION: We conclude that the prescription of bupropion for smokers with cardiovascular diseases proved to be safe and effective, especially during the treatment period (week 12).
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Doenças Cardiovasculares/complicações , Fumar/tratamento farmacológico , Adulto , Idoso , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversos , Abandono do Hábito de Fumar/métodos , Resultado do TratamentoRESUMO
A apolipoproteína (apo) B faz parte das frações lipídicas aterogênicas (Qm e VLDL remanescentes, LDL,Lp (a)) e a apo A-I da fração não-aterogênica (HDL). A determinação dessas apos é direta, automatizada, padronizada, com coeficiente de variação pequeno e não requer jejum. Os autores revisaram os principais estudos clinico-epidemiológicos e de intervenção terapêutica nas hiperlipidemias nos quais as apos B e A-I foram avaliadas. Esses estudos sinalizaram a importância das apos B e A-I no prognóstico de risco e permitiram que especialistas recomendassem a relação apo B / apo A-I como alternativa à já utilizada CT / HDL-c no cálculo de risco. Aguarda-se posicionamento futuro das Diretrizes para incluir as apos na avaliação do risco individual e objetivo terapêutico a ser atingido. Os autores sugerem que, na prática clínica, a determinação de apo B deve ser reservada ao coronariopatas com valores desejáveis de LDL-c ou na impossibilidade de seu cálculo e a de apo A-I, quando os valores de HDL-c são muito baixos.
Apolipoprotein (apo) B is present in atherogenic lipoproteins (remnant Qm and VLDL, LDL and Lp (a)) and apo A is present in non-atherogenic lipoprotein (HDL). Measurement of the apos is automated, standardized, with a small variation of coefficient and does not require fasting blood samples. The authors reviewed clinical, epidemiological and therapeutic trials on hyperlipidemia with apo B and A-I evaluation. These works showed the importance of apo B and A-I as cardiovascular risk factors. Experts recommended apo B / apo A-I ratio as an alternative to TC / HDL-c ratio for risk estimate. Future positioning from the Guidelines is expected to include apos in individual risk prediction and as a therapeutic target. The authors suggest that, in clinical practice, measurement of apo B is necessary for coronary heart disease patients with desirable LDLc levels or when this assessment is not possible and the measurement of apo A-I if HDL-c values are very low.
Assuntos
Humanos , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , Doença da Artéria Coronariana/sangue , Anticolesterolemiantes/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/prevenção & controle , Estudos Epidemiológicos , Hiperlipidemias/tratamento farmacológico , Lipoproteínas HDL/sangue , Prognóstico , Fatores de RiscoAssuntos
Doença da Artéria Coronariana/prevenção & controle , Hiperlipidemias/terapia , Metabolismo dos Lipídeos/fisiologia , Adulto , Distribuição por Idade , Idoso , Colesterol/sangue , Ácido Clofíbrico/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Dieta , Feminino , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/fisiopatologia , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Fatores de Risco , Distribuição por Sexo , Fumar/efeitos adversos , Triglicerídeos/sangueAssuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/prevenção & controle , Hiperlipidemias/terapia , Metabolismo dos Lipídeos/fisiologia , Distribuição por Idade , Hipolipemiantes/uso terapêutico , Colesterol/sangue , Ácido Clofíbrico/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Dieta , Hiperlipidemias/complicações , Hiperlipidemias/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Síndrome Metabólica/complicações , Naftalenos/uso terapêutico , Fatores de Risco , Distribuição por Sexo , Fumar/efeitos adversos , Triglicerídeos/sangueRESUMO
OBJETIVOS: Avaliar a efetividade e a tolerabilidade da bupropiona no tratamento de fumantes com doenças cardiovasculares atendidos em rotina de tratamento ambulatorial do tabagismo, e analisar as variáveis preditoras de sucesso ou fracasso. MÉTODOS: A bupropiona foi prescrita de forma exclusiva para tratamento do tabagismo em 100 pacientes cardiopatas durante 12 semanas. O seguimento foi de 52 semanas. As variáveis estudadas foram sexo, idade, número de cigarros, concentração de monóxido de carbono, escala de dependência de nicotina, escala de depressão, escala de ansiedade, consumo de álcool, número de diagnósticos adicionais ao tabagismo, eventos adversos, e consumo de medicamentos concomitantes à bupropiona. RESULTADOS: A taxa de sucesso depois de 12 semanas foi de 50 por cento e depois de 52 semanas, de 25 por cento. A análise de regressão logística revelou que o envelhecimento foi positivamente associado ao sucesso e que o agravo da condição clínica, observado pelo maior número de diagnósticos associados ao tabagismo, foi negativamente associado ao sucesso. CONCLUSÃO: A bupropiona mostrou-se segura e com boa efetividade no tratamento de fumantes portadores de doenças cardiovasculares, especialmente durante a fase de uso (semana 12).
