A systems biology approach to propose a new mechanism of regulation of repetitive prophylaxis of stable iodide on sodium/iodide symporter (NIS).

Our group showed that repetitive dose of potassium iodide (KI) for eight days offers an efficient protection for exposure to repeated radioactive emissions without adverse effects on adult rats. However, differential expression of genes implicated in Wolff-Chaikoff effect was observed. To understand the Wolff-Chaikoff regulation and its molecular constituents during repetitive administration of KI, a biochemical reaction network was constructed as a "geographical" map of the thyrocyte depicting iodide and thyroid hormone synthesis. Path analysis of the network has been performed to investigate the presence of a regulatory circuit of the node iodide to the node "nis transcription". NIS is responsible for the uptake of KI and plays an important role in the Wolff-Chaikoff effect. The map is a source for the most updated information about iodide and thyroid hormone metabolism. Based on this map, we propose a hypothesis that shows a putative mechanism behind NIS regulation and KI uptake.

The Iodine Content in Urine, Faeces and Selected Organs of Rats Fed Lettuce Biofortified with Iodine Through Foliar Application.

Iodine is an essential trace element for humans. Foliar application of micronutrients is successfully used in order to increase the concentration of essential elements in vegetables. The aim of this study was to evaluate the iodine absorption in the rat organism fed foliar biofortified lettuce. The presented study was consisted of the vegetative and animal experiment. In the vegetative experiment with lettuce, two combinations of foliar application were used: (1) control-without iodine application and (2) iodine application in the potassium iodide (KI) form. In the animal experiment, Wistar rats were divided to four groups, which received one of four diets: (1) C-control diet containing iodine in the KI form, (2) D-diet deficient in iodine, (3) D + BL-diet containing biofortified lettuce, and (4) D + CL-diet containing control lettuce (as the only source of iodine in diet, respectively). The diets contained 0.260, 0.060, 0.254 and 0.075 mg I/kg, respectively. In order to determine the iodine absorption in the rat organisms, the content of this trace element was measured in urine, faeces and in selected organs with the use of the ICP-OES technique. Foliar application of the KI increased the content of iodine in lettuce. The rats from the D + BL group excreted significantly less iodine in their urine and faeces and also accumulated more iodine in the organs than the rats from the C group. Iodine with biofortified lettuce was much bioavailable for rodents than iodine from control diet. Biofortified lettuce can be a source of iodine in a diet of human and can improve iodine nutrition.

Enhanced transport of materials into enamel nanopores via electrokinetic flow.

The ability to infiltrate various molecules and resins into dental enamel is highly desirable in dentistry, yet transporting materials into dental enamel is limited by the nanometric scale of their pores. Materials that cannot be infiltrated into enamel by diffusion/capillarity are often considered molecules with sizes above a critical threshold, which are often considered to be larger than the pores of enamel. We challenge this notion by reporting the use of electrokinetic flow to transport solutions with molecules with sizes above a critical threshold-namely, an aqueous solution with a high refractive index (Thoulet's solution) and a curable fluid resin infiltrant (without acid etching)-deep into the normal enamel layer. Volume infiltration by Thoulet's solution is increased by 5- to 6-fold, and resin infiltration depths as large as 600 to 2,000 µm were achieved, in contrast to ~10 µm resulting from diffusion/capillarity. Incubation with demineralization solution for 192 h resulted in significant demineralization at noninfiltrated histologic points but not at resin infiltrated. These results open new avenues for the transport of materials in dental enamel.

Iodine concentration and signs of apoptosis in the thyroid and pituitary of female rats after different single doses of potassium iodide.

OBJECTIVE: The aim of this work was to study the content of iodine as well as the expression of caspase 8 and caspase 32 in the thyroid and anterior pituitary in rats after a single dose of iodide. METHODS: A total of 49 inbred rat females weighing 250-300 g at the stage of diestrus and/or metestrus were used. Pituitaries and thyroids were dissected from 15 control rats and from the groups of 8 rats each given potassium iodide by gavage in doses of 1, 4, 8 and 25 µg/100 g at 48 h before sacrifice. In two rats of each group the level of iodine in thyroids and pituitaries was estimated in terms of weight percent of iodide in dry tissue (wt % I-2/dry tissue) using the wavelength dispersive spectrometry (WDS) quantitative analysis. The expression of caspase 8 and caspase 32 in thyroids and pituitaries in terms of the percentage of positive immunostained area (% PA) was measured by streptavidin-biotin method using specific polyclonal antibodies. RESULTS; In the thyroids, iodine concentration increased after 1 µg/100 g, but decreased after 8 and 25 µg/100 g, while that in the pituitaries significantly increased after all doses of iodide with the peak after 8 mg/100 g. After the same iodide dose also the peak of caspase 32 and caspase 8 appeared in the pituitary. However, in the thyroid only increased caspase 32 was found together with a decrease of iodine concentration. CONCLUSION: Several interrelations between iodine in the thyroid and pituitary were found. In addition, the signs of apoptosis appeared directly related to the concentration of iodine in the pituitary, but inversely related to iodine concentration in the thyroid.

