• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 25
  • 21
  • 10
  • 4
  • 3
  • 1
  • 1
  • 1
  • Tagged with
  • 84
  • 30
  • 20
  • 18
  • 16
  • 11
  • 9
  • 8
  • 7
  • 7
  • 6
  • 6
  • 6
  • 6
  • 6
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Postnatální změny koncentrace hormonů štítné žlázy jehňat / Postnatal dynamics of thyroid hormones in lambs

BURLEOVÁ, Barbora January 2013 (has links)
The aim of my work was to monitor and valorize of postnatal dynamics of thyroid hormones, thyroxine (TT4), triiodothyronine (TT3) and its free fractions (FT3 and FT4), in lambs up to 60 days of age. During the experiment 26 lambs were devided into two groups according to sex and were supplemented by iodine in concentration 0,7 ? 5 mg. Standard directed day ration for sheep is average 0,3 mg of iodine in 1 kilogram of dry mass (DM). One of the groups was also supplemented by selenium in concentration 0,2 ? 0,4 mg in 1 kilogram of DM.
72

Hormônios tireoidianos, TSH, desempenho e qualidade de carcaça e carne em suínos imunocastrados alojados em diferentes sistemas de criação / Thyroid hormones, tsh, performance, carcass and meat quality in immunocastrated pigs housed in different systems of creation

Carrazza, Leonardo Gomes 19 March 2012 (has links)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aimed to evaluate the influence of pig housing systems on serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), correlating with characteristics of animal performance, meat quality and carcass. Therefore, 48 male pigs with an average age of 84 days were divided into two distinct housing systems, the Intensive System of Rearing Pig (conventional system) and the Intensive System of Swine Raised Outdoors (SISCAL), being 24 animals per environment divided into six plots of four pigs each. The experiment lasted 105 days. Blood was collected at the beginning and end of the experiment when the animals were sent to slaughter in a slaughterhouse, where it proceeded to collect material and data for analysis. There were no statistical differences between the two systems, for percentage of intramuscular fat (GIM), pH 45 minutes, pH 24 hours, Intestinal length (CI), carcass length (CC), Backfat Thickness 1 (ET1), Backfat Thickness 2 (ET2), Backfat Thickness in Half Moon (ETML) Hot Carcass Weight (PCQ), carcass yield (RC) and Lean Meat Yield (RCM). Animals housed on the conventional system had higher values of weight gain (GP) (63.49 vs. 54.14 kg, P <0.05) and Average Daily Weight Gain (GPMD) (0.6163 vs. 0, 5255 kg P <0.05) than animals raised on SISCAL. The TSH serum level increased from the beginning to the end of the experiment (0.12 to 0.30 &#956;IU, P <0.05), whereas T4 decreased (6.44 to 3.11 mg/dL, P <0.05) did not differing between the two systems. The T3 level at the end of the housing was higher at SISCAL than in the conventional system (vs. 1.10. 0.75 ng/mL) at P <0.05. The concentrations of T3 and T4 had correlation of 0.48, while moderate and negative correlations were found between the levels of T3 and features of PCQ (-0.48), GP (-0, 48) and ET2 (-0.39) and between T4 and PCQ (-0.53), GP (-0.57) and ET2 (-0.34) P<0.005. / Objetivou-se avaliar a influência dos sistemas de criação de suínos sobre concentrações séricas de triiodotironina (T3), tiroxina (T4) e hormônio estimulante da tireóide (TSH), correlacionando com características de desempenho zootécnico, qualidade de carne e carcaça. Para isto, 48 suínos machos com idade média de 84 dias foram alocados em 2 sistemas de criação distintos, o Sistema Intensivo de Criação de Suínos (sistema convencional) e o Sistema Intensivo de Suínos Criados ao Ar Livre (SISCAL), sendo 24 animais por ambiente, divididos em 6 parcelas de 4 suínos cada. O experimento teve duração de 105 dias. O sangue foi coletado no início e fim do experimento, quando os animais foram encaminhados ao abate em matadouro frigorífico, onde procedeu-se coleta de material e dados para análises. Não foram encontradas diferenças estatísticas entre os 2 sistemas, para porcentagem de Gordura Intramuscular (GIM), pH 45 minutos, pH 24 horas, Comprimento Intestinal (CI), Comprimento de Carcaça (CC), Espessura de Toucinho 1 (ET1), Espessura de Toucinho 2 (ET2), Espessura de Toucinho na Meia Lua (ETML), Peso de Carcaça Quente (PCQ), Rendimento de Carcaça (RC) e Rendimento de Carne Magra (RCM). Animais alojados sobre o sistema convencional obtiveram maiores valores de Ganho de Peso (GP) (63,49 vs. 54,14 kg, P<0,05) e Ganho de Peso Médio Diário (GPMD) (0,6163 vs. 0,5255 kg P<0,05) que animais criados sobre o SISCAL. O nível sérico de TSH aumentou do início ao fim do experimento (0,12 para 0,30 &#956;IU, P<0,05), enquanto T4 diminuiu (6,44 para 3,11 &#956;g/dL, P<0,05), não diferindo entre os 2 sistemas. O nível de T3 ao final do alojamento foi maior no SISCAL que no sistema convencional (1,10 vs. 0,75 ng/mL) com P<0,05. As concentrações entre T3 e T4 tiveram correlação de 0,48, enquanto correlações moderadas e negativas foram encontradas entre os níveis de T3 e características de PCQ (-0,48), GP(-0,48) e ET2 (-0,39) e entre T4 e PCQ (-0,53), GP(-0,57) e ET2 (-0,34) P<0,05. / Mestre em Ciências Veterinárias
73

Avaliação tireoidiana de pacientes infectados pelo vírus da hepatite C: correlação com polimorfismos do gene CTLA4 / Thyroid evaluation of patients infected by hepatitis C virus: correlation with polymorphisms of CTLA4 gene

