1,721,081 research outputs found
Clinical therapy of patients contaminated with polonium or plutonium
No full textAlthough most of the harmful radionuclides are of anthropogenic origin and released from military or industrial processes, radioactive substances, such as uranium, also occur naturally in the environment. Low standards of care at nuclear facilities can lead to the contamination of employees with radionuclides due to inhalation of gases or dust or contamination of skin or wounds. Various sources for radionuclide exposure may present concerns for radioactive polonium or plutonium exposure, for instance, terrorist actions on the infrastructure, such as on drinking water basins. Early health effects after extensive radiation exposure may be vomiting, headaches, and fatigue, followed by bone marrow depression, fever, and diarrhea. The main purpose of radionuclide mobilization is to minimize the radiation dose. Since some of the important radionuclides, such as polonium and plutonium, have very long biological half-times after their deposition in bone, liver or kidneys, rapid initiation of chelation treatment is usually imperative after a contamination event. The antidote DMPS (dimercapto-propanesulfonate) is considered the drug of choice for polonium decorporation. DTPA (diethylenetriamine pentaacetate) is a potent chelator especially approved for radionuclide mobilization, including polonium and other actinides. Other chelators and drugs are under investigation as potential chelators of transuranic elements.Although most of the harmful radionuclides are of anthropogenic origin and released from military or industrial processes, radioactive substances, such as uranium, also occur naturally in the environment. Low standards of care at nuclear facilities can lead to the contamination of employees with radionuclides due to inhalation of gases or dust or contamination of skin or wounds. Various sources for radionuclide exposure may present concerns for radioactive polonium or plutonium exposure, for instance, terrorist actions on the infrastructure, such as on drinking water basins. Early health effects after extensive radiation exposure may be vomiting, headaches, and fatigue, followed by bone marrow depression, fever, and diarrhea. The main purpose of radionuclide mobilization is to minimize the radiation dose. Since some of the important radionuclides, such as polonium and plutonium, have very long biological half-times after their deposition in bone, liver or kidneys, rapid initiation of chelation treatment is usually imperative after a contamination event. The antidote DMPS (dimercapto-propanesulfonate) is considered the drug of choice for polonium decorporation. DTPA (diethylenetriamine pentaacetate) is a potent chelator especially approved for radionuclide mobilization, including polonium and other actinides. Other chelators and drugs are under investigation as potential chelators of transuranic elements.</p
Chelating principles in Menkes and Wilson diseases: Choosing the right compounds in the right combinations at the right time
No full textDysregulation of copper homeostasis in humans is primarily found in two genetic diseases of copper transport,
Menkes and Wilson diseases, which show symptoms of copper deficiency or overload, respectively. However,
both diseases are copper storage disorders despite completely opposite clinical pictures. Clinically, Menkes
disease is characterized by copper deficiency secondary to poor loading of copper-requiring enzymes although
sufficient body copper. Copper accumulates in non-hepatic tissues, but is deficient in blood, liver, and brain. In
contrast, Wilson disease is characterized by symptoms of copper toxicity secondary to accumulation of copper in
several organs most notably brain and liver, and a saturated blood copper pool. It is a challenge to correct copper
dyshomeostasis in either disease though copper depletion in Menkes disease is most challenging. Both diseases
are caused by defective copper export from distinct cells, and we seek to give new angles and guidelines to
improve treatment of these two complementary diseases. Therapy of Menkes disease with copper-histidine,
thiocarbamate, nitrilotriacetate or lipoic acid is discussed. In Wilson disease combination of a hydrophilic
chelator e.g. trientine or dimercaptosuccinate with a brain shuttle e.g. thiomolybdate or lipoate, is discussed.
New chelating principles for copper removal or delivery are outlined
Mercury in dental amalgams: a great concern for clinical toxicology in developing countries?
No full text[no abstract available
The role of xenobiotics and trace metals in Parkinson's Disease
No full textResearch on the etiopathogenesis of Parkinson's disease (PD) has in the very recent years earned many insightful cues about the involvement of xenobiotics and metal pollutants in the onset and exacerbation of this neurodegenerative disorder. Furthermore, particularly for metal pollutants, the hypothesis about the role exerted by impaired mitochondrial function is gaining a leading causative role. In this review, we outline the role of environmental pollution in the pathogenesis of PD, as the prolonged exposure to xenobiotics may account for the majority of PD reported cases, expanding the debate also about some suggested therapeutic approaches
Thymosin β4: a multi-faceted tissue repair stimulating protein in heart injury
No full textThymosin beta-4 (Tβ4) is known as a major pleiotropic actin-sequestering protein that is involved in tumorigenesis. Tβ4 is a water-soluble protein that has different promising clinical applications in the remodeling and ulcerated tissues repair following myocardial infarction, stroke, plasticity and neurovascular remodeling of the peripheral nervous system (PNS) and the central nervous system (CNS). On the other hand, similar effects have been observed for Tβ4 in other kinds of tissues, including cardiac muscle tissue. In recent reports, due to its activation of resident epicardial progenitor cells and modulation of inflammatory-caused injuries, Tβ4 has been suggested as a promoter of the survival of cardiomyocytes. Furthermore, Tβ4 may in skeletal muscle and different organs act in association/synergism with numerous other tissue repair stimulating factors, including melatonin and C-fiber-derived peptides. For these reasons, the present review highlights the promising role of Tβ4 in cardiac healing
Molecular targets in Alzheimer's Disease
No full textAlzheimer's disease (AD) is known as a devastating neurodegenerative disorder in aged subjects, which is related to multiple heterogeneous genetic factors. The two basic pathological aspects of AD are related to amyloid beta (Aβ) peptides and tau proteins. Some researchers have demonstrated plaques and tangles as apparently primary lesions. Also, experimental data propose that these two lesions are intimately related. In the present review, we highlight some molecular mechanisms linking tau and Aβ toxicities involving oxidative stress, aging, Aβ turnover, the contribution of thiol groups, and the role mitochondrial activities in the AD pathogenesis. Understanding the interplay of these mechanisms as parts of common pathophysiological pathways could reveal molecular targets to control or even treat AD
Iron and other metals in the pathogenesis of Parkinson's disease: Toxic effects and possible detoxification
No full textOf the documented cases of Parkinson's disease (PD), about 10% have a genetic background. The remaining cases of PD have unknown etiology. Thus, environmental factors appear to play a pathogenic role in most of the PD cases. Several of the so far known PD inducing chemicals appear to increase the formation of mitochondrial reactive oxygen species (ROS). A suspected environmental factor is the non-proteinogenic amino acid β-methylamino-L-alanine (BMAA), which may act to carry iron species into the brain and disrupt correct biosynthesis of proteins. In addition, in epidemiological studies, it has been reported a connection between PD and metal exposures, including iron, mercury, manganese, and lead. Research has shown elevated iron levels in the substantia nigra of PD patients. Mitochondrial dysfunction induced by genetic or environmental factors appears to evoke cascades of biochemical events, which include non-physiological leakage of ROS and arrest of the sensitive production of dopamine. A combination of increased ROS and loosely chelated iron causes neurotransmitter dysfunction. Recent research indicates that treatment with exogenous chelators, such as deferiprone, apomorphine, and hinokitiol, can inhibit PD progression. The endogenous chelator, neuromelanin, also appears to exert protection. In the present review, the pathogenic mechanisms and genetic susceptibilities to metals in PD are explored. The paper is also focused on strategies for the therapy of PD, mainly by using chelation therapy to reduce the level of iron
Iron chelation in the treatment of neurodegenerative diseases
No full textDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson’s disease
Exposure to environmental organic mercury and impairments in human fertility
No full text[no abstract available
Fibromyalgia and nutrition: Therapeutic possibilities?
No full textFibromyalgia (FM) is a complex chronic condition of unknown etiology, characterized by deep and widespread pain, sleep problems, cognitive impairment, fatigue, and other well-known functional symptoms. Recently, it has been proposed that an imbalance of nutritive components, including essential metal ions and vitamins, might play a critical role in the development of FM. Muscle pain has been associated with deficiencies in amino acids, magnesium, selenium, vitamins B and D, as well as with the harmful effects of heavy metals, such as mercury, cadmium, and lead. Research indicates that patients deficient in certain essential nutrients may develop dysfunction of pain inhibitory mechanisms together with fatigue and other FM symptoms. Additionally, mercury and other toxic elements may interfere with the bioavailability of essential nutrients. This review examines the many effects of metals and vitamins in pain evaluation of FM patients. Dietary guidance is therefore critical for FM patients to help them in correcting a suboptimal or deficient intake of essential nutrients. When optimal levels of nutrition are achieved, pain levels are usually lowered. Additional research is recommended in the field of FM and nutrition to disclose further possible relationships
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