Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains

Concentrations of 13 trace elements (Ag, Br, Co, Cr, Cs, Fe, Hg, K, Na, Rb, Sc, Se, Zn) in isolated subcellular fractions (whole brain, nuclei, mitochondria, microsomes) of temporal lobe from autopsied Alzheimer's disease (AD) patients and norma controls were determined utilizing instrumental neutron activation analysis. Comparison of AD and controls revealed elevated Br (whole brain) and Hg (microsomes) and diminished Rb (whole brain, nuclear and microsomes), Se (microsomes) and Zn (nuclear) in AD. The elevated Br and Hg and diminished Rb are consistent with our previous studies in AD bulk brain specimens. Comparison of element ratios revealed increased Hg/Se, Hg/Zn and Zn/Se mass ratios in AD. Se and Zn play a protective role against Hg toxicity and our data suggest that they are utilized to detoxify Hg in the AD brain. Overall our studies suggest that Hg could be an important toxic element in AD. Whether Hg deposition in AD is a primary or secondary event remains to be determined.     

Age-dependent and region-specific differences in the distribution of trace elements in 7 brain regions of Long-Evans Cinnamon (LEC) rats with hereditary abnormal copper metabolism

Cu, Mn, Mo, Rb and Zn concentrations of 7 brain regions in LEC rats were determined before (4 and 10 weeks old) and after (20 weeks old) the onset of jaundice. Cu in the LEC rat brain was less concentrated in all regions at 4 weeks of age and in synaptosomal fractions at 10 weeks but, conversely, more concentrated in 3 regions at 20 weeks than in control rats. Furthermore, Mo and Rb in 6 regions at 10 weeks of age and Mn at 20 weeks were more concentrated in the LEC rat brain than in control rats. These results showed that abnormal distributions of trace elements exist in the LEC rat brain before the onset of jaundice.     

Analysis of trace element concentrations in the cerebrospinal fluid using particle-induced X-ray emission

The authors used for first time the PIXE method ("particle induced X-ray emission") for determination of the concentration of in the cerebrospinal fluid of neurological patients. In 40 hitherto examined patients with epilepsy, multiple sclerosis, extrapyramidal syndromes, Little's syndrome, Guillain-Barré syndrome, cerebral strokes, tumours of brain and spine, vasomotor headaches, neuralgia and discopathy, the concentration of the following trace elements was determined: Br, Zn, CU, Pb, Rb, Fe, Ca, K, Cl, Sr, Zr, Cr, Mn, Ni, As. The ranges of the determined concentrations in ppm units mean values and mutual relations of some elements were presented. The concentration of trace elements in cerebrospinal fluid was lower than in the tissues. The authors continue further investigations in many neurological syndromes with analysis of various clinico-laboratory correlations.     

Distribution of trace elements in the brain of EL (epilepsy) mice

The association of essential trace elements with epileptic seizures is poorly understood. On the basis of the evidences that the release of zinc from the brain of epilepsy (EL) mice, an animal model of genetically determined epilepsy, is enhanced by the induction of seizures and that alteration of zinc homeostasis is responsive to susceptibility to seizures, the distribution of trace elements in the brain was studied using EL mice and ddY mice, which form the genetic background for the inbred EL mice. The multitracer technique was applied to determine the distribution of trace elements. Twenty-four hours after intravenous injection of the multitracer, the concentration of 65Zn and 56Co in the brain of untreated EL mice was higher than in ddY mice, while the concentration of 65Zn and 56Co in the brain was decreased in seized EL mice. 75Se concentration in the hippocampus, cerebral cortex and cerebellum of untreated EL mice was lower than in ddY mice, while 75Se concentration in the hippocampus was increased in seized EL mice. 83Rb, an element of homologous series to potassium, concentration in the hippocampus and cerebral cortex of untreated EL mice was lower than in ddY mice, and 83Rb concentration in the cerebral cortex was decreased in seized EL mice. The movement of zinc, cobalt and selenium in the brain may be altered by enhancement of susceptibility to seizures. These results suggest that alteration of homeostasis of zinc, cobalt and selenium in the brain may be involved in the susceptibility, development or termination of seizures in EL mice.     

