| 1. |
- Bjorklund, Geir, et al.
(författare)
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Metals and Parkinson's Disease : Mechanisms and Biochemical Processes
- 2018
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 25:19, s. 2198-2214
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Forskningsöversikt (refereegranskat)abstract
- Genetic background accounts for only 5 to 10% of the reported cases of Parkinson's disease (PD), while the remaining cases are of unknown etiology. It is believed that environmental factors may be involved in the causality of a large proportion of PD cases. Several PD genes are activated by xenobiotic exposure, and a link between pesticide exposure and PD has been demonstrated. Many epidemiological studies have shown an association between PD and exposure to metals such as mercury, lead, manganese, copper, iron, aluminum, bismuth, thallium, and zinc. This review explores the biological effects, the pathogenetic processes, genetic susceptibilities to metals as well as examining future strategies for PD treatment, such as chelation therapy.
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| 2. |
- Fireman, Elizabeth, et al.
(författare)
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Identification of metal sensitization in sarcoid-like metal-exposed patients by the MELISA (R) lymphocyte proliferation test - a pilot study
- 2016
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Ingår i: Journal of Occupational Medicine and Toxicology. - : Springer Science and Business Media LLC. - 1745-6673. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary function is often affected by the inhalation of metal particles. The resulting pathology might trigger various lung diseases, e.g., parenchymal lung fibrosis and granulomatous lung disorders. We previously demonstrated that 6 % of tissue-proven sarcoid patients had a positive beryllium lymphocyte proliferation test (BeLPT), thus correcting the diagnosis to chronic beryllium disease. The aim of this study was to examine if MEmory Lymphocyte Immnuno Stimulation Assay (MELISA (R)), currently used for non-pulmonary diseases, can identify metals other than beryllium that can also trigger sensitization and induce granulomatous disease. Methods: This pilot study included 13 sarcoid-like patients who underwent MELISA (R). Eleven patients also underwent BeLPT. Biopsy samples were tested for metal content by scanning electron microscope. Eleven study patients had been exposed to metals at the workplace and 2 had silicone implants. Results: Two patients who had undergone BeLPT were positive for beryllium. MELISA (R) detected 9 patients (9/13, 69 %) who were positive for at least one of the tested metals: 4 reacted positively to nickel, 4 to titanium, 2 to chromium, 2 to beryllium, 2 to silica, and one each to palladium, mercury and lead. Conclusion: It is proposed that MELISA (R) can be exploited to also identify specific sensitization in individuals exposed to inhaled particles from a variety of metals.
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| 3. |
- Klener, Pavel, et al.
(författare)
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The benefits of ascorbate to protect healthy cells in the prevention and treatment of oncological diseases
- 2020
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Ingår i: Journal of Applied Biomedicine. - : University of South Bohemia in Ceske Budejovice. - 1214-021X .- 1214-0287. ; 18:1, s. 1-7
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Forskningsöversikt (refereegranskat)abstract
- Health status is determined by the balance of oxidants and antioxidants which protects healthy cells against the threat of internal and external risk factors. Antioxidants such as ascorbate (vitamin C, ascorbic acid) are of fundamental importance in this respect. Ascorbate neutralizes potential damage caused by cellular oxidative stress which may be the greatest risk of damage to healthy tissue. Cellular oxidative stress is mediated by external factors (e.g. psychological stress, physical exertion, drugs, various diseases, environmental pollution, preservatives, smoking, and alcohol) and internal factors (products of cellular metabolism induding reactive oxygen species). When the products of oxidative stress are not sufficiently neutralized, healthy cells are at risk for both mitochondrial and DNA damage. In the short term, cell function may deteriorate, while an increased production of proinflammatory cytokines over time may lead to the development of chronic inflammatory changes and diseases, induding cancer. Although pharmaceutical research continues to bring effective chemotherapeutic agents to the market, a limiting factor is often the normal tissue and organ toxicity of these substances, which leads to oxidative stress on healthy tissue. There is increasing interest and imperative to protect healthy tissues from the negative effects of radio-chemotherapeutic treatment. The action of ascorbate against the development of oxidative stress may justify its use not only in the prevention of carcinogenesis, but as a part of supportive or complementary therapy during treatment. Ascorbate (particularly when administered parentally at high doses) may have antioxidant effects that work to protect healthy cells and improve patient tolerability to some toxic radio-chemotherapy regimens. Additionally, ascorbate has demonstrated an immunomodulatory effect by supporting mechanisms essential to anti-tumor immunity. Intravenous administration of gram doses of vitamin C produce high plasma levels immediately, but the levels drop rapidly. Following oral vitamin C administration, plasma levels increase slowly to relatively low values, and then gradually decay. With an oral liposomal formulation, significantly higher levels are attainable than with standard oral formulations. Therefore, oral administration of liposomal vitamin C appears to be an optimal adjunct to intravenous administration. In this review, the basic mechanisms and clinical benefits of ascorbate as an antioxidant that may be useful as complementary therapy to chemotherapeutic regimens will be discussed.
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| 4. |
- Manousek, Jan, et al.
(författare)
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Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA (R). Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA (R)); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity tometals (mercury in particular) evaluated by LTT-MELISA (R). We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.
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| 5. |
- Manousek, Jan, et al.
(författare)
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Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices
- 2018
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:9, s. e140-e147
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden.Methods and resultsThe cohort consisted of 20 men and 4 women (mean age: 62.3 +/- 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 +/- 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008).ConclusionOur findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.
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| 6. |
- Muss, Claus, et al.
(författare)
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The effectiveness of choline citrate infusions monitored by lymphocyte transformation test (LTT) in multiple sclerosis. A new approach to the diagnosis and treatment of the disease
- 2009
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Ingår i: Neuro - endocrinology letters. - 0172-780X. ; 30:3, s. 331-334
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of intravenous choline citrate infusions was investigated in 34 patients with multiple sclerosis (MS) by clinical evaluation and by monitoring of lymphocyte proliferation in vitro against fragments of myelin basic protein (MOG-35-55, MBP15-31, PLP 39-15) over a period of 12 weeks. Patients have been diagnosed with MS at least one year before entering the study and suffered from mild relapsing/remitting course to long-term chronic progressive disease. Twenty one patients exhibited positive lymphocyte proliferation to myelin fragments prior to treatment and were therefore selected for further studies. Choline citrate was administered with a dosage of 1200mg/ 2x week for a period of 3 months. This treatment resulted in a significant decrease of lymphocyte proliferation to neural fragments (MOG- 35-55, MBP15-31) in lymphocyte transformation test (LTT). There was no significant SI change of PLP Peptide (PLP 39-15) LTT found after treatment with choline citrate. During the 3 mo observation period, patients remained stable and no side-effects of the treatment were observed. In addition, some patients reported long-lasting improvement (less paresthesia and increase of muscle strength in lower extremities) which was demonstrated up to 3 years later. In one spectacular case a commercial pilot was able to return to duty again after treatment. This pilot was allowed back in to his position as a commercial flying cockpit member and is on duty for more than 4 yrs now.
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| 7. |
- Stejskal, Vera, et al.
(författare)
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Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease
- 2015
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Ingår i: Journal of Trace Elements in Medicine and Biology. - : Elsevier BV. - 0946-672X .- 1878-3252. ; 31, s. 230-236
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Tidskriftsartikel (refereegranskat)abstract
- Background: Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CID often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. Methods: Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjogren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA (R) (Memory Lymphocyte Immuno Stimulation Assay). Results: In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P< 0.0001). The most frequent allergens were nickel, mercury, gold and palladium. Conclusions: Patients with SLE, RA and SS have an increased frequency of metal DTI. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in Ds, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.
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| 8. |
- Stejskal, Vera, et al.
(författare)
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Metal-induced inflammation triggers fibromyalgia in metal-allergic patients
- 2013
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Ingår i: Neuro - endocrinology letters. - 0172-780X. ; 34:6, s. 559-565
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fibromyalgia (FM) is a disease of unknown etiology. Inflammation could be one of the mechanisms behind this disease. OBJECTIVES: We studied the frequency and clinical relevance of metal allergy in FM patients. METHODS: Fifteen female FM patients were included in the study. Metal allergy was measured by a lymphocyte transformation test, MELISA (R). Ten healthy age-matched women were used as controls for in vitro studies. Reduction of metal exposure in the FM patients was achieved by replacement of dental metal restorations and by the avoidance of known sources of metal exposure. Objective health assessment was performed 5 years after treatment. Subjective health assessment was established by a questionnaire, completed 2, 5 and in some cases 10 years after the start of the study. Follow-up MELISA was also performed. RESULTS: All FM patients tested positive to at least one of the metals tested. The most frequent reactions were to nickel, followed by inorganic mercury, cadmium and lead. Some healthy controls responded to inorganic mercury in vitro but most of the tests were negative. Objective examination 5 years later showed that half of the patients no longer fulfilled the FM diagnosis, 20% had improved and the remaining 30% still had FM. All patients reported subjective health improvement. This correlated with the normalisation of metal-specific responses in vitro. CONCLUSION: Metal allergy is frequent in FM patients. The reduction of metal exposure resulted in improved health in the majority of metal-sensitized patients. This suggests that metal-induced inflammation might be an important risk factor in a subset of patients with FM.
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| 9. |
- Stejskal, Vera
(författare)
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Metals as a Common Trigger of Inflammation Resulting in Non-Specific Symptoms : Diagnosis and Treatment
- 2014
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Ingår i: Israel Medical Association Journal. - 1565-1088. ; 16:12, s. 753-758
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Tidskriftsartikel (refereegranskat)abstract
- Background: The multiple symptoms of chronic fatigue syndrome (CFS) and fibromyalgia resemble those described in patients suffering from autoimmune/inflammatory syndrome induced by adjuvants (ASIA). It has been suggested that chronic metal-induced inflammation might play a role both in CFS and fibromyalgia as well as in ASIA. Humans are exposed to metal Mainly through the release of metal ions from corroding dental restorations and orthopedic implants, food, Vaccines and jewelry. Metals readily bind to sulphur and other groups in the mitochondria, enzymes and cell proteins. Metal-bound proteins are recognized by the immune system of susceptible subjects and might trigger an abnormal immune response, including allergy and autoimmunity. Objectives: To study three subjects with CFS and two with fibromyalgia, all cif whom suspected metal exposure as a trigger for their ill health. Methods: We measured delayed-type hypersensitivity to metals (metal allergy) using a validated lymphocyte transformation test, LTT-MELISA (R). All patients except one were sensitized to metals present in their dental restorations. The remaining patient reacted to metals in his Skull implant. The removal a sensitizing metals resulted in long-term health improvement. Nine healthy controls matched for gender and age showed only marginal reactivity to the metals tested. Conclusions: Patients with CFS and fibromyalgia are frequently sensitized to metals found in the environment or used in dentistry and surgery. This allergy to metals Might initiate or aggravate non-specific symptoms in metal-sensitized patients.
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| 10. |
- Yaqob, Amer, et al.
(författare)
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Metal-specific lymphocyte reactivity is downregulated after dental metal replacement
- 2006
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Ingår i: Neuro - endocrinology letters. - 0172-780X. ; 27:1-2, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study was done to evaluate the results and clinical relevance of an optimized lymphocyte proliferation test, MELISA, for metal-induced inflammation in patients with CFS-like symptoms. The treatment of patients consisted of the replacement of incompatible dental materials (RID) together with supportive anti-oxidant therapy. DESIGN OF THE STUDY: 513 patients were tested by MELISA at the beginning of the study. Out of this group, 248 patients were available for follow-up MELISA after RID. METHODS: In MELISA, lymphocytes are isolated from the blood and cultivated with different metal salts in tissue culture medium containing 10% inactivated human AB+ serum or autologous serum. After 5 days, the presence of metal-reactive lymphocytes are measured by isotope labelling of newly formed DNA in growing lymphoblasts and evaluated by calculating the Stimulation Index. RESULTS: Nickel was the most common sensitizer, followed by inorganic mercury, thimerosal, lead, cadmium, palladium and gold. After RID treatment, a decrease of metal-specific lymphocyte responses in patients who reacted to metals at the beginning of the study could be observed. The cultivation of lymphocytes in autologous and homologous serum did not significantly affect the results. Simultaneous, the health status of patients improved as well. CONCLUSIONS: Replacement of incompatible dental materials resulted in down-regulation of metal-induced lymphocyte sensitivity in vitro, as well as in the improvement of health status of majority of patients with unspecific CFS-like symptoms.
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