Debora Lucia Seguro Danilovic 15 October 2010 (has links)
INTRODUÇÃO: Manifestações auto-imunes são frequentes na infecção pelo vírus da hepatite C (VHC). Apesar da associação com doenças auto-imunes de tireóide (DAIT) ser controversa, sabe-se que distúrbios tireoidianos podem surgir ou piorar com tratamento com IFN e ribavirina. Os objetivos deste estudo foram avaliar a função tireoidiana em pacientes infectados pelo VHC, caracterizar distúrbios tireoidianos antes, durante e após tratamento com IFN e estudar as frequências dos genótipos dos polimorfismos do gene CTLA4, correlacionando-os com características clínicas e laboratoriais, presença de disfunção tireoidiana e evolução durante tratamento com IFN. MÉTODOS: Avaliação prospectiva de 112 indivíduos com infecção crônica pelo VHC, 30 tratados com IFN, e 183 controles. Realizaram-se avaliações clínica, hormonal e de auto-imunidade tireoidiana e ultra-sonografia de tireóide no início e durante tratamento. Avaliações de globulina transportadora de hormônios tireoidianos (TBG), de CXCL10 e de biópsia hepática foram feitas pré-tratamento. Análises dos polimorfismos do gene CTLA4 -318C>T, A49G e CT60 foram realizadas por PCR-RFLP e de AT(n) por análise de fragmento através de eletroforese capilar. RESULTADOS: A frequência de DAIT entre infectados por VHC não diferiu dos controles (10,7 vs 13,5%, p=0,585). Os limites de distribuição dos níveis de T3 (T3T) e T4 (T4T) totais foram superiores aos de referência (T3T 112-246 ng/dL; T4T 7,8-15,2 g/dL), assim como de TBG (17-47 mg/L). TBG correlacionou-se com T3T (r=0,654, p<0,001) e T4T (r=0,741, p<0,001). Heterogeneidade (p=0,027) e hipoecogenicidade de parênquima (p=0,002) foram mais frequentes nos pacientes com DAIT. Aumento de vascularização esteve presente em 49,2% dos infectados sem distúrbio tireoidiano. CXCL10 esteve aumentada nos infectados (p=0,006), mas não se relacionou com disfunção tireoidiana. Sua elevação correspondeu ao grau de atividade necro-inflamatória na biópsia hepática (p=0,006) e correlacionou-se com T3T (r=0,388, p=0,003), T4T (r=0,444, p=0,001) e TBG (r=0,551, p<0,001). Dezenove por cento dos pacientes desenvolveram tireoidites auto-imunes por IFN e 16% não auto-imunes. Em 14 pacientes sem alteração tireoidiana durante o uso de IFN, T3T diminuiu ao longo de 12 meses (p=0,038) concomitante à queda de ALT (p=0,055). T4T diminuiu com 3 (p=0,039) e 12 meses (p=0,008), T4 livre e TSH permaneceram estáveis. Encontrou-se maior frequência de oito repetições AT na região 3UTR do gene CTLA4 nos infectados por VHC (p=0,019). O alelo C do polimorfismo -318C>T esteve relacionado com infecção pelos genótipos 1 (p=0,020, OR 0,19) e 3 (p=0,008, OR 9,13), assim como o alelo G do polimorfismo A49G (p=0,002, OR 0,38 e p=0,004, OR 2,49, respectivamente). Não se identificou relação dos polimorfismos do gene CTLA4 com distúrbios tireoidianos, antes ou após tratamento com IFN. CONCLUSÕES: Não foi encontrada associação entre infecção por VHC e doenças tireoidianas. Indivíduos infectados por VHC têm maiores níveis de T3T e T4T, correlacionados com TBG. Aumento de CXCL10 não se associou com disfunção tireoidiana, mas se correlacionou com TBG, T3T e T4T. IFN provocou tireoidites auto-imunes e não auto-imunes, além de reduzir T3T e T4T coincidente com melhora de lesão hepática. Não se encontrou relação dos polimorfismos do gene CTLA4 com características clínicas e laboratoriais ou presença de disfunção tireoidiana prévia ou induzida por IFN / INTRODUCTION: Autoimmune disorders are frequent in patients infected by the hepatitis C virus (HCV). Although the association with autoimmune thyroid diseases (AITD) is controversial, thyroid disturbance could occur or worsen with IFN and ribavirin treatment. The aims of the study were evaluate thyroid function in HCV-infected patients, characterize thyroid disturbance prior and after IFN treatment and analyze the frequency of the genotypes of the polymorphisms of CTLA4 gene, and their relation to clinical and laboratorial features, presence of thyroid dysfunction and disturbance along IFN treatment. METHODS: Prospective evaluation of 112 chronically HCV-infected subjects, 30 treated with IFN, and 183 controls. Clinical, hormonal, thyroid autoimmunity and ultrasound exams were performed before and during treatment. Thyroxine-binding globulin (TBG), CXCL10 and hepatic biopsies were also evaluated before treatment. Analysis of polymorphisms of CTLA4 gene -318C>T, A49G and CT60 were made by PCR-RFLP and AT(n) polymorphism analysis by capillary electrophoresis in automatic sequencer. RESULTS: The frequency of AITD among HCV-infected subjects was similar to the rate among controls (10.7 vs 13.5%, p=0.585). Total T3 (T3T) and T4 (T4T) distributions were right shifted (T3T 112-246 ng/dL; T4T 7.8-15.2 g/dL), as was TBG (17-47 mg/L). TBG correlated to both T3T (r=0.654, p<0.001) and T4T (r=0.741, p<0.001). Thyroid heterogeneity (p=0.027) and hipoechogenicity (p=0.002) were associated with AITD and, most notably, increased vascularization was present in 49.2% of HCV-infected patients without thyroid disturbance. CXCL10 was higher in HCV-infected group (p=0.006) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.006) and correlated to T3T (r=0.388, p=0.003), T4T (r=0.444, p=0.001) and TBG (r=0.551, p<0.001). Nineteen percent of subjects treated with IFN presented autoimmune thyroiditis and 16% had non-autoimmune thyroiditis. In 14 subjects without IFN-induced thyroid dysfunction, T3T decreased along 12 months of follow-up (p=0.038) concomitant to ALT decrease (p=0.055). T4T decreased within 3 (p=0.039) and 12 months (p=0.008), while both free T4 and TSH remained stable. Eight AT repetitions in 3UTR site of the CTLA4 gene were more frequent among HCV-infected subjects. The C allele of -318C>T polymorphism was associated with genotype 1 (p=0.020, OR 0.19) and 3 infections (p=0.008, OR 9.13), similar to allele G of A49G polymorphism (p=0.002, OR 0.38 and p=0.004, OR 2.49, respectively). No association of the polymorphisms of CTLA4 gene and thyroid disorders, prior or induced by IFN treatment, was found. CONCLUSIONS: No association between HCV-infection and thyroid diseases was found. HCV-infected subjects had higher T3T and T4T which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction, but correlated to TBG, T3T and T4T. IFN induced autoimmune and non-autoimmune thyroiditis. IFN also reduced T3T and T4T levels commensurately with liver improvement. The polymorphisms of CTLA4 gene were not associated with clinical and laboratorial features or presence of thyroid dysfunction, prior or induced by IFN
74

Thermal, hormonal and cardiovascular responses to single and repeated nonhypothermic cold exposures in man

