Thyroid complications of SARS and coronavirus disease 2019 (COVID-19).

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

PREDICTIVE VALUE OF SOMATIC MUTATIONS FOR THE DEVELOPMENT OF MALIGNANCY IN THYROID NODULES BY CYTOPATHOLOGY.

OBJECTIVE: The purpose of our prospective longitudinal study was to evaluate the predictive efficacy of genetic testing for malignancies in fine-needle aspiration biopsy samples that are cytologically benign at the time of biopsy. METHODS: A total of 779 aspirated cytological samples collected from thyroid nodules of 626 patients were included in a 3-year follow-up study. Consecutive patients with cytologically benign thyroid nodules by the Bethesda System for Reporting Thyroid Cytopathology were enrolled in the study. At enrollment, somatic 1-point nucleotide polymorphisms of BRAF and RAS family genes were tested by melting-point analysis, while RET/PTC and PAX8/PPAR-gamma rearrangements were examined by real-time polymerase chain reaction. The genetic test was considered to be positive if a somatic mutation was found. Malignant cytopathologic diagnoses were confirmed by histopathology. RESULTS: In samples collected from 779 thyroid nodules, there were 39 BRAF, 33 RAS mutations, and 1 RET/PTC rearrangements found at the beginning of the study. No PAX8/PPAR-gamma rearrangement was identified. There were 52 malignant thyroid tumors removed during follow-up, out of which 24 contained a somatic mutation. The specificity of the presence of somatic mutations for malignancies was as high as 93.3%, and sensitivity was 46.2%. The negative predictive value of genetic testing reached 96.0%. CONCLUSION: Our results show that our set of genetic tests can predict the appearance of malignancy in benign thyroid nodules (at the beginning of follow-up) with high specificity and strong negative predictive value. ABBREVIATIONS: BRAF = v-raf murine sarcoma viral oncogene homolog B1 FLUS = follicular lesion of undetermined significance FNAB = fine-needle aspiration biopsy FTC = follicular thyroid carcinoma HRAS = homologous to the oncogene from the Harvey rat sarcoma virus KRAS = homologous to the oncogene from the Kirsten rat sarcoma virus NRAS = first isolated from a human neuroblastoma/neuroblastoma RAS = viral oncogene homolog PAX8 = paired box 8 PCR = polymerase chain reaction PPAR-gamma = peroxisome proliferator-activated receptor gamma PTC = papillary thyroid carcinoma RAS = rat sarcoma RET = rearranged during transfection tyrosine-kinase proto-oncogene SM = somatic mutation SNP = single-nucleotide polymorphism.

Polymorphisms of CSF1 and TM7SF4 genes in a case of mild juvenile Paget's disease found using next-generation sequencing.

Juvenile Paget's disease (JPD) is a rare autosomal-recessive condition. It is diagnosed in young children and characterized by a generalized increase in bone turnover, bone pain, and skeletal deformity. Our patient was diagnosed after a pathological fracture when she was 11 years old. When we first examined her at the age of 30 she had bone pain and deformity in both the femur and tibia. Serum alkaline phosphatase (ALP) level, radiology, bone scintigraphy, and densitometry were monitored. Next generation sequencing (NGS) technology, namely semiconductor sequencing, was used to determine the genetic background of JPD. Seven target genes and regions were selected and analyzed after literature review (TM7SF4, SQSTM1, TNFRSF11A, TNFRSF11B, OPTN, CSF1, VCP). No clear pathogenic mutation was found, but we detected missense polymorphisms in CSF1 and TM7SF4 genes. After treatment with zoledronic acid, infusion bone pain and ALP level decreased. We can conclude that intravenous zoledronic acid therapy is effective and safe for suppressing bone turnover and improving symptoms in JPD, but the long-term effects on clinical outcomes are unclear. Our findings also suggest that NGS may help explore the pathogenesis and aid the diagnosis of JPD.

[The impact of thyroid function in women of reproductive age: infertility, pregnancy and the postpartum period]. / A pajzsmirigymuködés jelentosége fertilis korú nokben: meddoség, terhesség és a post partum idoszak.

