Percentage of Myeloid Dendritic Cells in Peripheral Venous Blood Is Negatively Related to Incidence of Graves' Orbitopathy.

The aim of the study was to evaluate the distribution of blood dendritic cells (DCs) in patients with Graves' orbitopathy (GO) and to assess the influence of methylprednisolone therapy on subsets of peripheral blood mononuclear cells (PBMCs). Peripheral blood DC subsets were analyzed by flow cytometry in patients with active GO (n = 17), inactive GO (n = 8), and Graves' disease (GD) without GO (n = 8) and controls (n = 15); additionally, in patients with active GO (n = 17), analyses were done at three time points, i.e., before methylprednisolone treatment and after 6 weeks and after 12 weeks of the treatment. Percentage of myeloid DCs (mDCs) in PBMC fraction was significantly lower in patients with both active and inactive GO, compared to patients with GD without GO and controls (p < 0.05). In addition, mDCs were also documented to be an independent factor negatively associated with GO, however without essential differences between active and inactive phases. On the other hand, we did not observe any changes in the percentage of DCs after methylprednisolone therapy (p > 0.05). In the present study, we have succeeded to firstly demonstrate-according to our knowledge-that blood mDCs are negatively related to GO incidence.

Oxidative damage to membrane lipids in the thyroid - no differences between sexes.

It has long been observed that thyroid diseases are more prevalent in women than in men. However, there are limited experimental data demonstrating mechanisms by which sex differences in thyroid diseases may occur and exact molecular mechanisms involved are still far from clear. The aim of the study was to evaluate if there are sex differences concerning oxidative damage to membrane lipids in thyroid homogenates in response to Fenton reaction substrates, i.e., Fe2+ and/or H2O2, and, additionally, in response to potentially protective agent, i.e., melatonin. Homogenates of male or female thyroids collected from adult swine (Sus scrofa domesticus) at slaughter were incubated in the presence of H2O2 and/or Fe2+ without or with addition of melatonin. Malondialdehyde + 4-hydroxyalkenals concentration (LPO index) was measured spectrophotometrically. Neither H2O2 nor Fe2+, when used separately, did affect the level of lipid peroxidation in both male and female porcine thyroid homogenates. When H2O2 (0.5 mM) was used together with different concentrations of Fe2+, the level of lipid peroxidation increased significantly in both male and female porcine thyroid homogenates, with clear Fe2+ concentration-dependent stimulatory effect, but without differences between sexes. No sex-specific differences was found concerning oxidative damage to membrane lipids in porcine thyroid in response to Fenton reaction substrates and/or to melatonin. The lack of expected differences may be due to potentially lower sensitivity of membrane lipids comparing to other biological macromolecules to pro-/antioxidative agents in the thyroid. However, further studies should be performed to explain the discussed issue.

Melatonin reduces high levels of lipid peroxidation induced by potassium iodate in porcine thyroid.

Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p < 0.05) revealed at concentrations of around 15 mM, thus corresponding to physiological iodine concentrations in the thyroid. Melatonin reduced LPO (MDA + 4-HDA levels: from ≈0.97 to ≈0,76 and from ≈0,64 to ≈0,49 nmol/mg protein, p < 0.05) induced by KIO3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.

Contribution of Ghrelin to the Pathogenesis of Growth Hormone Deficiency.

In this review we described the interactions between ghrelin and the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis in children and adults with growth hormone deficiency (GHD). A possible involvement of these interactions in the pathogenesis of unexplained cases of GHD was suggested. Current research provides more and more details to the knowledge on the circadian rhythm of ghrelin. We gathered reports on the decreasing effect of Helicobacter pylori-related chronic gastritis on the number of ghrelin immunopositive cells and the consequent decrease in ghrelin serum concentration. The gastrointestinal tract microflora modification of the ghrelin action, by the mechanism of molecular mimicry, was also stressed. Moreover, the mutual relationships between ghrelin and the TSH-FT4/FT3 axis in growth and metabolic processes are described. It is to be recalled that FT4 and FT3 exert a permissive impact on IGF-1 action and, in turn, GH, in reaction mediated by IGF-1, enhances the monodeiodination of FT4 to FT3. Finally, we discussed the latest attempts to use the GH secretagogue receptor (GHS-R) analogues for possible diagnostic and therapeutic purposes.