Korhonen, I. (Ilkka) 18 November 2008 (has links)
Abstract The purpose of this study was to find out and compare the physiological effects of different types of non-hypothermic cold exposure tests in man. In whole-body cold exposures lightly clothed subjects were exposed to 10°C for 2 hours (single exposure), as well as repeatidly for 2 h and 1 h on ten successive days in separate studies. For local cold exposures, cold pressor tests (immersion into ice-cold water) of both hands and both feet were used. In whole-body cold exposures, several hormonal and metabolic parameters as well as cold sensations were measured. In local cold exposures the measured parameters were blood pressure, heart rate and skin temperatures. The single 2-h whole-body cold air exposure decreased rectal and skin temperatures and body heat content, but increased the metabolic rate. At the same time the serum noradrenaline concentration increased indicating a general activation of the sympathetic nervous system. Serum free fatty acid concentration increased whereas cortisol, GH and prolactin concentrations fell. No significant changes were found in serum concentrations of adrenalin, TSH, T3, T4, testosterone or LH. Serum total proteins were enhanced apparently due to cold-induced hemoconcentration. After repeating the 2-h whole-body cold exposure for five days the increase in serum noradrenaline level was markedly lower in the cold. At the same time hemoconcentration, judged from serum protein concentrations, was attenuated and the subjects became habituated to the cold sensations. However, the results showed that the repeated 1-h cold exposure in 10°C was not sufficiently intensive to reduce the noradrenaline response. Comparison of the hand and foot cold pressor tests to whole-body cold exposure tests showed that all tests caused significant increases in systolic and diastolic blood pressures, but that heart rate increased significantly only in the cold pressor test of feet. During the 2-h cold air exposure the heart rate fell. This caused a reduction in rate pressure product (RPP, the product of heart rate and systolic blood pressure). In both cold pressor tests the rate pressure product increased, indicating the enhancement of the O2-need in the heart muscle. The results showed no significant correlation in systolic or diastolic blood pressures between whole-body and local cooling of hands or feet. The lack of the association between local and whole-body cold exposure tests may be due to differences in severity and site of the tests: whole-body cold exposure tests cause general cold discomfort while cold pressor tests cause local cold pain. / Tiivistelmä Tämän tutkimuksen tarkoituksena oli selvittää ja verrata eri tyyppisten lievien kylmäaltistustestien fysiologisia vaikutuksia ihmiseen. Yksittäisessä koko kehon kylmäaltistuksessa koehenkilöt olivat kevyesti vaatetettuina kahden tunnin ajan 10°C:n lämpötilassa. Toistetussa koko kehon kylmäaltistuksessa koehenkilöt oleskelivat myös 10°C:n lämpötilassa kahden tai yhden tunnin ajan kymmenenä perättäisenä päivänä. Paikallisessa kylmäaltistuksessa käytettiin kylmävesitestiä (ns. cold pressor koe). Testi tehtiin sekä käsille että jaloille. Koko kehon kylmäaltistuksessa mitattiin useita hormonaalisia, aineenvaihdunnan ja lämpötasapainon vasteita, sekä verenpainetta ja sydämen syketiheyttä. Paikallisissa kylmäaltistuksissa mitattiin verenpainetta, sydämen syketiheyttä ja iholämpötiloja. Yksittäinen koko kehon kahden tunnin kylmäaltistus laski syvälämpötilaa, iholämpötiloja ja kehon lämpösisältöä. Samanaikaisesti kehon lämmöntuotanto kasvoi. Seerumin noradrenaliinipitoisuus lisääntyi ilmentäen sympaattisen hermoston tehostunutta aktivoitumista. Seerumin vapaiden rasvahappojen pitoisuus kasvoi, samoin kokonaisproteiinipitoisuus, mutta kasvuhormonin, kortisolin ja prolaktiinin osalta todettiin pitoisuuksien vähenemistä. Merkitseviä muutoksia ei tapahtunut seerumin adrenaliinissa, TSH:ssa, T3:ssa, T4:ssä, testosteronissa tai LH:ssa. Toistetussa kahden tunnin pituisessa kylmäaltistuksessa seerumin noradrenaliinipitoisuudessa tapahtunut kasvu oli merkitsevästi vähäisempää viiden päivän jälkeen. Samanaikaisesti seerumin proteiinipitoisuus kylmässä väheni ja kylmätuntemukset muuttuivat lievemmiksi. Sen sijaan yhden tunnin toistettu altistus 10°C:ssa ei ollut riittävän voimakas vähentämään kylmän aiheuttamaa veren noradrenaliinipitoisuuden kasvua. Verenpaineen ja sydämen syketiheyden reaktioita verrattiin samoilla koehenkilöillä yksittäisessä kahden tunnin koko kehon kylmäaltistuksessa ja kylmävesitesteissä. Kaikki nämä testit kohottivat merkitsevästi systolista ja diastolista verenpainetta. Sydämen syketiheys laski koko kehon kylmäaltistuksessa. Jalkojen kylmävesitestissä sydämen syketiheys nousi merkitsevästi, mutta käsien testissä tämä nousu ei ollut merkitsevä. Verenpaineen nousu koko kehon kylmäaltistuksessa ei korreloinut merkitsevästi paikallisissa kylmäaltistuksissa mitattuihin verenpaineen nousuihin. Selittävänä tekijänä tähän lienee näiden kylmäaltistusmuotojen erilaisuus. Lievä koko kehon kylmäaltistus aiheuttaa yleistä epämiellyttävyyttä, kun taas äkilliseen, nopean iholämpötilan laskun aiheuttamaan paikalliseen kylmäaltistukseen liittyy usein kiputuntemuksia.
75

The Effect of Substituents and Solvents on the Deiodination Reactions of Thyroid Hormones by Iodothyronine Deiodinase Mimics

