Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a multiethnic population and their first degree relatives / Autoanticorpos transportadores de zinco 8 em pacientes com diabetes tipo 1 de uma população multiétnica e seus parentes de primeiro grau

Objective Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. Subjects and methods ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. Results The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). Conclusions ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background. .

Objetivo Os autoanticorpos transportadores de zinco 8 (ZnT8A) foram pouco estudados em indivíduos não caucasianos. Nosso objetivo foi investigar a prevalência de autoanticorpos ZnT8 em pacientes com T1D e seus parentes de primeiro grau (PPG) em uma população multiétnica, assim como a sua relação com os polimorfismos genéticos da insulina (INS) ou proteína tirosina fosfatase não receptora tipo 22 (PTPN22). Sujeitos e métodos ZnT8A foram analisados no soro de pacientes com T1D (n = 72, idade média de 30,3 ± 11,4 anos) de duração variável (15,7 ± 11,8 anos) e seus PPG (n = 72, idade média de 30,3 ± 11,4 anos) usando-se um ensaio de competição com radioligantes (RBA) para variantes dos autoanticorpos ZnT8 (ZnT8-RWQ). Os polimorfismos de nucleotídeo único para a INS e PTPN22 foram genotipados. Resultados A prevalência de ZnT8A foi mais alta em pacientes T1D do que nos PPG, para ZnT8TriploA (24% contra 4%, p = 0,001), ZnT8RA (24% contra 4%, p < 0,001) e ZnT8QA (15% contra 3%, p = 0,004). Todos os PPG com ZnT8A (n = 3) apresentaram positividade para pelo menos outro anticorpo. A heterozigose para PTPN22 foi associada a uma frequência mais alta de ZnT8TriploA (p = 0,039) e de ZnT8RA (p = 0,038). Conclusões Os ZnT8A foram observados em pacientes não caucasianos com T1D, mesmo depois de anos do início da doença, assim como em seus PPG. Nos parentes, houve uma sobreposição entre os ZnT8A e outros anticorpos para T1D. Os ZnT8A mostraram-se associados aos polimorfismos PTPN22. São necessários outros estudos longitudinais para se elucidar a importância desses achados na história natural de pacientes com T1D com antecedentes étnicos variados. .

Synthesis and antifatigue activities of new benzamide derivatives / 药学学报

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.

Radiosynthesis of peripheral benzodiazepine receptor radioligand N-methyl-(11)CPK 11195 as an imaging agent for positron emission tomography / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N-[(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR) using a commercial synthesizer and explore the quality control methods for the resulting product.</p><p><b>METHODS</b>(11)C-methyl iodide ((11)C-CH(3)I) was synthesized via liquid-phase distillation approach using a (11)C-iodomethane synthesizer. (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1-methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor with (11)C-CH(3)I and purified by semi-preparative reversed phase high performance liquid chromatography (HPLC). The radiochemical purity, chemical purity and stability of the product were evaluated by HPLC, and the toxicity was assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were also studied.</p><p><b>RESULTS</b>(11)C-PK11195 was successfully synthesized using the TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195 synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis with radio-analytical HPLC showed a radiochemical purity and chemical purity of the product both exceeding 99%, with a specific radioactivity of 30-65 GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195 synthesized was radiochemically stable at room temperature and showed low toxicity in normal mice.</p><p><b>CONCLUSION</b>The (11)C-PK11195 injection can be conveniently prepared using an automated synthesizer for clinical use in positron emission tomography.</p>

Association of glucocoid receptor binding activity and heat shock protein expressions after acute lung injury in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the association between decreased ligand binding activity of glucocoid receptor (GR) and heat shock protein 90 (Hsp90), the molecular chaperone of GR, after acute lung injury (ALI) in mice.</p><p><b>METHODS</b>In mouse models of oleic acid-induced ALI, the levels of GR, Hsp90 and Hsp70 were dynamically observed using Western blotting, and the binding capacity and binding affinity of GR assessed with radioligand binding assay.</p><p><b>RESULTS</b>After ALI, pulmonary edema was significantly aggravated in the mice with significantly increased lung body index and lung water ratio. GR increased within 1 h after the injury, but then decreased significantly to the lowest level at 12 h after the injury, and the levels of Hsp90 and Hsp70 was increased obviously and reached the highest at 12 h. Radioligand binding assay showed that the Bmax decreased gradually and Kd value increased, and these changes were consistent with the changes of Hsp90/GR.</p><p><b>CONCLUSION</b>The ligand binding activity of GR is related to the changes of Hsp90 after ALI.</p>

