NaI Water Research Articles

The association between endothelial function and autoimmune thyroiditis induced by iodine excess

BackgroundIodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. MethodsA total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. ResultsHere, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. ConclusionCollectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

Phononic Crystal Made of Silicon Ridges on a Membrane for Liquid Sensing.

We propose the design of a phononic crystal to sense the acoustic properties of a liquid that is constituted by an array of silicon ridges on a membrane. In contrast to other concepts, the ridges are immersed in the liquid. The introduction of a suitable cavity in the periodic array gives rise to a confined defect mode with high localization in the cavity region and strong solid-liquid interaction, which make it sensitive to the acoustic properties of the liquid. By using a finite element method simulation, we theoretically study the transmission and cavity excitation of an incident flexural wave of the membrane. The observation of the vibrations of this mode can be achieved either outside the area of the phononic crystal or just above the cavity. We discuss the existence of the resonant modes, as well as its quality factor and sensitivity to liquid properties as a function of the geometrical parameters. The performance of the proposed sensor has then been tested to detect the variation in NaI concentration in a NaI-water mixture.

Cordyceps sinensis-derived fungus Isaria felina ameliorates experimental autoimmune thyroiditis in mice

AimsThis study aimed to investigate the therapeutic effect of Cordyceps sinensis-derived fungus Isaria felina on experimental autoimmune thyroiditis (EAT). MethodsA NaI-induced EAT mouse model was established. The mice received oral administration of vehicle, low-dose Isaria felina (300 mg/kg), or high-dose Isaria felina (600 mg/kg) once a day for four weeks before euthanasia. Enzyme-linked immunosorbent assays (ELISA) was performed to measure serum thyroid-stimulating hormone (TSH) levels, thyroid antibodies, and cytokines. Hematoxylin and eosin (H&E) staining was conducted to assess histopathological changes in the thyroid tissue samples of mice. TUNEL and Bcl-2 immunohistochemistry (IHC) were performed to evaluate cell apoptosis, and cleaved caspase-3 IHC was performed to detect the relative expression in the thyroid tissue samples. ResultsCompared with KIO3 and KI water, NaI water consumption successfully induced EAT in mice, as evidenced by significantly increased circulating TSH and thyroid antibody levels, along with typical histopathological abnormalities of autoimmune thyroiditis (AIT) in the thyroid tissue samples. Compared with vehicle or low-dose Isaria felina, high-dose Isaria felina treatment resulted in significant reductions in white cell counts and circulating TSH, thyroid antibody, and cytokine levels of EAT mice. High-dose Isaria felina also alleviated histopathological abnormalities and attenuated TUNEL staining, Bcl-2 protein expression, and cleaved caspase-3 expression in the thyroid tissue samples. ConclusionHigh-dose Isaria felina treatment alleviates thyroid inflammation and cell apoptosis in EAT, serving as a novel, promising therapeutic agent for AIT.

High performance design for detecting NaI–water concentrations using a two-dimensional phononic crystal biosensor

In this research, the sensing NaI (sodium iodide)–water concentration is achieved by using a local resonant two-dimensional solid–liquid phononic crystal (PnC) design. The sensor design consists of a square arrangement from stainless steel as a host matrix and a periodic array of water-filled circular scatterers. The sensing mechanism is based on the resonance frequencies confined around the NaI waveguide embedded in the middle of the sensor structure. Numerical simulations are carried out based on the finite element method (FEM). Our results showed that the resonant peak frequency varies significantly with the different NaI–water concentrations in the waveguide. Also, the sensor can differentiate between concentrations from 6%–45% with a 1% step, which is very acceptable for accurate detection and can solve many challenges in medical applications. Further, the sensor provided high performance for all NaI–water concentrations. For example, for a concentration range of 6%7%, the sensor has a sensitivity of 1714 Hz, a resolution of 59.5 Hz, a quality factor of 1401, a figure of merit (FOM) of 28, and a signal-to-noise ratio of 2.

Agonistic anti-CD40 promotes early development and increases the incidence of severe thyroid epithelial cell hyperplasia (TEC H/P) in CD4-/- mice.

