The impact of dietary iodine intake on lipid metabolism in mice.

The present study has been designed to investigate the impact of dietary iodine intake on lipid metabolism in mice, including iodine deficiency and iodine excess. Different amounts of iodine mixed in the drinking water were continuously administered to mice. The body weights and the levels of urinary iodine were measured 8 months after the treatment. Thyroid hormones in the serum were detected by chemiluminescence immunoassay. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C) were determined enzymatically by automatic analyzer. Results showed that the urine iodine concentrations paralleled the amounts of iodine intakes. No statistical differences of body weights among different groups were found. The levels of thyroid hormones were dramatically decreased in iodine deficiency while no significant differences were found between iodine excess groups and normal iodine group. In iodine deficiency groups, the levels of TG, TC, and LDL were increased at varying degrees. In iodine excess groups, the levels of TG in the male mice and the levels of TC in the female mice were much lower than normal iodine group. In conclusion, dietary iodine intake may affect the metabolism of serum lipids. Hypothyroid function induced by iodine deficiency may be responsible for the changes of lipids. Higher iodine intake might benefit lipid metabolism.

[Combined rapamycin eye drop in nanometer vector and poly (lactic acid) wafers of cyclosporine A effectively prevents high-risk corneal allograft rejection in rabbits].

OBJECTIVE: To evaluate the combined effect of topical rapamycin (RAPA) eye drop in nanometer vector and poly (lactic acid) (PLA) wafers of cyclosporine A (CsA) in the prevention of acute allograft rejection after rabbit corneal transplantation. Methods It was an experimental study. RAPA was incorporated into the nanometer particles and CsA was incorporated into PLA wafers. A was syngeneic control whose both donor and recipient are New Zealand rabbit. Gray donor corneas were implanted into the 102 recipients of New Zealand albino rabbits with corneal neovascularization who were randomly divided into B, C, D, E, F, G 6 groups to receive the different types of therapy: B was no therapy control; C was eye drop of nanometer vector but no RAPA twice a day, 28 days; D was PLA wafers in the anterior chamber of rabbit eyes but no drugs; E was 0.5% RAPA eye drop of nanometer vector twice a day, 28 days; F was PLA wafers of CsA in the anterior chamber of rabbit eyes; G was PLA wafers of CsA in the anterior chamber of rabbit eyes and 0.5% RAPA eye drop of nanometer vector eye drop twice a day for 28 days together. Postoperative evaluation included slit-lamp biomicroscopy, histopathology and immunohistology, Cytokines related with neovascularization and immunosuppression in the corneal tissue by RT-PCR. The graft survival was assessed by One-Way ANOVA and q test. RESULTS: Corneal allograft survival time: A (100.00 +/- 0.00), B (8.44 +/- 1.24), C (8.89 +/- 2.57), D (8.56 +/- 2.30), E (43.11 +/- 5.58), F (43.67 +/- 9.54), G (72.00 +/- 15.34) d. Group G led to a statistically significant prolongation of transplant survival and was superior than group E and F which was a statistical prolongation compared with group B, C and D (qGE = 11.42, qGF = 11.24, qEB = 13.64, qEC = 13.38, qED = 13.46, qFB = 13.82, qFC = 13.56, qFD = 13.64; P < 0.01). Immunohistopathologically, the grafts were subjected to an immune response contained a dense infiltrate of neutrophils, CD4+ and CD8+ T lymphocytes in the group B, C and D. This cellular infiltrate was a significant reduction in group E,F,G. RT-PCR showed that the gene expression of IL-2 was inhibited earlier (3 days) in group F, G and VEGF gene expression being suppressed later (14 days) in group E, G. CONCLUSIONS: Combined therapy with topical application of RAPA eye drop of nanometer vector and CsA PLA wafers can significantly prolong the survival of allograft at high-risk. Moreover, topical combined treatment of them is more effective, lower dosage, less side-effects and cheaper than the treatment with topical individual immunosuppressive drug.

Characteristics of an scFv antibody fragment that binds to immunoglobulin G of Graves' disease patients and inhibits autoantibody-mediated thyroid-stimulating activity.

Thyroid-stimulating antibodies (TSAbs) are responsible for hyperthyroid Graves' disease (GD). Although two peptides that bind to GD immunoglobulin G (IgG), and some monoclonal antibodies to the TSH receptor (TSH-R), have been reported to inhibit stimulation of cAMP production by patient serum TSAb, our work is the first to use phage-display technology to produce a mouse single-chain Fv antibody fragment (scFv) that binds to GD IgG and acts as a powerful TSAb (and TSH) antagonist. The specificity characteristics and relative affinity (2.8 mol/L) of T17 were identified by competitive inhibition ELISA and thiocyanate elution. The purified T17 scFv was then tested for its effect on stimulation of cAMP production by Graves' patients' sera in TSH receptor-transfected Chinese hamster ovary (CHO) cells. T17 was an effective antagonist of TSAb activity in 13 of 16 patients with GD. In addition, (125)I-TSH binding to TSH-R was also inhibited by T17 (57% inhibition at 1 mg/mL). This new scFv suggests in vitro applications such as purification of TSAb or diagnosis of GD. In addition, it may have in vivo usefulness such as treatment of TSH-R mediated ophthalmic symptoms of Graves' disease.