Radioligand binding assay of progesterone receptors on normal fertile human sperm membrane / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the progesterone-binding site on the normal fertile human sperm membrane after 2 hours of in vitro capacitation.</p><p><b>METHODS</b>Viable spermatozoa were selected by a swim-up method. After 2 hours of in vitro capacitation, multipoint saturation binding experiments were performed. Sperm suspension and increasing concentrations of progesterone-11alpha-glucuronide-[125I] iodotyramine (125I-P) were added to 7 total binding tubes respectively, and equal amounts of sperm suspension and 125I-P were added to another 7 corresponding non-specific binding tubes in the presence of 10 micromol/L progesterone. After incubation for 1 hour at 4 degrees C, the radioactivity of both the tubes and the pellets after centrifugation was measured respectively. The equilibrium dissociation constant (Kd) and maximum binding capacity (Bmax) were calculated using the mathematical model of single site multi-point saturation method of Scatchard function and least-squares regression.</p><p><b>RESULTS</b>Kd was (0.61 +/- 0.04) nmol/L and Bmax was (830 +/- 344) sites/cell. The significance test of the regression equation indicated that r = -0.980, P < 0.01.</p><p><b>CONCLUSION</b>There is a high affinity and low capacity binding site for the progesterone (progesterone receptor) on the normal fertile human sperm membrane.</p>

Detection of binding activity and biologic effect of a novel alpha-melanocyte-stimulating hormone analogue / 药学学报

Binding activity and biologic effect of a novel alpha-melanocyte-stimulating hormone analogue were tested on cells transiently expressing the human melanocortin-1 (MC1), MC3, MC4, and MC5 receptors. The human MC1 and MC5 receptor genes were cloned into the expression vector pcDNA3. 1/ myc-his(-) B. The vectors were transferred to HEK-293 cells by the calcium phosphate method. Stable receptor populations were generated using G418 selection (900 microg x mL(-1)) for subsequent bioassay analysis. K(i) values of the novel alpha-MSH analogue for MC1, MC3, MC4, and MC5 receptors were obtained in competition with [125I]-NDP-MSH for binding studies. The cyclic AMP level was tested by using [3H]-cyclic AMP kit. It is showed that K(i) values of the novel alpha-MSH analogue for MC1, MC3, MC4, and MC5 receptors were (0.159 +/- 0.040), (35.430 +/- 6.743), (19.293 +/- 2.780) and (2.230 +/- 0.670) nmol L(-1), respectively. Its EC50 values for MC1, MC3, MC4, and MC5 receptors were (0.45 +/- 0.07), (7.80 +/- 0.65), (2.55 +/- 0.23) and (0.33 +/- 0.09) nmol L(-1), respectively. In these tests, the novel alpha-MSH analogue is a MC1R and MC5R selective agonist.

D2 receptor expression on immortalized human neural progenitor cell line hNPC-TERT in vitro and in vivo / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe D(2) receptor expression on human neural progenitor cell line hNPC-TERT before and after transplantation into rabbit central nervous system.</p><p><b>METHODS</b>D(2) receptor expression on cultured hNPC-TERT cells was verified and quantitatively analyzed with immunofluorescence assay and receptor radio ligand binding assay, respectively. 3 x 10(6) hNPC-TERT cells were implanted in the spinal cord of New Zealand rabbit with HeLa cells as the control. Two days after implantation, positron-emission tomography (PET) scan with (11)C-raclopride as the radiotracer was performed in the living animals or for the isolated spinal cords, and cryosections of the spinal cord containing the implanted cells were prepared for immunofluorescence assay.</p><p><b>RESULTS</b>Cultured hNPC-TERT cells showed high expression of D(2) receptor (Bmax=8 x 10(4)). PET scans of the rabbits identified visible radioactive accumulations at the site where hNPC-TERT cells were implanted but not at the site of HeLa cell implantation. Region of interest analysis showed a significant difference between the two cells in the maximal standard uptake value at the cell implantation sites. The results were further confirmed with ex vivo PET imaging of the spinal cord and tissue immunofluorescence assay.</p><p><b>CONCLUSION</b>Human neural progenitor cells hNPC-TERT highly express dopamine D(2) receptors and retain this capacity after implantation into the spinal cord, suggesting their potential for treatment of such nerve system disease as Parkinson syndrome.</p>