IFN-γ−/−NOD.H-2h4 mice develop thyroid epithelial cell hyperplasia (TEC H/P) characterised by abnormal proliferation of thyrocytes and infiltration of thyroids by CD4+ and CD8+ T cells, macrophages and dendritic cells. CD8+ T cells from mice with severe TEC H/P transfer similar lesions to SCID recipients, whereas CD4+ T cells transfer mild TEC H/P. CD4− and CD8− deficient IFN-γ−/−NOD.H-2h4 mice were generated to determine if CD4+ T cells were required for initial activation of the CD8+ T cells that transfer TEC H/P. After 6–8 months on NaI water, only 2 of 60 CD8−/− mice developed severe TEC H/P, whereas 31 of 101 CD4−/− mice developed severe TEC H/P and fibrosis comparable in severity to that of IFN-γ−/− mice. However, splenocytes from CD4−/− mice with severe TEC H/P did not effectively transfer severe TEC H/P to SCID recipients. When CD4−/− donors were given agonistic anti-CD40 mAb, most developed severe TEC H/P and their cells transferred severe TEC H/P to SCID recipients. These results indicate that agonistic anti-CD40 can provide an important signal for activation of autoreactive CD8+ T cells that transfer severe TEC H/P. Therefore, targeting or blocking CD40 could provide effective therapy for diseases involving hyperplasia and fibrosis mediated by CD8+ T cells.

Increased severity of spontaneous autoimmune thyroiditis (SAT) and salivary gland infiltration in NOD.H-2h4 mice lacking regulatory T cells (T reg) (143.25)

Abstract NOD.H-2h4 mice given NaI in the drinking water develop SAT with chronic inflammation of the thyroid by T and B cells and production of anti-thyroglobulin (Tg) autoantibody. CD28-/- NOD.H2-4 mice, which have greatly reduced numbers of CD4+CD25+FoxP3+ Treg, were developed in order to examine the role of T reg in SAT development in WT and B cell-deficient (B-/-) mice. CD28-/- NOD.H2-h4 mice given NaI water develop more severe SAT than WT mice with collagen deposition (fibrosis) and low serum T4. Lymphocyte infiltration of salivary glands is also increased compared to WT mice. Most 4-6 mo old CD28-/- mice not given NaI water also develop SAT, whereas WT NOD.H-2h4 mice not given NaI water rarely develop SAT until much later. Although anti-Tg autoantibody levels generally correlate with SAT severity in WT mice, CD28-/- mice have reduced anti-Tg autoantibodies. Over time, the percentage of splenic follicular B cells decreases and marginal zone B cells increase. B -/- NOD.H-2h4 mice are resistant to SAT, but they develop SAT after transient depletion of T reg. CD28-/-B-/- mice, which lack most T reg, develop SAT comparable to WT NOD.H-2h4 mice. In B-/- mice, a lack of B cells as APC during the initiation phase of SAT may lead to preferential activation of Treg leading to reduced activation of effector T cells and reduced SAT severity. T reg also regulate SAT development if B cells are present since severe SAT develops in CD28-/- mice lacking T reg. (Supported by NIH RO1 AI076395)

CD4+ T cells are required for CD8+ T-cell activation but not for CD8+ T cell effector function for induction of thyrocyte hyperplasia (TEC H/P) and fibrosis (93.7)

Abstract IFN-γ-/-NOD.H-2h4 mice develop TEC H/P and fibrosis characterized by abnormal proliferation of thyrocytes and infiltration of thyroids by CD4+ and CD8+ T cells. CD8+ T cells are the primary effector cells for TEC H/P. CD4-/- and CD8-/- IFN-γ-/- NOD.H-2h4 mice were generated to determine if CD4+ T cells were required for activation of CD8+ T cells that induce TEC H/P and fibrosis. 60-70% of IFN-γ-/- mice given NaI water for 6-7 mo develop severe TEC H/P and fibrosis, compared to 11 of 53 (21%) CD4-/- mice and only 2 of 42 (5%) CD8-/- mice. TEC H/P incidence in CD4-/- mice given splenocytes from CD8-/- mice is similar to that of IFN-γ-/- mice (60%). Splenocytes from IFN-γ-/- donors with severe TEC H/P transfer severe TEC H/P to SCID recipients after culture in vitro for 72 hr, and purified CD8+ T cells from the same donors also transfer severe TEC H/P to SCID recipients. Splenocytes from some CD4-/- donors with severe TEC H/P can transfer severe TEC H/P to SCID recipients, but more often they transfer only minimal disease. These results suggest that CD4+ T cells are required for optimal activation of CD8+ T cells that induce TEC H/P, and they may also be important for optimal in vitro activation of CD8+ T cells that induce severe TEC H/P. In contrast, after CD8+ T cells are fully activated, CD4+ T cells are not required for their mobilization to thyroids or for effector function leading to TEC H/P and fibrosis.