Vergleichende Untersuchungen über die Konzentration einiger Spurenelemente in menschlichen Hirnarealen durch Neutronenaktivierungsanalyse

Zusammenfassung Durch die Neutronenaktivierungsanalyse konnten die Konzentrationen der Elemente Cu, Se, Ag, Zn, Fe, Rb, Au, La und Ba in 14 Arealen des menschlichen Gehirns bestimmt werden. Die Zentren der extrapyramidalen Motorik wiesen eine höhere Konzentration dieser Elemente als die Areale mit überwiegend weißer Substanz auf. Die Ergebnisse werden den bisher veröffentlichten Untersuchungen gegenübergestellt und diskutiert.

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Comparative investigations of the concentrations of some trace elements in particular areas of the human brain by neutron activation analysis

Summary The concentrations of the elements Cu, Se, Ag, Zn, Fe, Rb, Au, La, and Ba were determined in 14 areas of the human brain by neutron activation analysis. The concentrations of these elements were higher in the centres of extrapyramidal motor activity than in the areas primarily consisting of white matter. The results are discussed and compared to work hitherto published.

     

Brain trace elements in Alzheimer's disease

Instrumental neutron activation analysis has been used to determine the concentrations of 16 elements in selected brain regions and separated gray- and white-matter specimens from histologically verified Alzheimer's disease (AD) and age-matched control patients. Significantly different (p less than 0.05) mean concentrations of Br, Cl, Cs, Hg, N, Na, P, and Rb were observed in AD bulk brain samples compared to controls, while no significant differences were observed for Ag, Co, Cr, Fe, K, Sb, Sc, and Se. The differences that are most persistent and largest in magnitude for the pooled bulk samples, males and females, left and right hemispheres, and separated gray and white matter are the elevation of Br and Hg and the depletion of Rb in AD compared to controls. Significant interelement correlations for the latter elements in both AD and control brains are also documented. Based on these studies, the possibility of an etiological role for trace elements in AD clearly deserves further investigation.     

新生鼠和成年鼠脑7种微量元素含量的比较

利用高频电感耦合等离子体原子发射光谱法（ICP－AES）测定Sprunge－Dawley大鼠新生期大脑皮层、海马、小脑、间脑和脑桥等部位的锌、铁、铜、锰、铬、锶、钼等7种微量元素的含量，并与成年动物做了比较。结果表明：（1）新生期大鼠全脑7种微量元素含量的多寡依次为：锌、铁、铬、锶、锰、铜、钼；成年期时钢跃居第四位，总含量低于新生期。（2）脑内不同部位微量元素的含量不同。新生大鼠海马和小脑内多数元素含量高于其他脑区，钼在间脑和海马中含量较高。成年鼠皮层、海马微量元素含量较高，皮层内铜、锶、钼含量最低。     

Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood‐brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid‐stimulating hormone (TSH), free thyroxine (T4) (FT4), total triiodothyronine (T3) (TT3), reverse T3 (rT3), thyroid‐releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT4/TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), whereas TT3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA. The high expression of FRα in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.     

Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate

Studies investigating the influence of antiepileptic drugs on thyroid hormones usually have compared patients chronically treated with antiepileptic drugs to controls. To date, this type of designs has produced divergent results both with regard to individual drugs and individual thyroid hormones. The present study comprised 31 patients with newly diagnosed epilepsy, commencing treatment with either carbamazepine or valproate. T3, T4, FT4, FT3, rT3, TSH, T3 resin uptake and blood folic acid, were determined before and during antiepileptic monotherapy, thus making the patient his own control. During treatment with carbamazepine, a significant decrease in T4, FT4, FT3, rT3 and TBG was observed. Valproate caused a decrease in T4, FT4 and T3. Neither of the drugs caused any changes in blood folic acid concentrations or persistent increases in the TSH values. None of the patients developed overt symptoms of hypothyreoidism. Conceivable mechanisms underlying these hormonal changes are reviewed.     

Changes in serum thyroid hormones in acute cerebrovascular apoplexy and their clinical significance

Serum thyroid hormones were measured in 62 cases of acute cerebrovascular apoplexy. Compared with the control group, T3, FT3 were markedly lowered and rT3, T4 and TSH were significantly increased with lowered T3/rT3 ratio. The patients were divided into two groups, according to whether there was hemorrhage in their CSF. Changes of serum thyroid hormones in cerebral haemorrhage were more remarkable than those observed in cerebral thrombosis. 16 cases with increased T4, FT4 were diagnosed as euthyroid hyperthyroxinemia. It was found that the amount of thyroid hormone changes appeared to be in proportion to the severity of acute cerebrovascular apoplexy. The determination of serum thyroid hormones would be useful in evaluating the severity of the strokes and in studying the thyroid function in acute cerebrovascular apoplexy.     

