Association of urinary iodine concentration with prediabetes/diabetes in adults: Analysis of the NHANES 2005–2016

Background & AimsIodine is required for synthesizing thyroid hormones and regulating human metabolism. Iodine deficiency can lead to thyroid function abnormalities, which are closely associated with disturbances in glucose-insulin homeostasis. Research on the relationship between iodine and diabetes/prediabetes in adults was sparse and inconsistent. We assessed trends in urinary iodine concentration (UIC) and diabetes/prediabetes prevalence and focused on the association between iodine and diabetes/prediabetes among U.S. adults.MethodsWe analyzed the National Health and Nutrition Examination Survey (NHANES) data from the 2005–2016 cycles. Linear regression was employed to evaluate UIC and prediabetes/diabetes prevalence trends over time. Both multiple logistic regression and restricted cubic splines (RCS) were performed to evaluate the association of UIC with diabetes/prediabetes.ResultsA distinctly declining trend in median UIC and a significant increase in diabetes prevalence in U.S. adults from 2005 to 2016 were observed. The fourth quartile of UIC was associated with a 30% lower risk for prediabetes, compared with the first quartile (OR=0.70, 95% CI: 0.56–0.86, P_trend=0.001). However, UIC was not significantly associated with the prevalence of diabetes. The RCS model suggested a significant nonlinear relationship between UIC and the risk of diabetes (P for nonlinearity =0.0147). Stratification analysis showed that the negative associations of UIC with the risk of prediabetes were more pronounced in participants who were men, aged 46–65, overweight, light alcohol drinkers, and nonactive smokers.ConclusionsOverall, the adults’ median UIC in the U.S. population was a declining trend. However, diabetes prevalence increased significantly from 2005 to 2016. Higher UIC was associated with a lower risk of prediabetes.     

Correlated autoradiographic and ion-microscopic study of the role of iodine in the formation of “cold” follicles in young and old mice

Summary The role of iodine in the formation of cold follicles (not labeled on autoradiograms after radioiodine administration) was analysed in ICR female mice during aging and involution of thyroid hyperplasia, by use of light and electron microscopy and by comparing autoradiographic and analytical ion-microscopic images for the same follicle in serial sections. The proportion of cold and partly cold (displaying a patchy or ring labeling pattern on autoradiograms) follicles increased significantly during aging. This increase was more pronounced in old mice fed an iodine-rich diet as compared to mice fed a moderate iodine diet. Similarly, during goiter involution produced by refeeding iodine, the follicular heterogeneity of iodine metabolism was more accentuated with a high dose of iodine, regardless of the age of the mice. The follicular lumina of hot and cold follicles had the same concentration of stable iodine, as shown by analytical ion microscopy, and the cells of both types of follicles formed colloid droplets in response to TSH. Furthermore, when a goitrogenic treatment was induced in aged mice, some cold follicles persisted after 8 days, but all follicles resumed hot after 16 days. By analytical ion microscopy, ¹²⁷iodine was also found inside thyroid cells of old mice, but the cytoplasmic patches of ¹²⁷iodine were not labeled with ¹²⁵iodine. They corresponded to lipofuscin pigments and secondary lysosomes, as observed in serial sections at the electron-microscopic level. This intracellular stable iodine could constitute a slow turnover compartment not used for hormone synthesis.Portions of this work were presented at the 15th and 17th Annual Meetings of the European Thyroid Association (Stockholm 1986; Montpellier 1988). This work was supported in part by the Association de la Recherche sur le Cancer (ARC) and a cooperative programme Communauté Française de Belgique-France     

Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging

In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer’s disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [¹⁸F]4-dimethylamino-4′-fluoro-chalcone ([¹⁸F]DMFC) and [¹⁸F]4′-fluoro-4-methylamino-chalcone ([¹⁸F]FMC), as Aβ imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by ¹⁸F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [¹⁸F]DMFC and [¹⁸F]FMC. In a biodistribution study using normal mice, [¹⁸F]DMFC and [¹⁸F]FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2?min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30?min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved Aβ imaging agent ([¹⁸F]Florbetapir), meaning the improvement of the probability of detecting Aβ plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant Aβ peptides, [¹⁸F]DMFC and [¹⁸F]FMC showed high binding affinity to recombinant Aβ aggregates at the K_d values of 4.47 and 6.50?nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [¹⁸F]DMFC and [¹⁸F]FMC markedly accumulated only in a region with abundant Aβ plaques, indicating that they clearly recognized human Aβ plaques in vitro. These encouraging results suggest that [¹⁸F]DMFC and [¹⁸F]FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy.     

