P16 Noninvasive positive pressure ventilation in patients with blunt chest trauma and acute respi... more P16 Noninvasive positive pressure ventilation in patients with blunt chest trauma and acute respiratory failure S Milanov, M Milanov P17 Helium-oxygen (He-O 2 ) enhances oxygenation and increases carbon dioxide clearance in mechanically ventilated patients JAS Ball, R Cusack, A Rhodes, RM Grounds P18 Optimal method of flow and volume monitoring in patients mechanically ventilated with helium-oxygen (He-O 2 ) mixtures JAS Ball, A Rhodes, RM Grounds
Intensive care unit treatment in patients >65 yrs with a first-day sequential organ failure asses... more Intensive care unit treatment in patients >65 yrs with a first-day sequential organ failure assessment score >15 is not futile To the Editor: With great interest, we read the study by Kaarlola and colleagues (1), concerning long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients. In their study, outcome and quality aspects were investigated in 882 patients older than 65 yrs. We were intrigued by their sentence under the Discussion that all patients in their study with a day-1 Sequential Organ Failure Assessment (SOFA) score Ͼ15 died in the intensive care unit (ICU). This seemed to differ from our experience. After a explorative database analysis of prospectively collected data, we found that in 13,989 consecutive patients admitted to our ICU, 7,984 patients were Ͼ65 yrs of age. Of these elderly patients, 131 had a day-1 SOFA score Ͼ15. The hospital mortality of these patients was 65 of 131. A hospital survival rate of 50% in those Ͼ65 yrs with a day-1 SOFA of Ͼ15 contrasts with the 100% mortality reported by Kaarlola et al. Under the Discussion, it is stated that a systematic bias toward overestimated quality-adjusted life years may exist if intensive care is withheld from elderly patients or selection in admission occurs and not all elderly patients are included in the analysis. It is possible, therefore, that the reported 100% mortality rate with day-1 SOFA score in patients Ͼ65 yrs could have been perceived as futile therapy, resulting in overestimated quality-adjusted life years. We agree with the authors that older age alone is not a valid reason to withhold intensive care; we disagree with their implicit statement that ICU treatment in patients Ͼ65 yrs with a first-day SOFA score Ͼ15 is futile. The authors have not disclosed any potential conflicts of interest.
Journal of Trace Elements in Medicine and Biology, Apr 1, 2009
In critical ill states the plasma selenium levels are low and inversely correlated with the sever... more In critical ill states the plasma selenium levels are low and inversely correlated with the severity and outcome of the disease. The plasma selenium levels indicate the amount of circulating selenoproteins and selenoenzymes. These are important for the maintenance of the redox system, modulating the immune system and also for thyroid hormone metabolism. Not only all three deiodinases (D1-3) are selenoenzymes, but within the thyroid gland there are several other selenoenzymes, which are important for the maintenance of normal thyroid function. In critical ill states also triodothyronine (T3) is low and reverse T3 elevated, and also TSH and thyroxin (T4) are low, correlating like low plasma selenium with the severity of the disease. Subsequently, several intervention trials had been performed to evaluate whether an adjuvant selenium supplementation might attenuate the course of the disease and improve outcome. The selenium supplementation improved outcome and even reduced mortality in some but not all prospective randomized trials. A few prospective randomized intervention trials with selenium supplementation had also been performed to evaluate the hypothesis, whether low selenium is the cause of low-T3-syndrome, however, with conflicting results and no clear evidence that low D1 activity is due to the selenium deficiency in critical illness. Because D1 catalyses the conversion of T4 to T3 and also the clearance of reverse T3, low D1 activity would sufficiently explain low plasma T3 and elevated reverse T3. It had been, however, clearly shown that cytokines are responsible for the inhibition of D1 activity, but D2 and D3 are even higher during acute inflammation in critically ill patients. One of the most important effects of selenium on the immune system seems to be the reduction of cytokine release and therefore an indirect connection between low selenium and low D1 activity has to be postulated and not a lower D1 activity due to lower availability of selenium for the D1 expression.