Utilisation of iodine from different sources by sows and their progeny.

OBJECTIVES: The aim of the study was to compare iodine utilization from different sources by sows and their progeny and the levels of T3 and T4 in their serum. DESIGN: Pregnant Czech Large White × Landrace sows were fed with an experimental KPK diet (a diet for lactating sows) 14 days before parturition until weaning (at a piglet age of 28 days). In group A (n=50, 10 sows, 40 piglets) the feed was supplemented with KI (0.6 mg of iodine per kg of feed). Iodine enriched alga Chlorella spp. (0.6 mg of iodine per kg of feed) was used as a supplement in group B (n=50, 10 sows, 40 piglets). In group C (n=50, 10 sows, 40 piglets) the sows were injected i.m. with IFAE at a dose of 100 mg of iodine per sow. Iodine, T3 and T4 were measured in each group for comparison of iodine utilization. RESULTS: The use of IFAE resulted in higher serum concentrations in sows compared to KI and alga. In contrast, iodine concentrations in milk and piglets were lower when IFAE were used. We found a wide variation in the concentrations of T3 and T4 in the serum of piglets in all groups. CONCLUSION: Our results indicate a good utilization of iodized oil by sows. However, its transfer into milk is lower compared to the other iodine sources.

Expression of NIS in the thyroid and pituitary of female rats after a single dose of potassium iodide.

OBJECTIVE: The aim of this work was to study the expression of NIS in the thyroid and anterior pituitary in rats after a single dose of iodide appropriate to the content of iodide in iodine-positive points in the thyroid and pituitary. METHODS: A total of 41 inbred rat females of local laboratory strain weighing 250-300 g at the stage of diestrus and/or metestrus were used. Pituitaries and thyroids were dissected from 15 control rats at the same time as these from four groups of 6-8 rats each which were given various doses of potassium iodide dissolved in 0.5 ml distilled water (6 rats - 1 µg/100 g body weight; 8 rats - 4 µg/100 g ; 6 rats - 8 µg/100 g ; 6 rats - 25 µg/100 g.) by gavage at 48 h before sacrifice. In 6 rats of control group the concentration of iodine in thyroids and pituitaries was estimated in terms of percent by weight in dry tissue (wt% I-2 dry tissue) using the wavelength dispersive spectrometry (WDS) quantitative analysis. The expression of NIS in thyroids and pituitaries in terms of the percentage of positive immunostained area (% PA) was measured by streptavidin-biotin method using specific polyclonal antibodies. RESULTS: In thyroids, the concentration of iodine in iodine-positive points ranged from 2.5 to 59.3 (mean of 16.7±3.0) in terms of wt% I-2 dry tissue (100 % iodine-positive points), while in pituitaries it ranged from 0.17 to 6.3 (mean of 1.4±0.3) in all points and 2.2±0.4 in iodine-positive points. Histochemical reaction for NIS in the pituitaries at 48 hours after iodide administration showed a dose related increase beginning from 4 µg/100 g (from 1.8±0.7 to 12.9±1.0 % PA, respectively to the dose of iodide), while such increase in the thyroids started from 8 µg/100g (from 3.7±1.2 to 9.1±2.0 % PA). It remained still increased in pituitaries after the dose of 8 µg/100g (11.4±1.0 % PA) and 25 µg/100g (13.9±1.5 % PA), while such increase in thyroids was found only after the dose of 25 µg/100g (11.9±2.8 % PA). CONCLUSION: It was found that in the pituitaries of rat females the expression of NIS started after the dose of 4 µg iodide/100g, while that in the thyroids started after 8 µg iodide/100g. Thus, it may be suggested that the pituitary appears more susceptible to the level of iodide in blood.

Biofortification of lettuce (Lactuca sativa L.) with iodine: the effect of iodine form and concentration in the nutrient solution on growth, development and iodine uptake of lettuce grown in water culture.