Management of hyperthyroid patients following radioactive iodine therapy,with a specific emphasis on Graves’ disease

Radioactive iodine (RAI) therapy is commonly used for hyperthyroid patients. The post-RAI management greatly depends on RAI treatment goal (ablative vs. non ablative) and the underlying thyroid disease (Graves’ disease vs. thyroid functional autonomy). Communication with patients improves quality and safety of RAI. Standardization of follow-up is required for patients with Grave's disease who are exposed to hypothyroidism, thyrotoxic flare and thyroid eye disease (de novo or worsening Graves’ ophthalmopathy).     

Effects of rapeseed‐press cake glucosinolates and iodine on the performance,the thyroid gland and the liver vitamin a status of pigs

Rapeseed press cake (per kg DM 181 g EE, 341 g CP and 23.3 mmol glucosinolates) was tested in a long‐term experiment with a total of sixty pigs (live weight range 24 to 104 kg). The 3×2 factorial design consisted of three rapeseed press cake levels (no rapeseed press cake ‐ control, 75g or 150g rapeseed press cake per kg diet) each with two iodine dosages (125 or 250 μg supplementary iodine per kg diet). Reduced feed intake and depressed weight gain were found in groups receiving 150 g rapeseed press cake per kg diet, which correspond to 3.2mmol glucosinolates per kg diet. At an inclusion level of 75 g rapeseed‐press cake per kg diet no differences in feed intake and growth intensity were recorded in comparison to the rape feed free control. The rapeseed‐press cake diet increased the weight of thyroid gland and liver and decreased the serum thyroxine (T₄) concentration. Higher iodine dosage increased the serum T₄ concentration of pigs receiving 75 g rapeseed press cake per kg diet ( = 1.6 mmol glucosinolates per kg diet) to the level of the control group and retarded the enlargement of the thyroid gland. Intake of rapeseed products lowered the iodine content of the thyroid gland, however, there was no significant difference between groups given 1.6 and 3.2 mmol glucosinolates per kg diet. The vitamin A content of the whole liver and the vitamin A serum concentration were not influenced by the diets tested. However, rapeseed press cake and the glucosinolates, respectively, decreased the vitamin A concentration per gram liver due to the organ enlargement and the resulting dilution effect.     

Iodine concentration of milk in a dose–response study with dairy cows and implications for consumer iodine intake

Most feed is poor in iodine and iodine supplementation of cow's diets must guarantee milk iodine concentrations for humans that contribute to prevention of the deficiency and minimize the risk of exceeding an upper limit of iodine intake. Five Holstein cows were fed four iodine doses (via Ca(ΙO₃)₂·6H₂O). In four sequential 14-d periods, doses of 0.2 (basal diet), 1.3, 5.1, and 10.1 mg iodine kg^?1 diet dry matter (DM) were administered. Samples of milk were collected during each period; blood was also sampled from each cow for each iodine dosage. In an 18-d depletion period, a non-supplemented diet was provided. Iodine was determined by inductively coupled plasma-mass spectrometry. The iodine content of milk and serum reflected the iodine dosages in feed significantly. The levels for the four doses tested in milk were 101±32, 343±109, 1215±222, and 2762±852 μg iodine kg^?1. The total amount of iodine in milk per day was 30–40% of ingested supplemental iodine. Omitting additional iodine resulted in a short-term reduction of serum and milk iodine following an exponential decay function. The iodine supplementation of 0.5–1.5 mg kg^?1 diet DM represents the requirement of the cow, resulting in 100–300 μg iodine L^?1 milk, which optimally contributes to human supply. The maximum dietary levels of former and present EU legislations (10 and 5 mg iodine kg^?1 cow feed) increase the risk of iodine excess in humans.     