Variantes de la diabetes mellitus: enfoque actual desde la genética y la biología molecular / Variant of the diabetes mellitus: current approach from the genetics and the molecular biology

La Diabetes Mellitus (DM), de acuerdo a la definición clásica, es una enfermedad metabólica caracterizada por la hiperglucemia. Esta a su vez resulta de un defecto en la secreción de insulina, en su acción, o en ambos factores a la vez. Por ello tempranamente se consideró a la DM como heterogénea y de origen multifactorial. Las dos formas típicas son la DM insulinodependiente, infantojuvenil, (DM tipo 1) y la DM no-insulinodependiente, diagnosticada en los adultos (DM tipo 2).Sin embargo, hoy se percibe un panorama mucho más complejo, donde los refinamientos en la subagrupación fenotípica de otras variantes de DM y la nomenclatura propuesta, (DM latente, o LADA, DM tipo 1 del adulto, DM tipo 2 insulinorrequiriente, DM tipo 1 y 1/2 etc.) condujo más a la confusión que a la precisión diagnóstica. Los avances contemporáneos de la genética y de la biología molecular comienzan a brindar las bases etiopatogénicas de la DM en sus distintas variantes. A partir de ello, por ejemplo, se puede comprender mejor la naturaleza de los condicionamientos multigénicos que se traducen en la susceptibilidad para padecer la DM tipo 1, dentro de un grupo mayor de enfermedades autoinmunes. En esta área el reciente desarrollo de los autoantígenos recombinantes a nivel internacional, e incluso local, ha contribuído sustancialmente a la creación de una nueva plataforma analítica de apoyo para la medicina dibetológica. El actual screening precoz y preciso de las formas de DM asociadas a autoinmunidad sirve para la predicción de la enfermedad con hasta una década de antelación y también para disipar algunos de los dilemas que suelen presentarse en los pacientes diabéticos sobre la intervención terapéutica con hipoglucemiantes orales o con insulina, orientando su elección correcta y oportuna.

Inhibitory effect of kaempferol against binding of platelet activating factor to its receptor / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the platelet activating factor (PAF) antagonistic effect of kaempferol.</p><p><b>METHOD</b>The specific binding of [3H] PAF to rabbit platelet receptor was investigatedwith radio ligand binding assay (RLBA). Platelet adhesion induced by PAF was measured with spectrophotometry. The elevation of inner free calcium concentration in rabbit polymorphonuclear leukocytes (PMNs) induced by PAF was determined with Fura-2 fluorescent technique.</p><p><b>RESULT</b>The 1, 2 or 4 nmol x L(-1) [3H]PAF specific binding to rabbit platelet receptor was inhibited by Kae dosage dependently and the IC50 were 30.8, 74.6 and 92.0 micro mol x L(-1), respectively. The PAF induced reactions of rabbit platelet adhesion and PMNs inner free calcium concentration elevation were inhibited by Kae in a dose-dependent manner. The IC50 of Kae to inhibit platelet adhesion was 65 micromol x L(-1).</p><p><b>CONCLUSION</b>Kae is effective in inhibiting the action of PAF and it is a new PAF receptor antagonist.</p>

Direct evidence of the existence of specific LPS binding sites on vascular endothelial cells / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the binding characteristics of endothelial cell (EC) with LPS free from the participation of serum factors.</p><p><b>METHODS</b>Laser confocal microscope was employed in the observation of the binding of EC with FITC-LPS. The KD and the binding sites of each EC were calculated by radioligand binding assay of receptors (RBA) using [(3)H]-LPS.</p><p><b>RESULTS</b>The binding of EC with LPS was saturable, time and concentration dependent and it could be competed with overdosed LPS of the same type. The fluorescence mainly distributed in cytoplasm, especially near the nucleus, which could also be stained.</p><p><b>CONCLUSIONS</b>There might be some specific LPS binding sites existing on ECs and LPS could function intracellularily.</p>

