These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different. Immune system
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking)
and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown 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 result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres. Diagnosis
Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.
Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. In advanced cases, skeletal fluorosis causes painful damage to bones and joints. Symptoms
Symptoms are mainly promoted in the bone structure. Due to a high fluoride concentration in the body, the bone is hardened and thus less elastic, resulting in an increased frequency of fractures. Other symptoms include thickening of the bone structure and accumulation of bone tissue, which both contribute to impaired joint mobility. Ligaments and cartilage can become ossified. Most patients with skeletal fluorosis show side effects from the high fluoride dose such as ruptures of the stomach lining and nausea. Fluoride can also damage the parathyroid glands, leading to hyperparathyroidism, the uncontrolled secretion of parathyroid hormones. These hormones regulate calcium concentration in the body. An elevated parathyroid hormone concentration results in a depletion of calcium in bone structures and thus a higher calcium concentration in the blood. As a result, bone flexibility decreases making the bone more susceptible to fractures. Causes
Common causes of fluorosis include inhalation of fluoride dusts or fumes by workers in industry and consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe.) In India, especially the Nalgonda region (Telangana), a common cause of fluorosis is fluoride-rich drinking water that is sourced from deep-bore wells. Over half of groundwater sources in India have fluoride above recommended levels.Fluorosis can also occur as a result of volcanic activity.