帕金森氏病人头发,血清中微量元素含量的研究（附74例分析）

从１９８８年以来我们对７４例帕金森氏病人的头发和血清中微量元素含量研究并与５４例正常对照组对比，检测的结果发现ＰＤ病人头发铜、锌、铁、锰低于对照组（Ｐ＜０．０１）。病人血清铜、锌、锰也低于对照组。血清铜、锰含量随病情加重而递减，且有剂量效应关系。血清与头发相关性分析无相关关系（Ｐ＞０．０５）。其结果说明ＰＤ的发病原因与体内微量元素代谢缺陷可能有关系。     

血管性帕金森综合征和帕金森病患者血中微量元素的变化

目的研究血管性帕金森综合征(vascular parkinsonism,VP)和帕金森病(Parkinson’s disease,PD)患者血中微量元素铜(Cu)、硒(Se)、锌(Zn)和铅(Pb)水平的变化。方法选择20例VP、17例PD患者和10例对照者,采用石墨炉原子吸收分光光度法检测血清Zn、Cu和全血Pb水平,采用荧光分光光度法检测血清Se水平,并进行分析。结果 (1)VP和PD组血清总体Cu和Se水平均明显高于对照组(P0.05),VP和PD组间无统计学差别(P0.05)。(2)VP、PD组总体血清zn和全血Pb水平较对照组无统计学差别(P0.05)。(3)VP组病程5年的患者血清Cu、Se和Zn水平明显高于对照组(P0.05),全血Pb水平与对照组无统计学差别(P0.05);病程5年的患者血清cu和zn水平明显低于对照组(P0.05),血清Se和全血Pb水平与对照组无统计学差别(P0.05)。(4)PD组Ⅰ—Ⅱ期患者血清Cu、Se和Zn水平明显高于对照组(P0.05),全血Pb水平与对照组无统计学差别(P0.05);Ⅲ—Ⅴ期患者血清Cu和全血Pb水平均明显高于对照组(P0.05),血清Se和Zn水平明显低于对照组(P0.05)。结论 VP和PD组血清总体Cu和Se水平明显升高;VP组病程5年的患者血清Cu、Se和Zn水平明显升高,病程5年的患者血清Cu和Zn水平明显降低;PD组Ⅰ—Ⅱ期患者血清Cu、Se和zn水平明显升高,Ⅲ—Ⅴ期患者血清Cu和全血Pb水平明显升高,血清Se和Zn水平明显降低。微量元素可能在VP和PD的发生、发展和转归中起重要作用。     

Trace element imbalances in hair and nails of Alzheimer's disease patients

The concentrations of 17 elements in the hair and nails of 180 Alzheimer's disease (AD) and control subjects have been determined by instrumental neutron activation analysis (INAA). Comparisons of trace element levels of properly matched AD and control groups revealed significant imbalances in the concentrations of six elements (Br, Ca, Co, Hg, K, and Zn) between disease and control groups. It is noteworthy that each of these has previously been shown by our group, or others, to be altered in some AD brain region(s). Geometric means for each element in both hair and nails of AD and control subjects are presented, and significant differences noted. The significance of these alterations with regard to the possible role of trace elements in the etiology of AD is discussed.     

高原地区MS血清某些微量元素的含量变化及其意义探讨

目的　探讨高原环境下多发性硬化 (MS)血清某些微量元素含量的变化与发病的相关性。方法　以电感耦合等离子体发射光谱法测定 19例 MS患者血清 Zn、Cu、Fe、Mn、Al等 5种微量元素水平。结果　 MS患者血清 Mn、Al水平显著高于正常对照组 ,而 Cu含量则较低。 Zn和 Fe无明显变化。结论　微量元素的改变可能与 MS的发病机制有一定联系。     

Changes in thyroid hormones, thyroid stimulating hormone and cortisol in acute spinal cord injury.

To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors.     

Enhanced analgesic effects of tramadol and common trace element coadministration in mice

Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail‐flick (TF) and hot‐plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol‐alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.     