Anti‐CD20 depletion of B cells inhibits spontaneous autoimmune thyroiditis (SAT)

All NOD.H‐2h4 wild type (WT) mice given NaI water develop SAT, but B cell‐deficient (B−/−) mice are resistant. B cells presumably function as APC for activation of CD4+ T cells. B −/− mice develop SAT comparable to WT mice after transient depletion of T reg, suggesting T reg are preferentially activated if autoantigen is presented by non‐B cells. Anti‐CD20 or isotype control was given to young (1–2 wk) or adult (7 wk) WT mice; all mice were given NaI water at 8 wk, and SAT was evaluated 8 wk later. WT mice given anti‐CD20 at 1 and 2 wk of age developed minimal SAT, although B cells had repopulated by 6–8 wk of age. Transient depletion of T reg during B cell depletion reversed the effects of anti‐CD20, and all mice developed SAT. SAT was also inhibited in adult mice given anti‐CD20 if B cell depletion in blood was maintained for 8 wk. Transient B cell depletion of adult mice did not inhibit SAT development. Anti‐CD20 depleted most circulating B cells, but only 60–80% of splenic B cells in adults. Most follicular B cells were depleted, but marginal zone B cells were resistant. The results suggest that in the absence of B cells, other APC activate T reg. This may be one mechanism by which B cell depletion inhibits autoimmune disease. The effects of B cell depletion and the underlying mechanisms may differ depending on when anti‐CD20 is administered. (Supported by Arthritis Natl. Res. Fdn). Anti‐CD20 was provided by Drs. M. Kehry and R. Dunn, Biogen, Idec.

CD4 +CD25 + naturally occurring regulatory T cells and not lymphopenia play a role in the pathogenesis of iodide-induced autoimmune thyroiditis in NOD-H2 h4 mice

NOD-H2 h4 mice, which express I-A k on the NOD background, spontaneously develop autoimmune thyroiditis, a model of Hashimoto thyroiditis in humans, by adding iodide in the drinking water. Parental NOD mice have previously been shown to have intrinsic numerical abnormalities in peripheral lymphocytes and lymphocyte subpopulations such as CD4 +CD25 + naturally occurring regulatory T cells (Treg). Therefore we first investigated whether the similar abnormalities exist in NOD-H2 h4 mice. We observed that, compared with other non-autoimmune disease prone BALB/c and C57BL/6 mice, NOD-H2 h4 mice have lower numbers of splenocytes, CD3 +T, CD4 +T and CD8 +T cells but the ratios of Treg to CD4 +T cells were comparable. Increasing the numbers of peripheral lymphocytes by Complete Freund's Adjuvant immunization or splenocyte transfer did not affect development of thyroiditis, indicating that lymphopenia does not play a critical role in the pathogenesis of thyroiditis. We next examined the significance of Treg by depleting this lymphocyte subset with anti-CD25 antibody. Treg depletion, performed 4 days before the administration of NaI water for 8 weeks, significantly exacerbated thyroiditis ( p < 0.01). Anti-thyroglobulin antibody titers also increased by Treg depletion ( p < 0.01) without changing the IgG2b to IgG1 ratios. In addition, expression levels of mRNA for IFN-γ and IL-4 were enhanced in parallel. However, T 4 levels were similar between antibody-treated and untreated groups. Additional anti-CD25 administration at 3 weekly intervals did not influence these results. These data, together with previous studies on other mouse models of inducible thyroiditis and Graves’ disease, indicate the role played by Treg in keeping anti-thyroid autoimmune reaction in check in experimental autoimmune thyroid diseases.

B cell-deficient NOD.H-2h4 mice have CD4+CD25+ T regulatory cells that inhibit the development of spontaneous autoimmune thyroiditis.

