Multi-scale simulation of plant stem reinforcement by brachysclereids: A case study in apple fruit peduncles.

Sclereid formation in addition to or in gaps of fragmented fibre rings is common in dicotyledonous plant stems. Whether this sclereid formation is force-triggered remains open so far. In fruit peduncles of several Malus species as modified plant stems, for example, the persistent fibre ring is displaced to the centre by formation of cortex parenchyma during growth. Parenchyma cells subsequently differentiate into an additional layer of brachysclereids, previously interpreted as an adaptation to continuously rising fruit loads. The present study pursues a multi-scale numerical modelling approach, to verify the important effect for different cellular architectures in both sclerenchyma categories on the stiffness of these tissues and the entire peduncle. First, different material properties are simulated analogue to plant tissues on the basis of three cell types. A regular three-dimensional and a random Voronoi microstructure combined with various mechanical cell wall parameters are applied. Using homogenisation simulations based on HILL's principle, numerical calculations predict a lower effective homogenised tissue stiffness of isodiametric brachysclereids compared to those of fibres, confirming experimentally obtained data from Malus fruit peduncles. Furthermore, a curved peduncle model with a complex arrangement of different material layers is generated. Diverse material sets are tested under three representative loadings, using an adaptive diffuse domain approach (AMDiS). The model explains the function of sclereids as considerable contributors to the stiffness against bending and tensile deformations, as well as torsion, especially in consequence of superimposed load conditions in the case of a curved plant stem.

Thyroid (dys-)function in normal and disturbed pregnancy.

INTRODUCTION: During pregnancy, physiologic changes in maternal thyroid function take place especially due to hormonal as well as metabolic processes. Human chorionic gonadotropin activates the maternal thyroid gland leading to increased thyroid hormone production. A sufficient availability of maternal thyroid hormones is essential for fetal development, especially during the first trimester of pregnancy, when the fetal thyroid gland is not yet functional. MATERIALS AND METHODS: Current knowledge of thyroid dysfunction including thyroid autoimmunity, hypothyroidism or hyperthyroidism is summarized with special focus on miscarriage and pregnancy disorders. Therefore, a Medline research as well as an analysis of current guidelines on thyroid function and pregnancy was performed. RESULTS: A study focusing on TSH levels in normal and disturbed pregnancies, the risk of miscarriage in association with thyroid autoantibodies, and (subclinical) hypothyroidism in infertile and fertile women were included. CONCLUSION: Maternal thyroid dysfunction negatively affects pregnancy outcome. Besides a routine iodine supplementation in pregnant women and treatment of hypo as well as hyperthyroidism, TSH levels should routinely be measured in women during childbearing years and adjusted to concentrations <2.5 mIU/l in order to optimize maternal health and fetal development.

High (but not low) urinary iodine excretion is predicted by iodine excretion levels from five years ago.

BACKGROUND: It has not been investigated whether there are associations between urinary iodine (UI) excretion measurements some years apart, nor whether such an association remains after adjustment for nutritional habits. The aim of the present study was to investigate the relation between iodine-creatinine ratio (ICR) at two measuring points 5 years apart. METHODS: Data from 2,659 individuals from the Study of Health in Pomerania were analyzed. Analysis of covariance and Poisson regressions were used to associate baseline with follow-up ICR. RESULTS: Baseline ICR was associated with follow-up ICR. Particularly, baseline ICR >300 µg/g was related to an ICR >300 µg/g at follow-up (relative risk, RR: 2.20; p < 0.001). The association was stronger in males (RR: 2.64; p < 0.001) than in females (RR: 1.64; p = 0.007). In contrast, baseline ICR <100 µg/g was only associated with an ICR <100 µg/g at follow-up in males when considering unadjusted ICR. CONCLUSIONS: We detected only a weak correlation with respect to low ICR. Studies assessing iodine status in a population should take into account that an individual with a low UI excretion in one measurement is not necessarily permanently iodine deficient. On the other hand, current high ICR could have been predicted by high ICR 5 years ago.

[Menopausal hormone therapy: internal-endocrine point of view]. / Die menopausale Hormontherapie aus internistisch endokrinologischer Sicht.