In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations... more In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n = 18), levothyroxine plus 100 µg sodium-selenite (group B, n = 13), or levothyroxine plus 200 µg sodium-selenite (group C, n = 18). Mean age at diagnosis was 12.2 ± 2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6 ± 0.5 µg/kg body weight to lower TSH to the treatment goal of 1-2 µU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p = 0.03 and p = 0.01), but not in group B (p = 0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 µg daily nor given in the "adult" supplementation dose of 200 µg daily.
We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrat... more We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 µg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 µg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) (n = 9), another group which received placebo started to take 200 µg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly (p = 0.004) decreased from 625 ± 470 U/ml to 354 ± 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly (p = 0.017) from 450 ± 335 to 708 ± 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 ± 940 vs. 1724 ± 1112 U/ml, p = 0.555). In contrast, the patients who received 200µg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 ± 723 to 643 ± 477 U/ml.
basal und nach Stimulation mit GnRH normal (2,4 bzw. 43,1 mE/ml). Humanes-Chorion-Gonadotropin ni... more basal und nach Stimulation mit GnRH normal (2,4 bzw. 43,1 mE/ml). Humanes-Chorion-Gonadotropin nicht nachweisbar. TSH (basal und nach Stimulation mit TRH), fTt3, fT4, Prolaktin (Blutabnahme vor körperlicher Untersuchung!), Dehydroepiandrosteron-Sulfat (DHEAS), 17-OH-Progesteron (17-OHP), Cortisol (vor und nach ACTH-Gabe), hGH und IGF-I im Normalbereich. Ebenso rotes und weißes Blutbild, Nierenretentionsparameter, Leberenzyme und Bilirubin, Elektrolyte, Eiweiß und Nüchternblutzucker im Bereich der Norm.
Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor... more Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as well as H2O2 and might be attenuated by antioxidants. Therefore, we examined the apoptotic index induced by these substances in selenium-treated vs untreated human thyroid follicular cells. Reconstituted human thyroid follicles were incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none. The follicles were then distributed to 24-well plates and incubated with potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-beta (5 ng/mL), or H2O2 (100 muM). Apoptosis was determined by a mitochondrial potential assay and the number of apoptotic cells counted by two independent, experienced technicians and the glutathione peroxidase (GPx) activity was determined. Asignificant increase of apoptic cells was obtained in control thyroid follicles treated with iodine (5, 10, or 20 microM), thyroidstimulating hormone (TSH) 1, or 10 mU/mL in combination with 5 and 10 microM iodine, EGF (5 ng/mL) and TGF-beta (5 ng/mL), or H2O2 (100 microM) (p < 0.001). In contrast, in thyroid follicles preincubated with 10 or 100 nM sodium selenite, the apoptototic index was identical to the basal rate. In H2O2-treated follicles, the apoptotic index was still significantly elevated but 50% lower compared to control cells. The GPx activity increased from 1.4 +/- 0.2 to 2.25 +/- 0.4 mU/microg DNA with 10 nMselenite and 2.6 + 0.4 mU/microg DNA with 100 nM selenite. Sodium selenite might increase the antioxidative potential in human thyroid follicles in vitro and therefore diminish the apoptosis induced by TGF-beta, EGF, iodide, and even H2O2.
Aspergillus fumigatus is increasingly recognized as an important nosocomial pathogen in severely ... more Aspergillus fumigatus is increasingly recognized as an important nosocomial pathogen in severely immunocompromised patients. Infection is difficult to diagnose antemortem and typically has a fatal outcome. Here we report the case of a cardiac transplant recipient with disseminated A. fumigatus infection which clinically presented as thyrotoxicosis due to massive involvement of the thyroid gland.
For further investigating the mechanism of the known autoregulation of thyroid follicle growth an... more For further investigating the mechanism of the known autoregulation of thyroid follicle growth and function by iodine, we tried to detect iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone) in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on EGF induced thyroid cell proliferation as well as on TSH induced cycli AMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase catalyzed iodination of arachidonic acid. With gas chromatography-mass spectrometry a molecular mass of 391 m/z corresponding to the derivatization product of iodolactone was found. An ethanol/chloroform extract of isolated thyroid follicles preincubated with KI (10uM) and arachidonic acid (1uM) revealed an identical substrate. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 uM) dose-dependently inhibited EGF induced thyroid cell growth. This growth inhibiting effect of iodolactone was found t...