Correction to: High normal TSH is associated with lower mannan-binding lectin in women of childbearing age.

An amendment to this paper has been published and can be accessed via the original article.

High normal TSH is associated with lower mannan-binding lectin in women of childbearing age.

BACKGROUND: Mannan-binding lectin (MBL) is a main component of the lectin pathway of the complement system. Lower MBL levels are associated with, among other conditions, hypothyroidism and adverse pregnancy outcomes. In turn, adverse pregnancy outcomes and infertility may result from hypothyroidism, even in patients with high normal Thyroid-stimulating hormone (TSH). The aim of this study was to determine if MBL level differs between women of reproductive age with low normal (< 2.5 mIU/l) and high normal (≥2.5 mIU/l) TSH. Associations with other parameters potentially affected by hypothyroidism were also evaluated. METHODS: Ninety five (95) patients with normal thyroid tests (TSH 0.27-4.2 mIU/l), aged 18-48 years, were prospectively enrolled. Several laboratory parameters were measured, including MBL level, thyroid tests and lipid profile. RESULTS: Serum MBL level was lower in women with TSH ≥ 2.5 mIU/l than with TSH < 2.5 mIU/l. This association was confirmed by univariate regression analysis. MBL level was significantly lower in patients with abnormally low HDLC/cholesterol ratio and a positive correlation was found between MBL level and HDL/cholesterol ratio. CONCLUSION: In women of reproductive age with normal thyroid tests, lower MBL is associated with high normal TSH and with less favourable lipid profile. Therefore treatment with L-thyroxine should be considered in women of reproductive age with TSH ≥ 2.5 mIU/l.

Sexual Dimorphism of NADPH Oxidase/H2O2 System in Rat Thyroid Cells; Effect of Exogenous 17ß-Estradiol.

It has long been observed that females are more susceptible to thyroid diseases than males. Epidemiological and experimental data show that actions of hormonal factors-especially estrogens-may explain such disparity. However, the exact cause and mechanisms of this sexual dimorphism remain so far unknown. Therefore, we aimed at evaluating the effect of 17ß-estradiol on the redox balance in thyroids of male and female rats. Expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, i.e., dual oxidase 1 (DUOX1), dual oxidase 2 (DUOX2) and NADPH oxidase 4 (NOX4), and hydrogen peroxide (H2O2) levels were evaluated in the primary cell cultures derived from thyroid glands of adult male or female Wistar rats. The measurement was made before and after treatment with 17ß-estradiol alone or with addition of one of its receptor antagonists. We found that under basal conditions female thyroid cells are exposed to higher concentrations of H2O2, most likely due to NOX/DUOX enzymes activity. Additionally, exogenous 17ß-estradiol stimulated NOX/DUOX expression as well as H2O2 production, and this effect was mainly mediated through ERα. In conclusion, oxidative processes may constitute mechanisms responsible for sexual dimorphism of thyroid diseases. Exogenous 17ß-estradiol may play a crucial pathogenic role in thyroid diseases via oxidative mechanisms, however without any gender differences.

TSH ≥2.5 mIU/l is Associated with the Increased Oxidative Damage to Membrane Lipids in Women of Childbearing Age with Normal Thyroid Tests.