Wild-type (WT) NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) when given 0.05% NaI in their drinking water, whereas B cell–deficient NOD.H-2h4 mice are SAT resistant. To test the hypothesis that resistance of B cell–deficient mice to SAT was due to the activity of regulatory CD4+CD25+ T (T reg) cells activated if autoantigen was initially presented on non–B cells, CD25+ T reg cells were transiently depleted in vivo using anti-CD25. B cell–deficient NOD.H-2h4 mice given three weekly injections of anti-CD25 developed SAT 8 wk after NaI water. Thyroid lesions were similar to those in WT mice except there were no B cells in thyroid infiltrates. WT and B cell–deficient mice had similar numbers of CD4+CD25+Foxp3+ cells. Mice with transgenic nitrophenyl-specific B cells unable to secrete immunoglobulin were also resistant to SAT, and transient depletion of T reg cells resulted in severe SAT with both T and B cells in thyroid infiltrates. T reg cells that inhibit SAT were eliminated by day 3 thymectomy, indicating they belong to the subset of naturally occurring T reg cells. However, T reg cell depletion did not increase SAT severity in WT mice, suggesting that T reg cells may be nonfunctional when effector T cells are activated; i.e., by autoantigen-presenting B cells.

Volumetric Parameters of Interaction of Monosaccharides (D-xylose, D-arabinose, D-glucose, D-galactose) with NaI in Water at 298.15 K

Densities for monosaccharide (D-xylose, D-arabinose, D-glucose, D-galactose)–NaI–water solutions were measured at 298.15 K and were used to calculate the apparent molar volumes of these saccharides and NaI. Infinite dilution apparent molar volumes for the saccharides (VΦ,S∘) in aqueous NaI and those for NaI (VΦ,E∘) in aqueous saccharide solutions and partial molar volumes of the saccharides (VS) and NaI (VE) at each composition have been evaluated, together with the standard transfer volumes of the saccharides (Δtr VS∘) from water to aqueous NaI and those of NaI (ΔtrVE∘) from water to aqueous saccharide solutions. It was shown that the Δ tr VS∘ and ΔtrVE∘ values are positive and increase with increasing co-solute molalities. Volumetric parameters indicating the interactions of NaI with saccharides in water were also obtained and applied to explore the interactions between saccharides and NaI in water. A comparison of the νES value for NaI with those for NaCl and NaBr showed that for a given saccharide, except for glucose, the νES value for NaBr is the largest of three sodium halides (NaCl, NaBr and NaI). These were interpreted in terms of the apparent molar electrostriction volumes (Δ Ve) and the structure interaction model.

Role of TGFbeta in development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice.

Nearly 100% of NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and produce anti-mouse thyroglobulin autoantibodies when they receive 0.05% NaI in their drinking water beginning at 8 wk of age. Our previous studies showed that TGFbeta1 mRNA was constitutively expressed in thyroids and spleens of normal NOD.H-2h4 mice but not other strains of mice. To determine whether TGFbeta might have a role in SAT, mice were given anti-TGFbeta mAb at various times during development of SAT. Anti-TGFbeta markedly inhibited development of SAT and production of anti-mouse thyroglobulin IgG1 autoantibodies. Anti-TGFbeta was most effective in inhibiting SAT when given during the time thyroid lesions were developing, i.e., starting 4 wk after administration of NaI water. The active form of the TGFbeta1 protein was present in thyroids of mice with SAT but not in normal NOD.H-2h4 thyroids. However, thyrocytes of normal NOD.H-2h4 thyroids did express latent TGFbeta1. TGFbeta1 protein expression in the thyroid correlated with SAT severity scores, and administration of anti-TGFbeta inhibited TGFbeta1 protein expression in both the thyroid and spleen. TGFbeta1 was produced primarily by inflammatory cells and was primarily localized in areas of the thyroid containing clusters of CD4(+) T and B cells. Depletion of CD8(+) T cells had no effect on TGFbeta1 protein expression. Activation of splenic T cells was apparently not inhibited by anti-TGFbeta, because up-regulation of mRNA for cytokines and other T cell activation markers was similar for control and anti-TGFbeta-treated mice. TGFbeta1 may function by promoting migration to, or retention of, inflammatory cells in the thyroid.