It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement ma... more It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement may be due to paracrine mitogenic factors released by epithelial thyroid cells. To study this paracrine growth regulating communication between thyroid cells and endothelial cells in vitro, culture medium from isolated porcine thyroid follicles was investigated for a growth promoting effect on porcine aortal endothelial cells. Serum-free conditioned medium (CM) from thyroid follicles in suspension culture contains a dose-related mitogenic activity which stimulates endothelial cell growth up to 197%. Stimulation of the thyroid follicles with TSH (1 mil/ml) significantly reduced the mitogenic activity for endothelial cells in CM to 131%. Thyroid hormones had no influence on mitogenic activity in CM. When follicles were treated with iodide (20 HM) during CM production, no proliferation of endothelial cells was observed by this CM. In contrast, CM from epidermal growth factor-treated thyroid follicles significantly enhanced the mitogenic activity for endothelial cells up to 235%. The mitogenic activity was precipitable by saturated ammonium sulfate, showed high affinity to heparin by chromatography on heparin-sepharose, and was abolished after treatment of CM with trypsin. On gel electrophoresis the heparin-binding fraction showed a double band with a mol wt of 15 and 15.5 k. These data show a paracrine mitogenic activity on endothelial cells released by thyroid follicles which is regulated by TSH, epidermal growth factor, and iodide in parallel with the direct effect of these substances on thyroid cell growth. The data suggest that the mitogenic factor is a polypeptide, which belongs to the heparin-binding growth factors.
Experimental and Clinical Endocrinology & Diabetes, 2009
Twelve human cancer cell lines and one nonmalignant cell line were investigated with respect to a... more Twelve human cancer cell lines and one nonmalignant cell line were investigated with respect to a potential antiproliferative/cytotoxic activity of molecular iodine and iodolactones. Except CCL221 colon carcinoma cells, the growth of ali cancer celllines decreased if the cells were cultured in the presence of 10 11M molecular iodine (12) for at least two days. ô-iodolactone (Il, 511M) was found to have a similar effect. SH-SY5Y neuroblastoma cells turned out to be most susceptible to both iodine compounds (total inhibition), followed by MCF-7 mammary carcinoma cells (60% and 77.7 %inhibition in the presence of 1 2 respect. lL) and HS24 lung carcinoma cells (36.3 % respect. 40.3 % inhibition). In contrast, MCF-lO normal mammary epithelial cells were much less affected by the iodine treatment. ln both, SH-SY5Y and MCF-7 cells, 12 and IL also abolished EGF-induced promotion of cell growth completely. This effect was, however, not due to an interfering with EGF-signaling, because 12 and IL did not affect the phosphorylation of EGFreceptors, EGF-induced activation of MAP-kinase (Erk1/2), ar EGF-induced lamellar actin protrusion. A disruption by molecular iodine of mitochondrial transmembrane electrical potential, which was prevented by a pre-treatment of the cells with N-acetyl-cysteine, supports a mitochondria-mediated apoptotic mechanism.
Iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone), an iodinated derivative of arachidonic... more Iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone), an iodinated derivative of arachidonic acid, was found to be synthesized in rat thyroid slices; however, the physiological role of this compound is still unknown. We tried to detect iodolactone in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on epidermal growth factor-induced thyroid cell proliferation and TSH-induced cAMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase-catalyzed iodination of arachidonic acid in the presence of trace amounts of [125I]- and [3H]arachidonic acid. After purification by silica gel chromatography, HPLC of the reaction products revealed one main peak containing trace amounts of both [125I]- and [3H]arachidonic acid. With gas chromatography-mass spectrometry (GC-MS) a molecular mass of 391 m/z, corresponding to the derivatization product of iodolactone, was found. An ethanol-chloroform extract of isolated thyroid follicles preincubated with KI (10 microM) and arachidonic acid (1 microM) revealed peaks in HPLC and GC comparable with those of in vitro synthesized iodolactone. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 microM) dose-dependently inhibited epidermal growth factor-induced thyroid cell growth. This growth-inhibiting effect of iodolactone was 50-fold more pronounced than the inhibitory effect of KI (4 X 10(-5) microM) on thyroid cell proliferation. In contrast to the effect of iodide, the inhibitory effect of iodolactone on thyroid cell growth could not be abolished by methimazole (1 mM). Basal as well as TSH (0.5 U/liter)-induced cAMP formation were not changed by iodolactone. These experiments suggest a physiological role of iodolactone as a mediator of the known inhibitory effect of iodide on thyroid growth.