Assessment of human AT1 binding affinity of some novel 2-alkylthio 1- [4- [N-alpha-ethoxycarbonyl-benzyl] aminobenzyl] -5 hydroxymethylimidazoles

Antagonists of various components of the renin-angiotensin system have been the subject of many studies for the control of blood pressure. Compounds with a phenoxyphenylacetic acid moiety that mimic the structure of losartan which is a powerful competitive antagonist of angiotensin receptor, have shown to be effective. In this study, the affinity of some 2-alkylthio-1-[4-[N- alpha -ethoxycarbonylbenzyl]aminobenzyl]-5-hydroxymethyl imidazoles for the human AT1 receptor was assessed in a radioligand binding assay. It was found that an alkyl chain of appropriate length would be most suitable if situated on the imidazole ring. Furthermore, variations of the lower phenyl rings demonstrated that introduction of a methyl group in this position will account for the most desired effect

Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms.</p><p><b>METHODS</b>Responsiveness to the beta-adrenergic agonists isoprenaline, BRL37344, forskolin, and dibutyryl cyclic AMP (DBcAMP) was examined in samples from 10 older patients by using a cellular function test. A radioligand binding assay was performed using the non-selective beta-adrenergic receptor ligand [3H]-dihydroalprenolol ([3H]-DHA). Specimens from 10 young men were used as controls.</p><p><b>RESULTS</b>There were no age-dependent changes in contractile response to KCl. The relaxation responses to isoprenaline, BRL37344, and forskolin decreased in the aged group by 15.0%, 17.6%, and 12.6%, respectively (P < 0.001). The pD2 values for isoprenaline and BRL37344 also declined significantly. There was no difference in the responsiveness to dibutyryl cyclic AMP (DBcAMP) between the two groups; the maximum binding site decreased significantly with increasing age, but the equilibrium-dissociation constant did not change.</p><p><b>CONCLUSIONS</b>There is an age-related decline in beta-adrenergic responsiveness which might be one of the causative factors of reduced bladder compliance in the elderly. A decrease in cAMP level caused by reduced receptor density and adenylyl cyclase activity might be the underlying molecular mechanism of the changes in beta-adrenergic responsiveness.</p>

Synthesis and pharmacology of 8-amino-3-(tetrahydro-2-furanyl)methyl benzomorphan / 药学学报

<p><b>AIM</b>To design and synthesize new chiral 8-(substituted) amino-analogues of 3-[(tetrahydro-2-furanyl)methyl] benzomorphans, to expand knowledge of the structure-activity relationship (SAR) for 8-aminobenzomorphan.</p><p><b>METHODS</b>Target compounds were synthesized from the 8-triflate of the optically active 3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphans using Pd-catalyzed aminations. Opioid receptor binding experiments were performed to evaluate their biological activities.</p><p><b>RESULTS</b>Both 8-amino and 8-phenylamino analogues showed lower binding affinity for mu, delta and kappa receptors than corresponding 8-hydroxy-3-[(tetrahydro-2-furanyl)methyl]-2,6-methano-benzomorphan in vitro.</p><p><b>CONCLUSION</b>The relative poor binding affinity of the target compounds did not warrant conducting the in vivo studies to determine if they have the profile(kappa agonist/mu antagonist) that will be potentially useful in the treatment of drug addiction. Further study is in progress.</p>

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.

Oxytocin and Oxytocin Antagonist Metabolism in the Plasma of Pregnant Women / 대한산부인과학회잡지

OBJECTIVE: Oxytocin antagonists maybe useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235. The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in pregnant human. METHODS: Blood samples from pregnant women not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45 and 60 minute intervals for oxytocin analysis and at 0, 10, 60 and 360 minutes for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction while TT-235 was analyzed by radioreceptor assay. RESULTS: In human blood, oxytocin was readily metabolized with greater than 83% disappearance over the 60 minute incubation period. In contrast, TT-235 was stable up to 360 minutes of incubation. CONCLUSION: This study suggests that: (1) blood from pregnant human does contain oxytocinase at least in vitro; and (2) TT-235 was resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have prolonged activity in vivo in humans.