According to current recommendations, a TSH value of <2.5 mIU/l should be maintained during preconception and pregnancy. The same recommendation, however, does not relate to all women of childbearing age. The aim of the study was to evaluate relationship between lipid peroxidation (LPO; index of oxidative damage to membrane lipids) and thyroid tests and other parameters, which may be affected by thyroid dysfunction, in euthyroid women of childbearing age. Ninety nine female inpatients with normal thyroid tests (TSH 0.27-4.2 mIU/l), aged 18-48 years, were prospectively enrolled. Blood concentrations of malondialdehyde+4-hydroxyalkenals (LPO index) were measured spectrophotometrically. Thyroid tests (TSH, FT4, FT3), thyroid antibodies and other laboratory parameters [cholesterol, HDL cholesterol (HDLC), LDL cholesterol, HDLC/cholesterol ratio, triglycerides, glucose, CRP, iron] were measured with standard methods. Blood LPO level was higher in women with TSH≥2.5 mIU/l than in women with TSH<2.5 mIU/l. Positive correlation was found between TSH concentration and LPO level (r=0.210, p=0.037). In the univariate regression analysis, blood LPO level did constitute the only independent factor associated with TSH≥2.5 mIU/l. Abnormal HDLC/cholesterol ratio occurred more frequently in subjects with TSH≥2.5 mIU/l. Additionally, LPO level correlated positively with triglyceride concentration (r=0.340, p=0.001), whereas it correlated negatively with HDLC concentration (r=-0.335, p=0.001) and with HDL/cholesterol ratio (r=-0.331, p=0.001). In conclusion, in women of childbearing age with normal thyroid tests, TSH≥2.5 mIU/l is associated with higher oxidative damage to membrane lipids and less favorable lipid profile, which supports our standpoint that TSH of less than 2.5 mIU/l should be maintained in all women of childbearing age.

Low dairy calcium intake is associated with overweight and elevated blood pressure in Polish adults, notably in premenopausal women.

OBJECTIVE: Dietary Ca is now being recognized to play an important role not only in skeletal integrity, but also in the regulation of energy and metabolism. The aim of the present study was to estimate the relationship of dairy Ca intake with BMI and blood pressure (BP) in a sample derived from the Polish population. DESIGN: Ca intake was calculated from an interviewer-administered semi-quantitative FFQ. BMI was calculated from measured weight and height, and BP was measured by a physician. SETTING: Cross-sectional epidemiological study on osteoporosis risk factors in Poland. SUBJECTS: Randomly selected healthy adult persons (n 1259; 750 women and 509 men). RESULTS: Dairy Ca intake was significantly lower in individuals with overweight/obesity (BMI≥25·00 kg/m2) and/or with elevated BP (systolic/diastolic ≥140/≥90 mmHg) than in those with normal body mass and BP, respectively. Ca intake was negatively correlated with BMI (r=-0·12, P<0·001), systolic BP (r=-0·11, P<0·001) and diastolic BP (r=-0·08, P<0·01). Daily dairy Ca intake below 1000 mg was a predictor for BMI≥25·0 kg/m2 (OR=1·44, P<0·005). This relationship was stronger in women, particularly premenopausal women. CONCLUSIONS: The obtained results indicate the role of low dairy Ca intake in the development of obesity and hypertension, notably in premenopausal women.

Protective effect of KI in mtDNA in porcine thyroid: comparison with KIO3 and nDNA.

PURPOSE: Iodine, bivalent iron (Fe²âº), and hydrogen peroxide (H2O2), all significantly affecting the red-ox balance, are required for thyroid hormone synthesis. Intracellular iodine excess (≥10⁻³ M) transiently blocks thyroid hormonogenesis (an adaptive mechanism called Wolff-Chaikoff effect). The aim of the study was to evaluate the effects of iodine, used as potassium iodide (KI) or potassium iodate (KIO3), in concentrations corresponding to those typical for Wolff-Chaikoff effect, on the level of oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) isolated from porcine thyroid under basal conditions and in the presence of Fenton reaction (Fe²âº+H2O2 → Fe³âº+(·)OH + OH⁻) substrates. METHODS: Thyroid nDNA and mtDNA were incubated in the presence of either KI or KIO3 (2.5-50 mM), without/with FeSO4 (30 µM) + H2O2 (0.5 mM). Index of DNA damage, i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine, was measured by HPLC. RESULTS: Neither KI nor KIO3 increased the basal level of 8-oxodG in both nDNA and mtDNA. KI-in all used concentrations-completely prevented the damaging effect of Fenton reaction substrates in mtDNA, and it partially prevented this damage in nDNA. KIO3 partially prevented Fe²âº+H2O2-induced oxidative damage in both DNA only in its highest used concentrations (≥25 mM). CONCLUSIONS: Without additional prooxidative abuse, both iodine compounds, i.e., KI and KIO3, seem to be safe in terms of their potential oxidative damage to DNA in the thyroid. The superiority of KI over KIO3 relies on its stronger protective effects against oxidative damage to mtDNA, which constitutes an argument for its preferential utility in iodine prophylaxis.