Thyroxine (T 4) or triiodothyronine (T 3) was covalently linked to bovine thyroglobulin (bTg) in ... more Thyroxine (T 4) or triiodothyronine (T 3) was covalently linked to bovine thyroglobulin (bTg) in a molar ratio of 25: l (T 4 :bTg) or 30:1 (T 3 :bTg) using a water-soluble carbodiimide. The conjugates of T 4-bTg and T 3-bTg were used for immunisation of rabbits. After 6 booster-injections all rabbits immunized with T 4-bTg had antibody titers from 1:4000 or 1:8000, whereas the rabbits vaccinated with T 3-bTg had titers from 1:10000 to 1:40000. Two of the T 4-antisera revealed maximal T 4-binding between pH 3.8 and 4.2 with affinity constants of 7.8 X 10 9 1/mol and 6.0 X 10 9 1/mol. With these two antisera a simple, rapid, protein-independent T 4 radioimmunoassay at pH 4.0 in unextracted serum was established without using thyroxine binding globulin blocking agents. Precision of the T 4 radioimmunoassay is documented by an interassay coefficient of variation (CV) calculated from 10 different assays of 5.7% at a mean T 4 concentration of 43 Mg/1 T 4 ,3.5% at 76 jug/1 T 4 and 6.4% at 165 jug/1 T 4. The intra-assay CV was calculated to be 3.7%, 2.8% and 4.7% at these concentrations. Accuracy of the T 4-RIA is documented by identical standard curves when T 4 standards were diluted in 1 g/1 human serum albumin in phosphate buffer, in 40 g/1 human serum albumin in phosphate buffer, or in T 4-free serum, and by recovery studies and dilution curves of hyperthyroid patients. G rtner, Kewenig, Horn and Scriba: T 4 and T 3 radioimmunoassay in unextracted serum at extreme pH ranges Wir erhielten drei T 3-Antiseren.mit einem Bindungsoptimum bei pH 4,0 und drei T 3-Antiseren mit einem Bindungsoptimum im Bereich von pH 8,5 bis pH 10,0. Wir konnten einen T 3-RIA im unextrahierten Serum nach vorheriger Denaturierung von Thyroxin bindendem Globulin mit 0,1 mol/1 NaOH und anschlie ender Inkubation bei pH 9,2 aufbauen. Die Pr zision des T 3-RIA konnte mit einem Interassay-Variationskoeffizienten (n = 20) von 8,6% bei einer T 3-Konzentration von 0,91 Mg/1 T 3 ,8,5% bei einer T 3-Konzentration von 1,72 μg/l T 3 und 5,8% bei 4,15 μg/l T 3 gezeigt werden. Der Intraassay-Variationskoeffizient, berechnet aus Zehnfach-Bestimm ngen, betrug 5,8%, 3.1% und 3.4% bei den obengenannten T 3-Konzentrationen. Die Richtigkeit des T 3 4UA wurde mit Wiederfindekurven, Serumverd nnungskurven und identischen T 3-Standardkurven, wobei T 3-Stand rds entweder in 40 g/l Humanserumalbumin in Phosphatpuffer oder T 3-freiem Serum gel st waren, bewiesen.