Zinc influences on brain development, pituitary an thyroidfunction iniodine-deficient pregnant and neonatal rats

BACKGROUND: Zinc (Zn) has been shown to greatly influence brain development. Zn supplements may reduce injury to cell membranes of the thyroid gland due to iodine deficiency. OBJECTIVE: To establish an iodine deficiency rat model using low-iodine food, which was supplemented with compound Zn and Zn gluconate, to observe the effects of Zn on brain development, as well as pituitary gland and thyroid gland function in iodine-deficient rats. DESIGN, TIME AND SETTING: Randomized grouping study of neural development was performed in the central laboratory of Shandong Institute for Prevention and Treatment of Endemic Disease from 1998 to 1999. MATERIALS: A total of 270 Wistar, female rats, one month after weaning, were used in this study, including 150 pregnant and 120 neonatal rats. Rats were randomly divided into six groups: normal control, model, iodine, compound Zn, iodine and compound Zn, and zinc gluconate. Each group contained 25 pregnant rats and 20 nenoatal rats. METHODS: The pregnant rats and 20 neonatal rats, and well as the normal group, were fed standard chow and allowed free access to tap water (containing 5 μ g/L iodine and 1 mg/L Zn). The remaining five groups were fed low-iodine chow. However, the model group received distilled water, the iodine group received potassium-iodide distilled water (containing 300 μ g/L iodine), the compound Zn group received distilled water and intragastrically administrated 10 mL/kg compound Zn solution, once per day, the iodine and compound Zn group received distilled water with 300 p g/L iodine and intragastrically administrated 10 mL/kg compound Zn solution, once per day. All treatments lasted 90 days. MAIN OUTCOME MEASURES: All pregnant rats were sacrificed on the day 21 of pregnancy. Body mass, number and rate of fetal absorption, as well as fetal death and malformation, were determined. Thyroid and pituitary gland weights were measured, as well as serum levels of thyroid hormone, gonadotropin, and sex hormones. In the experimental study of neonatal rats, the animals normally gave birth at day 21. At day 45 after birth of the neonatal rats, thyroid and pituitary gland weights were measured, and protein, DNA, and RNA concentrations were measured. RESULTS: Pregnant rats in the iodine group exhibited decreased urine iodine and body mass (F= 7.37, P < 0.01 ), increased thyroid absolute and relative weight (F= 7.01, 50.27, P < 0.01 ), as well as decreased T<,4> and FT<,4> (F = 7.01, 29.32, P < 0.01 ) and increased T<,3> and FT3 (F = 41.20, 5.94, P < 0.01 ). Gonadotrupic and sexual liorrnones were abnormal. The pregnant rats displayed decreased weight gain, and the rates of malformation, dead, and absorbed fetuses were increased. Compared with the control group, the neonatal rats with iodine deficiency exhibited lower brain weights (P < 0.01 ). Brain protein, DNA, and RNA, concentrations were decreased, with a rate of RNA/DNA (F = 5.70, 55.86, 25.65, 5.44, P < 0.01 ). Body mass was gradually increased (F= 6.74, P< 0.01), and the thyroid glands were enlarged (F= 50.01, 76.13, P< 0.01). Following Zn administration, thyroid gland weight was decreased in pregnant rats (P < 0.01 ). Thyroid hormone, gonadotropic hormones, and sexual hormones were restored to some degree. Fetal weight was increased, and the rates of malformation, dead, and absorbed fetuses were decreased. At the same time, neonatal rats gained body weight, displayed decreased thyroid gland weight, as well as increased protein, DNA, and RNA concentrations in the brain. The ratio of RNA/DNA and protein/DNA increased following Zn administration (P < 0.01 ). CONCLUSION: Zn supplementation may decrease the degree of goiter, ameliorate thyroid hormone disorder, as well as gonadotropic and sexual hormone disorders, and increase protein, DNA, and RNA content. Zn supplementation antagonized reproductive abnormalities in pregnant rats, decreased fetal growth,     

