In this study, we investigated the effects of exposition to IC
dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on ...HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.
The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra‐physiological doses of nandrolone ...decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells), Bcl‐2 (B‐cell lymphoma 2), SMAC/DIABLO (second mitochondria‐derived activator of caspases/direct IAP‐binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long‐term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF‐κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF‐κB. It has been argued that one of the pathways leading to the activation of NF‐κB could be under reactive oxygen species (ROS)‐mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF‐κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF‐κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF‐κB, and that this negative regulation of ROS is the means through which NF‐κB counters programmed cells.
It is widely accepted that airborne pollution causes adverse health effects in humans (Gauderman et al. 2007). In addition to the concentration of particulate matter (PM), these effects have been ...related to innate particle toxicity. Stoeger et al. (2009) recently showed that, with a slope that significantly depends on particle structure, surface, and organic carbon content, combustion-derived nanoparticles behave in a different manner in in vitro systems and when reacting with lung surface (i.e. after particle-lung interaction).
Cancer Risk and GSTM1 and GSTT1 Polymorphisms Cetta, Francesco; Dhamo, Armand; Moltoni, Laura ...
Environmental health perspectives,
07/2009, Letnik:
117, Številka:
7
Journal Article
An inherited predisposition and environmental factors are the main determinants of human malignancies. Although uniquely, they represent the two outer boundaries of cancerogenesis, in most cases they ...act in combination, in particular when multiple tumors concomitantly affect the same individual or the same kindred. Inherited multi-tumoral syndromes are caused by germline mutations of tumor suppressor genes, which can result in either malignant or benign tumors as well as various nontumoral alterations. However, multiple tumors, i.e. solid tumors that are not causally related to each other, are increasingly observed in the same individual in the absence of genetically determined syndromes. This may simply be due to the increased life expectancy and/or to improvements in the early diagnosis and treatment of tumors, and thus an improved long-term survival after removal of the first tumor. However, at least three modern-day conditions may act as independent factors for the increased occurrence of multiple solid tumors in the same individual:
Radiotherapy and/or chemotherapy, or a combination of both, are increasingly used at the highest doses. Powerful antimetabolic, antiblastic, antibiotic drugs, together with immunosuppression and immunomodulation facilitate the occurrence of second tumors, sometimes within the first decade after treatment.Environmental pollution or inappropriate waste treatment has increased our exposure to carcinogens and other toxic agents. This has lead to increased frequencies of some cancers, particularly in subjects genetically more sensitive to these agents. Polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines are known carcinogens found in cigarette smoke and in air pollution. Transitional metals (Fe, Cr, Cu, Pb, Cd, V), fibers such as asbestos, pollutants from metropolitan areas, as well as long-term and long-distance side-effects of nuclear accidents (such as Chernobyl or similar nuclear disasters) are certainly responsible for an increased number of tumors, i.e., in addition to those usually occurring in the natural history of each individual.Patients undergoing organ transplantation, such as liver transplantation, in the treatment of malignant disease require immunosuppression. In these patients, in addition to recurrence of the primary tumor, new tumors, related to chronic immunosuppression, may develop.
Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is characterized by multiple phenotypic conditions such as acute disseminated encephalomyelitis, optic neuritis, and myelitis. MOGAD’s ...spectrum is expanding, with potential symptoms of increased intracranial pressure that are similar to idiopathic intracranial hypertension (IIH). We report a boy with new-onset continuous headache and a brain MRI at onset suggesting idiopathic intracranial hypertension (IIH). The patient showed resistance to treatment with acetazolamide and, after one month, developed optic neuritis in the left eye. Laboratory tests documented positive MOG antibodies (anti-MOG) in the serum. The final diagnosis was MOGAD, with the initial symptoms resembling IIH.
Non-congenital viral infections of the central nervous system in children can represent a severe clinical condition that needs a prompt diagnosis and management. However, the aetiological diagnosis ...can be challenging because symptoms are often nonspecific and cerebrospinal fluid analysis is not always diagnostic. In this context, neuroimaging represents a helpful tool, even though radiologic patterns sometimes overlap. The purpose of this pictorial essay is to suggest a schematic representation of different radiologic patterns of non-congenital viral encephalomyelitis based on the predominant viral tropism and vulnerability of specific regions: cortical grey matter, deep grey matter, white matter, brainstem, cerebellum and spine.
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