The acute effects of dimethoate on the muscarinic-receptors of rat brains and the relationship between muscarinic-receptors and cholinesterase / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the acute effects of dimethoate on the muscarinic-receptors(M1, M2) in the brain of rats.</p><p><b>METHODS</b>24 Sprague-Dawley rats were divided into 4 groups randomly. They were administered subcutaneously with 0, 25, 50, 100 mg/kg dimethoate, respectively. Brains were removed after 48 hours of administration. Radioligand binding assay was used to determine the density and affinity of M1 and M2 receptors.</p><p><b>RESULTS</b>Rats in the treated group showed low density of M1 and M2 receptors compared with the control rats. The brain M1 receptor density of the rats in the highest dosage group was significantly lower than that in the control group while brain M2 receptors density had a decrease trend with increasing dosage, but the difference showed no significance. However, there were no differences of the affinity of both M1 and M2 among different treated groups. Correlation analysis showed there is positive relationship between cholinesterase activity and density of M1 receptors(r = 0.583, P < 0.01).</p><p><b>CONCLUSION</b>M1 and M2 receptors density decreased with the increasing dosage of dimethoate. It is suggested that the alleviating of cholinergic symptoms may be due to the decrease of M1 and M2 receptors in rat brain.</p>

Modification of ovine luteinizing hormone subunits with SMPT and its effect on subunit recombination, immunological activity, receptor binding and steroidogenic activity.

The increasing use of heterobifunctional cross-linking agents in the design of defined conjugates for selective targeting and inducing immune response has prompted us to study the role of epsilon-NH2 group modification of oLH subunits, their recombination and effect on immunoreactivity, receptor binding and biological activity. The epsilon-NH2 groups of alpha oLH and beta oLH subunits were separately modified by using SMPT. The alpha oLH-SMPT modified derivatives hybridize to beta oLH. Similarly, the beta oLH-SMPT derivatives recombined with alpha oLH. The recombination was judged by gel filtration chromatography and RP-HPLC analysis. The sequential modification of subunits led to progressive reduction in immunoreactivity and receptor binding activity. The modification of six or more epsilon-NH2 groups in alpha oLH although recombine fully with native beta oLH but failed to react to anti-oLH antibody. Moreover, the steroidogenic activity was also abolished. Introduction upto four SMPT groups in alpha oLH compromised immunological and biological activities but further addition of two or more SMPT groups completely abolished antibody reactivity, receptor binding and steroidogenic activity indicating the importance of later two amino groups in the receptor binding and steroidogenic activity. The present investigation clearly demonstrate that only 1:2-3 molar ratio of oLH subunits:SMPT could generate the site(s) in the subunits of the oLH that retained reasonable immunological, receptor binding and biological activity of the hormone. Therefore, this molar ratio may be used in future for the design and synthesis of bioeffective hormonotoxins.

Determinación de los niveles séricos de 25-hidroxivitamina D y sus variaciones estacionales en una población normal joven / Determination of 25-hydroxyvitamin D serum levels and its seasonal variations in a healthy young population

25-hydroxyvitamin D has a longer half life and its serum levels have less daily variations than calcitrol. Thus, its measurement is a better indicator of vitamin D status. Vitamin D was measured using a competitive protein binding radioassay in 61 subjects (27 males) aged 21 to 57 years old, during july to august (winter) and february and march of the next year (summer). 25-hydroxyvitamin levels were 28.8ñ1.5 and 30.9ñ2.3 ng/ml during winter and summer respectively. No differences were found between men and women. Ninety five percent confidence levels were between 13 and 50 ng/ml. Levels in 1 patient with malabsorption were 9.3 ng/ml, in 2 patients with hypophosphemic osteomalacia were 2.1 and 9.3 ng/ml, in 12 patients with alcoholic cirrhosis were 16.4ñ1.3 ng/ml, in 4 patients with primary osteoporosis were 23.3ñ0.7 and in 3 patients receiving vitamin D were 334ñ33.2 ng/ml. Normal levels of 25-hydroxyvitamin D range from 13 to 50 ng/ml in normal adults, there are no differences between men and women and seasonal variations are minimal