This article reviews the management and diagnosis of thyroid dysfunction during pregnancy and postpartum, which was published by any of the endocrine societies in 2012. The author presents human data based on these clinical practice guidelines, however, there are also many unresolved questions. Especially, there are inconsistencies about screening using plasma TSH measurement. In pregnancy the main causes of hyperthyroidism are Graves's disease and gestational transient thyrotoxicosis. Generally, gestational transient thyrotoxicosis does not require medication, whereas Graves's disease needs antithyroid drug therapy. Postpartum thyroiditis occurs more frequently in antithyroid peroxidase-positive women, who should be screened using serum thyrotropin measurements at 6 to 12 gestation weeks and at 3 and 6 months postpartum. Because overt maternal hypothyroidism, due to autoimmune pathophysioloical mechanisms, negatively affects the fetus, timely recognition and treatment are important. The subclinical form of maternal hypothyroidism should also be treated. A link between thyroid dysfunction and infertility has been warranted.

[Impact of vitamin D in neurological diseases and neurorehabilitation: from dementia to multiple sclerosis. Part I: the role of vitamin D in the prevention and treatment of multiple sclerosis]. / A D-vitamin jelentosége neurológiai kórképekben és a neurorehabilitációban: a dementiától a sclerosis multiplexig. I. rész: a D-vitamin szerepe a sclerosis multiplex megelozésében és kiegészíto kezelésében.

The world-wide incidence of vitamin D deficiency is high, independently of age. Multiple sclerosis is a chronic disorder, occuring in those who possess or are exposed to a combination of genetic and environmental risk factors. One of the environmental factors associated with the development is vitamin D. Vitamin D is an immunomodulatory agent, its role is verified in many of autoimmune diseases. Vitamin D inhibits IL-6, IL-17 and IL-23 secretions which are crucial in Th1 and Th17 differentiation and also decreases proinflammatorical cytokine production. Moreover it enhances the immunosuppressive IL-10 cytokine secretion and inhibits the T-reg cell development. These cytokines and cells are essential for the pathomechanism of multiple sclerosis. Data have shown, that the vitamin D levels above 100 nmol/l (40 ng/ml) is essential for the prevention of multiple sclerosis. Below this level the vitamin D supplementation is reasonable. In pregnancy, the vitamin D deficiency at the last two semester increases the risk for the multiple sclerosis of the infant. The optimal vitamin D level for multiple sclerosis patients is 100-150 nmol/l (40-60 ng/ml). There is no consensus for the role of vitamin D in multiple sclerosis yet, but until the achieving this, the diagnosis and the treatment of the vitamin D deficiency is crucial for scelrosis multiplex patients and in cases of elevated risk. Data shows, that in patient with multiple sclerosis the normal vitamin D level is suboptimal, however the exact role of vitamin D and doses must be clarified by interventional studies.

The role of vitamin D, estrogen, calcium sensing receptor genotypes and serum calcium in the pathogenesis of prostate cancer.

INTRODUCTION: Prostate cancer is the second leading cause of cancer death among men in developed countries. Estrogen receptor-alpha (ER-α), vitamin D receptor (VDR), and the calcium-sensing receptor (CaSR), partly through their effects on calcium levels are implicated in the proliferation and carcinogenesis in the prostate gland. VDR, ER-α and CaSR genes show polymorphisms in humans that appear to have clinical significance in many pathological conditions, such as prostate cancer. Our aim was to evaluate the role of ER-α (PvuII, XbaI), VDR (BsmI) and CaSR (A986S) gene polymorphisms and serum calcium levels in the pathogenesis of prostate cancer. MATERIAL AND METHODS: Two hundred four patients with prostate cancer and 102 healthy controls were recruited into a hospital-based case control study. After genotyping, the relationship between the individual genotypes and prostate cancer was investigated. RESULTS: Both the ER-α XbaI and the VDR BsmI polymorphisms were significantly related to the risk of prostate cancer. An age adjusted logistic regression limited to controls and patients not receiving bisphosphonate therapy showed that higher corrected serum calcium and the VDR Bb/BB genotypes independently increased the risk of prostate cancer. CONCLUSIONS: ER-α XbaI and VDR BsmI genetic polymorphisms had a significant association with the risk of prostate cancer. Both VDR BsmI genotypes and serum calcium levels were independently related to the risk of prostate cancer, suggesting an influence of VDR on the development of this malignancy.

[Comparative study of somatic oncogene mutations in normal thyroid tissues and thyroid neoplasms]. / Szomatikus onkogén mutációk összehasonlító vizsgálata egészséges és tumoros pajzsmirigy-szövetmintákban.