BACKGROUND: Iodine is an essential trace element for humans. Two billion individuals have insufficient iodine intake. Biofortification of vegetables with iodine offers an excellent opportunity to increase iodine intake by humans. The main aim was to study the effect of iodine form and concentration in the nutrient solution on growth, development and iodine uptake of lettuce, grown in water culture. RESULTS: In both a winter and summer trial, dose rates of 0, 13, 39, 65, and 90 or 129 microg iodine L(-1), applied as iodate (IO(3)(-)) or iodide (I(-)), did not affect plant biomass, produce quality or water uptake. Increases in iodine concentration significantly enhanced iodine content in the plant. Iodine contents in plant tissue were up to five times higher with I(-) than with IO(3)(-). Iodine was mainly distributed to the outer leaves. The highest iodide dose rates in both trials resulted in 653 and 764 microg iodine kg(-1) total leaf fresh weight. CONCLUSION: Biofortification of lettuce with iodine is easily applicable in a hydroponic growing system, both with I(-) and IO(3)(-). I(-) was more effective than IO(3)(-). Fifty grams of iodine-biofortified lettuce would provide, respectively, 22% and 25% of the recommended daily allowance of iodine for adolescents and adults.

A gamma camera re-evaluation of potassium iodide blocking efficiency in mice.

The protection of the thyroid against radioiodine uptake has been an important safety concern for decades. After several studies examined potassium iodide blockade efficacy in the 1960's and 1970's, a standard dosage was prescribed by both the World Health Organization and the U.S. Food and Drug Administration. In this paper, we tested the effectiveness of a scaled version of that standard dosage in comparison to higher doses in mice. A novel gamma camera was employed with a high spatial resolution for precisely quantifying activity within the thyroid and a field of view large enough to image the entire mouse body. Thyroid and whole-body 125I biodistribution was analyzed immediately after exposure and 1 and 7 days later. It was found that 1 h after exposure five times the scaled human dose blocked thyroid uptake about 40% more effectively than the 1X scaled dose. Even after 1 d and 7 d, five times the recommended scaled human dose blocked approximately 10% more effectively than the 1X dose. These data suggest the need for continued evaluation of the effectiveness of KI as a blocking agent and the application of novel, non-invasive technologies to this important human health issue.

Yoduro potásico en el tratamiento de la estafilococcia recurrente de la piel / Potassium iodide in the treatment of recurrent staphylococcalskin

Un estudio clínico abierto fue realizado para conocer el valor terapéutico del yoduro potásico administrado en forma de solución saturada (SSKI) para el tratamiento de la estafilococcia recurrente de la piel. Los casos incluidos presentaban tres cuadros clínicos de la infección: 16 casos con foliculitis, 10 casos con forúnculos y 4 casos de antrax. Para ser incluidos los pacientes debieron portar una afección de tres o más años de evolución y tener seis o más recidivas anuales en las que debió emplearse un tratamiento sistémico con antibióticos. La SSKI se administró a una concentración de 47 mg/gota durante 12 meses a una dosis inicial de 1.41 g/día, aumentando 0,705 mg cada 6-7 días hasta una dosis diaria de 4.23 g/día. En la primera consulta se empleó también el tratamiento sistémico y tópico con antibióticos. Las recidivas desaparecieron y terapia con antibióticos sistémicos no fué necesaria desde el segundo mes de tratamiento. No se observaron recaídas de la infección en los meses siguientes como tampoco a los de 12 meses de haber concluido el tratamiento No se observaron reacciones adversas por el empleo de SSKI durante los dos años de seguimiento. Se concluye que lal SSKI es útil para el tratamiento de la estafilococcia recurrente de la piel. La SSKI no crea resistencia bacteriana y preserva el empleo de antibióticos para otras infecciones más graves

An open clinical study was performed to know the therapeutic value of the potassium iodide administered in saturated solution form (SSKI) for the treatment of recurrent staphylococcal skin infections. The included cases presented three clinical forms of the infection: 76 cases of follculitis, 70 cases with furuncles and 4 cases with carbuncle. To be included the patients they should behave an affection of three or more years of evolution and to have six or more annual relapses in those a treatment with systemic antibiotic should be used. The SSK/ was administered to a concentration of 47 mg/drop during 72 months to an initial dose of 7.47 g/day, increasing 0,705 mg every 6-7 days until a daily dose of 4.23 g/day. In the first consultation it was also used a treatment with systemic and topic antibiotics. The relapses disappeared and the therapy with systemic antibiotics were not necessary after the second month of treatment. Relapses of the infection were not observed in the following months as neither after 72 months after having concluded the treatment. Adverse reactions were not observed by the employment of SSKI during the two years of follow-up. It is considered that the SSKI is useful for the treatment of recurrent staphylococcal skin infections. The SSKI does not create bacterial resistance and it preserves the employment of antibiotics for other more serious infections

X-ray microanalysis of cryopreserved human skin to study the effect of iontophoresis on percutaneous ion transport.

