Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new euthyrox research articles will be listed here shortly after becoming available to us.
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Medical research on euthyrox
Curr Eye Res. 2008 Jul; 33(7): 575-586
Huang L, Yappert MC, Jumblatt MM, Borchman D
Thyroxine-treated human lens epithelial cells, HLE B-3, were grown in either a normoxic or hyperoxic atmosphere as a first step in identifying factors related to their increased viability. Reactive oxygen species, ROS, and the apparent mitochondrial membrane potential, Delta Psi(m), were measured using fluorescent probes. ROS were significantly higher in HLE B-3 cells grown in a hyperoxic atmosphere for both thyroxine-treated and untreated samples. However, treatment with thyroxine produced 40% lower ROS levels than untreated cells. A mitochondrial uncoupler concomitantly reduced ROS generation. In cells that were grown in a hyperoxic atmosphere, the Delta Psi(m) was significantly higher for samples treated with thyroxine compared to those that were untreated. ROS generation correlated inversely with the apparent Delta Psi(m) and the amount of cardiolipin, and correlated with the amount of lipid oxidation products. These correlations were valid whether cardiolipin and the Delta Psi(m) were decreased as a result of oxygen or increased as a result of thyroxine treatment. Therapies that protect mitochondria from damage and reduce damaging ROS generation may potentially ameliorate the effects of oxidation that occur in aging tissues and in diseases such as cataract.
Dietary Induced Hyperthyroidism Marginally Affects Neonatal Testicular Development.
J Androl. 2008 Jul 3;
Rijntjes E, Wientjes AT, Swarts HJ, de Rooij DG, Teerds KJ
The objective of this study was to determine whether dietary induced mild fetal/neonatal hyperthyroidism influenced the initiation of spermatogenesis and the development of the adult-type Leydig cell population. Previously, the effects of neonatally induced hyperthyroidism have been investigated in rats using rather high doses (5 to 10 microg/100 g body weight) of tri-iodothyronine (T3), which not only influenced testicular development, but also negatively affected the general body condition of the animals. To induce hyperthyroidism the diet of the dams was supplemented with 15 microg thyroxine (T4)/100 g body weight two weeks prior to mating and the dams and their offspring were kept on this diet until sacrifice. Pups were killed between days 7 and 64 after birth. At the age of 12 days plasma thyroid stimulating hormone (TSH) levels tended to be lower in hyperthyroid pups, while from the age of 15 days onwards plasma TSH levels were significantly lower in hyperthyroid animals. Concomitantly, plasma T4 levels were significantly elevated. From the age of 12 days onwards, plasma follicle stimulating hormone (FSH) levels were lower in hyperthyroid animals compared to age-matched control groups. Sertoli cell differentiation did not seem to be influenced by the mild hyperthyroid condition, as no difference in tubule lumen formation was observed between euthyroid and hyperthyroid animals. Nevertheless, a small effect on the progression of spermatogenesis was observed 15 days after birth, as the most advanced type of germ cells in the control testis were pachytene spermatocytes, while in the hyperthyroid testis these were leptotene and zygotene spermatocytes. Leydig cell proliferation was decreased in the hyperthyroid pups at the age of 15 days and slightly elevated at later ages, suggesting a possible slower onset of the proliferative activity of these cells than in the euthyroid control animals. Taken together, the present results suggest that even mild dietary induced hyperthyroidism transiently affects the development of the adult-type Leydig cell population as well as the initial progression of spermatogenesis.
J Med Food. 2008 Jun; 11(2): 376-381
Parmar HS, Kar A
ABSTRACT Peel extracts from Citrus sinensis, Punica granatum, and Musa paradisiaca were investigated for their effects on tissue lipid peroxidation (LPO) and on the concentration of thyroid hormones, insulin, and glucose in male rats. In vitro inhibition of H(2)O(2)-induced LPO in red blood cells of rats by 0.25, 0.50, 1.0, and 2.0 mug/mL C. sinensis, P. granatum, and M. paradisiaca peel extracts was observed in a dose-specific manner. Maximum inhibition was observed at 0.50 mug/mL C. sinensis, 2.0 mug/mL P. granatum, and 1.0 mug/mL M. paradisiaca. In the in vivo investigation, out of four different concentrations of each peel extract, 25, 200, and 100 mg/kg C. sinensis, P. granatum, and M. paradisiaca, respectively, were found to maximally inhibit hepatic LPO. The most effective doses were further evaluated for effects on serum triiodothyronine (T(3)), thyroxine (T(4)), insulin, and glucose concentrations. C. sinensis exhibited antithyroidal, hypoglycemic, and insulin stimulatory activities, in addition to inhibition of LPO, as it significantly decreased the serum T(4) (P < .05) and glucose (P < .001) concentrations with a concomitant increase in insulin levels (P < .05). P. granatum decreased LPO in hepatic, cardiac, and renal tissues (P < .01, P < .001, and P < .05, respectively) and serum glucose concentration (P < .01). M. paradisiaca strongly inhibited the serum level of thyroid hormones (P < .01 for both T(3) and T(4)) but increased the level of glucose (P < .05). These findings reveal the hitherto unknown potential of the tested peel extracts in the regulation of thyroid function and glucose metabolism. Besides antiperoxidative activity, C. sinensis extract has antithyroidal, hypoglycemic, and insulin stimulatory properties, which suggest its potential to ameliorate both hyperthyroidism and diabetes mellitus.