P16 Noninvasive positive pressure ventilation in patients with blunt chest trauma and acute respi... more P16 Noninvasive positive pressure ventilation in patients with blunt chest trauma and acute respiratory failure S Milanov, M Milanov P17 Helium-oxygen (He-O 2 ) enhances oxygenation and increases carbon dioxide clearance in mechanically ventilated patients JAS Ball, R Cusack, A Rhodes, RM Grounds P18 Optimal method of flow and volume monitoring in patients mechanically ventilated with helium-oxygen (He-O 2 ) mixtures JAS Ball, A Rhodes, RM Grounds
Intensive care unit treatment in patients >65 yrs with a first-day sequential organ failure asses... more Intensive care unit treatment in patients >65 yrs with a first-day sequential organ failure assessment score >15 is not futile To the Editor: With great interest, we read the study by Kaarlola and colleagues (1), concerning long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients. In their study, outcome and quality aspects were investigated in 882 patients older than 65 yrs. We were intrigued by their sentence under the Discussion that all patients in their study with a day-1 Sequential Organ Failure Assessment (SOFA) score Ͼ15 died in the intensive care unit (ICU). This seemed to differ from our experience. After a explorative database analysis of prospectively collected data, we found that in 13,989 consecutive patients admitted to our ICU, 7,984 patients were Ͼ65 yrs of age. Of these elderly patients, 131 had a day-1 SOFA score Ͼ15. The hospital mortality of these patients was 65 of 131. A hospital survival rate of 50% in those Ͼ65 yrs with a day-1 SOFA of Ͼ15 contrasts with the 100% mortality reported by Kaarlola et al. Under the Discussion, it is stated that a systematic bias toward overestimated quality-adjusted life years may exist if intensive care is withheld from elderly patients or selection in admission occurs and not all elderly patients are included in the analysis. It is possible, therefore, that the reported 100% mortality rate with day-1 SOFA score in patients Ͼ65 yrs could have been perceived as futile therapy, resulting in overestimated quality-adjusted life years. We agree with the authors that older age alone is not a valid reason to withhold intensive care; we disagree with their implicit statement that ICU treatment in patients Ͼ65 yrs with a first-day SOFA score Ͼ15 is futile. The authors have not disclosed any potential conflicts of interest.
Journal of Trace Elements in Medicine and Biology, Apr 1, 2009
In critical ill states the plasma selenium levels are low and inversely correlated with the sever... more In critical ill states the plasma selenium levels are low and inversely correlated with the severity and outcome of the disease. The plasma selenium levels indicate the amount of circulating selenoproteins and selenoenzymes. These are important for the maintenance of the redox system, modulating the immune system and also for thyroid hormone metabolism. Not only all three deiodinases (D1-3) are selenoenzymes, but within the thyroid gland there are several other selenoenzymes, which are important for the maintenance of normal thyroid function. In critical ill states also triodothyronine (T3) is low and reverse T3 elevated, and also TSH and thyroxin (T4) are low, correlating like low plasma selenium with the severity of the disease. Subsequently, several intervention trials had been performed to evaluate whether an adjuvant selenium supplementation might attenuate the course of the disease and improve outcome. The selenium supplementation improved outcome and even reduced mortality in some but not all prospective randomized trials. A few prospective randomized intervention trials with selenium supplementation had also been performed to evaluate the hypothesis, whether low selenium is the cause of low-T3-syndrome, however, with conflicting results and no clear evidence that low D1 activity is due to the selenium deficiency in critical illness. Because D1 catalyses the conversion of T4 to T3 and also the clearance of reverse T3, low D1 activity would sufficiently explain low plasma T3 and elevated reverse T3. It had been, however, clearly shown that cytokines are responsible for the inhibition of D1 activity, but D2 and D3 are even higher during acute inflammation in critically ill patients. One of the most important effects of selenium on the immune system seems to be the reduction of cytokine release and therefore an indirect connection between low selenium and low D1 activity has to be postulated and not a lower D1 activity due to lower availability of selenium for the D1 expression.
In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations... more In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n = 18), levothyroxine plus 100 µg sodium-selenite (group B, n = 13), or levothyroxine plus 200 µg sodium-selenite (group C, n = 18). Mean age at diagnosis was 12.2 ± 2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6 ± 0.5 µg/kg body weight to lower TSH to the treatment goal of 1-2 µU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p = 0.03 and p = 0.01), but not in group B (p = 0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 µg daily nor given in the "adult" supplementation dose of 200 µg daily.