OBJECTIVES: To evaluate the effectiveness of and tolerability to sustained-release bupropion, in smokers with cardiovascular diseases treated in a smoking cessation service, as well as to investigate variables predictive of success or failure in smoking cessation. METHODS: Sustained-release bupropion was prescribed to 100 current smokers with cardiovascular disease for 12 weeks. Patients were followed for 52 week. The variables studied were gender, age, number of cigarettes, exhaled carbon monoxide, nicotine dependence (Fagerstrom Tolerance Questionnaire), depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), alcohol consumption (Alcohol Use Disorders Identification Test), number of diagnoses other than smoking, adverse events, and use of medications concomitantly with sustained-release bupropion. RESULTS: Abstinence rate was 50 percent at week 12 and 25 percent at week 52. The logistic regression analysis showed that ageing was positively associated with success, whereas the worsening of the condition, as verified by the presence of a higher number of other health conditions associated with smoking, was negatively associated with success. CONCLUSION: We conclude that the prescription of bupropion for smokers with cardiovascular diseases proved to be safe and effective, especially during the treatment period (week 12).
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Doenças Cardiovasculares/complicações , Fumar/tratamento farmacológico , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Seguimentos , Abandono do Hábito de Fumar/métodos , Fumar/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Metabolic syndrome and abdominal obesity are risk factors for cardiovascular diseases in middle age women but, not completely understood in older people. In this study we analyzed the association between metabolic syndrome and abdominal obesity and the occurrence of cardiovascular events in these elderly women. METHODS: A prospective follow-up study included 516 consecutive women aged 60-84 years who sought medical care at a geriatric outpatient facility. The presence of metabolic syndrome and higher quartiles of waist circumference and waist-to-hip ratio were analyzed as predictive variables, and were adjusted for age, smoking, and previous cardiovascular diseases. The outcomes were the occurrence of stroke, myocardial infarction, evidence of coronary artery disease, or cardiovascular death. RESULTS: During a mean follow-up of 6.6 years, 94 (18.2%) cardiovascular events were observed (48 fatal and 46 non-fatal). Metabolic syndrome was diagnosed in 206 women (39.9%). After adjustments for confounding variables, metabolic syndrome and waist-to-hip ratio above the 75th percentile (>0.98) were predictors of the outcomes, but greater waist circumference (>96 cm) was not. Adjusted hazard ratios for these variables were: metabolic syndrome, 1.66, 95% CI -1.11 to 2.47, p=0.01; waist-to-hip ratio, 1.72, 95% CI -1.05 to 2.82; p=0.03 and waist circumference, 1.37, 95% CI -0.91 to 2.07, p=0.12. CONCLUSION: Metabolic syndrome and high waist-to-hip ratio were associated with increased risk of cardiovascular events in the studied sample.
Assuntos
Doenças Cardiovasculares/etiologia , Síndrome Metabólica/complicações , Obesidade/complicações , Abdome , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores SexuaisRESUMO
A aterosclerose na infância e na adolescência, freqüentemente associada à obesidade, tem sido o foco de estudos internacionais que procuram entender a sua ontogênese. Devido às graves conseqüências possíveis, a aterosclerose na infância e na adolescência não só demanda ações preventivas multidisciplinares capazes de reduzir os fatores de risco já amplamente identificados, como obesidade, hipercolesterolemia familiar, tabagismo e sedentarismo, dentre outros, mas também clama pelo controle de fatores não tão claramente identificados, mas que podem contribuir para a sua patogênese. Dentre as variáveis ainda pouco conhecidas, que poderiam estar envolvidas na ontogênese da aterosclerose, encontram-se os fatores psicológicos e o stress emocional. Neste artigo, os autores versam sobre os aspectos psicológicos envolvidos na prevenção da aterosclerose e enfatizam a necessidade de uma mudança acentuada de estilo de vida, tanto no que se relaciona às atividades físicas e nutricionais como também às relacionadas às medidas anti-stress. Hábitos inadequados utilizados como estratégias de enfrentamento do stress emocional excessivo, como comer em excesso, entre outros, devem ser objeto de medidas preventivas na infância e na adolescência, visando substituí-los por estratégias de coping adequadas que reduzam o risco envolvido. Profissionais da área da saúde devem estar alertas para esses fatores subjacentes que podem contribuir para o desenvolvimento da doença aterosclerótica. Este trabalho foi compilado durante as discussões para a elaboração das I Diretrizes de Prevenção da Aterosclerose na Infância e na Adolescência e serviu de base para as recomendações incluídas na seção denominada "Aspectos Psicológicos na Prevenção da Aterosclerose" das Diretrizes.