Raja, K January 2016 (has links) (PDF)
Thyroid hormones (THs; T4 and T3), secreted from thyroid gland, play an important role in human growth and development. T3 (3,5,3′-triiodothyronine) is the active hormone and the conversion of T4 (3,3′,5,5′-tetraiodothyronine) to T3 in cells is mediated by iodothyronine deiodinases enzymes (DIOs). DIOs are selenocysteine containing enzymes and are classified into three types (DIO1, DIO2 and DIO3). DIO1 catalyzes the outer-ring deiodination (ORD; T3 formation) and inner-ring deiodination (IRD; rT3 formation) reactions, involving in the activation (T4 to T3 conversion) and inactivation (T4 to rT3 conversion), respectively. DIO2 and DIO3 catalyse the ORD and IRD reactions, respectively. This homeostasis is regulated tightly and any deviation would lead to diseases like hyperthyroidism or hypothyroidism. Recently it is of interest to many research groups to develop iodothyronine deiodinase mimics and we have developed naphthalene-based peri-substituted thioselenol pair at 1,8-positions (1.25), which remove iodine selectively from inner-ring of T4. When selenium atom is substituted in place of sulfur (selenol-selenol pair; 1.26), the deiodination activity was ca. 90 times faster than with 1.25. This thesis deals with various aspects of the effect of substituents on the naphthalene-1,8-diselenol and solvent effect on the thyroid hormone deiodination by naphthalene-based iodothyronine deiodinase mimics. Figure 1. (A) Deiodination reactions by DIOs. (B) Chemical structure of 1.25 and 1.26. The thesis consists of five chapters. The first chapter provides a general overview about sialoproteins, thyroid hormone biosynthesis, thyroid hormone metabolism, halogen bonding, iodothyronine deiodinase mimics and proposed mechanisms for the deidoination of thyroid hormones. This chapter also introduces peri-naphthalene-1,8-diselenol (1.26), which is the key compound in this thesis and discusses about proposed mechanism for the deiodination of thyroxine involving co-operative halogen bonding and chalcogen bonding mechanism. Figure 2. (A) TH action. (B) Proposed mechanism for the deiodination of T4 by 1.26 involving cooperative halogen bonding and chalcogen bonding. Chapter 2 discusses about the synthesis, characterization and deiodination activity of a series of naphthalene-based peri-substituted-1,8-diselenols (Figure 3). These diselenols regioselectivity remove iodine from inner ring of thyroxine and other thyroid hormones, (T3 and 3, 5-T2). Substitution with different groups on the naphthalene ring did not change the regioselectivity of deiodination, indicating that the deiodination activity does not depend on the nature of substituents. Secondary or tertiary amine side chain group attached at the 2nd position of the naphthalene ring showed better activity. It is due to the secondary interaction, which facilitates the iodine removal. It was further confirmed with the substitutions at the 4th position of the ring to discriminate the possibility of electronic effect. The higher deiodination rate owing to the t-butyl group at second position of the ring also suggests that the steric effect may also play a role in the deiodination reaction (Figure 4). It is proposed that peri substituted naphthalene-1,8-diselenols remove iodine from thyroid hormones through halogen bonding-chalcogen bonding mechanism (Figure 2). The investigation of Se···Se bond distance from the crystal structures and through DFT calculation and NMR experiment showed that the stronger chalcogen bond could be the reason for the increase in the reactivity observed with substituted peri-naphthalene-1,8-diselenols. Figure 3. peri-substituted naphthalene-1,8-diselenols used for the study. Figure 4. Relative deiodinase activity of substituted-peri-naphthalene-1,8-diselenols with T4. In Chapter 3, we have discussed about the effect of chalcogen atom substitution in a series of deiodinase mimics on the deiodination of thyroid hormones. Moving from thiol-selenol pair (1.25) to selenol-selenol pair (1.26) in naphthalene based peri-substituted mimics, an increase in the activity was observed. In this chapter, we have shown that substituting with tellurium, as tellurium-thiol pair (3.3) and ditellurol (3.4) increases the reactivity of deiodination to several times and also regioselectivity of deiodination is changed from IRD in the case of 1.26 to both IRD and ORD for 3.3 and 3.4. The presence of two tellurol moieties (3.4) or a thiol-tellurol pair (3.3) can mediate sequential deiodination of T4, to produce all the possible thyroid hormone derivatives under physiologically relevant conditions (Figure 5). This study provided the first experimental evidence that the regioselectivity of the thyroid hormone deiodination is controlled by the nucleophilicity and the strength of halogen bond between the iodine and chalcogen atoms. Figure 5. (A) HPLC chromatograms of deiodination reaction of T4 with 3.3 and 3.4. (B) Chemical structure of 3.3 and 3.4. (C) Sequential deiodination reaction of T4 by 3.3 and 3.4. Chapter 4 describes the effect of alkyl conjugation at 4′-OH position of THs on the deiodination by iodothyronine mimics. In addition to the deiodination, iodothyronines undergo conjugation with sulfate and glucuronic acid group at 4′-hydroxyl position. Conjugation alters the physico-chemical properties of iodothyronines. For example, it is known that sulfate conjugation increases the rate of deiodination to a large extend. We have conjugated alkyl group at 4′-hydroxyl position of iodothyronines and investigated the deiodination reactions with reported peri-substituted naphthalene-1,8-diselenols. We observed that similar to sulfated thyroid hormones O-methylthyroxine also undergoes both phenolic and tyrosyl ring deiodination reactions and overall the rate of deiodination is increased at least by 5 times as compared with T4 under identical conditions. The phenolic iodine removal is favored by conjugation as compared to the tyrosyl ring iodine, which is similar to the observation made for T4S. Interestingly, when the acetamide group is conjugated at 4′-OH position, the regioselectivity of deiodination is changed exclusively to 5′-iodine. DFT calculations show that the positive potential on the iodine increase upon conjugation, which leads to stronger halogen bonding interaction with selenol, might be the reason for the change in the regioselectivity of deiodination. Figure 6. (A) HPLC chromatogram of deiodination reaction of T4(Me) with 1.26. (B) Initial rate comparison of T4 and T4(Me).(C) HPLC chromatogram of deiodination reaction of T4(AA) with 1.26 showing the formation of T3(AA) (ORD product). (D) Electron potential map of T4, T4(Me) and T4(AA) showing the increase in electro positive potential on 5′-iodine upon conjugation. Chapter 5 deals with the solvent effect on the deiodination reactions of THs by iodothyronine deiodinase mimics. As discussed in the earlier chapters, the deiodination reaction of thyroxine by naphthalene based-1,8-diselenols under physiological conditions produce, rT3 (IRD) as the only observable products. Surprisingly, when the deiodination reaction was performed in DMF or DMSO in the presence of 1.26, the regioselectivity of reaction was changed and the formation of both T3 (ORD) and rT3 was observed. In DMF or in DMSO, the deiodination reactivity of 1.26 was found to be 1000 fold higher than the reaction performed in phosphate buffer at pH 7.4. Figure 7. (A) HPLC chromatogram for the deiodination reaction of T4 in DMF by 1.26 showing both IRD and ORD. (B) A comparison of initial rate for the deiodination reactions of T4, T3 and 3,5-T2 in DMF and in DMSO by 1.26. (C) HPLC chromatograms for the deiodination reaction of T4 in DMF by 1.26 in the presence of TEMPO, showing the inhibition of deiodination (i) 0 mM TEMPO (ii) 10 mM of TEMPO (iii) 30 mM TEMPO. (D) HPLC chromatograms for the deiodination reaction of T4 in DMSO by 1.26 in the presence of TEMPO showing the inhibition of deiodination (i) 0 mM TEMPO (ii) 10 mM of TEMPO (iii) 30 mM TEMPO. 3,5-DIT was not denominated under physiological conditions, however, in DMF and in DMSO, 3,5-DIT was deiodinated by 2.4 to produce 3-MIT. We also observed that the control reactions in DMF or DMSO also showed a little deiodination activity. The very high reactivity observed in the presence of DMF or DMSO implied that the mechanism of denomination in these solvents may be different. It has been reported that DMSO or DMF radicals can be formed with small amounts of a base. Reaction mixture consisting of NaBH4 (for generating selenol from diselenide) and NaOH (T4 solution) may facilitate the radical formation. We also performed the reaction in the presence of TEMPO (free radical scavenger) and observed the inhibition of deiodination reaction. However, it is not clear whether the radical pathway could be one of the possible mechanisms of deiodination in these solvents by compounds 1.26 and 2.4. Further studies are required to propose a radical mechanism in different solvents such as DMF and DMSO.
76