It is established that numerous somatic oncogene mutation (BRAF, NRAS, HRAS, KRAS) and gene translocations (RET/PTC, PAX8/PPAR-gamma) are associated with the development of thyroid cancer. In this study 22 intraoperative thyroid tissue samples (11 pathologic and 11 normal) were examined. Somatic single nucleotide polymorphisms were analyzed by LigthCycler melting method, while translocations were identified by real-time polymerase chain reaction technique. In tumorous sample 3 BRAF, 2 NRAS and one HRAS mutations were found, as well as one RET/PTC1 translocation. Results confirm international data showing that these oncogene mutations and translocations are linked to thyroid cancer. Cytological examination completed with genetic data may support the diagnosis of thyroid malignancies. In addition, genetic alterations may indicate malignant transformation and may become prognostic factors in future.

Gene expression patterns in the bone tissue of women with fibrous dysplasia.

Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in the fibro-osseous lesions. The aim of our investigation was to identify genes that are differently expressed in fibrous versus non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from female patients with fibrous dysplastia (FD) and seven bone tissue samples from women without FD (non-FD) were examined. The expression differences of selected 118 genes were analyzed by the TaqMan probe-based quantitative real-time RT-PCR system. The Mann-Whitney U-test indicated marked differences in the expression of 22 genes between FD and non-FD individuals. Nine genes were upregulated in FD women compared to non-FD ones and 18 genes showed a downregulated pattern. These altered genes code for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines, and lipid metabolism-affected substrates. Canonical variates analysis demonstrated that FD and non-FD bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. The remarkable changed gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

[Verner-Morrison syndrome: a case study]. / Verner-Morrison-szindróma egy esete.

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1.

[Changes of gene expression and its role in pathogenesis in fibrous and non-fibrous dysplastic bone tissues in women]. / A génexpresszió változásai és patogenetikai jelentôségük fibrosus dysplasiás és nem fibrosus dysplasiás nôk csontszövetében.

UNLABELLED: Fibrous dysplasia is an isolated skeletal disorder caused by a somatic activating mutation of GNAS1 gene with abnormal unmineralized matrix overproduction and extensive undifferentiated bone cell accumulation in fibro-osseous lesions. The aim of the investigation was to identify genes that are differently expressed in fibrous vs. non-fibrous human bone and to describe the relationships between these genes using multivariate data analysis. MATERIALS AND METHODS: Six bone tissue samples from fibrous dysplastic female patients and 7 bone tissue samples from non-fibrous dysplastic women were examined. The 6 female fibrous samples were taken from the fibrous dysplastic lesion itself while the control samples of 7 non-fibrous dysplastic females were taken from the femoral neck during the hip replacement procedure. The expression differences of selected 118 genes were analyzed in TaqMan probe based quantitative real-time RT-PCR system. RESULTS: The Mann-Whitney U test indicated significant differences in the expression of 27 genes of fibrous dysplasial and non fibrous dysplasial individuals (p≤0.05). Nine genes were significantly up-regulated in fibrous dysplasial women compared to non fibrous dysplasial ones and eighteen genes showed a down-regulated pattern. These significantly altered genes coding for minor collagen molecules, extracellular matrix digesting enzymes, transcription factors, adhesion molecules, growth factors, pro-inflammatory cytokines and lipid metabolism-affected substrates. Canonical variety analysis demonstrated that fibrous dysplastic and non fibrous dysplastic bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via a G-protein coupled pathway and BMP cascade as well as genes coding for extracellular matrix composing molecules. CONCLUSIONS: The significantly altered gene expression profile observed in the fibrous dysplastic human bone tissue may provide further insight into the pathogenetic process of fibrous degeneration of bone.

[The role of vitamin D in the prevention and the additional therapy of cancers]. / A D-nap. A D-vitamin helye a daganatprevencióban és a kiegészíto kezelésben.

The active metabolite of vitamin D apart from a crucial role in maintaining mineral homeostasis and skeletal functions, has antiproliferative, apoptosis and differentiation inducing as well as immunomodulatory effects in cancer. It is well known that with increasing sunshine exposure the incidence of breast, prostate and colorectal cancer is decreasing. A number of in vitro and in vivo experiments documented the effects of vitamin D in the inhibition of the tumorigenesis. In studying the role of vitamin D in cancer, it is imperative to examine the potential pathways that control local tissue levels of vitamin D. The enzyme 24-hydroxylase converts the active vitamin D to inactive metabolite. Extra-renal production of this enzyme is observed and has been increasingly recognized as present in cancer cells. This enzyme is rate limiting for the amount of local vitamin D in cancer tissues and elevated expression is associated with an adverse prognosis. 24-hydroxylase may be a predictive marker of vitamin D efficacy in patients with cancer as an adjunctive therapy. There are many vitamin D analogs with no pronounced hypercalcemizing effects. Some analogs are in phase 1 and 2 clinical test, and they might have a role in the therapy of several types of cancer. At present our main task is to make an effort to decrease the vitamin D deficiency in Hungary. Speer G. The D-day. The role of vitamin D in the prevention and the additional therapy of cancers.