Childhood and adolescent atherosclerosis, frequently associated with obesity, has been the focus of international studies that try to understand its development. Given its serious consequences, childhood and adolescent atherosclerosis not only demands multidisciplinary preventive actions that are capable of reducing the already very well identified risk factors, such as obesity, smoking, inactivity and familial hypercholesterolemia - just to mention some - but also calls for the control of factors that have not been clearly identified but that can contribute to its pathogenesis. Psychological factors and emotional stress are among the variables that are not yet fully known but nevertheless could be involved in the development of atherosclerosis. In this article, the authors discuss the psychological aspects involved in the prevention of atherosclerosis and emphasize the need for a dramatic change in lifestyle, which includes changing the levels of physical activity and eating habits and finding ways to fight or avoid stress. Inadequate habits employed as strategies to cope with excessive emotional stress, such as binge eating and others, should be targeted for preventive actions in childhood and adolescence and substituted by adequate coping strategies that have lower levels of risk. Health care professionals need to be watchful for these additional factors that can contribute to the development of atherosclerotic disease. This work was compiled during the discussion phase of the "I Guideline for Preventing Atherosclerosis in Childhood and Adolescence" and served as the basis for the recommendations included in its "Psychological Aspects in Preventing Atherosclerosis" section.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Estresse Psicológico , Adolescente , Aterosclerose , Estilo de VidaRESUMO
Advanced complicated atherosclerotic lesions have been related to many factors, including inflammation, infectious agents, and growth factors. Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP), inflammation, and growth factors have been associated with severe atherosclerotic lesions in necropsy material in recent work at our lab. The present study intends to clarify the pathogenesis of atherosclerosis, analyzing which of these elements (macrophages, MP, CP, lymphocytes, and growth factors) are associated with initial development of atherosclerotic lesions, discriminating elements related to stabilization of the plaque versus those related to subendothelial active accumulation of macrophages in living patients. Surgical ascending aorta fragments presenting mild atherosclerotic lesions from 30 coronary atherosclerotic patients were immunohistochemically quantified regarding CP, MP, T cells (CD4, CD8), B cells (CD20), macrophages (CD68), and growth factors [platelet-derived growth factor A (PDGF-A), PDGF-B, transforming growth factor-beta (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Cases were grouped according to the presence or not of active accumulation of macrophages at the subendothelium that indicates atheroma in development: group I (GI) fragments with <4 CD68+ cells/x400 field, in normal distribution (mean 1.8 +/- 1) representing stable atherosclerotic mild lesion, and GII fragments presenting >or=4 CD68+ cells/x400 field, in a non-normal distribution, mean (8.9 +/- 4.8, atheromas in progress), which was followed by increased number of lymphocytes. The median number in GI was significantly lower than that in GII: CD4 T (2.5 vs. 7.7), CD8 T (1.0 vs. 5.5), and CD20 B (1.5 vs. 5.5) cells/x400 field, p < 0.001. Percentage area positive for CP antigens was significantly lower in GI than in GII: 1.0 vs. 9.2, p < 0.001. There was a higher percentage area occupied by MP than CP in both GI and GII (7.8 vs. 13.8). There was no difference regarding mean number of growth factor-positive cells/x400 field: PDGF-A, 1.4 vs. 3.9; PDGF-B, 3.4 vs. 5.7; TGF-beta, 0.9 vs. 2.2; and GM-CSF, 2.0 vs. 2.2. Considering all cases, a positive correlation was seen between inflammatory cells and CP+ cells (r > 0.5 and p < 0.01). Growth factors did not correlate with inflammatory cells, CP, or MP and were usually seen in smooth muscle cell and fibrotic areas. Study of initial atherosclerotic lesions showed that MP is present in both kinds of lesion: stable and active subendothelial accumulation of macrophages. Stabilization was related to proportional increase of both infectious agents, which were also related to increased amount of PDGF-A and PDGF-B. Active macrophage accumulation lesions were related to higher elevation in CP concentration at subendothelial regions, in association with B cells, but not of MP and growth factors. MP and CP, inflammation, and growth factors, which were already described in severe atherosclerotic lesions in necropsy material, are also present in mild lesions in living patients, strongly favoring a pathogenetic role for these bacteria in the pathogenesis of atherosclerosis. Predominance of CP in relation to MP may favor progression of the plaque, which is associated with increased B-cell proliferation. PDGF-A and PDGF-B are associated with plaque stability, at least in arterial segments not prone for development of complicated lesions.