Post radiation therapy hypothyroidism in patients with head and neck cancer at Pietersburg Hospital, Limpopo Province, South Africa

Manavalan, Tijo Jospaul Davis January 2022 (has links)
Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2022 / Background Hypothyroidism in head and neck cancer patients after radiotherapy is known to occur, yet thyroid function tests are not routinely monitored in all patients post radiation therapy. Routine post radiation therapy thyroid function testing is currently not part of the follow-up protocol in these patients at Pietersburg Hospital. The aim of this study is to evaluate post radiation therapy hypothyroidism among head and neck cancer patients treated with radiotherapy at Pietersburg Hospital Methods A prospective (cohort) observational study was carried out among head and neck cancer patients receiving radiotherapy at the radiation oncology department in Pietersburg Hospital. Sample size of n=37 was calculated using Statistica V13.0. Thyroid function tests were performed at the start of radiation therapy and repeated on the first day of follow up, 6 weeks after completing radiation therapy. During follow up, participants were also interviewed for the presence of symptoms of hypothyroidism such as dry skin, dry hair, fatigue, cold intolerance, or weight gain. Data analysis was done with STATA version 16. Descriptive statistics were used to characterise variables, and summarised in tables, graphs and charts. Changes in thyroid function tests and other variables were analysed. A p-value of 0.05 was deemed statistically significant. Results Thirty-seven patients were enrolled in the study, 26 males and 11 females. The mean age of the patients was 53.1 ±12.3 standard deviation [SD]) with a range of 40.8 to 65.4 years. The most common diagnoses were cancer of the larynx and hypopharynx, forming 29.7% and oral cavity cancer, 29.7%. Only three patients (8%) had an early stage cancer (Stages 1 and 2), 11 patients (29.7%) moderately advanced cancer (Stage 3) while the majority (62%; n =23) had locally advanced cancer (Stage 4). Majority of the patients received 70Gy in 35 daily fractions, five fractions per week via 3-D conformal radiotherapy. Only 29 patients who had complete pre- and post radiotherapy thyroid function tests were included in the final analysis. Of these, none had clinical hypothyroidism at 3 months. Two patients (6.8%) had sub-clinical hypothyroidism, with post radiation therapy TSH values greater than 3.5mIU/ml. The mean post radiation therapy TSH values increased by 8.3% and the mean fT4 values decreased by 2.05% compared to the pre-radiation therapy values. Both changes were not statistically significant (p=0.99 and p=0.82 respectively). There was no statistically significant correlation between changes in TSH and fT4 versus age (p=0.88 and p=0.92 respectively), sex (p=0.55 and p=0.15 respectively), cancer stage (p=0.21 and p=0.78 respectively), and cancer site (p=0.17 and p=0.74 respectively). The most common post radiotherapy symptom was fatigue (62%) followed by cold intolerance (54%), weight gain (43%) and dry skin or dry hair (43% each). Conclusion The results of the study suggest that sub-clinical hypothyroidism is detectable early post radiation therapy presenting as clinical symptoms.
77

Interactions entre comportement et variations de la croissance des juvéniles de la sole (Solea solea) dans les nourriceries des pertuis Charentais.

Laffargue, Pascal 11 October 2004 (has links) (PDF)
L'objectif de cette thèse était d'identifier certains processus liés au fonctionnement des nourriceries de la<br />sole Solea solea (L.) dans les pertuis Charentais, bassin ostréicole de 1er rang européen et nourriceries majeures<br />pour la sole du golfe de Gascogne. Les juvéniles de la sole dépendent d'habitats côtiers et estuariens, ce qui<br />implique (i) une capacité d'adaptation à la variabilité environnementale de ces milieux et (ii), l'accès à l'intégralité<br />d'un habitat essentiel au cycle biologique de l'espèce. La nourricerie réalisée rend compte des ajustements que le<br />poisson doit opérer entre les contraintes liées à l'habitat et sa capacité à gérer ces contraintes, à travers la<br />sélection des aires de nourrissage, de repos et de refuge. Couplant travaux de terrains et expériences en<br />mésocosme, des méthodes basées sur des estimateurs intégratifs ont été retenues, taux de croissance, indice de<br />condition de Fulton et statut endocrine de ces poissons. Ces résultats ont été confrontés à une approche<br />comportementale visant à déterminer comment les soles utilisent l'espace (pistage par télémétrie acoustique) et<br />accèdent à la nourriture (régime alimentaire et estimation de la ration en équivalent carbone) dans un habitat sous<br />influence conchylicole.<br />La croissance des juvéniles du pertuis Breton, sub-maximale durant la période de croissance rapide, tend<br />vers un plateau autour de l'équinoxe d'automne. Une expérience en mésocosme confirme que la température in<br />situ ne peut entraîner ce ralentissement de la croissance. Or en même temps, ces juvéniles présentent une<br />condition médiocre, les niveaux d'hormones thyroïdiennes circulantes les plus faibles et l'activité alimentaire la plus<br />basse de l'année. Cet état suggère des contraintes propres à la mer des Pertuis, système de baies semi-fermées<br />sous influence modérée de panaches estuariens. Il semble qu'un environnement marin moins favorable en fin d'été<br />et/ou des effets en cascade sur le réseau trophique ne permettent pas à l'intégralité de la classe d'âge 0 d'y grandir<br />en fonction des potentialités de l'espèce. Dans le contexte climatique actuel néanmoins, une partie d'entre eux est<br />capable d'hiverner dans ces nourriceries où ils recouvrent des niveaux hormonaux élevés et restaurent leur activité<br />alimentaire. Les contraintes environnementales des pertuis Charentais, si elles sont d'ordre à moduler la<br />croissance des soles, ne semblent pas altérer leur comportement. Nous avons pu montrer par une expérience en<br />mésoscosme que ni l'effet des structures d'élevage, ni celui des modifications d'habitat liées à la biodéposition ne<br />restreignent l'accès aux zones placées sous emprises ostréicoles. Vérifier ces résultats en mer sera nécessaire<br />avant de conclure que les juvéniles accèdent à l'intégralité des nourriceries dans les pertuis Charentais. Toutefois,<br />deux cycles d'alimentation de 30 h dans le pertuis d'Antioche démontrent la capacité de très jeunes soles à ajuster<br />leurs rythmes d'activité et l'intensité de la prise alimentaire selon, vraisemblablement, le contexte hydrodynamique,<br />qu'il soit imposé par le cycle des marées de quinzaine ou par le vent. Cela a également permis une première<br />estimation de la ration journalière des jeunes soles en carbone organique, ce qui permettra de compléter les<br />modèles de réseau trophique actuellement développés. Enfin, l'infestation importante des soles des pertuis par les<br />métacercaires d'un Bucephalidae, enkystées dans différents organes sensibles, révèle des interactions biotiques<br />inattendues. Les cercaires de ce parasite étant propagées par les élevages de moules, cette parasitose donne un<br />nouvel éclairage aux interactions existant entre la fonction de nourricerie des habitats côtiers et la conchyliculture.
78