We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrat... more We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 µg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 µg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) (n = 9), another group which received placebo started to take 200 µg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly (p = 0.004) decreased from 625 ± 470 U/ml to 354 ± 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly (p = 0.017) from 450 ± 335 to 708 ± 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 ± 940 vs. 1724 ± 1112 U/ml, p = 0.555). In contrast, the patients who received 200µg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 ± 723 to 643 ± 477 U/ml.
basal und nach Stimulation mit GnRH normal (2,4 bzw. 43,1 mE/ml). Humanes-Chorion-Gonadotropin ni... more basal und nach Stimulation mit GnRH normal (2,4 bzw. 43,1 mE/ml). Humanes-Chorion-Gonadotropin nicht nachweisbar. TSH (basal und nach Stimulation mit TRH), fTt3, fT4, Prolaktin (Blutabnahme vor körperlicher Untersuchung!), Dehydroepiandrosteron-Sulfat (DHEAS), 17-OH-Progesteron (17-OHP), Cortisol (vor und nach ACTH-Gabe), hGH und IGF-I im Normalbereich. Ebenso rotes und weißes Blutbild, Nierenretentionsparameter, Leberenzyme und Bilirubin, Elektrolyte, Eiweiß und Nüchternblutzucker im Bereich der Norm.
Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor... more Apoptosis of thyroid follicular cells is induced by high doses of iodide, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), as well as H2O2 and might be attenuated by antioxidants. Therefore, we examined the apoptotic index induced by these substances in selenium-treated vs untreated human thyroid follicular cells. Reconstituted human thyroid follicles were incubated with sodium selenite (10 or 100 nM) for 72 h; controls received none. The follicles were then distributed to 24-well plates and incubated with potassium iodide (5, 10, or 20 nM), EGF (5 ng/mL), TGF-beta (5 ng/mL), or H2O2 (100 muM). Apoptosis was determined by a mitochondrial potential assay and the number of apoptotic cells counted by two independent, experienced technicians and the glutathione peroxidase (GPx) activity was determined. Asignificant increase of apoptic cells was obtained in control thyroid follicles treated with iodine (5, 10, or 20 microM), thyroidstimulating hormone (TSH) 1, or 10 mU/mL in combination with 5 and 10 microM iodine, EGF (5 ng/mL) and TGF-beta (5 ng/mL), or H2O2 (100 microM) (p < 0.001). In contrast, in thyroid follicles preincubated with 10 or 100 nM sodium selenite, the apoptototic index was identical to the basal rate. In H2O2-treated follicles, the apoptotic index was still significantly elevated but 50% lower compared to control cells. The GPx activity increased from 1.4 +/- 0.2 to 2.25 +/- 0.4 mU/microg DNA with 10 nMselenite and 2.6 + 0.4 mU/microg DNA with 100 nM selenite. Sodium selenite might increase the antioxidative potential in human thyroid follicles in vitro and therefore diminish the apoptosis induced by TGF-beta, EGF, iodide, and even H2O2.
Aspergillus fumigatus is increasingly recognized as an important nosocomial pathogen in severely ... more Aspergillus fumigatus is increasingly recognized as an important nosocomial pathogen in severely immunocompromised patients. Infection is difficult to diagnose antemortem and typically has a fatal outcome. Here we report the case of a cardiac transplant recipient with disseminated A. fumigatus infection which clinically presented as thyrotoxicosis due to massive involvement of the thyroid gland.
For further investigating the mechanism of the known autoregulation of thyroid follicle growth an... more For further investigating the mechanism of the known autoregulation of thyroid follicle growth and function by iodine, we tried to detect iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone) in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on EGF induced thyroid cell proliferation as well as on TSH induced cycli AMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase catalyzed iodination of arachidonic acid. With gas chromatography-mass spectrometry a molecular mass of 391 m/z corresponding to the derivatization product of iodolactone was found. An ethanol/chloroform extract of isolated thyroid follicles preincubated with KI (10uM) and arachidonic acid (1uM) revealed an identical substrate. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 uM) dose-dependently inhibited EGF induced thyroid cell growth. This growth inhibiting effect of iodolactone was found t...