Assuntos
Aorta Torácica/patologia , Doenças da Aorta/patologia , Aterosclerose/patologia , Citocinas/análise , Bactérias Gram-Negativas/isolamento & purificação , Peptídeos e Proteínas de Sinalização Intercelular/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos CD20/análise , Antígenos de Diferenciação Mielomonocítica/análise , Aorta Torácica/química , Aorta Torácica/imunologia , Aorta Torácica/microbiologia , Doenças da Aorta/imunologia , Doenças da Aorta/metabolismo , Doenças da Aorta/microbiologia , Aterosclerose/imunologia , Aterosclerose/metabolismo , Aterosclerose/microbiologia , Linfócitos B/patologia , Biópsia , Chlamydophila pneumoniae/isolamento & purificação , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Humanos , Inflamação/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/isolamento & purificação , Fator de Crescimento Derivado de Plaquetas/análise , Linfócitos T/patologia , Fator de Crescimento Transformador beta/análiseRESUMO
Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP) antigens are encountered in complicated atheromas and may be implicated in the diversity of atherosclerotic lesions. Mycoplasma can downregulate the immune system, altering levels of inflammation, which may favor the proliferation of other co-infectious agents. In the present study we analyze whether initially stable human atheromas exhibit different ratios of MP/CP antigens compared to ongoing atheromatous lesions. Two groups were examined for the presence of inflammatory cells, macrophages, growth factors and infectious agents: Group I (GI), n=16, early stable atheromas, <4 CD68(+) macrophages/400 x field, showing a normal distribution and a fibrous cap; Group II (GII), n=14, growing atheromas, > or =4 CD68+ cells/400 x field, lacking a fibrous cap, showing a non-normal macrophage distribution. The amounts of CP (but not MP) antigens and lymphocytes in GI were significantly lower than in GII. MP/CP ratios were higher in GI. MP correlated with CP and PDGFB in GI (r=0.79 and r=0.83, p<0.001), but not in GII (r=-0.4 and r=-0.08, p=0.81). MP and CP antigens are already present in early atheromas, and a higher MP/CP ratio correlates with increased growth factors, lower inflammation and plaque stability.
Assuntos
Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/microbiologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/análise , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Contagem de Células , Chlamydophila pneumoniae/imunologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/microbiologia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Inflamação/patologia , Macrófagos/citologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/imunologia , Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
Os autores ressaltam a importância de uma classificação das dislipidemias aceita pela comunidade científica, o que facilita o estabelecimento do diagnóstico e a melhor terapêutica, bem como o prognóstico das mesmas. Além da propedêutica dos distúrbios lipoprotéicos, são abordados aspectos genéticos das principais dislipidemias.
Assuntos
Masculino , Feminino , Humanos , Hiperlipidemias , Lipoproteínas/análise , Lipoproteínas/classificação , HDL-Colesterol , Hipercolesterolemia/complicações , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/etiologiaRESUMO
A importância do tratamento das dislipidemias na prevenção da doença aterosclerótica é sobejamente reconhecida. Neste artigo são abordados aspectos farmacológicos e terapêuticos de medicamentos, em uso habitual, com ação predominante na hipercolesterolemia e na hipertrigliceridemia. Ao final, são apresentados os medicamentos em desenvolvimento, incluindo aqueles capazes de elevar a fração HDL-colesterol. Para a escolha do hipolipemiante, devem ser considerados: o diagnóstico preciso da dislipidemia (primária e secundária), possível interação com outros fármacos, idade, fases pré e pós menopausal, co-morbidades, presença de alteração hepática ou renal, etilismo e disponibilidade em farmácias institucionais. Quanto à associação de hipolipemiantes com diferentes mecanismos de ação, além de adequar as doses, exige-se maior atenção aos efeitos adversos(clínicos e/ou laboratoriais).