The history of menopausal hormone therapy (MHT) started in 1942 in the US and became very popular in the 1960s worldwide because of the beneficial effects on vasomotor-vegetative and vulvovaginal symptoms. These symptoms may begin already in the premenopausal period, and can last for more than 10 years with reduced quality of life. Many women with vasomotor-vegetative symptoms do not visit a gynaecologist first but primarily a general physician or cardiologist because of instable blood pressure and palpitations, leading to the focus on the heart. To avoid unnecessary examinations and treatment with ß-blockers or antidepressants, an interdisciplinary look is necessary. In most cases, appropriate and low dose hormone replacement will relieve the symptoms and restore quality of life. In addition, it is worthwhile to know about the long-term effect of hormone deficiency as well as replacement on the different organ systems and the possible influences of hormone replacement therapy including contra indications. This is especially necessary after the uncertainties raised after the first deleterious announcements of the currently corrected results of the WHI (women's health initiative) study.

The role of iodine and delta-iodolactone in growth and apoptosis of malignant thyroid epithelial cells and breast cancer cells.

OBJECTIVE: As we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy-eicosatrienoic acid (delta-iodolactone). In this communication we compare the effect of iodide, molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines (B-CPAP cells, FTC-133 cells and 8505C cells) as well as on human breast cancer cells (MCF 7). METHODS: Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and MCF 7 cells in Rowswell Park Memorial Institute (RPMI) culture medium, both containing 10% (v/v) Fetal Calf Serum (FCS), until they were confluent. Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM (thyroid cancer cells) or in RPMI medium (MCF 7 cells) both containing 5% FCS. Thereafter, different concentrations of iodide, iodine or delta-iodolactone were added for 24 h. Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells. Apoptosis was determined by a mitochondrial potential assay. RESULTS: The growth rate of B-CPAP cells was unaffected by iodide, but was reduced by high concentreations of molecular iodine (100 and 500 microM). However, delta-iodolactone significantly reduced cell proliferation already with low concentrations (5 microM and 10 microM) and further in a dose-dependent manner up to 82%. FTC-133 and 8505C cells were unaffected by iodide, iodine or delta-iodolactone. In contrast, in MCF 7 cells, molecular iodine (100 microM) inhibited growth from 100% to 83% but delta-iodolactone (1, 5 and 10 microM) dose-dependently decreased growth rate from 100% to 82% and 62%, respectively. The inhibition of growth was through apoptosis, and not necrosis, as the amount of apoptotic cells corresponded to the growth inhibition. CONCLUSION: delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells.

Thyroid diseases in pregnancy.

PURPOSE OF REVIEW: Thyroid disorders are common in pregnancy and affect maternal and fetal outcome. RECENT FINDINGS: The reference values for normal thyroid function during first and second trimester had been re-evaluated recently. Hypothyroxinemia affects the neuropsychological development of the child. Maternal thyroid dysfunction or only the presence of thyroid-specific antibodies is associated with increased risk for early abortion, preterm delivery and neonatal morbidity. Pregnant women under levothyroxine treatment are often undertreated or overtreated. Screening for thyroid dysfunction of pregnant women is recommended and cost-effective. SUMMARY: Recently, the recommended dose for iodine intake during pregnancy had been increased from 200 to 250 microg/day, because recent studies revealed that even mild-to-moderate iodine intake might affect the neuropsychological development of the child. About 5-18% of all pregnant women exhibit elevated thyroid-specific antibodies, but only 0.3% develop overt hypothyroidism and 0.1-0.4% overt hyperthyroidism. However, those pregnant women with autoimmune thyroiditis and normal thyroid function may have a restricted thyroid reserve, followed by hypothyroxinemia and/or thyroid-stimulating hormone increase during pregnancy. The incidence of miscarriage, preterm delivery and small for date offspring might be increased and probably a delayed neuropsychological development. Routine thyroid function testing at least as early as possible in all pregnant women is emphasized.

Dose-related influence of sodium selenite on apoptosis in human thyroid follicles in vitro induced by iodine, EGF, TGF-beta, and H2O2.

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.

[Modern diagnostic approach to autoimmune thyroiditis]. / Der Ultraschall zeigt, was hinter der Funktionsstörung steckt.