It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement ma... more It has been proposed from in vivo studies that thyroid angiogenesis during thyroid enlargement may be due to paracrine mitogenic factors released by epithelial thyroid cells. To study this paracrine growth regulating communication between thyroid cells and endothelial cells in vitro, culture medium from isolated porcine thyroid follicles was investigated for a growth promoting effect on porcine aortal endothelial cells. Serum-free conditioned medium (CM) from thyroid follicles in suspension culture contains a dose-related mitogenic activity which stimulates endothelial cell growth up to 197%. Stimulation of the thyroid follicles with TSH (1 mil/ml) significantly reduced the mitogenic activity for endothelial cells in CM to 131%. Thyroid hormones had no influence on mitogenic activity in CM. When follicles were treated with iodide (20 HM) during CM production, no proliferation of endothelial cells was observed by this CM. In contrast, CM from epidermal growth factor-treated thyroid follicles significantly enhanced the mitogenic activity for endothelial cells up to 235%. The mitogenic activity was precipitable by saturated ammonium sulfate, showed high affinity to heparin by chromatography on heparin-sepharose, and was abolished after treatment of CM with trypsin. On gel electrophoresis the heparin-binding fraction showed a double band with a mol wt of 15 and 15.5 k. These data show a paracrine mitogenic activity on endothelial cells released by thyroid follicles which is regulated by TSH, epidermal growth factor, and iodide in parallel with the direct effect of these substances on thyroid cell growth. The data suggest that the mitogenic factor is a polypeptide, which belongs to the heparin-binding growth factors.
Experimental and Clinical Endocrinology & Diabetes, 2009
Twelve human cancer cell lines and one nonmalignant cell line were investigated with respect to a... more Twelve human cancer cell lines and one nonmalignant cell line were investigated with respect to a potential antiproliferative/cytotoxic activity of molecular iodine and iodolactones. Except CCL221 colon carcinoma cells, the growth of ali cancer celllines decreased if the cells were cultured in the presence of 10 11M molecular iodine (12) for at least two days. ô-iodolactone (Il, 511M) was found to have a similar effect. SH-SY5Y neuroblastoma cells turned out to be most susceptible to both iodine compounds (total inhibition), followed by MCF-7 mammary carcinoma cells (60% and 77.7 %inhibition in the presence of 1 2 respect. lL) and HS24 lung carcinoma cells (36.3 % respect. 40.3 % inhibition). In contrast, MCF-lO normal mammary epithelial cells were much less affected by the iodine treatment. ln both, SH-SY5Y and MCF-7 cells, 12 and IL also abolished EGF-induced promotion of cell growth completely. This effect was, however, not due to an interfering with EGF-signaling, because 12 and IL did not affect the phosphorylation of EGFreceptors, EGF-induced activation of MAP-kinase (Erk1/2), ar EGF-induced lamellar actin protrusion. A disruption by molecular iodine of mitochondrial transmembrane electrical potential, which was prevented by a pre-treatment of the cells with N-acetyl-cysteine, supports a mitochondria-mediated apoptotic mechanism.
Iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone), an iodinated derivative of arachidonic... more Iodolactone (6-iodo-8,11,14-eicosatrienoic-delta-lactone), an iodinated derivative of arachidonic acid, was found to be synthesized in rat thyroid slices; however, the physiological role of this compound is still unknown. We tried to detect iodolactone in isolated porcine thyroid follicles and investigated the effects of in vitro synthesized iodolactone on epidermal growth factor-induced thyroid cell proliferation and TSH-induced cAMP formation. In vitro synthesis of iodolactone was performed with lactoperoxidase-catalyzed iodination of arachidonic acid in the presence of trace amounts of [125I]- and [3H]arachidonic acid. After purification by silica gel chromatography, HPLC of the reaction products revealed one main peak containing trace amounts of both [125I]- and [3H]arachidonic acid. With gas chromatography-mass spectrometry (GC-MS) a molecular mass of 391 m/z, corresponding to the derivatization product of iodolactone, was found. An ethanol-chloroform extract of isolated thyroid follicles preincubated with KI (10 microM) and arachidonic acid (1 microM) revealed peaks in HPLC and GC comparable with those of in vitro synthesized iodolactone. This indicates the ability of thyroid follicles to form iodolactone. Iodolactone (0.1-1.0 microM) dose-dependently inhibited epidermal growth factor-induced thyroid cell growth. This growth-inhibiting effect of iodolactone was 50-fold more pronounced than the inhibitory effect of KI (4 X 10(-5) microM) on thyroid cell proliferation. In contrast to the effect of iodide, the inhibitory effect of iodolactone on thyroid cell growth could not be abolished by methimazole (1 mM). Basal as well as TSH (0.5 U/liter)-induced cAMP formation were not changed by iodolactone. These experiments suggest a physiological role of iodolactone as a mediator of the known inhibitory effect of iodide on thyroid growth.
