Pathophysiology, Asbestos,Immunosupressive Properties

Asbestos fibres have been indicated to alter the function and secretory properties of macrophages, which ultimately creates conditions that favour mesothelioma developmeny. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals. These are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to encourage asbestos carcinogenicity. These oxidants participate in the oncogenic process by directly and indirectly interacting with DNA which consequently, modifies membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have indicated to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may end up in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β). This in turn, may bring about the chronic stimulation and proliferation of mesothelial cells after injury by asbestos which is then classified as advanced mesothelioma.

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This mesothelioma video on asbestos constructed homes contends that house built before 1980 usually have asbestos products in various parts of the houses. It is important to have the house surveyed by asbestos experts for professional removal for people’s safety.

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Steve Mc Queen, the famous actor died of cancer. As a young man, he worked in a shipyard where he was first exposed to asbestos. It takes 12-50 years for mesothelioma to develop from the first asbestos exposure. So a very detailed occcupational history is required to determine if a person can initiate a lawsuit.

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Mesothelioma - Pathophysiology and Asbestos

The mesothelium is described as consisting of a single layer of flattened to cuboidal cells which form the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. With the deposits of asbestos fibres in the parenchyma of the lung , this may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, consequently leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved; however, it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.

Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than “feathery fibers” (chrysotile or white asbestos fibers).However, current evidence that smaller particles may be more dangerous than the larger fibers. Remaining suspended in the air, they can be inhaled, and can penetrate more easily and deeper into the lungs. “We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately,” said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for “World Trade Center syndrome” or respiratory ailments from brief one to two day exposure of asbsetos near the collapsed buildings.

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, fibre transport to the pleura is critical to the pathogenesis of mesothelioma. This is definitely supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed. Moreover, the cellular changes within the lesion culminated in a morphologically malignant tumour.

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and progression. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres is of course unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype after being exposed to asbestos fibres has not yet been achieved. In general, asbestos fibres do act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.

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Mesothelioma - Screening

Currently, no universally agreed protocol for screening asbestos-exposed individuals exist. However, some research have pointed out that the serum osteopontin level may be applicable in screening asbestos-exposed individuals for mesothelioma. The level of soluble mesothelin-related protein is increased in the serum of about 75% of patients at diagnosis for mesothelioma.
Moreover, it has been suggested that it may be applicable for screening mesothelioma.

Mesothelioma - Staging

If the cancer is discovered merely on the membrane surface where it started, mesothelioma is described as being localized.
If mesothelioma has spread beyond the original membrane surface to other various parts of the body, such as the lymph nodes, chest wall, lungs or abdominal organ.

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