Thyroid hormone metabolism in primary cultures of fetal rat brain cells

The metabolism of thyroxine 3,5,3',5'-tetraiodothyronine, (T4) and 3,5,3'-triiodothyronine (T3) was studied in primary cultures of dispersed fetal rat brain cells. Cultured brain cells actively metabolized both T4 and T3 by enzyme catalyzed deiodination reactions which increase (type II 5'-deiodinase) or decrease (type I 5'-deiodinase and type III 5-deiodinase) the bioactivity of thyroid hormone. Homogenates of cultured brain cells showed both type I and type II 5'-deiodinating activities and these two enzymes tended to differ in their time course of appearance. Cultures exposed to 10 microM cytosine arabinoside for 16 h showed up to a 70% reduction in type I activity without decreasing the type II enzyme suggesting that the type II enzyme is associated with non-dividing neuronal cells. The predominant pathway for T4 and T3 metabolism in situ was tyrosyl-ring or type III 5'-deiodination which followed first order kinetics with a t1/2 of 70 min. T4 to T3 conversion by the type II enzyme was consistently observed after correcting for the degradation of newly formed T3 by the type III enzyme. In situ, both type II and type II enzymes were thiol-dependent and both activities were inhibited by iopanoic acid. Type III 5-deiodination of T4 produced 34 fmol 3,3,5'-triiodothyronine (rT3)/h per 10(6) cells at 10 mM dithiothreitol (DTT) and 97 fmol of rT3/h per 10(6) cells at 50 mM DTT. T3 production by the type II enzyme was 1.2 and 4.4 fmol of T3/h per 10(6) cells at 10 and 50 mM DTT, respectively. Thyroid hormone deficient culture conditions increased type II enzyme activity by 4-5-fold within 48 h and this was prevented in a dose-dependent fashion by supplementing the media with increasing amounts of T3. These data indicate that primary cultures of dispersed brain cells mimic the intact cerebral cortex with respect to the metabolism of thyroid hormone and the regulatory mechanisms which defend cerebrocortical T3 levels. The vigorous metabolism of both T4 and T3 by these cultures may explain some of the difficulties in demonstrating thyroid hormone-dependent biochemical changes at physiologically relevant levels of thyroid hormone.     

Developments observation of serum thyrohormone level in schizophrenics]

Measure of serum T3, T4, RUR, FT4I was made at admission, sixth weeks after admission and discharged from hospital for 42 cases schizophrenic. T4, FT4I value of sixteen patients was higher than in normal controlled group, but there was no difference between other 26 cases schizophrenic and controlled group. The authors reported that abnormal levels of T4, FT4I in 16 cases patients relate to disease course and severe symptoms and suggested that the change of serum T4, FT4I in some cases was related to the disease in itself.     

The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate

PURPOSE: The aim of this study was to evaluate the effects of short-term oxcarbazepine (OXC) and valproate (VPA) monotherapy on thyroid functions in children. METHODS: Fifty-five newly diagnosed epileptic children with normal thyroid functions (confirmed with the thyrotropin releasing hormone stimulation test) participated in this study. VPA treatment was started in 30 patients and OXC in 25 patients. Serum thyroxine (T(4)), free thyroxine (fT(4)), triiodothyronine (T(3)), free triiodothyronine (fT(3)), reverse T3 (rT(3)), thyroid peroxidase antibodies (TPO-ab), and urine iodine levels were evaluated at baseline and at the third and sixth months of therapy. RESULTS: In the OXC group, serum T(4), fT(4), T(3), fT(3), and rT(3) levels were found to be decreased at the third and sixth months, the differences were significant compared to the baseline values except for fT(3) levels at the third month and fT(4) and rT(3) levels at the sixth month (p < 0.05). At the sixth month, serum T(4) level dropped below the normal reference value in 8 (32%), fT(4) in 5 (20%), T(3) in 4 (16%), and fT(3) in 3 (12%) patients. In the VPA group, mean T(4), fT(4), T(3), fT(3), and rT(3) levels at 3 and 6 months remained similar compared to the baseline values (p > 0.05). Mean serum thyroid stimulating hormone levels increased significantly at the sixth month compared to the baseline values in the VPA group (p < 0.05) while it remained unchanged in the OXC group (p > 0.05). There was no effect of either drug on urinary iodine excretion and serum TPO-ab levels remained in normal ranges throughout the study. CONCLUSIONS: In this prospective study, it is documented that children under short-term OXC or VPA therapy showed altered thyroid functions similar to the changes observed after long-term treatment. Although, the clinical significance of these results need to be evaluated with future studies, this observation of altered thyroid functions points out that thyroid functions may need to be monitored closely in children receiving antiepileptic treatment, even in the short-time interval.