Drug News Perspect. 2008 Jun; 21(5): 258-66
Julius RL, Hawthorne MF
Misfolding and subsequent aggregation of any of a number of proteins leads to the accumulation of amyloid fibrils, which have been associated with a variety of diseases. One such amyloidogenic protein is transthyretin (TTR), a 55-kDa homotetrameric protein found in the blood plasma and cerebrospinal fluid where it binds and transports thyroxine. In humans, the T119M-TTR variant has been shown to be protective against familial amyloid polyneuropathy, a TTR amyloid disease, through kinetic stabilization of the unliganded tetrameric structure. Studies have indicated that a diverse range of small molecules may also bind TTR in the thyroxine-binding pocket and subsequently kinetically stabilize the protein's native conformation in vitro, preventing the misfolding that has been implicated in the progression of several diseases. However, cyclooxygenase inhibition is a common unwanted side effect among such small-molecule kinetic stabilizers. The recent development of transthyretin stabilizers not subject to cyclooxygenase inhibition may prove attractive for the long-term treatment of TTR misfolding diseases in humans. Such compounds are attained by incorporating aromatic carborane icosahedra at strategic points in their structures.
Euthyroid patient with elevated serum free thyroxine.
Clin Chem. 2008 Jul; 54(7): 1239-41
van der Watt G, Haarburger D, Berman P
Rejuvenation Res. 2008 Jun; 11(3): 605-9
Weiss EP, Villareal DT, Racette SB, Steger-May K, Premachandra BN, Klein S, Fontana L
Abstract Caloric restriction (CR) decreases circulating triiodothyronine (T(3)) concentration. However, it is not known if this effect is due to body fat mass reductions or due to CR, per se. The purpose of this study was to test the hypothesis that plasma T(3) concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise. Sedentary, nonobese 50- to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were randomly assigned to 12 months of caloric restriction (n = 18) or exercise-induced weight loss (n = 17) or to a control group (n = 9). Body weight and composition and plasma concentrations of the thyroid hormones T(3), thyrotropin (TSH), thyroxine (T(4)), and free thyroxine (FT(4)) were measured at baseline and 12 months. Fat mass changed significantly in the CR (-6.3 +/- 1.0 kg) and exercise (-5.5 +/- 1.0 kg) groups but not in the control group (-0.6 +/- 1.4 kg). The changes were not significantly different between the CR and exercise groups. Plasma T(3) concentration decreased in the CR group (-9.8 +/- 2.0 ng/dL, p < 0.0001) but not in the exercise (-3.8 +/- 2.1 ng/dL, p = 0.07) or control (-1.3 +/- 2.8 ng/dL, p = 0.65) groups. TSH, T(4), and FT(4) did not change in any of the study groups. Twelve months of CR decreased circulating T(3) concentrations in middle-aged adults. This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T(3) concentration was not observed in response to an exercise-induced fat mass reduction.
Endocr Regul. 2008 Mar; 42(1): 53-61
Hampl R, Ostatnikova D, Celec P, Putz Z, Lapcík O, Matucha P
Objective. Since soy isoflavones may influence the thyroid hormone feedback system by interference with their biosynthesis, secretion and metabolism, we tested whether their controlled shortterm consumption affects thyroid function. Methods. Eighty six volunteers - university students (32 males and 54 females) were eating unprocessed boiled natural soybeans (2 g/kg body weight/day) for 7 consecutive days. Thyrotropin, free thyroid hormones, antibodies to thyroid peroxidase and to thyroglobulin, and actual levels of unconjugated major soy phytoestrogens, daidzein and genistein, were measured in sera collected before, at the end and one week after finishing soy meal consumption. Results. Both phytoestrogens increased significantly (p
Maternal Thyroid Hypofunction and Pregnancy Outcome.
Obstet Gynecol. 2008 Jul; 112(1): 85-92
Cleary-Goldman J, Malone FD, Lambert-Messerlian G, Sullivan L, Canick J, Porter TF, Luthy D, Gross S, Bianchi DW, D'Alton ME,
OBJECTIVE: To estimate whether maternal thyroid hypofunction is associated with complications. METHODS: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used. RESULTS: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P
BMC Pediatr. 2008 Jun 30; 8(1): 26
Ng SM, Turner MA, Gamble C, Didi M, Victor S, Malamateniou C, Parkes LM, Tietze A, Gregory L, Sluming V, Abernethy L, Weindling AM
ABSTRACT: BACKGROUND: Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis. METHODS: The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and /or oxygen requirement and chronic lung disease. All infants recruited to the TIPIT study will be consented separately to have cranial MRI scans at term equivalent. This protocol describes the study we will perform on the infants that have cranial MRI scans.
Toxicology. 2008 May 23;
Sun H, Shen OX, Xu XL, Song L, Wang XR
Effects of pesticides on the function of thyroid have attracted lots of attention because thyroid hormones (THs) play a major role in mammalian brain development. In order to screen for compounds that acted on the thyroid hormone receptor (TR) signaling pathway, we transiently transfected the vector pGal4-L-TRbeta1 (Gal4 DBD fused to hTRbeta1 LBD) and Gal4-responsive luciferase reporter pUAS-tk-Luc into HepG2 cell, developing a reporter gene assay which showed good response to triiodothyronine (T3) and thyroxine (T4) with the median effective concentration (EC(50)) of 0.46 and 25.53nM, respectively. Bisphenol A exhibited weak anti-thyroid hormone activity with median inhibitory concentration (IC(50)) value of 6.45x10(-5)M. The assay showed acceptable repeatability to T3 with intra coefficient of variability (CV) of 5.9% and inter CV of 11.7%. Carbaryl, 1-naphthol (1-NAP) and 2-naphthol (2-NAP) were tested for their agonist and antagonist activities. As a result, we found that all the three related chemicals possessed TR antagonist activity and none of them showed the agonist activity. These results further indicated that TR might be the targets of industrial chemicals. And this assay provided a useful tool for investigating the effects of environment chemicals on thyoid function.