Higher lipid peroxidation in former-smokers vs. never-smokers - study in postmenopausal women.

OBJECTIVES: One of the most spectacular exogenous prooxidative agents is cigarette smoking, constituting a well documented risk factor for several diseases. In turn it is suggested that hormone replacement therapy (HRT) in postmenopausal women can contribute to oxidative status. The aim of the study was to evaluate the level of oxidative damage to membrane lipids in blood serum collected from never-smokers and former-smokers. The study was performed in postmenopausal women, who were or were not HRT users. METHODS: Ninety (90) female volunteers, aged from 46 to 67 years, were enrolled. Two major groups were considered, i.e. never-smokers (n=44) and formersmokers (n=46), which were additionally subgrouped to HRT users (HRT+) and HRT non-users (HRT-). Anthropometric parameters related to obesity were also calculated. The main groups were well matched at baseline in terms of age. The level of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the index of LPO, was measured spectrophotometrically. RESULTS: The level of LPO was higher in former-smokers than in never-smokers, regardless of HRT use. The level of LPO did constitute the only independent factor associated with past smoking in the entire examined group, as well as after stratification to HRT users and HRT non-users. LPO level was not associated with HRT treatment. No positive correlations were found between LPO level and anthropometric parameters. CONCLUSION: Past smoking is independently associated with the increased damage to membrane lipids regardless of the use of HRT in postmenopausal women. Smoking cessation is not always associated with complete reversion of excessive oxidative damage to all biological macromolecules.

Comparison of potential protective effects of melatonin and propylthiouracil against lipid peroxidation caused by nitrobenzene in the thyroid gland.

BACKGROUND: Nitrobenzene is a carcinogen, which induces-among others-thyroid tumors. Melatonin is an effective antioxidant, whereas some antioxidative effects of propylthiouracil (PTU; an antithyroid medication used for the treatment of thyrotoxicosis) were also found. The aim of the study was to compare protective effects of melatonin and PTU against lipid peroxidation in homogenates of porcine thyroids, incubated in the presence of nitrobenzene. METHODS: Homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 mM). The level of lipid peroxidation products (malondialdehyde + 4-hydroxyalkenals) was measured spectrophotometrically. Nitrobenzene (7.5 and 10.0 mM) increased lipid peroxidation in the homogenates of porcine thyroids. Subsequently, homogenates of porcine thyroids were incubated for 30 min in the presence of nitrobenzene (7.5 mM) plus one of the antioxidants: melatonin (0.000001, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM) or PTU (0.01, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mM). RESULTS: Lipid peroxidation caused by nitrobenzene was effectively prevented by melatonin, with the lowest effective concentration of 0.0001 mM, being only two orders of magnitude higher than physiological blood concentration in humans. At the same time, PTU revealed protective effects only in the highest used concentration (7.5 mM), which is practically never reached during pharmacological treatment in patients with thyrotoxicosis. CONCLUSIONS: Melatonin can serve as an effective agent in protection against nitrobenzene-induced lipid peroxidation in porcine thyroid.

Increased oxidative damage to membrane lipids following surgery for breast cancer.

OBJECTIVES: To evaluate the level of oxidative damage to membrane lipids due to the breast cancer surgery in the early postoperative period. PATIENTS AND METHODS: Blood samples were collected on the preoperative day and 24 hours postoperatively in 71 women operated for breast cancer, and preoperatively in 38 female patients with benign breast tumour. Lipid peroxidation (LPO) in the blood samples was estimated by measuring the concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA) with spectrophotometry. CLINICAL DATA INCLUDED: tumour site, tumour histological findings, cancer stage, grade, tumour volume, state of lymph nodes, type of surgery for breast, type of surgery for axilla. RESULTS: Blood LPO level was similar in breast cancer patients and benign tumour patients (2.01±0.46 nmol/ml vs. 1.92±0.39 nmol/ml, respectively; p>0.05). In cancer patients, MDA+4-HDA increased on the first postoperative day, i.e. from 2.01±0.46 nmol/ml to 2.58±0.98 nmol/ml (p=0.0001). In women with benign breast tumour, LPO did not relate to the histological finding (p=0.8915). In the breast cancer group, preoperative LPO did not correlate with age, tumour volume and number of metastatic lymph nodes. Level of MDA+4-HDA was similar in stages I/II (2.03±0.46 nmol/ml) compared to stages III/IV (1.69±0.26 nmol/ml, p=0.1521). Consequently, levels of MDA+4-HDA did not relate to disease stage (p=0.1364). CONCLUSIONS: Surgery for breast cancer causes peripheral increase in oxidative damage to macromolecules in the early postoperative period. Therefore, perioperative antioxidant supplementation should be considered.

