Differential susceptibility following beta-amyloid peptide-(1-40) administration in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive deficits and the glutathione system response

Considerable evidence supports the role of oxidative stress in the pathogenesis of Alzheimer's disease (AD). Previous studies suggest that the central nervous system (CNS) administration of beta-amyloid peptide, the major constituent of senile plaque in AD, induces oxidative stress in rodents which may contribute to the learning and memory deficits verified in the beta-amyloid model of AD. In the present study, we compared the effects of a single intracerebroventricular (i.c.v.) injection of aggregated beta-amyloid peptide-(1-40) (Abeta(1-40)) (400pmol/mouse) on spatial learning and memory performance, synaptic density and the glutathione (GSH)-dependent antioxidant status in adult male C57BL/6 and Swiss albino mice. Seven days after Abeta(1-40) administration, C57BL/6 and Swiss mice presented similar spatial learning and memory impairments, as evaluated in the water maze task, although these impairments were not found in Abeta(40-1)-treated mice. Moreover, a similar decline of synaptophysin levels was observed in the hippocampus (HC) and prefrontal cortex (PFC) of both Swiss and C57BL/6 mice treated with Abeta(1-40), which suggests synaptic loss. C57BL/6 mice presented lower levels of glutathione-related antioxidant defences (total glutathione (GSH-t) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activity) in the HC and PFC in comparison to Swiss mice. Despite the reduced basal GSH-dependent antioxidant defences observed in C57BL/6 mice, Abeta(1-40) administration induced significant alterations in the brain antioxidant parameters only in Swiss mice, decreasing GSH-t levels and increasing GPx and GR activity in the HC and PFC 24h after treatment. These results indicate strain differences in the susceptibility to Abeta(1-40)-induced changes in the GSH-dependent antioxidant defences in mice, which should be taken into account in further studies using the Abeta model of AD in mice. In addition, the present findings suggest that the spatial learning and memory deficits induced by beta-amyloid peptides in rodents may not be entirely related to glutathione-dependent antioxidant response.     

Are There Any Differences Between Nutcracker Esophagus With and Without Reflux?

“Nutcracker esophagus” (NE) is a primary esophageal motor disorder, first described in patients with noncardiac chest pain. In recent years NE has been associated with gastroesophageal reflux disease (GERD). In this study we compare patients with NE with and without GERD, as defined by pHmetry or endoscopy, with respect to clinical, endoscopic, radiologic, and manometric findings. Fifty-two patients with NE were studied. They were divided in two groups: GERD (17–32.6%) and non-GERD (35–67.4%) patients. Females predominated in both groups, with no significant difference in age (p > 0.05). Chest pain was the chief complaint in both groups (p > 0.05). Clinical findings in patients with and without reflux included chest pain (52.9% and 51.4%), dysphagia (58.8% and 42.8%), and heartburn (64.7% and 42.8%), followed by regurgitation, dyspepsia, ear, nose, and throat (ENT) complaints, respiratory symptoms, and odynophagia (p > 0.05). Erosive esophagitis was found in three patients (5.7%). There were no differences between groups in the findings of barium swallow studies and all manometric findings were similar for both groups (p > 0.05). We conclude that there were no differences in patients with NE with or without associated reflux disease. It is important to diagnose reflux properly so patients can be treated adequately.     

Liver haemangioma: common and uncommon findings and how to improve the differential diagnosis

Haemangiomas are common focal liver lesions, generally detected in the work-up of asymptomatic patients. From the pathological point of view, they can be classified as small (capillary) or large, with cavernous vascular spaces that may show thrombosis, calcifications and hyalinisation. The polymorphic imaging appearance of haemangiomas depends on their histological features and flow pattern. The widespread use of cross-sectional imaging has allowed an increased detection rate and a better characterisation of this benign tumour. Recent developments of ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) providing high spatial and temporal resolution, together with the use of new contrast agents and/or pulse sequences has broadened the spectrum of imaging findings, contributing to diagnostic refinement in difficult cases. The scope of the present article is to provide an overview of the range of appearances of haemangiomas, explored with recent cross-sectional imaging modalities, emphasising its atypical findings as explored by temporally resolved contrast-enhanced imaging.     

The role of the silicatein-α interactor silintaphin-1 in biomimetic biomineralization

Biosilicification in sponges is initiated by formation of proteinaceous filaments, predominantly consisting of silicateins. Silicateins enzymatically catalyze condensation of silica nanospheres, resulting in symmetric skeletal elements (spicules). In order to create tailored biosilica structures in biomimetic approaches it is mandatory to elucidate proteins that are fundamental for the assembly of filaments. Silintaphin-1 is a core component of modularized filaments and also part of a spicule-enfolding layer. It bears no resemblance to other proteins, except for the presence of an interaction domain that is fundamental for its function as scaffold/template. In the presence of silicatein silintaphin-1 facilitates the formation of in vitro filaments. Also, it directs the assembly of γ-Fe₂O₃ nanoparticles and surface-immobilized silicatein to rod-like biocomposites, synthetic spicules. Thus, silintaphin-1 will contribute to biomimetic approaches that pursue a controlled formation of patterned biosilica-based materials. Its combination with γ-Fe₂O₃ nanoparticles and immobilized silicatein will furthermore inspire future biomedical applications and clinical diagnostics.     

Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats

Currently, methylprednisolone sodium succinate (MPSS) is the standard treatment following acute spinal cord injury (SCI) as a consequence of the results obtained from the National Acute Spinal Cord Injury Studies. However, many have questioned the efficacy of MPSS because of its marginal effects. Additionally there has been criticism of both study design and statistical interpretation. The functional consequences of experimental SCI have been assessed in many ways. The purpose of this investigation was to determine the effects of MPSS vs. saline solution (SS) following moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale, the inclined plane, the beam walk, footprint analysis and the horizontal ladder. To optimize the precision and accuracy of functional results we examined the locomotion on a treadmill using three-dimensional (3D) analysis. Stereology was used to estimate the amount of damaged tissue. The results of the traditional functional methods showed that administration of the NASCIS dosage of MPSS following acute spinal cord contusion did not lead to any significant differences in the functional recovery of MPSS- vs. SS-treated animals. More importantly, the results of the 3D kinematic showed that the MPSS administration did not affect the flexion/extension of the hip, knee and ankle joints during the step cycle. Finally, stereological results revealed no statistically significant differences between the two experimental groups. Altogether, our results support data previously reported by several authors, suggesting that MPSS does not lead to improved functional outcome following experimental acute SCI.     

Immunohistochemical expression of DNA methyltransferases 1, 3a and 3b in oral leukoplakias and squamous cell carcinomas

Over-expression of DNA methyltransferases DNMT1, DNMT3a and DNMT3b has been reported in various cancers and precancerous lesions.

Objective

To investigate DNMT1, DNMT3a and DNMT3b enzymes in oral squamous cell carcinoma (SCC) and leukoplakia, and their relationship with histopathologic/clinical parameters.

Study design

Immunohistochemistry was carried out to evaluate the three DNMTs in 60 samples of oral SCC and 37 samples of oral leukoplakia.

Results

DNMT3a immunoreactivity in the three groups of oral SCC (39.8%) was significantly higher than in control (22.6%) (ANOVA, Student–Newman–Keuls test, P < 0.05), but not when compared to oral leukoplakia groups (28.2%). For DNMT1 and DNMT3b, there were no statistically significant differences between oral SCC groups (65% and 74.7%), oral leukoplakia groups (68.3% and 70.9%) and control (65.4% and 76.5%). There was a significantly higher mean percentage of DNMT1 immunoreactivity in non-smokers (ANOVA, P = 0.048), and a higher DNMT3a immunoreactivity in alcohol users (ANOVA, P = 0.01).

Conclusions

Higher DNMT3a immunopositivity may be associated with oral SCC and alcohol use, whilst lower levels of DNMT1 may be related with smoking habit. However, there was a significantly higher mean percentage of DNMT1 immunoreactivity in non-smokers (ANOVA, P = 0.048), and a higher DNMT3a immunoreactivity in alcohol users (ANOVA, P = 0.010).     

Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus

The cell wall of Staphylococcus aureus is characterized by an extremely high degree of cross-linking within its peptidoglycan (PGN). Penicillin-binding protein 4 (PBP4) is required for the synthesis of this highly cross-linked peptidoglycan. We found that wall teichoic acids, glycopolymers attached to the peptidoglycan and important for virulence in Gram-positive bacteria, act as temporal and spatial regulators of PGN metabolism, controlling the level of cross-linking by regulating PBP4 localization. PBP4 normally localizes at the division septum, but in the absence of wall teichoic acids synthesis, it becomes dispersed throughout the entire cell membrane and is unable to function normally. As a consequence, the peptidoglycan of TagO null mutants, impaired in wall teichoic acid biosynthesis, has a decreased degree of cross-linking, which renders it more susceptible to the action of lysozyme, an enzyme produced by different host organisms as an initial defense against bacterial infection.     

Kidney Transplantation With Corticosteroid-Free Maintenance Immunosuppression: A Single Center Analysis of Graft and Patient Survivals

The purpose of this study was to assess the impact of a corticosteroid-free maintenance immunosuppression on graft survival in kidney transplantation. We analyzed 79 patients who were transplanted between June 1, 2006 and May 31, 2007. We excluded hyperimmunized patients, second transplantations, living donors, and black recipients. Patients underwent induction with thymoglobulin or basiliximab, followed by treatment with mycophenolate mofetil (MMF), tacrolimus, and methylprednisolone. On the 5th day, the patients were divided into 2 groups: group A (n = 45) discontinued steroid therapy; group B (n = 34) continued prednisone therapy. We performed a comparative analysis of incidence of delayed graft function (DGF), acute rejection episodes (ARE), renal function at 6 and 12 months, graft and patient survivals, causes of graft loss, and mortality. The 2 groups were similar for donor, recipient, and graft characteristics. The incidences of DGF were 8.9% in group A and 14.7% in group B; those for ARE were 2.3% in group A and 13.8% in group B (P = .077). The mean serum creatinine levels at 6 and 12 months were similar. There were 8 graft losses: 3 in group A (3 deaths with functioning grafts) and 5 in group B (1 death, 3 vascular causes, 1 kidney nonfunction). The 4 deaths were due to infection (n = 3) or neoplasia (n = 1). Graft survivals at 1 year were 98% in group A and 85% in group B, and patient survivals were 98% and 97%, respectively. An immunosuppressive regimen using antibody induction and steroid-free treatment proved to be effective in low-risk patients.