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Protective Effects of Garlic Oil on Hepatocarcinoma Induced by N-Nitrosodiethylamine in Rats
Cui-Li Zhang, Tao Zeng, Xiu-Lan Zhao, Li-Hua Yu, Zhen-Ping Zhu, Ke-Qin Xie
International Journal of Biological Sciences , 2012,
Abstract: To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.
Protective role of Methanol extract of Phyllanthus Polyphyllus against N-nitrosodiethylamine induced liver tumor in rat  [cached]
Naina Mohamed Pakkir Maideen, Ravichandiran Velayutham and Gobinath Manavalan
Bangladesh Journal of Pharmacology , 2010,
Abstract: The protective role of methanol extract of Phyllanthus polyphyllus was evaluated in N-nitrosodiethylamine-induced experimental liver tumor in male Wistar albino rats. Administration of extract (200 and 400 mg/kg) effectively suppressed liver tumor as revealed by decrease in elevated levels of Phase I enzymes like cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase and glycoproteins like hexose, hexoseamine and sialic acid. The extract produced an increase in phase II enzymes like UDP-glucuronyl transferase and glutathione-S-transferase levels when compared to liver tumor bearing animals. This study suggests that methanol extract of P. polyphyllus may extend its protective role by modulating the levels of glycoproteins and phase I metabolizing enzymes and augmenting phase II metabolizing enzymes.
Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins
Naina Mohamed Pakkir Maideen,Ravichandiran Velayutham,Gobinath Manavalan
Advanced Pharmaceutical Bulletin , 2012,
Abstract: Purpose: The objective of the present study was to evaluate the protective effect of methanol extract of Prosopis cineraria (MPC) against N-nitrosodiethylamine (DEN, 200mg/kg) induced Phenobarbital promoted experimental liver tumors in male Wistar rats. Methods: The rats were divided into four groups, each group consisting of six animals. Group 1 served as control animals. Liver tumor was induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group 4 animals received MPC 400mg/kg. Results: Administration of DEN has brought down the levels of membrane bound enzymes like Na+/ K+ ATPase, Mg2+ ATPase and Ca2+ATPase which were later found to be increased by the administration of Prosopis cineraria (200 and 400mg/kg) in dose dependent manner. The MPC extract also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic acid when compared to liver tumor bearing animals. Conclusions: Our study suggests that MPC may extend its protective role by modulating the levels of membrane bound enzymes and suppressing glycoprotein levels.
Ethanolamine utilization in Vibrio alginolyticus
Khatri Neelam,Khatri Indu,Subramanian Srikrishna,Raychaudhuri Saumya
Biology Direct , 2012, DOI: 10.1186/1745-6150-7-45
Abstract: Ethanolamine is used as an energy source by phylogenetically diverse bacteria including pathogens, by the concerted action of proteins from the eut-operon. Previous studies have revealed the presence of eutBC genes encoding ethanolamine-ammonia lyase, a key enzyme that breaks ethanolamine into acetaldehyde and ammonia, in about 100 bacterial genomes including members of gamma-proteobacteria. However, ethanolamine utilization has not been reported for any member of the Vibrio genus. Our comparative genomics study reveals the presence of genes that are involved in ethanolamine utilization in several Vibrio species. Using Vibrio alginolyticus as a model system we demonstrate that ethanolamine is better utilized as a nitrogen source than as a carbon source. Reviewers This article was reviewed by Dr. Lakshminarayan Iyer and Dr. Vivek Anantharaman (nominated by Dr. L Aravind).
Alteraciones genéticas en lesiones preneoplásicas y neoplásicas de la vesícula biliar Genetic alterations in preneoplastic and neoplastic injuries of the gallbladder
JONATHAN CASTILLO A,PATRICIA GARCíA M,JUAN CARLOS ROA S
Revista médica de Chile , 2010,
Abstract: This article aims to review the most relevant morphological and molecular aspects involved in gallbladder (GB) cancer. In Chile, gallbladder cancer is the main cause of death due to cancer, among women older than 40 years. However, there is almost none information about the morphological changes and the genetic alterations in-volved in the beginning and development of this neoplasia. Two carcinogenic ways have been described. The sequence adenoma-carcinoma is accepted to be less frequent and important. The most important is the sequence where a metaplasia evolves to displasia that progresses to carcinoma in situ and fnally it becomes invasive. This progress requires 10 to 15 years approximately. During this time, a continue progression of injuries have been described. Molecular research studies show genetic anomalies in some genes which are temporary events in preneoplastic injuries of the gallbladder. Some of them even exist before the frst morphological changes, while the expression of tumor suppressor genes like p53, adhesion molecules and oncogenes, among others, can be related to late GB carcinogenesis. The K-ras gene seems to play a role in this neoplasia, mainly in those that present an abnormal biliopancreatic union. The microsatelital instability has been found in a small subset of preneoplastic and neoplastic lesions. The existence of methylation in the promotor gene areas has been related to the cellular proliferation, invasion and metastasis and also in cases of chronic cholecystitis, suggesting that this epigenetic phenomenon represents a crucial early event in GB carcinogenesis.