Persistent remission of Graves` disease or evolution from Graves' disease to Hashimoto's thyroiditis in childhood - a report of 6 cases and clinical implications.

BACKGROUND: The main clinical manifestations of autoimmune thyroid diseases are Graves' disease (GD) and Hashimoto's thyroiditis (HT). Graves' disease is the cause of most cases of hyperthyroidism in childhood. Indications for radical therapy (surgery or 131I treatment) in children are still a matter of discussion, as sustained (sometimes very long) remission of GD is possible, while the radical therapy almost always leads to hypothyroidism. Spontaneous evolution from GD with hyperthyroidism to HT with hypothyroidism may also be observed. OBJECTIVE: The aim of the study was to analyze the clinical course of 6 cases of hyperthyroid girls with GD in whom a normalization of previously increased autoantibodies against thyrotropin (TSH) receptor (anti-TSHR) was observed together with a significant increase in autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg), with concomitant hypo- or euthyroidism but no recurrence of hyperthyroidism. SUBJECTS: Patients' age at diagnosis ranged from 5.0 to 16.5 years. Two (2) patients had Turner syndrome, another one (1), diabetic, was on insulin therapy. RESULTS: In all the girls, antithyroid drugs were administered and euthyroid state was achieved during the first 2.0-3.5 months of the treatment. Mild side effects were observed in only one case. The therapy was continued up to 1.5-4.0 years. Relapses during the therapy were observed in 2 cases. Up to now, no relapses have been observed for 0.5-7.5 years since the therapy withdrawal in 5 patients (1 patient was lost to follow-up), 2 patients are currently treated with levothyroxine due to hypothyroidism. CONCLUSIONS: It seems that the prolonged pharmacotherapy with antithyroid drugs, followed by observation after remission of hyperthyroidism, may be an appropriate therapeutic option at least in some children with GD as they can be cured without radical therapy and the potential risks of such treatment.

Protective Effects of Melatonin against Carcinogen-Induced Oxidative Damage in the Thyroid.

Melatonin, primarily synthesized in the pineal gland, plays a crucial role in regulating circadian rhythms and possesses significant antioxidative properties. By neutralizing free radicals and reducing oxidative stress, melatonin emerges as a promising agent for the prevention and therapy of many different disorders, including cancer. This paper reviews the relationship between the thyroid gland and melatonin, presenting experimental evidence on the protective effects of this indoleamine against oxidative damage to macromolecules in thyroid tissue caused by documented carcinogens (as classified by the International Agency for Research on Cancer, IARC) or caused by potential carcinogens. Furthermore, the possible influence on cancer therapy in humans and the overall well-being of cancer patients are discussed. The article highlights melatonin's essential role in maintaining thyroid health and its contribution to management strategies in patients with thyroid cancer and other thyroid diseases.

Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.