A prototype of an electric-discharge gas flow oxygen−iodine laser: I. Modeling of the processes of singlet oxygen generation in a transverse cryogenic slab RF discharge

The existing kinetic model describing self-sustained and electroionization discharges in mixtures enriched with singlet oxygen has been modified to calculate the characteristics of a flow RF discharge in molecular oxygen and its mixtures with helium. The simulations were performed in the gas plug-flow approximation, i.e., the evolution of the plasma components during their motion along the channel was represented as their evolution in time. The calculations were carried out for the O₂: He = 1: 0, 1: 1, 1: 2, and 1: 3 mixtures at an oxygen partial pressure of 7.5 Torr. It is shown that, under these conditions, volumetric gas heating in a discharge in pure molecular oxygen prevails over gas cooling via heat conduction even at an electrode temperature as low as ~100 K. When molecular oxygen is diluted with helium, the behavior of the gas temperature changes substantially: heat removal begins to prevail over volumetric gas heating, and the gas temperature at the outlet of the discharge zone drops to ~220–230 K at room gas temperature at the inlet, which is very important in the context of achieving the generation threshold in an electric-discharge oxygen?iodine laser based on a slab cryogenic RF discharge.     

Dose-related influence of sodium selenite on apoptosis in human thyroid follicles in vitro induced by iodine, EGF, TGF-β, and H2O2

Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor (EGF), transforming growth factor-β (TGF-β), as well as H₂O₂ and might be attenuated by antioxidants. Therefore, we examined the apoptotic index induced by these substances in selenium-treated vs untreated human thyroid follicular cells. Reconstituted human thyroid follicles were incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none. The follicles were then distributed to 24-well plates and incubated with potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-β (5 ng/mL), or H₂O₂ (100 μM). Apoptosis was determined by a mitochondrial potential assay and the number of apoptotic cells counted by two independent, experienced technicians and the glutathione peroxidase (GPx) activity was determined. A significant increase of apoptic cells was obtained in control thyroid follicles treated with iodine (5, 10, or 20 μM), thyroid-stimulating hormone (TSH) 1, or 10 mU/mL in combination with 5 and 10 μM iodine, EGF (5 ng/mL) and TGF-β (5 ng/mL), or H₂O₂ (100 μM) (p<0.001). In contrast, in thyroid follicles preincubated with 10 or 100 nM sodium selenite, the apoptototic index was identical to the basal rate. In H₂O₂-treated follicles, the apoptotic index was still significantly elevated but 50% lower compared to control cells. The GPx activity increased from 1.4±0.2 to 2.25±0.4 mU/μg DNA with 10 nM selenite and 2.6+0.4 mU/μg DNA with 100 nM selenite. Sodium selenite might increase the antioxidative potential in human thyroid follicles in vitro and therefore diminish the apoptosis induced by TGF-β, EGF, iodide, and even H₂O₂     

A comparative analysis of karyotypes of three species of Macleaya—producers of a complex of isoquinoline alkaloids

Using a set of methods (C-banding, DAPI-staining, fluorescence hybridization in situ (FISH) with probes of 26S and 5S rDNA, and analysis of meiosis), the first comparative cytogenetic study of three species of Macleaya, producers of complex isoquinoline alkaloids, cordate Macleaya cordata (Willd.) R. Br. (2n = 20), small-fruited Macleaya microcarpa (Maxim.) Fedde (2n = 20) and Macleaya kewensis Turrill (2n = 20), was first carried out. On the basis of morphometric analysis, formulas of karyotypes were made for each species. Species ideograms for M. cordata, M. microcarpa, and M. kewensis were constructed taking into account the polymorphic variants of the C-banding patterns and indicating the location of 26S and 5S rDNA sites. A comparative study revealed that the karyotypes of M. microcarpa and M. kewensis have more in common with each other than with M. cordata. Analysis of meiotic chromosomes suggests of genetic stability of Macleaya genomes. The results of chromosome analysis were used to confirm the close relationship of Macleaya and to clarify their phylogenetic relationships.     

Effect of γ-Irradiation on Development of Lachrymator of Onion

A thermosensitive uracil requiring mutant of Bacillus subtilis Marburg 168 thy trp₂ ts42 was examined as to the colony forming ability at the permissive and nonpermissive temperatures. The viability of the mutant cells decreased rapidly at the restrictive temperature in the modified Woese’s (MW) medium. However, the cells retained viability when sodium succinate or potassium chloride was added to the medium at that temperature although uracil deficiency was unchanged. A little but significant incorporation of adenine-8-¹⁴C into RNA still continued even after the incorporation of N-acetyl-³H-d-glucosamine into acid insoluble fraction of the cells terminated in the MW medium at 48°C. Both incorporations as well as increase of absorbance were slowed down in the presence of sodium succinate at 48°C. This mutant, ts42, was more sensitive to deoxycholate (DOC) than the parent strain. The restoration of colony forming ability after the temperature shift back from 48 to 37°C was suppressed by the addition of DOC to the medium. However, the cell became resistant to DOC when uracil was added to the medium prior to the temperature shift.     