Thyroxine (T 4) or triiodothyronine (T 3) was covalently linked to bovine thyroglobulin (bTg) in ... more Thyroxine (T 4) or triiodothyronine (T 3) was covalently linked to bovine thyroglobulin (bTg) in a molar ratio of 25: l (T 4 :bTg) or 30:1 (T 3 :bTg) using a water-soluble carbodiimide. The conjugates of T 4-bTg and T 3-bTg were used for immunisation of rabbits. After 6 booster-injections all rabbits immunized with T 4-bTg had antibody titers from 1:4000 or 1:8000, whereas the rabbits vaccinated with T 3-bTg had titers from 1:10000 to 1:40000. Two of the T 4-antisera revealed maximal T 4-binding between pH 3.8 and 4.2 with affinity constants of 7.8 X 10 9 1/mol and 6.0 X 10 9 1/mol. With these two antisera a simple, rapid, protein-independent T 4 radioimmunoassay at pH 4.0 in unextracted serum was established without using thyroxine binding globulin blocking agents. Precision of the T 4 radioimmunoassay is documented by an interassay coefficient of variation (CV) calculated from 10 different assays of 5.7% at a mean T 4 concentration of 43 Mg/1 T 4 ,3.5% at 76 jug/1 T 4 and 6.4% at 165 jug/1 T 4. The intra-assay CV was calculated to be 3.7%, 2.8% and 4.7% at these concentrations. Accuracy of the T 4-RIA is documented by identical standard curves when T 4 standards were diluted in 1 g/1 human serum albumin in phosphate buffer, in 40 g/1 human serum albumin in phosphate buffer, or in T 4-free serum, and by recovery studies and dilution curves of hyperthyroid patients. G rtner, Kewenig, Horn and Scriba: T 4 and T 3 radioimmunoassay in unextracted serum at extreme pH ranges Wir erhielten drei T 3-Antiseren.mit einem Bindungsoptimum bei pH 4,0 und drei T 3-Antiseren mit einem Bindungsoptimum im Bereich von pH 8,5 bis pH 10,0. Wir konnten einen T 3-RIA im unextrahierten Serum nach vorheriger Denaturierung von Thyroxin bindendem Globulin mit 0,1 mol/1 NaOH und anschlie ender Inkubation bei pH 9,2 aufbauen. Die Pr zision des T 3-RIA konnte mit einem Interassay-Variationskoeffizienten (n = 20) von 8,6% bei einer T 3-Konzentration von 0,91 Mg/1 T 3 ,8,5% bei einer T 3-Konzentration von 1,72 μg/l T 3 und 5,8% bei 4,15 μg/l T 3 gezeigt werden. Der Intraassay-Variationskoeffizient, berechnet aus Zehnfach-Bestimm ngen, betrug 5,8%, 3.1% und 3.4% bei den obengenannten T 3-Konzentrationen. Die Richtigkeit des T 3 4UA wurde mit Wiederfindekurven, Serumverd nnungskurven und identischen T 3-Standardkurven, wobei T 3-Stand rds entweder in 40 g/l Humanserumalbumin in Phosphatpuffer oder T 3-freiem Serum gel st waren, bewiesen.
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Papers by Roland Gärtner