Homocysteine as a Biomarker for Predicting Disease-Free Survival in Breast Cancer

Introduction: Breast cancer is the leading cause of cancer mortality among women. Some biomarkers and clinical features are used for the diagnosis and prognosis of this tumor, but no prognostic or predictive marker is routinely available specifically for hormone receptor positive tumors. Homocysteine is well known as a risk factor in atherosclerotic vascular diseases, but its participation in cancer biology is still unclear. The aim of this study was to evaluate serum Homocysteine and Cysteine as biomarkers of disease progression in breast tumor. As a secondary objective, the effect of a short course (one month) of hormonal treatment on Homocysteine, Cysteine and DNA methylation levels was also evaluated. Methods: Blood samples, tumor samples and normal adjacent tissue were collected during the initial biopsy (pre-treatment) and after one month of hormonal therapy (post-treatment). Serum Homocysteine and Cysteine were analyzed by HPLC and tissue global DNA methylation was determined by the Methylation-Sensitive Restriction Enzyme (MSRE) technique. Results: Variations in Homocysteine levels were significantly correlated with Disease-Free Survival. Cox proportional risk model demonstrated that nodal status and Homocysteine levels were independent prognostic factors for disease-free survival (DFS). A significant difference was observed between pre-and post-treatment levels of Homocysteine and Cysteine in advanced tumors, suggesting a prognostic role in patients with poor clinical characteristics. Conclusion: Although more studies are needed to confirm these results, our research suggests that Hcy might be used as a prognostic biomarker for breast cancer.

High- and Low-Rearing Rats Differ in the Brain Excitability Controlled by the Allosteric Benzodiazepine Site in the GABA_(A) Receptor

Rearing is an exploratory behavior induced by novelty, such as exposure to an open field. Stimulation of certain brain regions, including the hippocampus, induces both rearing and clonic convulsions. Brain excitability is controlled by gamma-aminobutyric acid (GABA) inhibitory neurotransmission through its ionotropic GABAA/allosteric benzodiazepine site. Drugs that decrease GABAA receptor fast inhibitory neurotransmission induce clonic convulsions and rearing when injected into the hippocampus. Therefore, individual differences in rearing behavior may be related to the susceptibility to clonic convulsions, which could involve differences in brain excitability controlled by GABAA/allosteric benzodiazepine site receptors. Adult, male Wistar rats were divided into high- (HR) and low-rearing (LR) groups based on the number of rearings in the open field test. Groups of HR and LR rats were challenged with convulsant drugs that antagonize GABA neurotransmission via different mechanisms of action (3-mercaptopropionic acid, a glutamate decarboxilase inhibitor;bicuculline, a GABAA receptor antagonist;pentylenetetrazol and picrotoxin, both GABAA receptor chloride channel blockers and DMCM, a benzodiazepine inverse agonist). The convulsant doses that induced 50% of clonic convulsions were determined for each drug. The LR rats had a higher susceptibility (a lower convulsant dose 50%) to clonic convulsions induced by DMCM than the HR rats, but there were no differences between the groups in the susceptibility to tonic convulsions induced by the same drug. There were no significant differences in the convulsant dose 50% for clonic convulsions between the groups for all other drugs injected. In another experiment, additional HR and LR rats were injected with a sedative-hypnotic dose of diazepam, which caused a significantly higher hypnotic effect (sleeping-time) in the LR rats than in the HR rats. The LR group was also shown to have a significantly lower density of [3H]-Flunitrazepam bound to the GABAA receptor in hippocampal membranes. Our data suggest that inter-individual differences in rearing are related, at least in part, to the GABA inhibitory neurotransmission controlled by the benzodiazepine allosteric site in the GABAA receptor.

Update on the use of portable monitoring system for the diagnosis of sleep apnea in specific population

The prevalence and severity of obstructive sleep apnea(OSA) is higher in specific population: children, elderly,obese and patients with pulmonary and cardiovascular diseases, compared to the general population. OSA is associated with greater morbidity and mortality in these patients. Although full-night polysomnography is still the gold standard diagnostic sleep study for OSA, it is a time consuming, expensive and technically demanding exam. Over the last few years, there is growing evidence on the use of portable monitors(PM) as an alternative for the diagnosis of OSA. These devices were developed specially for sleep evaluation at home, at a familiar environment, with easy selfapplication of monitoring, unattended. The use of PM is stablished for populations with high pre-test probability of OSA. However, there is a lack of studies on the use of PM in age extremes and patients with comorbidities. The purpose of this review is to present the studies that evaluated the use of PM in specific population, as well as to describe the advantages, limitations and applications of these devices in this particular group of patients. Although the total loss rate of recordings is variable in different studies, the agreement with fullnight polysomnography justifies the use of PM in this population.

Sleep disturbances as an adverse effect of propranolol use in children with infantile hemangioma

Infantile hemangiomas(IHs)are the most prevalent benign vascular tumor in children,with an estimated rate of 5-10%.Most IHs resolve spontaneously after the proliferation stage,but about 12-24%develop with sequelae and complications which require pharmacological interventions[1].The beta blocker propranolol is considered as the first-line treatment for complicated cases of IHs[2].