[The effects of iodine/selenium on the function of antigen presentation of peritoneal macrophages in rats].

OBJECTIVE: To observe the effects of iodine/selenium on the function of antigen presentation of peritoneal macrophages in rats and explore the immunological mechanisms of iodine/ selenium's role in pathogenesis of autoimmune thyroid diseases (AITD). METHODS: Female Lewis rats were randomly divided into four groups including (1) low selenium and normal iodine group (L(sE)N(I)) (2) low selenium and high iodine group (L(Se)H(I)) (3) normal selenium and normal iodine group (N(Se)N(I) ) (4) normal selenium and high iodine group (N(Se)H(I)). All rats were fed by a special diet with lower selenium and iodine in it and drunk ion-free water containing different levels of iodine and selenium for 3 months. Peritoneal macrophages of each group and OVA allergized T cells were prepared and cultured together. Then the function of antigen presentation were estimated by detecting the levels of IL-2 in the culture supernatant. The levels of the expression of co-stimulator CD86 in the spleen of each group were determined by RT-PCR. RESULTS: The level of IL-2 in the supernatant in N(Se)H(I) (43.22 +/- 3.27) pg/ml was much stronger than N(Se)N(I) [the level of IL-2 was (25.74 +/- 2.45) pg/ml, P < 0.05]. The level of IL-2 in L(Se)N(I) (15.79 +/- 2.13) pg/ml was significantly lower than N(Se)N(I) (P < 0.05). The expression of CD86 mRNA in N(Se)H(I) (CD86/beta-actin: 0.52 +/- 0.10) were higher than N(Se)N(I) (CD86/beta-actin: 0.35 +/- 0.04), P < 0.05. CONCLUSIONS: High iodine could promote the presentation function of macrophages to a higher state than normal. Therefore, high iodine intake might become an importantly inducing factor in thyroid autoimmunity. Low selenium could weaken the ability of recognizing and presenting OVA antigen of peritoneal macrophages which might destroy immunological homeostasis and thus the low selenium intake might also become an inducer of AITD.

Preparation of rapamycin-loaded chitosan/PLA nanoparticles for immunosuppression in corneal transplantation.

Rapamycin-loaded chitosan/polylactic acid nanoparticles with size of about 300 nm in diameter were prepared through nanoprecipitation method using cholesterol-modified chitosan as a stabilizer. The surface coating of chitosan, which was demonstrated by zeta potential measurement, endowed the nanoparticles good retention ability at the procorneal area, facilitating the sustained release of rapamycin on the corneal. The immunosuppression in corneal transplantation of the nanoparticles was investigated using rabbit as animal model, the median survival time of the corneal allografts treated with nanoparticles was 27.2+/-1.03 days and 50% grafts still remained surviving by the end of the observation, while the group treated with 0.5% rapamycin suspension was 23.7+/-3.20 days. The median survival time of drug-free nanoparticles group and untreated groups were 10.9+/-1.45 and 10.6+/-1.26 days, respectively. The results demonstrated the excellent immunosuppression of rapamycin-loaded chitosan/polylactic acid nanoparticles in corneal transplantation.

[Experimental study on effects of iodine deficiency and excess on thyroid autoimmunity].

OBJECTIVE: To observe the effects of iodine on the level of CD4/CD8 cells and the production of thyroglobulin autoantibody (TGAb) and thyroid peroxidase autoantibody (TPOAb) in Wistar rats and to investigate the role of iodine in thyroid autoimmunity. METHODS: Rat models with different iodine intakes including low iodine (LI,), normal iodine (NI,), 5 times normal iodine (5HI), 10 times normal iodine (10HI), 50 times normal iodine (50HI) and 100 times normal iodine (100HI) were established. The amount of iodine intake per rat per day in every group was about < 1, 6.15, 30.75, 61.50, 307.50, 615.00 microg separately. The levels of CD4 and CD8 immune cells in peripheral blood were measured by using flow cytometry. Radioimmunoassay (RIA) was used to determine the titers of TGAb and TPOAb in the serum. RESULTS: In peripheral blood, the level of CD4 cells in LI group was (57.9 +/- 4.3)%, being much higher than in NI group (51.2 +/- 4.9)%. When the level of CD8 cells in 100HI group was (18.4 +/- 3.1)% showing significantly lower than in NI group (26.5 +/- 4.1)%, thus making the ratio of CD4/CD8 cells in the above two groups (LI: 2.4 +/- 0.40 and 100 HI: 2.7 +/- 0.4) higher than in NI group (1.9 +/- 0.3). As comparing with NI group (2099 +/- 220) CPM, the level of TGAb in LI group (1510 +/- 221) CPM was significantly decreased; while in 50HI group (3986 +/- 286) and 100HI group (3550 +/- 378) CPM, the levels of TGAb were both increased, and the levels of TPOAb in 10HI group (2066 +/- 184) CPM and in 50HI group (2141 +/- 163) CPM were both distinctly lower than in NI group (2372 +/- 245) CPM. CONCLUSIONS: Iodine might exert influence on the level of CD4/CD8, and thus the production of thyroid antibodies might directly or indirectly take part in the process of thyroid autoimmunity. Both low iodine and 100 times normal iodine intakes might activate the immune state on some degrees. The effects of iodine on immune responses of TG and TPO antigen in thyroid autoimmunity might not be completely the same.