[Assessment of patient-reported outcomes by questionnaires in patients with Moderate and severe chronic obstructive pulmonary disease treated with glycopyrroniUm in the reaL lifE setTing in Hungary (AMULET)]. / Glikopirróniummal kezelt középsúlyos és súlyos krónikus obstruktív tüdobetegek állapotának kérdoíves értékelése valós körülmények között. AMULET-vizsgálat.

Introduction: Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder, therefore, airflow limitation alone does not reflect the full burden of COPD. In Hungary, no national data are available yet about the results obtained with the different COPD questionnaires in daily patient care, and about difficulties of questionnaires for patients. Aim and method: The aim of the study was to evaluate patient-reported outcomes with guideline-suggested questionnaires (CCQ, CAT, mMRC, EQ-5D-5L) in patients treated with glycopyrronium-bromide (therapy naïve, add-on combination or switch from another therapy) in the real life setting during 16 weeks treatment. This study was open-label, multi-centre, non-interventional, observational. Results: 527 patients were enrolled in the study (mean age: 63.8 ± 9.64 years, mean FEV1: 59.8 ± 15.12%). In all of the groups, the CCQ mean scores, all of the CCQ subscores, CAT and mMRC scores significantly decreased from visit 1 to visit 3. The EQ-5D-5L index and VAS scores increased significantly between visits. According to investigators' opinion, the CAT test reflects the patient's condition better (84.7%) than CCQ or mMRC; also, from the patient's point of view, CAT was simpler and easier to understand (83.2%). There was a positive, statistically significant correlation between CCQ and CAT (rs = 0.711, p<0.001), between CCQ and mMRC (rs = 0.524, p<0.001) and between CAT and mMRC scores at visit 3 (rs = 0.475, p<0.001). Conclusion: Our results suggest that the CAT test may be simpler and easier to understand for patients. Also, according to investigators' opinion, CAT reflects the patient's condition better, so CAT appears to be the most promising tool in COPD evaluation. Orv Hetil. 2020; 161(8): 295-305.

Transcriptional profiling of immune system-related genes in postmenopausal osteoporotic versus non-osteoporotic human bone tissue.

The functional interaction between the immune system and bone metabolism has been established at both molecular and cellular levels. We have used non-parametric and multidimensional expression pattern analyses to determine significantly changed mRNA profile of immune system-associated genes in postmenopausal osteoporotic (OP) vs. non-osteoporotic (NOP) bone tissue. Seven bone tissue samples from OP patients and ten bone tissue samples from NOP women were examined in our study. The transcription differences of selected 44 genes were analyzed in Taqman probe-based quantitative real-time RT-PCR system. Mann-Whitney test indicated significantly down-regulated transcription activity of 3 genes (FCGR2A, NFKB1 and SCARA3) in OP bone tissue which have prominent role in (antibody) clearance, phagocytosis, pathogen recognition and inflammatory response. According to the canonical variates analysis results, the groups of postmenopausal OP and NOP women are separable by genes coding for cytokines, co-stimulators and cell surface receptors affected in innate immunity which have high discriminatory power. Based on the complex gene expression patterns in human bone cells, we could distinguish OP and NOP states from an immunological aspect. Our data may provide further insights into the changes of the intersystem crosstalk between the immune and skeletal systems, as well as into the local immune response in the altered microenvironment of OP bone.

Postmenopausal expression changes of immune system-related genes in human bone tissue.