Mechanisms of action of the α-amylase of Micromonospora melanosporea

The -amylase of Micromonospora melanosporea was produced extracellularly during batch fermentation in a 5.0-1 fermentor. The absence of an organic nitrogen source in its growth medium facilitated subsequent purification of the enzyme by ammonium sulphate fractionation and two consecutive Superose-12 gel-filtration steps. The enzyme exhibited maxima for activity at pH 7.0 and 55° C and was 72% stable at pH 6.0–12.0 for 30 min at 40° C. It had a relative molecular mass of 45 000 and an isoelectric point at pH 7.6. The enzyme catalyses the conversion of starch to maltose (53%, w/w) as the predominant final end-product. Initial hydrolysis of this substrate, however, gave rise to the formation of maltooligosaccharides in the range maltotriose to maltohexaose. Maximum yields of these intermediate sugars accumulated to between 31 and 42% (w/w) as the reaction proceeded. The action of the M. melanosporea amylase on high concentrations of saccharides larger than maltotriose resulted in the formation of mainly maltose and maltotriose without concomitant glucose production. A combination of hydrolytic and transfer events is postulated to be responsible for this phenomenon and for the high maltose levels achieved. Correspondence to: C. T. Kelly     

Selection of optimal variants of Gō-like models of proteins through studies of stretching

The Gō-like models of proteins are constructed based on the knowledge of the native conformation. However, there are many possible choices of a Hamiltonian for which the ground state coincides with the native state. Here, we propose to use experimental data on protein stretching to determine what choices are most adequate physically. This criterion is motivated by the fact that stretching processes usually start with the native structure, in the vicinity of which the Gō-like models should work the best. Our selection procedure is applied to 62 different versions of the Gō model and is based on 28 proteins. We consider different potentials, contact maps, local stiffness energies, and energy scales—uniform and nonuniform. In the latter case, the strength of the nonuniformity was governed either by specificity or by properties related to positioning of the side groups. Among them is the simplest variant: uniform couplings with no i, i + 2 contacts. This choice also leads to good folding properties in most cases. We elucidate relationship between the local stiffness described by a potential which involves local chirality and the one which involves dihedral and bond angles. The latter stiffness improves folding but there is little difference between them when it comes to stretching.     

Mechanism of action of α-galactosidase

The effect ofpH on K_m and V_max values of coconut α-galactosidase indicates the involvement of two ionizing groups with pK_a values of 3.5 and 6.5 in catalysis. Chemical modification has indicated the presence of two carboxyl groups, a tryptophan and a tyrosine, at or near the active site of α-galactosidase. Based on these facts a new mechanism of action for α-galactosidase is proposed in which the ionizing group with a pK_a of 3.5 is a carboxyl group involved in stabilizing a carbonium ion intermediate and the ionizing group with a pK_a of 6.5 is a carboxyl group perturbed due to the presence of a hydrophobic residues in its vicinity which donates a H⁺ ion in catalysis.     

Chemistry of the “molecular trap” of protease-catalyzed splicing reaction of complementary segments of α-subunit of hemoglobin A