Spontaneous Recovery from Hypothyroidism in Autommune Thyroiditis / 대한내분비학회지

Background: A lifelong thyroxine therapy is indicated in all patients who have hypothyroidism as a result of autoimmune thyroiditis. However, it has been reported that some hypothyroid patients with autoimmune thyroiditis have spontaneous remission with restriction of iodine intake instead of thyroxine therapy. The purpose of study was to investigate how many hypothyroid patients with autoimmune thyroiditis can recover from hypothyroidism with restriction of iodine intake instead of thyroxine therapy and which factors predict recovery from hypothyroidism. Methods: We studied 64 patients with autoimmune thyroiditis(goitrous autoimmune thyroiditis 56, atrophic autoimmune thyroiditis 8). Thyroxine therapy was discontinued in patients with goitrous autoimmune thyroiditis on the way(group 1, n=32) or from the beginning(group 2, n=24) and atrophic autoimmune thyroiditis on the way(group 3, n-8). All patients were asked to avoid iodine-rich foods and thyroid function was monitored every one to two months for up to 35 months. Serum T3, T4, TSH concentrations, antithyroglobulin and antimicrosomal antibodies were measured by radioimmunoassay(RIA). TSH binding inhibitor immunoglobulin(TBII) was measured in serum using radioreceptor assay. Two hundred micrograms of thyrotropin releasing hormone (TRH) were given as intravenous bolus and TSH levels were measured in blood samples taken at 0, 30, and 60 minutes. All values were expressed as mean+-SEM. Statistical analysis was done with paired or non-paired t-test, ANOVA, and the Chi-square test. Statistical significance was defined as p-value below 0.05. Results: Thirteen(40.6%) of 32 patients in group 1 remained euthyroid after 12-35 months of discontinuation of thyroxine therapy. The other 19(59.4%) patients in group 1 had recurrences of hypothyroidism within 3 months after discontinuation of thyroxine therapy. In 11(45.8%) out of 24 patients in group 2, serum TSH concentrations declined below 5 mU/L within 3 months without thyroxine therapy. The other 13(54.2%) patients in group 2 remained hypothyroid till 2-16 months and the thyroxine was given. In contrast, all 8 patients in group 3 had recurrences of hypothy- roidism within 3 months after stopping thyroxine therapy. When we compared the recovered patients of goitrous autoimmune thyroiditis with the non-recovered patients of goitrous autoimmune thyroiditis, regardless of thyroxine therapy from the beginning, age at onset of disease of the 24 recovered patients was significantly younger than the 32 non-recovered patients(30.1+2.0 years vs. 40.2+ 2.4 years; p=0.004). Concl#usion: These findings suggest that 42.9% of hypothyroid patients with goitrous autoim- mune thyroiditis remain or become spontaneously euthyroid with restriction of iodine intake instead of thyroxine therapy. Young age may be a predicting factor of recovery from hypothyroidism in goitrous autoimmune thyroiditis.

Clinical Characteristics of Graves' Disease Patients with Undetectable Thyrotropin Binding Inhibitor Immunoglubulin (TB2) / 대한내분비학회지

Background: Graves disease is an autoimmune disease caused by TSH receptor antibodies. Thyrotropin binding inhibitor immunoglobulins(TBII) are detected in most Graves patients, but some patients have no TBII activities in their sera. It is unknown whether the clinical features of TBII-positive patients are different from those of TBII-negative patients. Methods: To evaluate the prevalence of TBII-negative Graves' patients and its clinical differences from TBII-positive patients, we examined TBII by radioreceptor assay in 686 consecutive untreated Graves patients. We found 84 TBII-negative patients(15 men and 69 women, mean age ±EM: 40.9±.4 years) and compared their clinical characteristics with 87 TBII-positive patients (22 men and 65 women, mean age±EM: 39.9±.5 years) who were selected randomly from the same patients group. Results: In this study, TBII was undetectable in 12.2% of patients with Graves' disease(84 of 686). TBII-negative group had a less weight loss than TBII-positive group. However, there was no significant differences in age, sex ratio, prevalence of ophthalmopathy, duration of illness and positive rate of family history for thyroid diseases between TBII-negative and