INTRODUCTION: The molecular and cellular interactions between the immune system and bone tissue have been established. Sex hormone deficiency after menopause has multifunctional role by influencing growth, differentiation, and metabolism of the skeletal and the immune system. DISCUSSION: We have used nonparametric and multidimensional expression pattern analyses to determine significantly changed mRNA profile of immune system-associated genes in postmenopausal (POST) and premenopausal (PRE) nonosteoporotic bone. Ten bone tissue samples from POST patients and six bone tissue samples from PRE women were examined in our study. The transcription differences of the selected 50 genes were analyzed in TaqMan probe-based quantitative real-time reverse transcriptase polymerase chain reaction system. Mann-Whitney test indicated significantly downregulated transcription activity of three genes (CD14, HLA-A/MHCI, ITGAM/CD11b) and upregulated expression of six genes (C3, CD86/B7-2, IL-10, IL-6, TGFB3, TNFSF11/RANKL) in postmenopausal bone. According to the canonical variate analysis results, the groups of POST and PRE women are separable by genes coding for cytokines, costimulator molecules, and cell surface receptors involved in antigen presentation and T cell stimulation processes which have high discriminatory power. Based on a complex gene expression pattern analysis of human bone tissue, we could distinguish POST and PRE states from an immunological aspect. Our data might provide further insight into the changes of the intersystem crosstalk between immune and skeletal homeostasis, as well as local immune response in the altered microenvironment of postmenopausal bone.

Abnormal glucose tolerance is associated with diminished postload change in leptin levels in women.

BACKGROUND: It is generally accepted that the metabolic effects of leptin are diminished in the obese due to leptin resistance. Hormone resistance may develop if diurnal (including meal-related) changes in hormone levels are disrupted. We sought to describe leptin changes after a 75 g oral glucose tolerance test (OGTT) in women with a prior diagnosis of gestational diabetes mellitus (a high risk group for the metabolic syndrome) compared to that in healthy controls. METHODS: In 2000 a retrospective cohort study was performed on women who had been diagnosed with gestational diabetes mellitus (WHO criteria 1985, n = 57) between 1996 and 1998 and on a healthy control female group (n = 36) all of whom had had a prior pregnancy without any diagnosis of diabetes. All the women underwent a standard 75 g OGTT. Serum leptin was measured by radioimmunoassay before and 90 min after the OGTT. RESULTS: Using multilevel models of change, fasting leptin levels were shown to be associated with body mass index; 10.1% (95% CI 8.1-12.1%) increase per 1 kg/m(2) increase in body mass index), homeostasis model assessment insulin sensitivity; 0.4% (95% CI 0.2-0.7%) decrease per 1% increase in insulin sensitivity); abnormal glucose tolerance (24% decrease, 95% CI 8-37%); and smoking (31% decrease, 95% CI 16-44%). Postload (90 min) leptin levels decreased significantly in women with normal glucose tolerance by 13% (95% CI 8-18%), while no significant change in postload leptin level was apparent in women with abnormal glucose tolerance (3% increase, 95% CI -4% to 29%). CONCLUSIONS: Disturbed leptin changes were found following an OGTT in women with abnormal glucose tolerance that might be either a cause or a consequence of leptin resistance.

Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population.

BACKGROUND: Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT) gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR) gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation. METHODS: 538 Hungarian subjects were studied: 278 patients with colorectal cancer and 260 healthy controls. Median follow-up was 17 months. After genotyping, the relationship between LCT 13910 C/T and CaSR A986S polymorphisms as well as tumor incidence/progression was investigated. RESULTS: in patient with colorectal cancer, a significantly higher LCT CC frequency was associated with increased distant disease recurrence (OR = 4.04; 95% CI = 1.71-9.58; p = 0.006). The disease free survival calculated from distant recurrence was reduced for those with LCT CC genotype (log rank test p = 0.008). In case of CaSR A986S polymorphism, the homozygous SS genotype was more frequent in patients than in controls (OR = 4.01; 95% CI = 1.33-12.07; p = 0.014). The number of LCT C and CaSR S risk alleles were correlated with tumor incidence (p = 0.035). The CCSS genotype combination was found only in patients with CRC (p = 0.033). CONCLUSION: LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC.

Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients.

BACKGROUND: Osteoprotegerin (OPG) is a marker and regulator of arterial calcification, and it is related to cardiovascular survival in haemodialysis patients. The link between OPG and aortic stiffening--a consequence of arterial calcification--has not been previously evaluated in this population, and it is not known whether OPG-related mortality risk is mediated by arterial stiffening. METHODS: At baseline, OPG and aortic pulse wave velocity (PWV) were measured in 98 chronic haemodialysis patients who were followed for a median of 24 months. The relationship between OPG and PWV was assessed by multivariate linear regression. The role of PWV in mediating OPG related cardiovascular mortality was evaluated by including both OPG and PWV in the same survival model. RESULTS: At baseline mean (standard deviation) PWV was 11.2 (3.3) m/s and median OPG (interquartile range) was 11.1 (7.5-15.9) pmol/L. There was a strong, positive, linear relationship between PWV and lnOPG (P = 0.009, model R(2) = 0.540) independent of covariates. During follow-up 23 patients died of cardiovascular causes. In separate univariate survival models both PWV and lnOPG were related to cardiovascular mortality [hazard ratios 1.31 (1.14-1.50) and 8.96 (3.07-26.16), respectively]. When both PWV and lnOPG were entered into the same model, only lnOPG remained significantly associated with cardiovascular mortality [hazard ratio 1.11 (0.93-1.33) and 7.18 (1.89-27.25), respectively). CONCLUSION: In haemodialysis patients OPG is strongly related to PWV and OPG related cardiovascular mortality risk is, in part, mediated by increased PWV.