High-resolution ultrasonography of the thyroid gland is the major primarytechnical diagnostic procedure in suspected autoimmune thyroiditis (AIT). A diffusely echo-poor thyroid is proof of the presence of AIT. Duplex sonography provides further information about the activity of the disease, and is of differential diagnostic importance for distinguishing postpartum thyroiditis from AIT, or for the investigation of an infiltrating carcinoma. Today, antibody determination serves merely to confirm the diagnosis, with TPO antibodies being the most specific for AIT. The TG antibodies may also be nonspecifically elevated in subacute thyroiditis (de Quervain) or irradiation or radioiodine treatment. For an evaluation of thyroid gland function in AIT, determination of basal TSH is needed.

Recent data on iodine intake in Germany and Europe.

Iodine is essential for the synthesis of thyroid hormones. These regulate metabolism, promote growth, development and maturation of all organs, especially the brain. Most iodine is found in oceans and most continental soil and ground water is deficient in iodine. Therefore, around 2 billion individuals are estimated to have insufficient iodine intake and are at risk of iodine deficiency disorders. The best carrier for save iodine supplementation is salt, as the daily intake of salt is mainly constant. Due to the collaboration between international and national organisations and the salt industry, many developing and developed countries introduced universal salt iodization (USI) or have mandatory or voluntary fortification programs. In Germany as in most European countries the use of iodized salt is voluntary not only in household but also in the food industry. Two recent epidemiological surveys in Germany revealed that 33% of children and 32% of adults are still suffering from mild to moderate iodine deficiency. The best surrogate parameter for iodine deficiency is goitre. The goitre prevalence is around 30% in children as well as in adults which is in accordance with the documented iodine deficiency. From other European countries epidemiological derived data on iodine intake are only available from Denmark and Poland. Further efforts are under way to reveal the iodine status with proper methods in all European countries. On this background it might be possible to establish adequate iodine fortification programs in all European countries.

Comparison of color-Doppler and qualitative and quantitative strain-elastography for differentiation of thyroid nodules in daily practice.

OBJECTIVE: Strain-elastography provides a new ultrasound-based method that can offer information about the stiffness of thyroid nodules as an indicator of malignancy. The aim of our study was to compare the utility of color-Doppler and strain-elastography in differentiating between benign and malignant nodules. DESIGN AND METHODS: 77 thyroid nodules (70 benign and 7 malignant) from 70 unselected patients (48 female/22 male, mean age 49.7±14.3 years) were evaluated with color-Doppler and elastography based on a five-scale elastogram score for qualitative elastography and strain ratio for quantitative elastography. As reference tissue we chose normal thyroid tissue [strain ratio a (SR a)] and cervical muscles [strain ratio b (SR b)]. The cytological or histological results were used as a reference standard. Diagnostic performances of qualitative and quantitative elastography were compared using ROC curves. RESULTS: Vascularization score 3 or 4 was associated with malignancy (p=0.024) as well as elastogram score 4 or 5 (p=0.070, n.s.s.). SR a was indicatively higher and SR b lower in the group of malignant nodules (p=0.065 and p=0.246, n.s.s.). The best cut-off points predicting malignancy were 3.32 for SR a (66.7% sensitivity, 83.3% specificity) and 0.10 for SR b (71.4% sensitivity, 67.1% specificity). CONCLUSION: In our study, the accuracy of elastography did not surpass other sonographic parameters in differentiating thyroid nodules. The technique can play a role as a supplementary parameter in assessment of malignancy to improve diagnostic efficacy. The best parameter is SR a, but SR b can serve as an alternative if SR a is not assessable.

[Osteoporosis in the elderly--diagnosis and treatment]. / Neue Osteoporose-Leitlinie für Senioren. Ab 75 sollten Sie das Risiko für Hüftfrakturen berechnen.

In contrast to postmenopausal osteoporosis, the overriding objective in senior citizens older than 75 years is to avoid fractures of the hip, which are associated with a high mortality rate. Bone density measurement obtained at the neck of the femur using DXA provides reliable data on the risk of an individual patient of sustaining a fracture close to the hip joint. A physical examination can help to assess the patient's risk of falling, while diagnostic laboratory studies can help to exclude secondary osteoporosis. As a preventive measure, physical activity can increase bone density also in old age. Calcium and vitamin D improve muscular strength and coordination, and thus also may be helpful in preventing falls. In manifest osteoporosis, risedronate and alendronate reduce the risk of fractures close to the hip and of vertebrae by 50%. In addition, raloxifene can be employed to prevent vertebral fractures.

