Impact of Essentiale L on ethanol-induced changes in rat brain and erythrocytes

INTRODUCTION: The present study was designed to investigate the effect of Essentiale L, a mixture of polyenylphospholipids from soybeans, on oxidative stress in various brain regions, on erythrocytes (RBC) and on RBC membrane composition in ethanol-administered rats. METHODS: Adult male albino rats of body weight 150-170 g were divided into four groups and administered either isocaloric glucose (5 g/kg body weight/day) or ethanol (6 g/kg body weight/day) through oral gavage. Essentiale L was administered to a set of ethanol-fed rats and the control rats at a dosage of 300 mg/kg body weight/day through oral gavage. The treatment protocol was carried out for 45 days. At the end of the experimental period, the animals were sacrificed, and the biochemical parameters related to the lipid profile, oxidative stress and thiol status were assayed in the brain regions, RBC and RBC membrane. RESULTS: Ethanol administration resulted in increased levels of lipid peroxidation products in RBC and different brain regions, such as the cortex, cerebellum, striatum, hippocampus and hypothalamus, and depletion of enzymatic and nonenzymatic antioxidants and alterations in oxidised glutathione/glutathione (GSSG/GSH) ratio and thiol groups (protein-bound and total), signifying oxidative stress. Ethanol-treated rats also showed significant alterations in protein content and lipid composition in RBC membranes. Significant differences in the relative proportions of hexose, hexosamine and sialic acid of the membranes were observed. Administration of Essentiale L prevented all the alterations induced by ethanol and returned their levels to near-normal. CONCLUSION: These findings suggest that Essentiale L, a therapeutic adjunct for liver diseases, also has bioprotective effects on nonhepatic tissues and cells.     

Comparison of ethylenediaminetetraacetic acid and sodium citrate as anticoagulants in collection of samples for cytomegalovirus pp65 antigen detection in renal transplant recipients with suspected cytomegalovirus disease

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients. Antigenemia and polymerase chain reaction (PCR) assay are used for diagnosis of CMV disease. A number of anticoagulants are used for the collection of blood samples for antigenemia assay. Thus, ethylenediaminetetraacetic acid (EDTA) and sodium citrate are evaluated for the collection of blood samples and their effects on antigenemia and PCR. Twenty renal transplant recipients with clinically suspected CMV disease and 10 healthy individuals were included in the study. Peripheral blood mononuclear cells (PBMCs) extracted from blood samples were subjected for antigenemia and PCR assay. In 15 out of 20 patients, the number of peripheral blood mononuclear cells obtained were higher in EDTA anticoagulated samples than in sodium citrate. CMV pp65 antigenemia was detected in 10 EDTA and 9 sodium citrate samples, respectively. Number of antigen positive cells in EDTA samples were significantly higher than that of sodium citrate (P<0.05). None of the anticoagulants had adverse effect on the detection of CMV DNA. Thus, EDTA was found to be a better anticoagulant for separation of PBMCs and thus, for CMV pp65 antigenemia assay than sodium citrate.     

First Human Case of Pulmonary Fungal Ball Due to a Perenniporia Species (a Basidiomycete)

Perenniporia species are basidiomycetes, resupinate shelf fungi responsible for white rot decay of wood. Here, we report for the first time an intracavitary pulmonary fungal ball due to a species of Perenniporia that has not been recognized so far as a human pathogen. The fungus was identified by sequencing of the partial ribosomal operon of a culture from a clinical specimen.     

The systems biology of mitochondrial fission and fusion and implications for disease and aging

Mitochondria organize themselves as dynamic populations within a cell, by undergoing continuous cycles of fission and fusion. The spatio-temporal distribution and abundance of mitochondria determines the cell’s energy budget and is thus intimately linked to the cell’s response to environmental stimuli during aging. The dynamic balance of mitochondrial fission and fusion can be studied in terms of antagonistic subpopulations that regulate the mitochondrial responses in space and time. The dynamic nature of these processes motivates mathematical modelling and the simulation of such complex process. In several neurodegenerative and metabolic diseases the dynamic balance of fission and fusion is disturbed. However, how this dynamics plays a role in the progression of diseases is largely unclear. Fission and fusion help mitochondria to regulate cellular energy (ATP) levels, and minimize accumulation of harmful oxidized material called reactive oxygen species which accelerate mutations in mitochondrial DNA (mtDNA) during aging. We discuss how systems biology approaches can be used to investigate the mechanisms controlling the fission–fusion dynamics under two categories: dissecting the design of its molecular regulatory motifs, and understanding complex mitochondrial responses through their population level interactions. This will help us to understand how different regulatory mechanisms regulate the ATP and mutation (mtDNA) landscape of mitochondria to a variety of environmental stimuli in order to maintain their function during aging.     