Deiodination of Thyroid Hormones by Iodothyronine Deiodinase Mimics

Manna, Debasish January 2013 (has links) (PDF)
Thyroxine is the main secretory hormone of thyroid gland and it is produced in thyroglobulin by thyroid peroxidase/hydrogen peroxide/iodide system. After biosynthesis and secretion of thyroxine, it undergoes multiple metabolic reactions. The most important metabolic pathway is the stepwise deiodination from the inner ring or outer ring. Removal of one of the outer ring or phenolic ring iodines of biologically less active T4, leads to the formation of 3,5,3'-triiodothyronine or T3, a compound which is biologically more active. On the other hand, removal of one of the inner ring or tyrosyl ring iodines gives 3,3',5'-triiodothyronine (3,3',5'-T3 or rT3) which is a biologically inactive thyroid hormone. Three enzymes involved in this activation and inactivation pathway of thyroid hormones are known as iodothyronine deiodinases (IDs), which are dimeric integral-membrane selenoproteins. Depending upon the sequence and substrate specificity, three iodothyronine deiodinase enzymes have been identified, iodothyronine deiodinase-1 (ID-1), iodothyronine deiodinase-2 (ID-2) and iodothyronine deiodinase-3 (ID-3). ID-1 can catalyze both inner ring and outer ring deiodination of thyroid hormones whereas, ID-2 is selective to the outer ring deiodination. The type-1 and -2 deiodinases (ID-1 and ID-2) produces the biologically active hormone 3,5,3′-triiodothyronine (T3). These two enzymes also convert 3,3′,5′-triiodothyronine (reverse T3 or rT3) to 3,3′-diiodothyronine (3,3′-T2) by outer-ring deiodination (Scheme 1). The type-3 deiodinase (ID-3) catalyzes the convertion of T4 to rT3 by an inner-ring deiodination pathway. Apart from deiodination, there are several alternate pathways of thyroid hormone metabolism, which include sulfate conjugation and glucoronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form thyroacetic acid and thyronamines, respectively. Glucoronidation and sulfate conjugation changes the physico-chemical properties of iodothyronines dramatically. This thesis consists of five chapters. The first chapter provides a general introduction of biosynthesis of thyroid hormones and followed by deiodination by three iodothyronine deiodinase enzyme. This chapter also provides an overview of thyroid hormone transport and different transport proteins and their mode of binding with thyroid hormones. Apart from this, this chapter also provides a brief overview on other thyroid hormone metabolites. In the second chapter of the thesis, initial attempts in the development of different iodothyronine deiodinase mimics have been discussed. Goto et al have shown that the sterically hindered selenol 1 converts the thyroxine derivative 3 (N¬butyrylthyroxine methyl ester) to the corresponding triiodo derivative 4 by an outer-ring deiodination (Scheme 2). Although the reaction was carried out in organic solvent and a relatively higher temperature (50 °C) and longer reaction time (7 days) were required for about 65% deiodination, this study also provides an experimental evidence for the formation of selenenyl iodide (2) in the deiodination of a thyroxine derivative by an organoselenol. However, only one iodine was removed from the outer ring of 3, no inner ring deiodination was detected (Scheme 2). Interestingly, when compound 5 was treated with selenol 1 under similar conditions, no deiodination was observed (Scheme 3). This leads to assumption that presence of free phenolic hydroxyl group is important for the deiodinase activity. Based on this experimental observation, they proposed a mechanism which involves an enol¬keto tautomerism of the phenolic hydroxyl group. In the case of thyroxine, the outer-ring can undergo enol-keto tautomerism, whereas due to lack of free hydroxyl group, the inner ring cannot undergo similar kind of tautomerism. The enol-keto tautomerism probably makes the outer ring iodines more reactive than the inner ring iodines of thyroxine. We have developed tthe first chemmical modell for the inneer ring deioddination of TT4 and T3 by type 33 deiodinase . We have shown that naphthyl-baseed selenol 6 bearing a thhiol group in the cloose proximitty to the sellenium act aas an excelleent model foor ID-3 by selectively deiodinatting T4 andd T3 to prodduce rT3 annd 3,3'-T2, rrespectively,, under physiological relevant conditions. When 2 equuivalent of ccompound 66 was emplooyed in the assay, an almost quuantitative cconversion oof T4 to rT3 was observeed within 300 hours and there was no indicaation of the fformation off T3 or 3,3'-TT2. When the selenol group was repplaced with a thiol group in compouund 7, the ddeiodinase activity wwas decreassed. On thee other handd, when thee thiol groupp was replaaced with selenol mmoiety in commpound 8, thhe deiodinasse activity drramatically iincreased wiithout any change iin the selecttivity. Comppounds 10 and 11 havving N-methhylamino grooup were found too be more aactive than the correspponding unssubstituted ccompounds 7 and 8, respectively. However, introduction of a secondary amine adjacent to the selenol moiety into the compound 9 significantly reduces the deiodinase activity. In the third chapter synthesis, deiodinase activity and mechanism of deiodination of a series of peri-substituted naphthalene derivatives is discussed. Iodobenzene was used as halogen bond donor for the DFT calculations. From the orbital analysis it is observed that there is perfect orbital symmetry match between the HOMO of compound 8 (selenolate form) and LUMO of iodobenzene. When the selenolate form of 1-selenonaphthol interacts with iodobenzene, a halogen bonded adduct is formed. The negative charge on the selenium center decreases as it donates electron pair to the σ* orbital of C–I bond in iodobenzene and as a consequence the positive charge on the iodine center decreases (Figure 1). Addition of iodobenzene to 1-selenonaphthol led to a significant downfield shift in 77Se NMR spectrum of 1-selenonaphthol and with an increase in the concentration of iodobenzene, more downfield shift in the signal was observed. Figure 1. The charges obtained from Natural Bond Orbital (NBO) analysis for the selenolate form of (a) 1-selenonaphthol (b) iodobenzene, (c) halogen-bonded adduct On the basis of experimental end theoretical data, a mechanism for the deiodination of T4 by compound 8 is proposed. According to the mechanism, the initial interaction of one of the selenol moieties with an iodine leads to the formation of halogen bond. The transfer of electron density from selenium to the σ* orbital of the C−I bond generates a σ-hole or partial positive charge on the selenium atom, which facilitates an interaction between the halogen bonded selenium atom and the free selenol (selenolate) moiety (intermediate 12). The selenium−selenium interaction (chalcogen bond) strengthens the halogen bond, leading to a heterolytic cleavage of the C−I bond. The protonation of the resulting carbanion leads to the formation of rT3. On the other hand, the formation of an Se−Se bond produces the diselenide 13 with elimination of iodide as HI. The reductive cleavage of the Se−Se bond in compound 13 regenerates the diselenol 8 (Figure 2). In the fourth chapter deiodination of sulfated thyroid hormones is discussed. Sulfate conjugation is an important step in in the irreversible inactivation of thyroid hormones. Sulfate conjugation of the phenolic hydroxyl group stimulates the inner ring deiodination of T4 and T3 but it blocks the outer ring deiodination of T4 by ID-1. The thyroxine sulfate (T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4. Only ID-1 catalyzes the deiodination of sulfated thyroid hormones. In contrast, ID-2 and ID-3 do not accept T4S and/or T3S as substrate. We have shown that iodothyronine sulfates can be readily deiodinated by synthetic deiodinase model compound 8 and its derivatives. In contrast to the inner ring-selective deiodination of T4, the synthetic compounds loses the selectivity and mediate both inner and outer-ring deiodination of T4S and outer ring deiodination of rT3S. From this study, we have also proposed that the enol-keto tautomerism is probably not required for the outer ring deiodination and the strength of halogen bonding controls the regioselective deiodination by model compounds. In the fifth chapter, the mechanism of inhibition of iodothyronine deiodinases by PTU and IAA is discussed with the help of model compounds. In the model study, it has been observed that compound 8 does not form a stable Se-I intermediate (14), which is essential for the formation of Se-S covalent bond with PTU. As a consequence, the deiodination of T4 by compound 8 is not inhibited by PTU. This study supports the proposal that ID-3 does not follow a ping-pong bi-substrate pathway for deiodination and may not form a stable E-Se-I intermediate, which is responsible for the insensitivity of ID-3 towards PTU. The biphenyl based diselenol 15 reacts with IAA and iodoacetamide to form the corresponding carboxymethylated product 17. On the other hand, compound 8 does not undergo the expected carboxymethylation by IAA and iodoacetamide, but they readily deiodinate both IAA and iodoacetamide. Based on this model study, a possible model is proposed for the insensitivity of ID-3 towards IAA. Iopanoic acid (18) is a well known radiocontrast agent and is used as adjunctive therapy with PTU and CBZ for the treatment of thyrotoxicosis.[9] We show in this chapter that iopanoic acid undergoes monodeiodination by compound 8 under physiological relevant conditions. The deiodinated products (19 and 20) from iopanoic acid are characterized by NMR spectroscopy and single crystal X-ray crystallography. It is observed that after monodeiodination, the strength of halogen bonding decreases and therefore, the monodeiodinated products do not undergo further deiodination.
79