Emerging research underscores the pivotal role of adipose tissue in regulating systemic aging processes, particularly when viewed through the lens of the endocrine hypotheses of aging. This study delves into the unique adipose characteristics in an important animal model of aging - the long-lived Ames dwarf (df/df) mice. Characterized by a Prop1df gene mutation, these mice exhibit a deficiency in growth hormone (GH), prolactin, and TSH, alongside extremely low circulating IGF-1 levels. Intriguingly, while surgical removal of visceral fat (VFR) enhances insulin sensitivity in normal mice, it paradoxically increases insulin resistance in Ames dwarfs. This suggests an altered profile of factors produced in visceral fat in the absence of GH, indicating a unique interplay between adipose tissue function and hormonal influences in these models. Our aim was to analyze the gene expression related to lipid and glucose metabolism, insulin pathways, inflammation, thermoregulation, mitochondrial biogenesis, and epigenetic regulation in the visceral (perirenal and epididymal) adipose tissue of Ames dwarf and normal mice. Our findings reveal an upregulation in the expression of key genes such as Lpl, Adrß3, Rstn, Foxo1, Foxo3a, Irs1, Cfd, Aldh2, Il6, Tnfα, Pgc1α, Ucp2, and Ezh2 in perirenal and Akt1, Foxo3a, PI3k, Ir, Acly, Il6, Ring1a, and Ring 1b in epididymal fat in df/df mice. These results suggest that the longevity phenotype in Ames dwarfs, which is determined by peripubertal GH/IGF-1 levels, may also involve epigenetic reprogramming of adipose tissue influenced by hormonal changes. The increased expression of genes involved in metabolic regulation, tumor suppression, mitochondrial biogenesis, and insulin pathways in Ames dwarf mice highlights potentially beneficial aspects of this model, opening new avenues for understanding the molecular underpinnings of longevity and aging.

Exogenous Melatonin Protects against Oxidative Damage to Membrane Lipids Caused by Some Sodium/Iodide Symporter Inhibitors in the Thyroid.

The thyroid gland is the primary site of sodium/iodide symporter (NIS), an intrinsic plasma membrane protein responsible for the active uptake of iodine, which is indispensable for thyroid hormone synthesis. Since exposure of the thyroid to NIS inhibitors can potentially have harmful effects on the entire organism, it is important to investigate the potential protective effects of known antioxidants, such as melatonin and indole-3-propionic acid (IPA), against pro-oxidative action of classic NIS inhibitors. The study aimed to check if and to what extent melatonin and IPA interact with some confirmed NIS inhibitors regarding their effects on oxidative damage to membrane lipids in the thyroid. For comparison with the thyroid gland, in which NIS is typically present, the liver tissue-not possessing NIS-was applied in the present study. Thyroid and liver homogenates were incubated in the presence of tested NIS inhibitors (i.e., NaClO3, NH4SCN, KSeCN, KNO3, NaF, KClO4, and BPA) in different ranges of concentrations with/without melatonin (5 mM) or IPA (5 mM). The malondialdehyde+4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. NaClO3 increased LPO in the thyroid and in the liver, but these pro-oxidative effects were not prevented by either melatonin or IPA. Instead, pro-oxidative effects of NH4SCN observed in both tissues were prevented by both indole substances. KSeCN and NaF increased LPO only in the thyroid, and these pro-oxidative effects were prevented by melatonin and IPA. KNO3, KClO4, and BPA did not increase LPO, which can be due to their low concentrations resulting from restricted solubility. In conclusion, as melatonin prevented oxidative damage to membrane lipids in the thyroid caused by some sodium/iodide symporter inhibitors, this indoleamine shoud be considered as a potential protective agent when produced appropriately in living organisms but also as an exogenous substance recommended to individuals overexposed to NIS inhibitors.

The Protective Effect of Exogenous 17ß-Estradiol against Experimentally Induced Oxidative Damage to Membrane Lipids Is Stronger in Male vs. Female Porcine Thyroids: Preliminary Results.

It is well-known that thyroid diseases are more prevalent in women than in men. The contribution of sex hormones may explain such disparity. The aim of this study was to check if there are any differences between sexes concerning the effects of 17ß-estradiol on oxidative damage to membrane lipids (lipid peroxidation) in porcine thyroid homogenates under basal conditions and in the presence of Fenton reaction (Fe2+ + H2O2→Fe3+ + •OH + OH-) substrates. We observed that 17ß-estradiol did not change the basal level of lipid peroxidation (measured spectrophotometrically as concentrations of malondialdehyde + 4-hydroxyalkenals) in thyroid homogenates, and no differences were found between sexes. The lipid peroxidation level in response to Fe2+ + H2O2 plus 17ß-estradiol was lower in male thyroids. In turn, in male thyroids, 17ß-estradiol reduced experimentally induced lipid peroxidation in as low of a concentration as 0.1 µM, whereas in female thyroids the lowest effective concentration of 17ß-estradiol was 10 µM, i.e., 100 times higher than in males. In conclusion, the protective effects of exogenous 17ß-estradiol against experimentally induced oxidative damage to membrane lipids is stronger in male than in female thyroids. Our observation suggests that female tissue is less sensitive to the protective effects of exogenous 17ß-estradiol. This sexual dimorphism of oxidative processes in the thyroid may constitute one of the mechanisms of the different prevalence of thyroid diseases in women and in men.