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.

The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx). METHODS: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy. CONCLUSIONS: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.

High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the prevalence of autoimmune thyroiditis (AIT) in patients with polycystic ovary syndrome (PCOS). DESIGN: Over a period of 30 months, 175 patients with PCOS were recruited to a prospective multicenter study to evaluate thyroid function and morphology; 168 age-matched women without PCOS were studied as a control group. METHODS: PCOS was defined as a- or oligomenorrhea, hyperandrogenism and exclusion of other disturbances of estrogen or androgen synthesis. All laboratory parameters were determined with automated immunoassays. Thyroid morphology was assessed by ultrasound. RESULTS: PCOS patients were characterized by an increased LH/FSH ratio, low progesterone, elevated testosterone and a high prevalence of hirsutism (PCOS 83%, control 3%; mean hirsutism score 12+/-5 and 3+/-2 respectively), but no differences in estrogen levels were found. Thyroid function and thyroid-specific antibody tests revealed elevated thyroperoxidase (TPO) or thyroglobulin (TG) antibodies in 14 of 168 controls (8.3%), and in 47 of 175 patients with PCOS (26.9%; P<0.001). On thyroid ultrasound, 42.3% of PCOS patients, but only 6.5% of the controls (P<0.001) had a hypoechoic tissue typical of AIT; while thyroid hormone levels were normal in all subjects, PCOS patients had a higher mean TSH level (P<0.001) and a higher incidence of TSH levels above the upper limit of normal (PCOS 10.9%, controls 1.8%; P<0.001). CONCLUSION: This prospective study demonstrates a threefold higher prevalence of AIT in patients with PCOS, correlated in part with an increased estrogen-to-progesterone ratio and characterized by early manifestation of the disease.

Selenium in the treatment of autoimmune thyroiditis.

We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg 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 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg 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 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.

Interrelations between thyrotropin levels and iodine status in thyroid-healthy children.

BACKGROUND: Worldwide, iodine prophylaxis measures have improved iodine status in populations. Several studies have reported an increase in thyrotropin (TSH) levels coinciding with this prophylaxis. Whether this implies an increased risk for hypothyroidism or simply reflects a physiologic TSH adaptation mechanism is not clear. METHODS: Data on iodine and thyroid status of 6-17 year old children and adolescents (n=9175), collected between 2003 and 2006 in the German-wide Health Interview and Examination Survey for Children and Adolescents (KiGGS) Study, provided the basis for the analyses of mutual relationships of urinary iodine status (assessed by iodine/creatinine ratio in spot urines), serum TSH levels, and thyroid volume (determined by ultrasound). For data analyses (multivariable linear regression analysis), only those children were included for whom none of the available parameters (including free triiodothyronine [fT3], free thyroxine [fT4], and thyroperoxidase antibody [TPO-Ab] measurements) indicated a potential pathophysiologic thyroid status (n=6101). RESULTS: In this population-based sample of thyroid-healthy children, higher urinary iodine excretion was associated with higher TSH levels (p<0.05), adjusted for sex, age, body surface area, body mass index, fT3/fT4 ratio, and time of blood sampling. Higher TSH levels were not associated with a higher prevalence of TPO-Ab but with lower thyroid volume (p<0.001, fully adjusted). For the present study sample, one-time spot measurements of urinary iodine excretion were not related to thyroid volume, the long-term marker of iodine status. CONCLUSION: Our findings show for the first time in thyroid-healthy children that smaller thyroid volume is associated with higher normal TSH levels. A decreased thyroid cell mass and cell amount, as induced by an improved iodine status, does presumably require a higher TSH signal to maintain a constant thyroid hormone production, suggesting an underlying physiologic adaptation. Correspondingly, an increased TSH level should not be used as the single criterion to evaluate the prevalence of hypothyroidism, and the repeatedly observed parallel increases of iodine supply and TSH levels should not readily be interpreted as evidence for an increased hypothyroidism risk. These insights, contradicting conventional interpretations, may contribute to dispel uncertainties about the safety of iodine prophylaxis measures.