The complementary fragments of human Hb α, α_1–30, and α_31–141 are spliced together by V8 protease in the presence of 30%n-propanol to generate the full-length molecule (Hb α-semisynthetic reaction). Unlike the other protease-catalyzed protein/peptide splicing reactions of fragment complementing systems, the enzymic condensation of nonassociating segments of Hb α is facilitated by the organic cosolvent induced α-helical conformation of product acting as the “molecular trap” of the splicing reaction. The segments α_24–30 and α_31–40 are the shortest complementary segments that can be spliced by V8 protease. In the present study, the chemistry of the contiguous segment (product) α_24–40 has been manipulated by engineering the amino acid replacements to the positions α²⁷ and α³¹ to delineate the structural basis of the molecular trap. The location of Glu²⁷ and Arg³¹ residues in the contiguous segment α_24–40 (as well as in other larger segments) is ideal to generate (i, i+4) side-chain carboxylate-guanidino interaction in its α-helical conformation. The amino acid residue replacement studies have confirmed that the side chains at α²⁷ and α³¹ facilitate the semisynthetic reaction. The relative influence of the substitute at these sites on the splicing reaction depends on the chemical nature of the side chain and the location. The γ-carboxylate guanidino side-chain interaction appears to contribute up to a maximum of 85% of the thermodynamic stability of the molecular trap. The studies also demonstrate that the thermodynamic stability of the molecular trap is determined by two interdependent conformational aspects of the peptide. One is an amino acid-sequence-specific event that facilitates the induction of an α-helical conformation to the contiguous segment in the presence of organic cosolvent that imparts some amount of protease resistance to Glu³⁰-Arg³¹ peptide bond. The second structural aspect is a site-specific event, ani, i+4 side-chain interaction in the α-helical conformation of the peptide which imparts an additional thermodynamic stability to the molecular trap. The results suggest that conformationally driven “molecular traps” of protease-mediated ligation reactions of peptides could be designed into products to facilitate the modular assembly of peptides/proteins.     

Association of the subunits of the calcium-independent receptor of α-latrotoxin

CIRL-1 also called latrophilin 1 or CL belongs to the family of adhesion G protein-coupled receptors (GPCRs). As all members of adhesion GPSR family CIRL-1 consists of two heterologous subunits, extracellular hydrophilic p120 and heptahelical membrane protein p85. Both CIRL-1 subunits are encoded by one gene but as a result of intracellular proteolysis of precursor, mature receptor has two-subunit structure. It was also shown that a minor portion of the CIRL-1 receptor complexes dissociates, producing the soluble receptor ectodomain, and this dissociation is due to the second cleavage at the site between the site of primary proteolysis and the first transmembrane domain. Recently model of independent localization p120 and p85 on the cell surface was proposed. In this article we evaluated the amount of p120-p85 complex still presented on the cellular membrane and confirmed that on cell surface major amount of mature CIRL-1 presented as a p120-p85 subunit complex.     

Kinetics of renaturation and self-assembly of intermediates on the pathway of folding of the β2-subunit of Escherichia coli tryptophan-synthetase

The kinetics of renaturation of the β₂-subunit of Escherichia coli tryptophan-synthetase (l-serine hydrolyase (adding indole) E.C. 4.2.1.20) and those of its two proteolytic fragments F₁ and F₂ are studied and compared. Steps corresponding to the refolding of F₁, to the association of the folded F₁ and F₂ fragments, and to an isomerization of the associated protein are identified. These steps are ordered on the pathway of renaturation and some of their kinetic parameters are determined. This leads to a tentative kinetic model for the renaturation of nicked-β₂ starting from the denatured F₁ and F₂ fragments.The step corresponding to the refolding of the F₁ domain, as well as that corresponding to the last rate-limiting isomerization leading to the native protein, is shown to be the same in the refolding of the entire, uncleaved β₂-protein. It is concluded that the refolded F₁ fragment corresponds to a folding intermediate on the pathway of renaturation of the β₂-subunit.     

Determination of the number of degrees of freedom of the trapeziometacarpal joint–An in vitro study

ObjectiveMost of the studies about trapeziometacarpal joint assume that it exhibits only two independent degrees of freedom, but the experimental or theoretical support for considering a two-degrees of freedom model is not always clear.Materials and methodsTherefore, an in vitro kinematic study has been designed to demonstrate, from experimental data, that only two of the trapeziometacarpal degrees of freedom (i.e., flexion/extension and adduction/abduction) are non-null and independent. Several movements of maximal amplitude in flexion, abduction and circumduction have been realized and the relative position and orientation of the segment coordinate system embedded on the first metacarpal with respect to that embedded on the trapezium have been collected using electromagnetic sensors. The trapeziometacarpal rotations have been described using a joint coordinate system and the joint displacements have been evaluated on the axes of this coordinate system.ResultsThe root mean square (RMS) values of the joint displacement components have been found small enough to assume that the trapeziometacarpal joint has no translation degrees of freedom. A paraboloid coupling equation has been found between the internal/external rotation angle and the two other, flexion/extension and adduction/abduction, angles.ConclusionThus, this study demonstrates that the trapeziometacarpal joint has only two independent rotational degrees of freedom, and further, the described methodology could also be used to determine the coupling laws between degrees of freedom of various joints.