Decreased mannan-binding lectin level in adults with hypopituitarism; dependence on appropriate hormone replacement therapies.

Background: Mannan-binding lectin (MBL) is a main component of the lectin pathway of the complement system. Although there are some studies showing links between endocrine and immune systems, the ones concerning hypopituitarism are limited. The aim of this study was to check whether there is any association between blood MBL level and pituitary hormone deficiencies and whether this relationship is affected by appropriate hormone replacement therapies. Methods: One hundred and twenty (120) inpatients, aged 18-92, were divided into two main groups, i.e. control individuals (21/120) and patients with pituitary diseases (99/120). The latter were diagnosed either with hypopituitarism (n=42) or with other pituitary diseases (not causing hypopituitarism) (n=57). Additionally, hypopituitary patients on appropriate replacement therapies (compensated hypopituitarism) were compared to patients on inappropriate replacement therapies (non-compensated hypopituitarism). Several parameters in blood serum were measured, including MBL level, pituitary and peripheral hormones and different biochemical parameters. Results: Serum MBL level was significantly lower in patients with hypopituitarism comparing to controls (1358.97 ± 244.68 vs. 3199.30 ± 508.46, p<0.001) and comparing to other pituitary diseases (1358.97 ± 244.68 vs. 2388.12 ± 294.99, p=0.015) and this association was confirmed by univariate regression analysis. We evaluated the distribution of patients with relation to MBL level; there was a clear difference in this distribution between control individuals (among whom no subjects had MBL level <500 ng/mL) and patients with hypopituitarism (among whom 43% of patients had MBL level <500 ng/mL). Moreover, patients with non-compensated hypopituitarism had lower mean and median MBL levels comparing to patients with compensated hypopituitarism (1055.38 ± 245.73 vs. 2300.09 ± 579.93, p=0.027; 488.51 vs. 1951.89, p=0.009, respectively) and this association was confirmed in univariate regression analysis. However, mean and median MBL levels in patients with compensated hypopituitarism vs. controls did not differ significantly (2300.09 ± 579.93 vs. 3199.30 ± 508.46, p=0.294; 1951.90 vs. 2329.16; p=0.301, respectively). Conclusion: Hypopituitarism in adults is associated with a decreased blood concentration of mannan-binding lectin, a phenomenon which does not exist in hypopituitary patients on the appropriate hormone replacement therapies. Therefore measurement of mannan-binding lectin level in patients with hypopituitarism may be considered as a parameter contributing to adjust optimal doses of hormone replacement therapies.

Direct contribution of obesity to oxidative damage to macromolecules.

BACKGROUND: Obesity constitutes a common modifiable risk factor for certain non-communicable diseases (NCDs) associated with enhanced oxidative stress. OBJECTIVES AND METHODS: The aim of the study was to examine serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of lipid peroxidation (LPO), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) concentration in peripheral blood lymphocytes, as an index of nuclear DNA damage, in overweight and obese adult patients. LPO and 8-oxodG, as well as clinical and laboratory parameters, which are frequently affected by obesity, were evaluated in 58 overweight and obese adult patients, and in 20 healthy volunteers. RESULTS: Both LPO and 8-oxodG levels were increased in overweight and obese patients, with further increase observed with the increasing body mass index (BMI). LPO correlated positively with body mass, BMI, waist circumference, hip circumference, waist:hip ratio, systolic or diastolic blood pressure, glucose, C-reactive protein and ferritin concentrations. 8-oxodG correlated positively with body mass, BMI, hip circumference and triglyceride concentration, whereas it correlated negatively with iron concentration. Expectedly, positive correlation between LPO and 8-oxodG was also found. CONCLUSIONS: BMI constituted the only independent determinant (predictor) of LPO in overweight and obese patients. Consistently, LPO did constitute the only independent determinant of obesity. Overweight and obesity in adults are directly associated with increased oxidative damage to macromolecules.