[pt] NANOPARTÍCULAS SEMICONDUTORES FOTOLUMINESCENTES COMO SONDAS ÓPTICAS PARA DETERMINAÇÃO DE CAPTOPRIL, HISTAMINA, AMINOGLICOSÍDEOS E TIROXINA / [en] PHOTOLUMINESCENT SEMICONDUCTORS NANOPARTICLES AS OPTICAL PROBES FOR THE DETERMINATION OF CAPTOPRIL, HISTAMINE, AMINOGLYCOSIDES AND THYROXINE

20 December 2021 (has links)
[pt] Recentemente, os nanocristais semicondutores, também conhecidos como pontos quânticos, tornaram-se muito atrativos em abordagens de detecção por fotoluminescência devido as suas propriedades ópticas peculiares, tais como fluorescência intensa e com perfil estreito, comprimento de onda máximo ajustável através do controle do tamanho das partículas e maior fotoestabilidade em comparação com os corantes orgânicos convencionais. As nanopartículas sintetizadas foram avaliadas como sondas fotoluminescentes (na forma de dispersão aquosa) para a determinação de captopril, histamina, canamicina e tiroxina (analitos não fotoluminescentes na temperatura ambiente) evitando o uso de procedimentos complexos de derivatização química e permitindo quantificações de forma simples e com sensibilidade. Nanopartículas de CdTe modificadas com o ácido tioglicólico (TGA) e com o ácido 2-mercaptopropiônico (2MPA) e também nanopartículas de ZnS modificadas com L-cisteína foram sintetizadas pela abordagem em fase aquosa coloidal. Estas foram caracterizadas usando métodos microscópicos e espectroscópicos adequados. A fotoluminescência da nanopartícula 2MPA-CdTe foi consideravelmente mais intensa quando na presença de captropil. Sob condições ótimas, o modelo de calibração (isoterma de ligação de Langmuir) foi linear até 4,8 x 10-4 mol L-1 com constante de equilíbrio de ligação de 3,2 x 104 L mol-1 e limite de detecção (LOD) de 6,2 x 10-6 mol L-1 (1,3 (micro)g mL-1). Aplicações em soro sanguíneo humano fortificado com captropil e em formulações farmacêuticas foram demonstradas. A fotoluminescência das nanopartículas de TGA-CdTe foi reduzida (supressão) após adição de diferentes concentrações de histamina seguindo o modelo de Stern- Volmer. A resposta linear cobriu uma faixa de concentração até 5,7 x 10-4 mol L-1, com LOD de 9,6 x 10-6 mol L-1 (1,1 (micro)g mL-1). A abordagem proposta foi utilizada para determinação de histamina em carne de atum. Já a presença de aminoglicosídeos aumentou a fluorescência das nanopartículas de TGA-CdTe (seguindo o modelo da isoterma da adsorção de Langmuir). A kanamicina foi o aminoglicosídeo escolhido para estudar o efeito do aumento da intensidade da fotoluminescência das nanopartículas de TGA-CdTe disperso em solução aquosa. A faixa linear estendeu-se até 8,2 x 10-7 mol L-1 com LOD de 2,5 x 10-8 mol L-1 (14,2 ng mL-1). As constantes de ligação entre diversos aminoglicosídeos e TGACdTe foram calculadas e indicou que existe uma relação entre o número de grupos amino primários disponíveis e o aumento da luminescência. Essa abordagem foi aplicada com sucesso para a análise de amostras de leite e água de riacho, ambos fortificados com kanamicina, usando procedimento de extração em fase sólida com um polímero impresso molecularmente (MIP). A intensidade da fotoluminescência da nanopartícula cisteína-ZnS em solução contendo brometo de cetiltrimetilamônio (CTAB) foi reduzida (quenched) após adição de tiroxina. A redução total do sinal (quenching) seguiu o modelo de Stern-Volmer com resposta linear até 4,0 x 10-6 mol L-1 de concentração do analito, o LOD foi 6,2 x 10-8 mol L-1 (48,3 ng mL-1). A dispersão aquosa da cisteína-ZnS foi usada como sonda óptica para a determinação de tiroxina em formulações farmacêuticas e em saliva humana fortificada com analito. / [en] Recently, semiconductor nanocrystals, also known as quantum dots, have become very attractive for photoluminescence based sensing approaches due to their unique optical properties like intense photoluminescence with narrow profile, maximum wavelength adjustable by the control of particle size and higher photostability in comparison of conventional organic dyes. Different synthesized nanoparticles were evaluated as photoluminescent probes (as aqueous dispersions) for the determination of captopril, histamine, kanamycin and thyroxine (nonphotoluminescent analytes at room-temperature) avoiding the use of complex chemical derivatization procedures and enabling simple and sensitive quantifications. Thioglycolic acid (TGA) and 2-mercapoprionic acid (2MPA) modified CdTe nanoparticles and L-cysteine modified ZnS nanoparticles were synthesized via the colloid aqueous phase route. Their characterization was made using proper microscopic and spectroscopic methods. The emission intensity of 2MPA-Cdte is greatly enhanced in the presence of