PURPOSE: To study at the ultrastructural level which part of the skin is associated with percutaneous iodide transport by passive diffusion and iontophoresis. METHODS: Following passive diffusion or iontophoresis of iodide, the morphology and the ion distribution of the skin was preserved by rapid freezing. The skin was kept frozen until and during examination by transmission electron microscopy (TEM) and X-ray microanalysis (XRMA). The intrinsic electron absorbing characteristics of cryopreserved skin allow direct TEM examination without additional staining. XRMA can be used to obtain in a relatively nondestructive way in situ information on ion distributions across the skin. RESULTS: After passive diffusion, iodide was mainly found in the stratum corneum (SC), whereas there was little iodide in the viable epidermis. Iontophoresis up to 300 microA/cm2 did not significantly affect this distribution. With iontophoresis at 1,000 microA/cm2, the amount of iodide increased dramatically and was equally distributed over the SC and viable epidermis. The presence of iodide in the SC suggests that iodide is present inside corneocytes. CONCLUSIONS: Iontophoresis up to 300 microA/cm2 does not significantly perturb skin structures in contrast to iontophoresis at 1,000 microA/cm2. The presence of iodide inside corneocytes suggests the possibility of transcellular percutaneous iodide transport.

Evaluation in a mouse model of a thyroid-blocking protocol for 131I antibody therapy (short communication).

PURPOSE: We describe a murine model to evaluate variations of a published multicenter thyroid blocking protocol described for 131I antibody therapy, using doses of blocking agents proportional to those used in man. Variables include duration of super-saturated potassium iodide (SSKI) pretreatment and use of supplemental KClO4. MATERIALS AND METHODS: Whole-body activity measurements were performed 0, 24, 48 and 72 hours following 131I-NaI administration in control and thyroid-blocked mice. Retained whole-body activity was calculated as a percentage of the injected dose (%ID), primarily reflecting radioiodine sequestered in the thyroid gland. In blocked groups, SSKI was begun one or 7 days preceding 131I-NaI therapy, and was supplemented in one half of the cases with KClO4 from time of therapy. RESULTS: In control mice, %ID was 11.23 +/- 1.47%, 10.15 +/- 1.11% and 9.29 +/- 1.50% at 24, 48 and 72 hrs respectively. %IDs of blocked groups were markedly lower than controls (p = .0001). In the one day SSKI pretreatment group, %ID was reduced from 1.73 +/- 0.58, 1.42 +/- 0.45 and 1.20 +/- 0.38 at 24, 48 and 72 hours to 0.49 +/- 0.08, 0.50 +/- 0.07 and 0.44 +/- 0.06 with addition of supplemental KClO4. In the 7 day SSKI pretreatment group, %ID was reduced from 1.87 +/- 0.73, 1.48 +/- 0.49 and 1.36 +/- 0.57 at 24, 48 and 72 hours to 0.60 +/- 0.36, 0.45 +/- 0.13 and 0.41 +/- 0.14 with addition of supplemental KClO4. %IDs in the 7 day pretreatment animals were not statistically different from those in the one day pretreatment groups (all p >> 0.05). CONCLUSION: SSKI reduces retention of radioiodide approximately six-fold whereas supplemental KClO4 enhances thyroid blocking an additional three-fold. Seven day SSKI pretreatment appears no more effective than one day pretreatment.

Protection of the maternal and fetal thyroid from radioactive contamination by the administration of stable iodide during pregnancy. An experimental evaluation in chimpanzees.

The safety and efficacy of the administration of stable iodide to protect the fetal thyroid from exposure to radioactive iodide were investigated in chimpanzees in weeks 19 to 21 of pregnancy. The mean 24-h uptake of iodide in the fetal thyroid, determined with 123I-, was 1.8%. Administration of stable potassium iodide (KI), 0.65, 1.95 or 6.5 mg per kg body weight, 1 h before tracer injection reduced the fetal uptake satisfactorily. Only the higher doses were effective after 20 h. Excess iodide may impair a child's thyroid status. However, adverse effects were not found during the 11 days the animals ingested these doses. Tracer concentrations in the amniotic fluid were 30- to 130-fold lower than in the urine. The dose to the fetus from radioactivity in the maternal bladder was estimated by computer simulation. The potential increment of the risk from this dose during the ingestion of stable iodide is smaller than the reduction of risk achieved by inhibiting the uptake of radioactive iodide by the fetal thyroid. The conclusion of the experiments is that stable iodide can be used safely and effectively to protect the fetal thyroid against contamination with radioactive iodine.

[The valvular effect of the skin in electrophoresis with an alternating polarity of the electrodes]. / Klapannyi éffekt kozhi pri élektroforeze s peremennoi poliarnost'iu élektrodov.

The effectiveness of iontophoresis by means of changing current direction was investigated on the skin of piglets using labelled potassium iodide (125I and 131I). Permeability without current served control. Percutaneous uptake was measured by blood levels and elimination of the isotopes from the urine. About a 200-fold increase of uptake was found in iontophoresis involving current change every 120 seconds and the concentration of 0.25 g/l of potassium iodide. Anions and cations may be pumped through the horny layer if the a-c frequency is less than 1/15 s-i.