Chlamydophila pneumonia and increased TLR4 gene expression in leukocytes are associated with acute myocardial infarction.

We investigated the relationship of the positivity for Chlamydophila pneumoniae (Cpn) and Mycoplasma pneumonia (Mpn), inflammatory and metabolic markers, and mRNA expression and polymorphisms of the TLR2, TLR4, IL-6 and TNFA genes with acute myocardial infarction (AMI). Two hundred and eighteen individuals (98 AMI and 120 non-AMI) were selected at two Clinical Centers. Blood samples were drawn to extract DNA and RNA and to measure laboratory variables including anti-Cpn IgM and IgG. Cpn and Mpn genomic DNA as well as TLR2, TLR4, IL-6 and TNFA mRNA expression were evaluated by quantitative real-time PCR (qPCR). Gene polymorphisms were detected by PCR-HRM. AMI patients had higher positivity for Cpn-DNA (17.3%) than non-AMI group (6.7%, p=0.018). In addition, Cpn-DNA positivity was an independent predictor of risk for AMI (OR: 2.56, CI: 1.08 - 6.04, p=0.031). Positivity for anti-Cpn IgG and Mpn-DNA was similar between AMI and non-AMI (> 0.05). TLR4 mRNA expression was higher in AMI than non-AMI individuals (p=0.005). CD14 -260C> T, TNFA -308A> G, TLR2 c.2258G> A, TLR4 c.896A> G and TLR4 c.1196> T variants were not associated with increased risk for AMI (p> 0.05). In the AMI group, individuals carrying CD14 -260CC genotype had higher hsCRP levels than CT/TT carriers (p=0.041). These results are suggestive that Cpn-DNA positivity and increased TLR4 mRNA expression in blood leukocytes may be associated with AMI and could be useful markers to evaluate the severity and progression of the atherosclerotic disease in AMI patients.

Association between polymorphisms of the renin-angiotensin system and more severe histological forms of lupus nephritis.

AIMS: The pathogenesis of lupus nephritis (LN) has not been fully understood. The renin-angiotensin system (RAS) is implicated in various immunological and non-immunological phenomena, and the polymorphism of the RAS genes has been associated with cardiovascular and renal disease onset and outcome. Therefore, we evaluated the possible association between the polymorphism of the renin-angiotensin system genes and the development of the different types of histological lesions of lupus nephritis in Brazilian patients. METHODS: 72 LN patients and 65 healthy subjects (sex-and ethnic-matched) were enrolled and compared in this study. Following the extraction of genomic DNA from the leukocytes of the peripheral blood, the genotypes of the angiotensin converting enzyme (ACE I/D), of the angiotensinogen (AGT M235T) and of the angiotensin II type 1 receptor (AGTR1 A1166C) were determined by the polymerase chain reaction. The renal lesions of the patients with LN were classified by the histological findings according to the WHO criteria. In addition, the activity and chronicity indices were used to assess the severity of renal involvement. RESULTS: Among the 72 patients with LN, there were 17 class II, 8 class III, 40 class IV and 7 class V, according to the WHO criteria. Individuals with the III and IV classes of LN (WHO) showed a significantly increased DD genotype frequency of ACE I/D genes when compared to the control group (48% vs. 27.7%, chi2 = 4.885, df = 1, p = 0.0442). No difference was found in the distribution of the AGT M235T and AGTR1 A1166C genotype frequencies among the LN of the different histological classes (WHO) and healthy controls. There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied. CONCLUSIONS: This study suggests that the DD genotype of the ACE may be associated with the development of the more severe histological forms of lupus nephritis.

Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy.

Genetic polymorphisms of the renin-angiotensin system (RAS) has been associated with cardiovascular events and the progression of nephropathy in several diseases. The objective of this study was to evaluate a possible association of the genetic polymorphisms of RAS with the development and/or progression of lupus nephritis in a Brazilian population. Seventy-five SLE patients with lupus nephropathy (LN group) were compared to 72 SLE patients without LN (SLE group) and 65 healthy individuals (CONTROL group), of sex and ethnic matched, in a Brazilian population sample. Mean global follow-up was 9 +/- 6 years for lupus without nephropathy and 11 +/- 7 years for lupus nephropathy. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M(235)T) and angiotensin II type 1 receptor (AGTR1 A(1166)C) genotypes were determined by the polymerase chain reaction. No significant difference of ACE, AGT and AGTR1 genotypes distribution between groups was observed in this study. There was no significant association between the variables of the RAS genotypes and the presence of hypertension in SLE. However, an increased frequency ofDD genotype (ACE I/D) was observed in SLE patients with LN who progressed to CRF compared to healthy controls (DD 60%, DI 26.7%, II 13.3% versus 27.7%, 60% and 12.3%, respectively; chi2 = 6.299, P = 0.0429). In the population studied, there was no influence of the RAS genetic polymorphisms in the development of lupus nephropathy, but the progression to CRF was associated with ACE DD polymorphism.

[Iatrogeny in cardiology]. / Iatrogenia em cardiologia.

The word iatrogeny derives from the Greek and concerns any disorder caused to the patient by inaproppriate medical practice. Unfortunately, the rise of an iatrogenic disease is related to the daily handline of cardiac disease. There are two types of iatrogeny: that caused by a medical action and omission iatrogeny, caused by the lack of a medical action. Iatrogeny occurs in all steps of medical practice starting with the patient-doctor relationship including diagnosis treatment and finally prevention of diseases. This article makes a brief commentary about iatrogenic heart disease and mentions some examples of it.

Aspergillosis of the central nervous system.

The authors report an unusual case involving a 38 year-old man who developed a intracranial abscess caused by Aspergillus of the parietal lobe. Cerebral aspergilloma of an initial pulmonary origin developed in a patient with "Fungus Ball" secondary to tuberculosis sequelae. The diagnosis was made through the isolation of Aspergillus from the secretion of the brain abscesses. The patient was treated with drainage of the abscesses and Amphotericin B. He presented a progressive regression of the radiological images (brain and pulmonary) over a period of 55 days. This report emphasizes the importance of combined anti-fungal therapy and surgical resection as a treatment for cerebral aspergilloma. Furthermore, an early initiation of therapy should improve the prognosis in such cases.