captopril. Under optimum conditions, the calibration model (Langmuir binding isotherm) was linear up to 4.8 x 10-4 mol L-1 with equilibrium binding constant of 3.2 x 104 L mol-1 and limit of detection (LOD) of 6.2 x 10-6 mol L-1 (1.3 (micro)g mL-1). Applications in captopril fortified human serum and in pharmaceutical formulations were demonstrated. The photoluminescence of TGA-CdTe nanoparticles was quenched by histamine in a concentration dependent manner (Stern-Volmer model). The linear response covered the concentration range up to 5.7 x 10-4 mol L-1 with LOD of 9.6 x 10-6 mol L-1 (1.1 (micro)g mL-1). The proposed method was used for the analysis of tuna fish. The presence of aminoglycosides enhanced the photoluminescence of the TGA-CdTe nanoparticles (following a Langmuir binding isotherm model). Kanamycin was used as a model aminoglycoside in order to study its effect on the photoluminescence enhancement of TGA-CdTe quantum dots dispersed in aqueous solution. The linear range extended up to 8.2 x 10-7 mol L-1 with LOD of 2.5 x 10-8 mol L-1 (14.2 ng mL-1). Binding constants were calculated for several aminoglycosides indicating that there is a relationship between the number of available primary amino groups and the increasing in photoluminescence. This approach was successfully applied for determination of kanamycin fortified milk and in stream water samples after solid phase extraction using a molecular imprinted polymer produced using a kanamycin template. The photoluminescence intensity of cysteine-ZnS in solution containing cetyltrimethyl ammonium bromide (CTAB) was quenched by thyroxine. The overall quenching followed a Stern-Volmer model with linear response coveing an analyte concentration range up to 4.0 x 10-6 mol L-1. LOD was 6.2 x 10-8 mol L-1 (48.3 ng mL-1). The aqueous dispersion of cysteine-ZnS was used as optical probe for the determination of thyroxine in pharmaceutical formulations and in analyte fortified human saliva.
80

Associations between pituitary-thyroid hormones and depressive symptoms in individuals with anorexia nervosa before and after weight-recovery

Wronski, Marie-Louis, Tam, Friederike I., Seidel, Maria, Mirtschink, Peter, Poitz, David M., Bahnsen, Klaas, Steinhäuser, Jonas L., Bauer, Michael, Roessner, Veit, Ehrlich, Stefan 13 April 2023 (has links)
Background: There is sound evidence that the hypothalamic-pituitary-thyroid axis plays a role in mood regulation. Alterations in this axis, particularly low triiodothyronine syndrome, are a common neuroendocrine adaptation to semi-starvation in patients with anorexia nervosa (AN), who also frequently suffer from co-existing depressive symptoms. We therefore aimed to investigate the associations between pituitary-thyroid function and psychopathology, in particular depressive symptoms, at different stages of AN using a combined cross-sectional and longitudinal study design. Methods: Pituitary-thyroid status (FT3, free triiodothyronine; FT4, free thyroxine; conversion ratio FT3/FT4; TSH, thyroid-stimulating hormone) was assessed in 77 young acutely underweight females with AN (acAN) and in 55 long-term weight-recovered individuals with former AN (recAN) in a cross-sectional comparison to 122 healthy controls (HC). Further, pituitary-thyroid status of 48 acAN was reassessed after short-term weight-restoration. We performed correlation analyses of pituitary-thyroid parameters with self-reported measures of psychopathology. Results: AcAN showed significantly lower FT3, FT4, FT3/FT4 ratio, and TSH levels compared to HC. Pituitary-thyroid alterations were partly reversed after short-term weight-restoration. RecAN still had lower FT3 concentrations than HC. Lower FT3 concentrations and FT3/FT4 ratios were associated with more severe depressive symptoms in acAN, occurring prominently in cases of manifest low triiodothyronine syndrome. Longitudinally increasing FT3/FT4 ratios (change scores) were inversely correlated with depressive and general psychiatric symptoms after short-term weight-restoration. Conclusions: Our results suggest a potential modulation of the severity of depressive symptoms by temporarily decreased FT3 concentrations and inhibited thyroid hormone conversion (FT3/FT4 ratios) in acutely underweight AN. Associations between conversion ratios FT3/FT4 and psychopathology seem to persist across short-term weight-restoration. The findings of our study might have relevant clinical implications, ranging from thyroid monitoring to experimental low-dose thyroid hormone supplementation in certain patients with AN showing severe psychiatric impairment and overt thyroid hormone alterations.

Page generated in 0.1012 seconds