Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage,as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10–15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia. Wistar male rats received homocysteine (0.03 μmol/g of body weight) by subcutaneous injections twice a day and acetylsalicylic acid (25 mg/Kg of body weight) by intraperitoneal injections once a day from the 30th to the 60th postpartum day. Control rats received vehicle solution in the same volume. Results showed that rats subjected to chronic mild hyperhomocysteinemia significantly increased IL-1β, IL-6, and acetylcholinesterase activity and reduced nitrite levels. Homocysteine decreased catalase activity and immunocontent and superoxide dismutase activity, caused protein and DNA damage, and altered neurons ultrastructure. Acetylsalicylic acid totally prevented the effect of homocysteine on acetylcholinesterase activity and catalase activity and immunocontent, as well as the ultrastructural changes, and partially prevented alterations on IL-1β levels, superoxide dismutase activity, sulfhydryl content, and comet assay. Acetylsalicylic acid per se increased DNA damage index. In summary, our findings showed that chronic chemically induced model of mild hyperhomocysteinemia altered some parameters and acetylsalicylic acid administration seemed to be neuroprotective, at least in part, on neurotoxicity of homocysteine.     

Lateral Cord Stimulation Decreases Spastic Electromyographic Spreading: Responses in a Brain‐Damaged Pig Preparation

Objective. The aim of our work was to investigate whether lateral stimulation of the spinal cord, lateral cord stimulation (LCS), results in inhibition of the spastic phenomena of upper motor lesions in an animal model. Methods. This study was conducted using an animal model consisting of surgically brain damaged pigs subjected to unilateral cortical and subcortical brain lesions. A double laminectomy at cervical (C3–C4) and lumbar (L3–L6) was performed, and spastic thresholds of abnormal electromyographic responses, disseminated to adjacent segments, facilitated by spinal liberation, and produced by extradural electrical stimulation of the fourth lumbar root, were measured before and after cervical stimulation of the LCS. The variable studied was the minimal amount of current of LCS necessary to abolish electromyographic responses in the L7 myotome, away from the stimulated L4 nerve root. Results. Experiments in 12 animals showed a significant increase of threshold after LCS, with a marked posteffect, signaling a less abnormal threshold. Conclusions. This experiment demonstrated that LCS produces threshold increases to abolish abnormally propagated electromyographic evoked responses induced by the electrical stimulation of the fourth lumbar root in pigs with experimental cortical and subcortical brain lesions.     

Acute ethanol exposure disrupts actin cytoskeleton and generates reactive oxygen species in c6 cells

Central nervous system dysfunctions are among the most significant effects of exposure to ethanol and the glial cells that play an important role in maintaining neuronal function, are extremely involved with these effects. The actin cytoskeleton plays a crucial role in a wide variety of cellular functions, especially when there is some injury. Therefore the aim of the present study was to analyze the short-term effects of ethanol (50, 100 and 200 mM) on the cytoskeleton of C6 glioma cells. Here we report that acute ethanol exposure profoundly disrupts the actin cytoskeleton in C6 cells decreasing stress fiber formation and downregulating RhoA and vinculin immunocontent. In contrast, microtubule and GFAP networks were not altered. We further demonstrate that anti-oxidants prevent ethanol-induced actin alterations, suggesting that the actions of ethanol on the actin cytoskeleton are related with generation of reactive oxygen species (ROS) in these cells. Our results show that ethanol at concentrations described to be toxic to the central nervous system was able to target the cytoskeleton of C6 cells and this effect could be related with increased ROS generation. Therefore, we propose that the dynamic restructuring of the cytoskeleton of glial cells might contribute to the response to the injury provoked by binge-like ethanol exposure in brain.     

Periannular complications in infective endocarditis involving prosthetic aortic valves

The periannular extension of infection in prosthetic valve endocarditis (PVE) is a serious complication of infective endocarditis associated with high mortality. Periannular lesions in PVE occasionally rupture into adjacent cardiac chambers, leading to aortocavitary fistulae and intracardiac shunting. It is unknown whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinctive clinical characteristics of patients with PVE and either aortocavitary fistulization or nonruptured abscesses. In a retrospective multicenter study of >872 PVE episodes, 150 patients (17%) with periannular complications in PVE in the aortic position were identified (29 with aortocavitary fistulization and 121 with nonruptured abscesses). Early-onset PVE was present in 73 patients (49%). Rates of heart failure (p = 0.09), ventricular septal defect (p <0.01), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 128 patients (83%). In-hospital mortality in the overall population was 39%. Multivariate analysis identified heart failure (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6 to 6.8), renal failure (OR 2.5, 95% CI 1.2 to 5.2), and co-morbidity (OR 2.4, 95% CI 1.1 to 5.1) as independent risk factors for death. Fistulous tract formation was not associated with increased in-hospital mortality (OR 1.6, 95% CI 0.7 to 3.7). The actuarial 5-year survival rate in surgical survivors was 100% in patients with fistulae and 78% in patients with nonruptured abscesses (log-rank p = 0.14). In conclusion, aortocavitary fistulous tract formation in PVE complicated with periannular complications is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscesses. Despite the frequent complications, fistulous tract formation in the current era of infective endocarditis is not an independent risk factor for mortality.     