Preneoplastic lesions of the lung
Alissa K Greenberg, Herman Yee, William N Rom
Respiratory Research , 2002, DOI: 10.1186/rr170
Abstract: Lung cancer is the leading cause of cancer deaths worldwide [1] and the number of cases continues to increase. Smoking is the primary cause in the great majority of these cases. In Asia, particularly China, smoking rates continue to increase. Despite advances in therapy, the overall survival rate for lung cancer patients remains only 15%. This poor survival is probably due to the relatively advanced stage of disease at diagnosis. To date, screening trials have had no significant impact on survival [2]. Screening can detect small (2–3 mm in size), asymptomatic nodules, but even these nodules may already be malignant, and therefore late in the course of the disease. Tumor cells have been found in the peripheral blood and bone marrow of patients with lung cancer of all sizes and stages [3,4].If lung cancer could be identified earlier – at a preneoplastic stage, before angiogenesis, invasion and micrometastases can occur – we might have a greater chance of improving survival. At this point, we have little information about possible progenitor lesions. Which lesions are preneoplastic? How and why do they progress? Is there any treatment that can prevent progression? Advances in molecular biology and microdissection techniques, and greater understanding of genetic changes involved in malignant transformation will aid in answering some of these questions. Advances in computerized tomography (CT), bronchoscopy and genomics technology raise the possibility that we may be able to detect these early lesions in vivo. Therefore, if preneoplastic lesions can be defined, and if appropriate therapies can be found, screening may then significantly improve survival.To define preneoplastic lesions, we need to understand the molecular events that occur during bronchogenic carcinogenesis. Carcinogenesis is thought to be a multistep process consisting of the accumulation of gene mutations. Preneoplastic lesions may be morphological phenotypes of the different steps in this progression fr
Protective role of onion and garlic on physicochemical alterations and toxicity of heated soybean oil
OI Oyewole, ET Olayinka
African Journal of Biotechnology , 2007,
Abstract: Fresh and soybean oil heated with or without onion or garlic were analyzed for their physicochemical and toxicological properties. Darkened appearance, off flavors, rancid taste and significant reduction of iodine value was obtained for the heated oil. Acid value, peroxide value, viscosity and concentration of malondialdehyde of the thermooxidized soybean oil were also significantly elevated (P<0.05) with considerable loss of ascorbic acid and tocopherols. Heating with onion and garlic considerably preserved the quality of the oil as indicated in the significant reduction in levels of lipid peroxidation indicators as well as reduction in loss of ascorbic acid and tocopherol. Rats fed with diet containing heated oil for a period of four weeks showed significant elevation (P<0.05) in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) starting from the second week to the end of the experimental period. This might be as a result of cellular damage caused by peroxides and other lipid oxidation products which allowed the enzymes to leak out from the tissues. The levels of these enzymes were maintained close to the control in rats fed with diets containing heated oil with garlic and onion indicating their protective role in lipid oxidation.
Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix
Kathleen P Saavedra, Priscilla M Brebi, Juan Carlos S Roa
Clinical Epigenetics , 2012, DOI: 10.1186/1868-7083-4-13
Abstract: Cervical cancer (CC) is the second most prevalent neoplasia in women worldwide and the fifth cause of death by cancer in this population, posing a significant public health problem [1-3]. The incidence of CC and its precursor stages is high mainly in developing countries [4]. In 2008 an incidence of 15.8 and a mortality of 8.2 for every 100,000 women was estimated. Around 529,000 new cases are detected every year, with nearly half of these cases dying [5].The pathogenesis of CC begins as a slow process that interrupts the normal differentiation of the cervical squamous epithelium, thereby producing changes in its structure and physiology [6]. It initially presents through precursory lesions that evolve slowly and progressively, which can then advance to slight, moderate, and severe stages of dysplasia. CC may evolve into cancer in situ, which is limited to the epithelial surface, and/or into invasive cancer, in which case the involvement goes beyond the basement membrane [7]. Therefore, one of the characteristic factors of CC is its defined clinical stages, which are associated with the different evolutionary stages that lead to the development of the carcinogenesis [8].It has been firmly established, both biologically and epidemiologically, that the main cause of CC is due to a persistent infection of high-risk human papillomavirus (HPV) types, which are present in 99.7% of CC cases [9]. Nevertheless, the presence of a persistent high-risk HPV infection risk is not sufficient to immortalize and transform the epithelial cells of the host; it has been confirmed that the presence of genetic and epigenetic alterations are needed for the development of carcinogenesis. As a result, these factors taken together may alter the control of the cell cycle, causing the host cell to acquire an immortal phenotype and ultimately progress towards a malignant and invasive phenotype [10].HPV is a small, non-enveloped virus belonging to the Papillomaviridae family of viruses [11]. It
Uptake and kinetic properties of choline and ethanolamine in Plasmodium falciparum
H Ahiboh, AJ Djaman, FH Yapi, A Edjeme-Aké, ML Hauhouot-Attoungbré, ET Yayo, D Monnet
Tropical Journal of Pharmaceutical Research , 2008,
Abstract: Purpose: The asexual proliferation of Plasmodium, inside the erythrocyte, is accompanied by the synthesis of huge quantities of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn). These needful phospholipids for the cytoplasmic membrane of the merozoites are provided by the precursors choline and ethanolamine. PtdCho and PtdEtn are synthesized by the parasite because the erythrocyte is unable to do it. In order to assess the dynamism of the phospholipid pathways, we aimed to investigate the respective shape of the uptake of choline and ethanolamine by Plasmodium falciparum. Method: Time-course experiments and kinetic assays were performed respectively with fixed and ranged concentrations of radioactively-labelled choline and ethanolamine. The labelled-precursors were added in the culture of P. falciparum infected-erythrocytes and the incorporated molecules in phospholipids were measured with a scintigraph counter. Result: The results showed that the incorporation of precursors in the infected-erythrocyte occurred with a Michaelis-Menten\'s kinetic shape. According to the maximum rate (Vmax), the pathway of ethanolamine incorporation was faster than that of choline. Similarly, affinity for ethanolamine was greater than that of choline. Conclusion: Although PtdCho is the major phospholipid in the membrane, this study rules out that the influx of ethanolamine in the infected-erythrocyte, in vivo conditions, is more dynamic than choline.
Structural Insight into the Clostridium difficile Ethanolamine Utilisation Microcompartment  [PDF]
Alison C. Pitts, Laura R. Tuck, Alexandra Faulds-Pain, Richard J. Lewis, Jon Marles-Wright
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048360
Abstract: Bacterial microcompartments form a protective proteinaceous barrier around metabolic enzymes that process unstable or toxic chemical intermediates. The genome of the virulent, multidrug-resistant Clostridium difficile 630 strain contains an operon, eut, encoding a bacterial microcompartment with genes for the breakdown of ethanolamine and its utilisation as a source of reduced nitrogen and carbon. The C. difficile eut operon displays regulatory genetic elements and protein encoding regions in common with homologous loci found in the genomes of other bacteria, including the enteric pathogens Salmonella enterica and Enterococcus faecalis. The crystal structures of two microcompartment shell proteins, CD1908 and CD1918, and an uncharacterised protein with potential enzymatic activity, CD1925, were determined by X-ray crystallography. CD1908 and CD1918 display the same protein fold, though the order of secondary structure elements is permuted in CD1908 and this protein displays an N-terminal β-strand extension. These proteins form hexamers with molecules related by crystallographic and non-crystallographic symmetry. The structure of CD1925 has a cupin β-barrel fold and a putative active site that is distinct from the metal-ion dependent catalytic cupins. Thin-section transmission electron microscopy of Escherichia coli over-expressing eut proteins indicates that CD1918 is capable of self-association into arrays, suggesting an organisational role for CD1918 in the formation of this microcompartment. The work presented provides the basis for further study of the architecture and function of the C. difficile eut microcompartment, its role in metabolism and the wider consequences of intestinal colonisation and virulence in this pathogen.
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