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1.
Med Hypotheses ; 84(4): 336-40, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25659493

RESUMO

Type 1 diabetes (T1D), an autoimmune disease, breaks out in some of the children who has genetic susceptibility to T1D. Besides genetic susceptibility some environmental factor(s) are required to trigger the disease. The incidence of T1D in Finland is highest in the world, so we must seek an environmental factor, that is typical for Finland and can declare many aspects of T1D epidemiology and biology. In the literature most popular trigger has been enterovirus infections. It is difficult however to find why enteroviruses would be in this role in Finland in contrary to neighbouring countries e.g. Sweden. Colloidal amorphous silica (ASi) is typical for Finnish environment in consequency of the geohistory of Finland, great part of Finland is an ancient lake and sea bottom. ASi concentrations in natural waters are high in April-June and in November, only traces can be found in the rest of months. Pure colloidal ASi is not a strong trigger for T1D, but ASi particle which has surface adsorbed tetrahedrally coordinated zinc (ASiZn) is probably the trigger which has kept it's secret up to date. Zn functions as address label which conducts the ASiZn particle to the beta cell, whose content of zinc is highest in the body. ASi particle adheres to membrane proteins distorting their tertiary structure revealing new epitopes. If the fetus has not met these epitopes at proper time during intrauterine development, the consequence is that the negative selection of lymphocytes in the thymus and bone marrow and fetal liver is not perfect. When a child later in postnatal life becomes predisposed to ASiZn particles the immune system reacts to these as to nonself proteins. As a consequence the insulin producing beta cells are destroyed. Many observations from diabetes research support the hypothesis, some to mentioned. 1. Three common autoantigens (ZnT8, ICA512/IA-2, GAD65) are membrane proteins whose function zinc regulates. 2. Geographical variation in Finland is convergent with surface water manganese concentrations. Manganese is the principal Zn scavenger and high manganese in water reduces ASiZn particle formation and the incidence of T1D. 3. The incidence of T1D depends of drinking water pH. The highest incidence can be found within water pH 6.2-6.9. Zn coordination changes from octahedral (unphysiologic) to tetrahedral (physiologic) at pH 6.56. In the text are presented five more supporting observations e.g. the similarity between the soils in Sardinia and Finland in respect to ASi.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/etiologia , Surtos de Doenças/estatística & dados numéricos , Poluentes Ambientais/efeitos adversos , Modelos Biológicos , Pontos Quânticos/efeitos adversos , Dióxido de Silício/efeitos adversos , Coloides/efeitos adversos , Coloides/química , Poluentes Ambientais/análise , Finlândia/epidemiologia , Humanos , Incidência , Pontos Quânticos/química , Dióxido de Silício/química
2.
Arch Dermatol Res ; 264(2): 185-91, 1979 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-464638

RESUMO

Fresh human skin extract made in salt solution after a prior buffer extraction was shown to enhance the hydrolysis of N-alpha-benzoyl-DL-arginine beta-naphthylamide (BANA) by trypsin. This trypsin enhancing effect was further shown to be both stabilizing and activating. After chromatography on Sephadex G-100, the trypsin binding factor was found in fractions of void volume. Protease binding took place in physiological and hypotonic but not in hypertonic NaCl-solutions (0.5 mol/l). The proteinase binding factor was further purified by trypsin-Sepharose 4 B affinity chromatography. It was found to bind also chymotrypsin and elastase and to be thermostable (100 degrees C for 20 min), precipitable at acidic pH (3.5), and by acetone and ammonium sulphate (60% saturation). The bound proteinases were found to preserve their hydrolytic activity towards protein substrates. Bound trypsin and chymotrypsin could completely be inhibited by soybean trypsin inhibitor. The binding factor did not react with anti-human-alfa2-macroglobulin antiserum from rabbit.


Assuntos
Peptídeo Hidrolases/análise , Pele/análise , Benzoilarginina-2-Naftilamida , Cromatografia em Gel , Humanos , Ligação Proteica , Extratos de Tecidos/farmacologia , Tripsina/metabolismo
3.
Med Hypotheses ; 77(5): 815-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21862234

RESUMO

Previously, a curious observation was made that indicated high iodine concentrations in the raw (ground) water of a water treatment plant wells is associated with a high prevalence of autoimmune hypothyreosis in consumers. When fractionating this water with liquid chromatography (HPLC), iodine elutes in the same fractions as humic substances. Humic substances are determined by measuring light absorbance at 280 nm from the fractions. The prevalence of autoimmune hypothyreosis in the Finnish municipalities varies approximately ten fold. In Finland, water is distributed by the municipal water works, and every municipal water work has its own water source. Water sources in the municipalities with a high prevalence of autoimmune hypothyreosis are at least at times synclinal (the water flows from the flood lake to the aquifer). This kind of flood lake is a suitable environment for the synthesis of ternary system amorphous silica/humus/iodine nanocolloid (Asi/Hu/I) particles. According to our proposed hypothesis, Asi/Hu/I nanocolloid particles in tap water are internalised by thyrocytes via the sodium iodide symporter (NIS), indicating receptor-mediated endocytosis. Receptor-mediated endocytosis is quick and efficient so that enough amorphous silica nanoparticles are internalised inside thyrocytes to denature various intracellular proteins (e.g., thyroglobulin), thereby affecting the immunoreactivity of proteins, which triggers the autoimmunity process. In this article, we present observations that support this hypothesis.


Assuntos
Doenças Autoimunes/etiologia , Coloides/análise , Nanoestruturas , Dióxido de Silício/análise , Abastecimento de Água/análise , Finlândia , Humanos
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