Periannular complications in infective endocarditis involving native aortic valves

The extension of infection in native valve infective endocarditis (IE) from valvular structures to the periannular tissue is incompletely understood. It is unknown, for example, whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinct clinical characteristics of patients with aortocavitary fistulae and nonruptured abscesses in native valve IE and to evaluate the impact of fistulization on the outcomes of patients with native aortic valve IE complicated with periannular lesions. In a retrospective multicenter study of 2,055 native valve IE episodes, 201 patients (9.8%) with periannular complications in aortic valve IE were identified (46 with aortocavitary fistulization and 155 with nonruptured abscesses). Rates of heart failure (p = 0.07), ventricular septal defect (p <0.001), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 172 patients (86%), and in-hospital mortality in the overall population was 29%. Multivariate analysis identified age >60 years (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.3 to 5.2), renal failure (OR 3.0, 95% CI 1.5 to 6.0), and moderate or severe heart failure (OR 2.5, 95% CI 1.2 to 5.2) as independent risk factors for death. There was a trend toward increased in-hospital mortality in patients with aortocavitary fistulae (OR 1.5, 95% CI 0.7 to 3.0). The actuarial 5-year survival rate in surgical survivors was 80% in patients with fistulae and 92% in patients with nonruptured abscesses (log-rank p = 0.6). In conclusion, aortocavitary fistulous tract formation in the setting of native valve IE is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscess. Despite these higher rates of complications, fistulous tract formation in the current era of IE is not an independent risk factor for mortality.     

Comparison of high efficiency CZT SPECT MPI to coronary angiography

Background  

The recently introduced cadmium zinc telluride (CZT) SPECT cameras have the potential to reduce radiation exposure to patients and shorten imaging time. So far, there has been only one small study comparing the results of high efficiency CZT SPECT myocardial perfusion imaging (MPI) to invasive coronary angiography.     

Comparison of Sputum and Nasopharyngeal Aspirate Samples and of the PCR Gene Targets lytA and Spn9802 for Quantitative PCR for Rapid Detection of Pneumococcal Pneumonia

We aimed to compare sputum and nasopharyngeal aspirate (NpA) samples and the PCR gene targets lytA and Spn9802 in quantitative PCR (qPCR) assays for rapid detection of pneumococcal etiology in community-acquired pneumonia (CAP). Seventy-eight adult patients hospitalized for radiologically confirmed CAP had both good-quality sputum and NpA specimens collected at admission. These samples were subjected to lytA qPCR and Spn9802 qPCR assays with analytical times of <3 h. Thirty-two patients had CAP with a pneumococcal etiology, according to conventional diagnostic criteria. The following qPCR positivity rates were noted in CAP cases with and without pneumococcal etiology: 96% and 15% (sputum lytA assay), 96% and 17% (sputum Spn9802 assay), 81% and 11% (NpA lytA assay), and 81% and 20% (NpA Spn9802 assay), respectively. The mean lytA and Spn9802 DNA levels were significantly higher in qPCR-positive sputum samples from cases with pneumococcal etiology than in qPCR-positive sputum samples from CAP cases without pneumococcal etiology or qPCR-positive NpA samples from cases with pneumococcal etiology (P < 0.02 for all comparisons). For detection of pneumococcal etiology, receiver operating characteristic curve analysis showed that sputum specimens were superior to NpA specimens as the sample type (P < 0.02 for both gene targets) and lytA tended to be superior to Spn9802 as the gene target. The best-performing test, the sputum lytA qPCR assay, showed high sensitivity (94%) and specificity (96%) with a cutoff value of 10⁵ DNA copies/ml. In CAP patients with good sputum production, this test has great potential to be used for the rapid detection of pneumococcal etiology and to target penicillin therapy.     

In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways

In the present report 15 day-old Wistar rats were injected with 0.3 μmol of diphenyl ditelluride (PhTe)₂/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6 days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein—GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe)₂ significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe)₂ provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe)₂ treated striatal slices suggested apoptotic cell death. (PhTe)₂ exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe)₂-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis.