Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter.

Introduction: Papillary thyroid carcinoma (PTC) and colloid goiter (CG) represent the most common thyroid malignant and benign diseases, respectively. Oxidative stress is considered to have an important role in the pathogenesis of both diseases, but without sufficient and comprehensive data. The aim was to evaluate the redox profile, its influence on cell survival of PTC, comparing it with CG as a control and its relation with demographic, pathological and clinical parameters. Material and methods: We evaluated for the first time the PTC and CG tissue profile of advanced oxidation protein products (AOPP) and total thiols as parameters of redox metabolism and deoxyribonuclease I (DNase I) and deoxyribonuclease II (DNase II) activity as biomarkers of cell turnover and apoptosis. Tissue levels of biochemical parameters were quantified in PTC and CG tissue using spectrophotometric methods. Study parameters were evaluated in light of different demographic, clinical and pathological features of PTC and CG. Results: Papillary thyroid carcinoma tissue is characterized by increased antioxidant activity and a normal prooxidation level. Biochemical parameters show numerous correlations with demographic and clinical characteristics of PTC and CG patients. DNase I and II activities are dependent upon the AOPP concentration in PTC tissue. The size of CG can be predicted with combined use of AOPP, DNase I and DNase II. AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype. Conclusions: Evaluated parameters can be used for assessment of tumor redox and survival status and the clinical course of PTC and CG.

Chloroquine Attenuates Oxidative Stress in Gentamicin-Induced Nephrotoxicity in Rats.

The wider application of gentamicin is limited by potential adverse effects (nephrotoxicity and ototoxicity). The goal of our study was to investigate the effects of chloroquine on biochemical and oxidative stress parameters in gentamicin-induced nephrotoxicity in rats. Animals were randomly divided into 1 of 5 groups. First was Sham group (0.9% NaCl) (n = 8); second group received gentamicin (n = 8); while third (n = 8), fourth (n = 8) and fifth group (n = 8) received gentamicin and chloroquine in a dose of 0.3, 1 and 3 mg/kg, respectively. The urea and creatinine levels were significantly lower in chloroquine treated groups in doses of 0.3 mg/kg and 1 mg/kg (P < 0.001). Total oxidant status and the oxidative stress index showed significantly lower values in all chloroquine treated groups (P < 0.001; P < 0.005). Malondialdehyde was lower in chloroquine treatment in doses of 0.3 mg/kg (P < 0.005) and 3 mg/kg (P < 0.05). Chloroquine treatment markedly reduced the level of superoxide dismutase in doses of 1 mg/kg (P < 0.01) and 3 mg/kg (P < 0.05). Our study showed that chloroquine attenuates gentamicin-induced nephrotoxicity in rats regarding biochemical and oxidative stress parameters.

Child Neurology: Bartonella henselae Neuroretinitis in 2 Patients.

Neuroretinitis due to Bartonella henselae infection is a rare cause of vision loss in children. Two pediatric cases of acute unilateral vision loss accompanied by edema of the optic nerve on fundoscopic examination are presented. Severe causes of vision loss were excluded. During the course of the disease, macular stellate exudates emerged on control fundoscopic examinations, and diagnosis of neuroretinitis was made. A causative agent was confirmed by serologic examination, as high titers of IgM and IgG antibodies to Bartonella henselae were detected. Both patients significantly recovered after oral antibiotic treatment.

Profiling of Circulatory Elements Reveals Alteration of Essential and Toxic Trace Metals in Crohn's Disease.

The status of essential and toxic trace metals in the blood of Crohn's disease (CD) patients is unexplained. This study aimed to provide the first elemental profiling of the most recognized essential elements (Mn, Cu, Zn, Se) and selected toxic trace elements (As, Cd, Pb, and U) in sera and cell lysate (CL) samples of CD patients (n = 84). The results were compared with sex- and age-matched samples from the control group (CG). CD sera contained significantly higher levels of Mn, As, Cd, Pb, and U than did CG sera. An identical pattern, with the added inclusion of Cu (also higher in CD patients than in the CG), was obtained for CL samples. However, the most important finding was hypermanganesemia, which indicates that Mn could act as a toxic trace metal in CD. As, Cd, and U were the most significant toxic elements that showed antagonistic effects on the extrusion of essential Mn and Cu. Circulatory system screening markers for CD are hereby proposed (Mn/Cu, Mn/As, and Mn/Pb ratios). These three metal ratios were strongly and significantly correlated with F-Calprotectin levels, and deserve consideration as new markers of CD. The target metals and metal ratios should be taken into consideration as novel initiating and/or modifying factors for CD.

Circulatory Imbalance of Essential and Toxic Trace Elements in Pre-dialysis and Hemodialysis Patients.

The status of essential and toxic trace elements in patients with different stages of chronic kidney disease (CKD) is still unclear and not well characterized. The present study examined the circulatory levels of a wide panel of trace elements (Al, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Pb, and U) in hemodialysis patients (HD group) and pre-dialysis patients with stage 3 CKD (PD group). Comparisons were made between groups of patients and healthy individuals from the control group (CG). The levels of Al, Mn, Co, Ni, Cu, As, Se, Sr, and Pb were higher, while the levels of Cr, Zn, Rb, Cd, and U were lower in HD patients than in our CG. Higher levels of Al and Se, as well as lower levels of As, Sr, Zn, Rb, and U were significant and distinguished HD from PD. Among other analyzed elements, Co, Se, and U are the only trace elements that did not distinguish PD from CG at a statistically significant level. The HD group had lower serum U levels than the PD group, and this could be a result of hemodialysis. This study also revealed that the Cu/Zn ratio could be used as a marker for early and late detection of renal failure. Marked changes of essential and toxic trace element levels in sera indicate additional pathophysiological events in CKD, which could additionally contribute to the preexisting increased morbidity of HD patients. Measurement of trace elements in HD patients should be performed routinely.

Elemental Composition of Pheochromocytoma Resolved on Solid/Adrenal Tissue and Whole Blood Level.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients' healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients' blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC.

The usefulness of visual evoked potentials in the assessment of the pediatric multiple sclerosis.

BACKGROUND: To evaluate the significance of visual evoked potentials (VEP) in the early diagnosis of optic neuritis (ON) and detecting clinically silent lesions in pediatric multiple sclerosis (PedMS). This study represents one of the largest series of PedMS which evaluated characteristics of VEP in PedMS patients. METHODS: This was a retrospective study on 52 PedMS patients, aged 7-17 years. VEP analysis were done for all patients, after the first attack of disease and were compared to control subjects according to the pattern-reversal VEP findings. RESULTS: The mean age of patients was 15.65 ± 1.89 years with male to female ratio of 16 (30.8%): 36 (69.2%). All of the patients had a relapsing-remitting course of the disease. ON was discovered on the initial attack in 18 (34.6%) patients, while 30 (57.7%) patients had ON in the second attack. Pathological VEP findings were present in 40 (76.9%) patients, of which 22 (42.3%) PedMS patients had clinically silent lesions. Prolonged latency of P100 waves in the PedMS group was statistically significant when compared to control subjects. The amplitude N1P1 showed a correlation with residual visual deficit. CONCLUSION: Our results show that ON is a common initial manifestation of PedMS in the Serbian PedMS population. The prolonged P100 latency is the main indicator of ON. VEP is an objective, fast and accessible diagnostic method for detecting clinical and subclinical lesions. Thus, VEP deserves evaluation to be considered as an additional criterion for PedMS diagnosis.

Human biomonitoring of essential, nonessential, rare earth, and noble elements in placental tissues.

Exposure to certain metals has been recognized as a risk factor for numerous complications in vulnerable population groups, particularly pregnant women. This investigation evaluated the levels of essential (Cr, Mn, Co, Cu, Zn, Se, Mo) and nonessential trace metals with recognized toxicity (Be, Al, Ti, V, Ni, Ga, As, Rb, Sr, Cd, Sb, Ba, Tl, Hg, Pb, Bi, Th, U), together with rare earth elements (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu), and noble metals (Ru, Rh, Pd, Re, Os, Ir, Pt, Au, Ag) in the placental tissues of healthy pregnant women (n = 105). The selection of participants was undertaken with special reference to specific confounding factors that could influence the trace element profiles. Among trace elements, Zn was the most abundant and Lu was the least abundant. Cd and Os placental levels show a tendency to increase with women's age. Compared with literature data, high levels of Ni were found. This is the first study that provides the composition levels of essential and toxic trace elements, rare earth elements, and noble metals in human placental tissues. Also, for the first time, normal (reference) ranges for 50 (ultra)trace elements in placental tissues are proposed. Reference ranges are especially important in biomonitoring studies, which nowadays give increasing importance to the analysis of solid tissues instead of body fluids. Overall, the information provided in this study can serve as a starting point for further clinical trials and/or prediction of potential risks to pregnancy.

Evaluation of Genetic Damage in Persons Occupationally Exposed to Antineoplastic Drugs in Serbian Hospitals.

INTRODUCTION: Although useful in the treatment of malignant cells, antineoplastic drugs (ANPDs) as chemical genotoxic agents, can interfere with normal cell physiology causing genetic damage and unfavourable health effects, especially in occupationally exposed persons. The Cytokinesis-block Micronucleus (CBMN) Cytome assay has been widely used in human biomonitoring studies as a reliable biomarker of chemical genotoxic exposure. OBJECTIVES: Our comprehensive research was conducted in order to evaluate micronuclei as a marker for preventive medical screening purposes for persons occupationally exposed to ANPDs. METHODS: Using the CBMN Cytome test, peripheral blood lymphocytes of 201 control and 222 exposed subjects were screened for genetic damage. RESULTS: Age and gender influenced micronucleus (MN) frequency, but smoking habit did not. The mean micronuclei frequencies and other parameters of the CBMN Cytome test [numbers of binuclear lymphocytes with one (MN1) or two (MN2) micronuclei] were significantly higher in the group of exposed persons. Positive correlation between duration of occupational exposure and MN frequency was revealed. CONCLUSIONS: The results of our study performed on a large sample confirmed the capacity of the CBMN Cytome assay to serve as a reliable biomarker of long-term ANPD exposure.

Possible zinc deficiency in the Serbian population: examination of body fluids, whole blood and solid tissues.

Studies indicate that the soil, water and consequently foodstuffs in Serbia are significantly poor in zinc (Zn), and thus, it is likely that there is a Zn deficiency in the Serbian population. This study examined the Zn status in multiple clinical samples, including body fluids (serum, cerebrospinal fluid), whole blood and Zn-rich solid tissues (thyroid and brain tissue). Differences between sex and age were also considered, and comparative analysis of Zn status with other world populations was performed. Serum samples from a large number of Serbian adults approximately had twofold lower Zn amounts when compared to other populations. A similar trend was obtained for whole blood. Males had significantly higher amounts of Zn in serum, whole blood and thyroid tissue samples than females. Higher amounts of Zn were observed in the group older than 50 years. Importantly, in thyroid and brain tissues, Zn was 10- and 20-fold lower, respectively, than reported in the literature. Our results indicate that the population in Serbia could be considered Zn deficient. Therefore, adequate oral Zn supplementation and/or foodstuff fortification should be considered to prevent the deleterious effects caused by Zn deficiency.

Alteration of Trace Elements in Multinodular Goiter, Thyroid Adenoma, and Thyroid Cancer.

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases.

The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease. OBJECTIVE: Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice. METHODS: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation. RESULTS: In MIF-/-mice, TAA reduced transaminases, γ-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-γ, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols. CONCLUSION: MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.

The first insight into the trace element status of human adrenal gland accompanied by elemental alterations in adrenal adenomas.

BACKGROUND: The baseline status of trace metals in adrenal tissue is unresolved, while the elemental profile for any adrenal pathology has not been examined so far. This study aimed to determine the baseline status of important toxic (Ni, As, Cd, Pb, Th, U) and essential trace elements (Mn, Co, Cu, Zn, Se) in healthy adrenal tissues (HATs) as well as to examine whether there are alterations in the elemental composition of adenomatous adrenal tissues (AATs). Furthermore, this study aimed to find potential trace metals that could play a role in the pathogenesis of adrenal adenoma (AA). METHODS: The study included 45 patients diagnosed with AA. Impacts of relevant parameters such as gender, age, smoking habits and nodular sizes were considered. All samples were subjected to microwave digestion and the trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: This is the first study that provided an insight into the elemental status of HATs. It was also shown that AATs had altered trace metal contents. Compared to HATs, the most significant findings were related to the high content of essential (Cu, Mn, Se, Zn) and Pb as a non-essential metal. Although gender, age and smoking habits had a modest effect on metal profiles, the most significant alterations were related to the nodular diameter above 4 cm, indicating that the growth of benign tumor could influence changes in elemental composition. CONCLUSION: For the first time the baseline contents of essential and toxic trace metals in HATs were determined. The results of this study may highlight the role of toxic and essential trace metals in AAs and could provide new insights into the molecular basis of pathophysiological changes caused by the hazardous effects of trace metals on adrenal structure and function.

Oxidative Stress Profile in Genetically Confirmed Cases of Leber's Hereditary Optic Neuropathy.

The mechanisms of the complex pathophysiology of Leber's hereditary optic neuropathy (LHON) are still insufficiently clarified. The role of oxidative stress as an etiological factor has been proposed and demonstrated in vitro, but without conclusive data that rely on clinical samples. The aim of the study was to evaluate and characterize the existence of oxidative stress in the plasma of LHON patients and healthy individuals. Whole mitochondrial genome sequencing has been performed in order to identify primary LHON mutations. For the assessment of oxidative stress, the following biomarkers were determined in plasma: total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), while oxidative damage of cellular proteins was estimated by quantifying advanced oxidation protein products (AOPP). All three primary LHON mutations (m.3460G > A, m.11778G > A and m.14484 T > C) were identified as a genetic cause of the disease, where the most prevalent one was m.11778G > A. LHON patients have a highly significant increase of TOS and a marked decrease of TAS levels, which suggests the existence of substantial oxidative stress. OSI is high in LHON patients, which definitely implies the presence of redox imbalance. Elevated level of AOPP in LHON patients refers to the significant deleterious effects of oxidative stress on cellular proteins. Oxidative stress parameters do not significantly differ between LHON individuals with different primary mutations. Both symptomatic and asymptomatic LHON patients have an augmented level of oxidative stress which suggests that primary mutations exhibit a pro-oxidative phenotype. Gender and smoking habit significantly influence examined biochemical parameters when LHON patients are compared with the control group. Different mitochondrial haplogroups are characterized by altered levels of OSI in LHON group. The absence of physiological correlations between redox parameters reflects the deregulation of homeostatic oxidative/antioxidative balance in LHON patients. This is the greatest series of LHON patients that were evaluated for oxidative stress and the first case-controlled study that evaluated TOS, TAS, OSI, and AOPP and their influence on disease phenotype. It is evident that the presence of oxidative stress represents an important pathophysiological event in LHON and that it could potentially serve as a circulatory biomarker for a therapy efficacy understanding.

Characteristics of pediatric multiple sclerosis: A tertiary referral center study.

OBJECTIVE: The present study represents one of the largest series of pediatric multiple sclerosis (PedMS) in Western Balkan region. This is the first study aimed to evaluate the characteristics of PedMS in the Serbian population. METHODS: This retrospective study on 54 PedMS, aged 7-17 years, was performed at the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade, Serbia, a tertiary center for the diagnosis and treatment of children with neurological and psychiatric diseases. RESULTS: Female to male ratio was 37 (68.5%): 17 (31.5%). Family history of MS was noted in 9.3% and autoimmune diseases in 24.1% patients. Co-occurring migraine was in 7,4%. Monofocal onset of disease was present in 77.8% patients. The most common initial symptoms were optic neuritis (37%), sensory disturbances (31.5%), motor deficit (24.1%), cerebellar (18.5%) and brainstem lesions (16.7%), pain (9.3%), acute disseminated encephalomyelitis like symptoms (1.9%), and hearing loss (3.7%). Visual evoked potentials were pathological in 75.9% of patients. Oligoclonal bands were positive in 68.5% of patients. Magnetic resonance imaging showed periventricular (94.4%), infratentorial (77.8%), juxtacortical and cortical changes (55.6%) and changes in the cervical spinal cord (33.3%). The median EDSS score was 2.0. CONCLUSION: Our cohort significantly differs from the literature data regarding more frequent occurrence of optic neuritis, hearing loss as a first symptom, the relapsing-remitting course of the disease, higher proportion of early onset of disease, presence of co-occurring migraine and the frequent occurrence of epilepsy and other autoimmune diseases in the family.

Ectopic thyroid tissue in adrenal gland, case report and review of literature.

Ectopic thyroid tissue is a rare pathological finding bellow the diaphragm and extremely rare finding is ectopic thyroid tissue in the adrenal gland (ETTAG). Thyroid tissue can be located anywhere along the way of embryological migration pathway of thyroglossal duct. In most cases of ectopic thyroid tissue, it is located in the neck. Here we present a case of 29 years old patient that was laparoscopically operated because of adrenal incidentaloma which showed 28 mm in maximal diameter on MRI. The patient had normal adrenal function. Pathohistological finding confirmed ETTAG. Follicular cells express TTF-1, Thyroglobulin, PAX8, and cytokeratin 7, and lack expression of calretinin. This is the 15th such case described in literature. Women are much more affected than men (14:1), and it usually presents in the fifth decade (mean age 49). In all cases ETTAG was composed of normal follicular cells, and C cells were not found. Review of the literature reveals that adrenal ectopic thyroid tissue is almost always cystic, and has distinctive pathologic features. The most important thing is that ETTAG must be distinguished from metastatic deposits from thyroid gland carcinoma. Our patient had normal thyroid function, without any nodules in thyroid gland. We report the youngest patient with ectopic thyroid tissue located in the adrenal gland.

In silico model of mtDNA mutations effect on secondary and 3D structure of mitochondrial rRNA and tRNA in Leber's hereditary optic neuropathy.

The Leber's hereditary optic neuropathy (LHON) is a rare disease caused by mitochondrial DNA (mtDNA) mutations. Beside primary mutations, the effect of secondary mtDNA mutations in still unclear. We examined the effect of secondary mtDNA mutations on secondary structure of different mitochondrial RNAs. Whole mitochondrial genome sequence of LHON patients has been obtained from in six non related pedigrees by Sanger sequencing method. The effect of mutations located in mitochondrial RNA genes was examined by creating in silico models of RNA secondary and regional 3D structure, accompanied by sequence conservation analysis. All three primary LHON mutations (m.3460G>A, m.11778G>A and m.14484 T>C) were revealed in study families. Four mutations in MT-RNR1 gene (m.750A>G, m.956delC, m.1438A>G and m.1555A>G) were identified and only an m.1555A>G causes significant changes of secondary structure of mitochondrial 12S ribosomal RNA (rRNA), while it is the only mutation which does not alter its 3D structure. Five mutations (m.1811A>G, m.2706A>G, m.2831G>A, m.3010G>A and m.3197T>C) were discovered in MT-RNR2 gene and all of them induced substantial alterations of mitochondrial 16S rRNA secondary structure. Significant changes of mitochondrial 16S rRNA 3D structure are caused by m.1811A>G, m.2706A>G, m.3010G>A and m.3197T>C. A single insertion variant (m.15986insG) has been found in the MT-TP gene which encodes mitochondrial transfer RNA for Proline (tRNA Pro). This mutation does not cause substantial changes of tRNA for Proline secondary structure, while the 3D geometry remains without major changes. Most of the mutation loci exhibited high level of sequence conservation. Presence of multiple mutations in a single family appears to cause more extensive changes in mitochondrial 12S and 16S rRNA, then their individual influence. The effect of discovered mutations on in silico modelled RNA structure is in a significant correlation with the present knowledge about the potential of these mutation to participate in the pathophysiology of LHON and other human diseases. The presence of certain multiple mitochondrial RNA mutations could be a possible explanation of LHON clinical presentation in some families. All revealed mutations have been evaluated for the first time in terms of in silico structural modelling. The application of bioinformatics tools such as secondary and 3D RNA structure prediction can have a great advantage in better understanding of the molecular standpoint of the LHON pathophysiology and clinical phenotype.

Correction to: Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter.

The original version of this article unfortunately contained a mistake.

Significance of arsenic and lead in Hashimoto's thyroiditis demonstrated on thyroid tissue, blood, and urine samples.

Our previous investigation showed significantly increased arsenic (As) content in thyroid tissue samples of patients with Hashimoto's thyroiditis (HT). This research aimed to extend previous findings and provide reliable insight into the close relationship between As and other trace elements with HT by considering a greater number of thyroid tissue samples, accompanied by blood and urine samples. The essential trace elements for thyroid homeostasis (Mn, Cu, Zn, Se) and the main threatening toxic trace elements (Ni, As, Pb, Cd, U) was analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Relevant parameters that could affect the concentration of trace elements were considered. This research showed that there was a difference in the elemental profile between HT and control samples. The most important findings were related to the elevated As and Pb content in the thyroid tissue and HT blood samples. The obtained negative correlations between As and Pb with Se may explain the antagonistic effect of As and Pb on the extrusion of essential Se from the HT tissue. The reduced Se content in the blood and its increased content in urine samples may further confirm this hypothesis and explain the lack of Se in HT. Furthermore, the reported results may highlight the unresolved molecular basis of HT and could indicate the role of trace element effects on thyroid homeostasis.