Characteristics of Inflammatory Cells in Spontaneous Autoimmune Thyroiditis of NOD.H-2h4 Mice

Thyroid lesions develop in most NOD.H-2h4 mice 6 weeks after they are given 0.05% NaI in drinking water. B cells are required for spontaneous autoimmune thyroiditis (SAT) development, and anti-thyroglobulin autoantibody levels correlate with SAT severity. Immunohistochemical staining of thyroids obtained 2–10 weeks after administration of NaI water suggested that CD4+ T cells initially infiltrated the thryoid, followed by CD8+ T cells and B cells. Intrathyroidal CD4+ T cells are more numerous than CD8+ T cells. CD4+ T cells and B cells form aggregates in the thyroid, while CD8+ T cells are scattered throughout the thyroid. Intrathyroidal germinal centre-like structures could be observed in thyroid lesions with 2–3+ SAT and intrathyroidal B cells co-expressed OX40L. By RT–PCR, intrathyroidal expression of OX40L, OX40, CD40L, IL-2R, CTLA-4 and Igβ mRNA correlated closely with the SAT severity score. These molecules were not expressed in normal thyroids. In the spleen, OX40L-positive cells were detected at 2 weeks and increased 4–6 weeks after NaI water. OX40, OX40L, CD40L, IL-2R and B7-1 as well as IFN-γ and IL-4 mRNA were minimally expressed in normal spleens, usually began to be expressed at 2 weeks and increased to maximal level 4–8 weeks after NaI water. These results suggest that in NOD.H-2h4 mice, the OX40L, OX40, CD40L and B7 molecules, which increase in the spleen and thyroid of these mice after receiving NaI water, may play a role in SAT development, implying that one or more of these molecules might be good targets for the prevention or treatment of SAT.

Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

NOD.H-2h4 mice, which express I-Akon the NOD genetic background, spontaneously develop autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies. The incidence of SAT is nearly 100% in mice of both sexes 6–8 weeks after administration of 0.05% NaI in the drinking water. After reaching maximum severity, inflammation is chronic over the next 3–4 months. All mice that develop thyroid lesions also produce MTg-specific IgG1 and IgG2b autoantibodies. Thyroid lesions and anti-MTg autoantibodies did not develop in CBA/J (H-2k) or NOD.SWR(H-2q) mice after administration of NaI water. Both CD4+and CD8+T cells are involved in the initial development of SAT. Depletion of CD4+, but not CD8+, T cells after thyroid lesions have developed also markedly reduced SAT severity, indicating that CD4+T cells are required for both developing and maintaining SAT. Analysis of cytokine gene expression indicated that both Th1 and Th2 cytokines were expressed in thyroids of NOD.H-2h4 mice with SAT. Th1 and proinflammatory cytokines were maximally expressed 4–6 weeks after mice began receiving NaI water, while Th2 cytokine gene expression was greatest at 8–15 weeks, when lesions had reached maximal severity and were in the chronic phase. TGF-β was highly expressed in NOD.H-2h4 thyroids, irrespective of whether the mice had received NaI water or had thyroid lesions.

Dissolution enthalpy of NaI in water–alcohol mixtures at 288.15 and 308.15 K. Enthalpy of interaction in electrolyte–alcohol–water systems

The enthalpy of NaI solution was determined in water mixtures with methanol, ethanol, propanol, and isopropanol in the entire range of mixed-solvent concentration at 288.15 and 308.15 K, and in water mixtures with s-butanol and tert-butanol in the range of 0–5 mol% alcohol at 308.15 K. The dependence of [Formula: see text] on solvent composition was studied. The enthalpic pair interaction coefficients hEN for NaI–alcohol in water and NaI–water in alcohols were determined, and the effect of temperature on hEN values in the systems under study was analyzed.

Effects of Various Salts on the Mechanical Properties of Homogeneous Poly(2-hydroxyethyl methacrylate) Hydrogels

Dynamic mechanical measurements were carried out by a longitudinal vibration method on homogeneous poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels with added sodium chloride, sodium sulfate, and sodium iodide. Complex tensile moduli were measured at frequencies between 0.006 and 0.6 Hz and at various temperatures between 0 and 40°C. The effects of the addition of salts to PHEMA hydrogels on the shape of moduli and compliances and on the monomeric friction coefficient ζ were studied. It was found that the addition of sodium chloride and sodium sulfate to PHEMA hydrogels causes an increase in ζ and, that, on the other hand, sodium iodide acts as a plasticizer in the gels. The latter behavior was explained as due to specific ion—polymer interactions. The time—concentration superposition was performed for the system with added salts and the PHEMA gels without added salts, which were studied previously. The concentration reduction which was used in the superposition of the main transition region cannot be applied to the rubber-like region. The values of the reduced compliance in the rubber-like region decrease in the order of NaI—water>water>NaCl—water, Na2SO4water. This effect was interpreted in terms of the difference in the influence of the added salts to a diluent-induced structure in the PHEMA gels.