Ventricular arrhythmias and left ventricular myocardial function in chronic chagasic patients

To study the relationship of complex ventricular arrhythmias to the presence and extent of myocardial damage, 556 chronic chagasic patients were submitted to an extensive protocol, including left ventricular cineangiography and Holter monitoring, and properly classified according to clinical, electrocardiographic and hemodynamic findings. Stages of the clinical-hemodynamic classification corresponded to increasing degrees of myocardial damage, age, prevalence and complexity of ventricular arrhythmias. Myocardial damage (particularly left ventricular dilatation) was the most important clinical factor linked to the presence of complex ventricular arrhythmias. A clear difference in terms of ventricular function was found only when arrhythmias were grouped into simple (Lown grades I and II) and complex (grades III and IV) forms. It is recommended that any classification for chagasic patients must be based on signs of myocardial involvement, instead of clinical or electrocardiographic findings alone. Evaluation should include accurate determination of left ventricular myocardial function, along with the search for the presence of complex ventricular arrhythmias and abnormalities of conduction.     

Inhibition of 5-aminolevulinic acid-induced DNA damage by melatonin, N1-acetyl-N2-formyl-5-methoxykynuramine, quercetin or resveratrol

Porphyrias are defined as either inborn or acquired diseases related to enzymatic deficiencies in the heme biosynthetic pathway. Lead poisoning, hereditary tyrosinemia, and acute intermittent porphyria (AIP) are characterized by the absence of photosensitivity and the accumulation of 5-aminolevulinic acid (ALA) together with its increased urinary excretion. The main clinical manifestations of AIP are intermittent attacks of abdominal pain, neuromuscular weaknesses and neuropsychiatry alterations, and also an association with primary liver cancer, in which may be involved the oxidative potential of ALA which is able to cause DNA damage. The use of antioxidants in the treatment of ALA-induced oxidative stress is not well established. In the current work, we show the antioxidant efficacy of several compounds including melatonin, quercetin, resveratrol and N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), a melatonin oxidation product, in terms of their ability to limit DNA damage induced by ALA/Fe2+ in an in vitro system. Damage was measured by plasmid DNA strand breaks and detection of 8-oxo, 7-8-dihydro,2'-deoxyguanosine (8-oxodGuo) by high-performance liquid chromatography coupled with electrochemical detection. All compounds tested showed a dose-dependent protective action against free radical damage. These results could be the first step toward studies of the possible use of these antioxidants in oxidative stress promoted by ALA or other pro-oxidants.     

Continuous 5-day infusion of vinblastine for percutaneous hepatic arterial chemotherapy for metastatic breast cancer

We assessed the therapeutic efficacy and toxicity of continuous hepatic infusion of vinblastine in the treatment of breast cancer predominantly metastatic to the liver. Twenty-six patients previously treated with one or more chemotherapeutic regimens received vinblastine at a dose of 2.0 mg/m2 daily for 5 days, via percutaneously inserted intra-arterial catheters, at 3-4-week intervals. Nine of 25 evaluable patients (36%) achieved partial response and four (16%) had minor response. For responding patients, the median time to disease progression was 21 weeks (range, 12-99), with a median survival of 11 months (range, 4-29) from the beginning of hepatic arterial infusion. The toxicity of the treatment was acceptable, and drug-related effects were comparable to those seen in patients with breast cancer treated by iv continuous infusion of vinblastine at slightly lower doses. We observed two episodes of transient inappropriate antidiuretic hormone secretion. Percutaneous hepatic arterial infusion of vinblastine had significant activity in the treatment of breast cancer metastatic to the liver.     

The length of the Staphylococcus aureus protein A polymorphic region regulates inflammation: impact on acute and chronic infection

Staphylococcus aureus protein A (SpA) plays a critical role in the induction of inflammation. This study was aimed to determine whether the number of short sequence repeats (SSRs) present in the polymorphic region modulates the inflammatory response induced by SpA. We demonstrated that there is a dose-response effect in the activation of interferon (IFN)-β signaling in airway epithelial and immune cells, depending on the number of SSRs, which leads to differences in neutrophil recruitment. We also determined that a significant proportion of isolates from patients with chronic infections such as osteomyelitis and cystic fibrosis carry fewer SSRs than do isolates from patients with acute infections or healthy carriers and that there was an inverse correlation between the number of SSRs and the length of disease course. Given the importance of IFN signaling in eradication of S. aureus, loss of SSRs may represent an advantageous mechanism to adapt to and persist in the host.