[Osteoprotegerin: regulator, protector and marker]. / Osteoprotegerin: a regulátor, a protektor és a marker. Osszefoglalás irodalmi adatok és saját eredményeink alapján.

Experimental and clinical trials in the field of bone biology helped to clarify the role of receptors, which belong to the tumor necrosis factor family, such as osteoprotegerin and receptor activator of nuclear factor kappaB (RANK), in the regulation of bone remodeling. The ligand of the receptor activator of nuclear factor kappaB (RANKL) is a stimulator of bone resorption, while osteoprotegerin is the soluble "decoy" receptor to RANKL, protecting thereby bone from resorption. Pathological states of bone remodeling (like osteoporosis) are associated with imbalance in the activity of osteoprotegerin and the receptor activator of nuclear factor kappaB. Recent studies, however, also indicate that the osteoprotegerin/RANKL/RANK system has important roles in the regulation of the immune and vascular system as well. In this review we summarize the function and regulation of osteoprotegerin, its role in pathological states--primarily in cardiovascular diseases--and its relevance as a marker of cardiovascular risk. Finally, we present our prospective trial performed among the chronic dialyzed patients, where we examined the association between the cardiovascular mortality, osteoprotegerin levels and the arterial stiffness.

Effect of gypsum on proliferation and differentiation of MC3T3-E1 mouse osteoblastic cells.

Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable osteoconductive bone void filler. However, its exact mechanism of action on bone cells is yet unknown. In this study, the influence of gypsum on gene expression and proliferation of MC3T3-E1 mouse pre-osteoblastic cells was investigated. Cells were cultured on gypsum disc, slice, polymethylmethacrylate (PMMA), or plastic culture plate for 15 days. Cell viability, alkaline phosphatase (ALP) activity and expression profile of 15 genes involved in bone metabolism were measured in cultures. Cell proliferation on gypsum was increased by almost 2-fold, while an inhibitory effect of PMMA on proliferation rate of osteoblasts was noted. Cells cultured on gypsum disc surface exhibited an increased ALP activity and markedly different gene expression profile. Quantitative real-time PCR data indicated the expression of genes that might provide a basis for an osteoinductive potential. MC3T3-E1 cells expressed genes typical of bone fracture healing like type II collagen and fibronectin 1. These effects might be related to the calcium content of gypsum and mediated likely via SMAD3. Our results suggest that gypsum can support new bone formation by its calcium content and modulatory effect on gene expression profile of bone cells.

[Impact of CYP3A7*1C polymorphism on bone mineral content in postmenopausal women]. / A CYP3A7*1C-polimorfizmus hatása a csont ásványanyag-tartalmára posztmenopauzás nokben.

INTRODUCTION: CYP3A7*1C polymorphism has been shown to be associated with lower levels of serum dehydroepiandrosterone sulphate in men. The age-related decline of dehydroepiandrosterone sulphate levels is believed to contribute to the development of osteoporosis. We hypothesized that CYP3A7*1C may lead to bone loss through decreased levels of dehydroepiandrosterone sulphate in postmenopausal women. PATIENTS AND METHODS: 319 postmenopausal women were studied and divided into two subgroups: 217 women with osteoporosis and 102 aged-matched women without osteoporosis. The CYP3A7*1C polymorphism was genotyped. Serum dehydroepiandrosterone sulphate levels and bone mineral density were measured. RESULTS: Homozygous CYP3A7*1C carriers had significantly lower bone mineral density at lumbar spine than that of wild type (T-score with CYP3A7*1C mutant type: -3.27 +/- 1.02, T-score with wild type: -1.35 +/- 1.53, p = 0.041) after adjusting for age and DHEAS levels. No association was found between genotypes and dehydroepiandrosterone sulphate levels. CONCLUSION: Our data suggest that CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum dehydroepiandrosterone sulphate concentrations.