Crosslinked chitosan: its physical properties and the effects of matrix stiffness on chondrocyte cell morphology and proliferation

Chitosan [beta(1-4)-2 amino-2-deoxy-D-glucose], the natural polyaminosaccharide derived from N-deacetylation of chitin [beta(1-4)-2 acetamide-2-deoxy-D-glucose], has been shown to possess attractive biological and cell interactive properties. Recently chitosan and chitosan analogs have also been shown to support the growth and continued function of chondrocytes. In the present study, chitosan substrates are crosslinked with a functional diepoxide (1,4 butanediol diglycidyl ether) to alter its mechanical property, and the viability and proliferation of the canine articular chondrocytes seeded on the crosslinked surface are further assayed. Of interest is the impact of substrate stiffness on the growth and proliferation of articular canine chondrocytes. Crosslinked scaffolds were also subjected to degradation by chitosanase to examine the impact of crosslinking on enzyme-assisted degradation. The hydrophilicity and compression modulus of the crosslinked surfaces were measured via contact-angle measurements and compression tests, respectively. Scanning electron microscopy (SEM) and fluorescent staining were used to observe the proliferation and morphology of chondrocyte cells on noncrosslinked and crosslinked surfaces. The crosslinked chitosan was found to be nontoxic to chondrocytes and more hydrophilic. Its compression modulus and stiffness increased, which may improve the scaffold resistance to wear and in vivo shrinkage once implanted. The increased stiffness also seemed to serve as an additional mechanical stimulus to promote chondrocyte growth and proliferation. The cell morphology on crosslinked scaffolds seen by SEM and fluorescent stain was the typical chondrocytic rounded shape. The method proposed provides a nontoxic way to increase the mechanical strength of the chitosan scaffolds.     

Controversies in surgical pathology: minimal involvement of sentinel lymph node in breast carcinoma: prevailing concepts and challenging problems

Sentinel lymph node biopsy has attained "standard of care' status in the management of breast carcinoma. However, the pathological interpretation and clinical consequences of "minimally involved' sentinel lymph nodes remain controversial. Herein, we present some of the complex and challenging pathological problems inherent in this evolving setting. Clearly, at least some of our current concepts regarding "minimally involved' sentinel lymph nodes need reappraisal.     

Non-familial juvenile polyposis with histological evidence of adenomatous transformation.

A 14-year-old male presented with abdominal pain, diarrhoea and a sensation of something prolapsing through the anus during defecation, and was found to have diffuse colonic polyposis. There was no evidence of mucocutaneous hyperpigmentation and family history was negative, suggesting a diagnosis of non-familial juvenile polyposis. Histological analysis of multiple endoscopic biopsies showed features typical of juvenile or retention type (hamartomatous) lesions: dilated cystic glands lined by mucocus-secreting epithelium and prominent, inflamed and congested lamina propria. However, admixed with these features, focal areas of atypical adenomatous changes were recognized. Even the intervening normal-looking colonic mucosa showed some dysplastic changes. These findings indicate that hamartomatous and atypical adenomatous epithelial changes can co exist in non-familial juvenile polyposis and the latter may confer a risk of malignant transformation in this otherwise non-neoplastic disease.     

Treatment of benign orbital pseudolymphomas with the monoclonal anti-CD20 antibody rituximab

OBJECTIVE: To report the results of treating patients with orbital pseudolymphomas with the anti-CD20 monoclonal antibody rituximab. PATIENTS AND METHODS: Patients were included in the study if they had an orbital mass and biopsy-proven orbital pseudolymphomas between January 1, 1998, and December 31, 2005. The study focused on patients treated with rituximab. RESULTS: Ninety-eight patients were evaluated, and the biopsy results revealed malignant non-Hodgkin lymphoma in 72 (73%); the other 26 (27%) had a pseudolymphoma. Eleven (42%) of the 26 patients with a pseudolymphoma were treated with rituximab, 375 mg/m2, intravenously each week for 4 doses, and 10 (91%) of the 11 responded. Seven patients were either treated with maintenance rituximab or successfully retreated with rituximab after relapse. None of the 10 responders has become refractory to rituximab. CONCLUSION: Benign lymphoproliferative tumors are responsive to monoclonal antibody therapy targeted to B lymphocytes. Rituximab should be considered a treatment option for orbital pseudolymphomas.     

Prostaglandin E2 and IL‐23 plus IL‐1β Differentially Regulate the Th1/Th17 Immune Response of Human CD161+CD4+ Memory T Cells

Prostaglandin E2 (PGE2), interleukin (IL)‐23, and IL‐1beta (β) propagate inflammatory bowel disease (IBD) by enhancing the development and function of IL‐17 producing CD4⁺ T helper (Th17) cells. CD4⁺ T cells that express the C‐type lectin‐like receptor CD161 have been proposed to be the physiologic pool of circulating Th17 cells implicated in IBD. We sought to understand how PGE2, alone and in combination with IL‐23 and IL‐1β, modulate human peripheral CD161⁺CD4⁺ memory T cells. We found that CD161⁺ cells comprise a significant proportion of human peripheral CD4⁺ memory T cells. PGE2 and IL‐23 plus IL‐1β synergistically induced early IL‐17A secretion from CD161⁺CD4⁺ memory T cells and the selective enrichment of IL‐17A⁺CD161⁺CD4⁺ memory T cells in culture. Conversely, IL‐23 plus IL‐1β partially opposed the PGE2‐mediated repression of early interferon gamma (IFN‐γ) secretion from CD161⁺ cells, as well as the PGE2‐mediated depletion of IFN‐γ⁺CD161⁺ cells. Our results suggest that PGE2 and IL‐23 plus IL‐1β induce the Th17 immune response preferentially in CD161⁺CD4⁺ memory T cells, while divergently regulating their ability to express IFN‐γ. We hypothesize that Th17‐mediated chronic inflammation in IBD depends on the net response of CD161⁺CD4⁺ memory T cells to both PGE2 and IL‐23 plus IL‐1β. Clin Trans Sci 2011; Volume 4: 268–273     

Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold

Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (∼5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan–n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity.