- Klíčová slova
- P-AscH - vysokodávkový intravenózní vitamin C,
- MeSH
- antioxidancia terapeutické užití MeSH
- antitumorózní látky škodlivé účinky terapeutické užití MeSH
- intravenózní podání MeSH
- kyselina askorbová aplikace a dávkování farmakokinetika farmakologie MeSH
- lidé MeSH
- nádory * imunologie patofyziologie MeSH
- oxidační stres imunologie účinky léků MeSH
- synergismus léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
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 including 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, including 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.
- Klíčová slova
- podpůrná léčba,
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- kvalita života MeSH
- kyselina askorbová * aplikace a dávkování farmakologie imunologie MeSH
- lidé MeSH
- nádory * farmakoterapie imunologie MeSH
- nežádoucí účinky léčiv farmakoterapie prevence a kontrola MeSH
- oxidační stres fyziologie MeSH
- reaktivní formy kyslíku škodlivé účinky MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Pro kvalitu zdravotního stavu je důležitá rovnováha oxidantů a antioxidantů, které chrání zdravé buňky před hrozbou vnitřních a vnějších rizikových faktorů. Antioxidanty, jako je askorbát (vitamin C, kyselina askorbová), mají v tomto ohledu zásadní význam. Askorbát neutralizuje potenciální poškození způsobené buněčným oxidačním stresem, které může být největším rizikem pro poškození zdravé tkáně. Buněčný oxidační stres je způsoben vnějšími faktory (např. psychickým stresem, fyzickou námahou, léčivy, různými chorobami, znečištěním životního prostředí, konzervačními látkami, kouřením a alkoholem) a vnitřními faktory (produkty buněčného metabolismu včetně reaktivních forem kyslíku).
Aims: To 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 results: The 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). Conclusion: Our 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.
- MeSH
- aktivace lymfocytů MeSH
- alergie epidemiologie etiologie MeSH
- antimon škodlivé účinky MeSH
- cín škodlivé účinky MeSH
- defibrilátory implantabilní škodlivé účinky MeSH
- implantace protézy * MeSH
- infekce spojené s protézou epidemiologie MeSH
- kovy škodlivé účinky MeSH
- kožní nemoci epidemiologie MeSH
- látky znečišťující životní prostředí škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mangan škodlivé účinky MeSH
- molybden škodlivé účinky MeSH
- nikl škodlivé účinky MeSH
- platina škodlivé účinky MeSH
- pooperační bolest epidemiologie MeSH
- pooperační komplikace epidemiologie MeSH
- prostředky srdeční resynchronizační terapie škodlivé účinky MeSH
- rtuť škodlivé účinky MeSH
- senioři MeSH
- slitiny MeSH
- titan škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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®. 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®); 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 to metals (mercury in particular) evaluated by LTT-MELISA®. 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.
- MeSH
- aktivace lymfocytů imunologie MeSH
- dospělí MeSH
- kovy imunologie MeSH
- léková alergie imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- pozdní přecitlivělost imunologie MeSH
- revmatoidní artritida imunologie MeSH
- rtuť imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- takotsubo kardiomyopatie imunologie MeSH
- životní prostředí MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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®), 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®. 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® 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® can be exploited to also identify specific sensitization in individuals exposed to inhaled particles from a variety of metals.
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Environmental factors can play an important role in the development of autoimmune thyroiditis (AT) and other autoimmune diseases. This article reviews the role of heavy metals and infectious agents in AT. Currently, the genes responsible for a metal-induced pathology are known in experimental animals but similar knowledge is lacking in man. Metals such as nickel or mercury induce delayed type T cell hypersensitivity (allergy) which is relatively common, especially in women. T-cell allergy can be studied with the lymphocyte transformation test, LTT-MELISA. It has been found that patients with AT and other autoimmune diseases, such as multiple sclerosis, psoriasis, systemic lupus erythematosus and atopic eczema, show increased lymphocyte reactivity in vitro to inorganic mercury, nickel and other metals compared to healthy controls. The important source of mercury is dental amalgam. Replacement of amalgam in mercury-allergic subjects resulted in improvement of health in about 70% of patients. Several laboratory parameters such as mercury-specific lymphocyte responses in vitro and anti-thyroid autoantibodies were normalized as well. In contrast, no changes in health and laboratory results were observed in mercury-allergic patients who did not have their amalgams replaced. The same was true for non-allergic patients who underwent amalgam replacement. Infectious agents such as Helicobacter pylori (Hp) may cause chronic inflammation and autoimmune reactivity in susceptible subjects. The results of in vitro experiments performed with lymphocytes from Hp infected patients indicate that Hp can cause immunosuppression which might be eliminated by successful eradication therapy. In conclusion, heavy metals and Hp infection may play an important role in AT. Laboratory tests, such as LTT-MELISA, can help to determine the specific etiological agents causing inflammation in individual patients. The treatment of AT and other autoimmune diseases might be improved if such agents are eliminated and any future exposure restricted.
- MeSH
- aktivace lymfocytů účinky léků MeSH
- autoimunitní tyreoiditida chemicky indukované komplikace imunologie MeSH
- Helicobacter pylori imunologie MeSH
- lidé MeSH
- těžké kovy škodlivé účinky MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- zánět chemicky indukované komplikace imunologie MeSH
- zubní amalgam škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Helicobacter pylori (Hp) contributes to the development of gastric and extra-gastric diseases such as autoimmune thyroiditis (AT), and causes persistent life-long infection despite local and systemic immune response. We determined the specific cellular immune response to Hp antigens and PWM (control mitogen) in two groups of Hp infected patients--group A (n = 21), involving patients with autoimmune thyroiditis and group B (n = 13) of patients without AT--using modified lymphocyte transformation test before and after eradication therapy in comparison with healthy controls (group C, n = 15). Immune reactivity to the majority of Hp antigens (aHp, hHp, HpAg, CagA) was significantly lower in group B before eradication therapy in comparison with healthy Hp negative controls. A significant increase in immune reactivity was observed in group B to certain Hp antigens after successful eradication. The same levels (but insignificant) of immune reactivity were shown in group A. Our results indicate that Hp can cause the inhibition of the specific cellular immune response in Hp infected patients with or without autoimmune diseases such as AT, which can be abrogated by successful eradication of Hp. Lymphocyte transformation test appears to be a good tool for detection of immune memory cellular response in patients with Hp infection
- MeSH
- antigeny bakteriální imunologie MeSH
- autoimunitní tyreoiditida imunologie komplikace MeSH
- dospělí MeSH
- financování organizované MeSH
- Helicobacter imunologie MeSH
- imunologická tolerance MeSH
- infekce vyvolané Helicobacter pylori imunologie klasifikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty imunologie MeSH
- proliferace buněk MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
OBJECTIVE: Corrosion products of different metallic alloys used in prosthetic dentistry often cause the development of a bluish-grey pigmentation of gingiva and oral mucosa. The aim of this study was to determine the content of metals in metallic pigmentations and evaluate the immune response to metals found in the oral cavity. MATERIAL AND METHODS: The local tissue reactions were investigated clinically by electron microscopy and by energy dispersive x-ray microanalysis. An extensive anamnesis of the patients was recorded as well as earlier contacts with health care institutions. The immunological response to metallic components of dental alloys was evaluated in 34 patients by MELISA, a modified test for lymphocyte proliferation. In addition, cytokines in culture media were determined in 10 persons by the Human Inflammation Antibody Array. RESULTS: Dense particles containing metals were found in the matrix among collagen fibrils and in close proximity of the lamina basalis of the gingival epithelium. Particles were also localized intracellularly in fibroblasts, macrophages, and endothelial cells. Metallic depositions consisted predominantly of silver accompanied by selenium and sulphur. Twenty five out of 34 patients revealed high lymphocyte reactivity (positive MELISA test) to one or more metal components of dental restorations. A correlation between the positivity in MELISA test and number of dental alloys in the oral cavity was also found. Twenty MELISA positive patients suffered from serious health problems (various allergies, autoimmune diseases, Parkinson's syndrome etc.). Nickel and inorganic mercury were the most common sensitizers in vitro. The cytokine assay revealed that mercury chloride activated predominantly TH2 lymphocytes, while nickel chloride activated mainly TH1 lymphocytes. CONCLUSIONS: Metallic pigmentations in the oral cavity demonstrate a corrosion process and may pose a risk immunologically susceptible patients.
- MeSH
- aktivace lymfocytů MeSH
- alergie etiologie MeSH
- chronická nemoc MeSH
- dospělí MeSH
- gingiva patologie účinky léků MeSH
- koroze MeSH
- kovy škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroanalýza elektronovou sondou MeSH
- poruchy pigmentace etiologie MeSH
- senioři MeSH
- ústní sliznice patologie účinky léků MeSH
- zubní slitiny škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
