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Journal Article 2018; 39(4): 325-330 PubMed PMID: 30531702 Citation  Keywords:  Adolescent, Adult, Diet, Dietary Exposure, Female, Humans, Meat, Milk, Human:chemistry, Trichothecenes:analysis, Turkey, Young Adult, Zearalenone:analysis,.   

INTRODUCTION: Zearalenone (ZEA) and deoxynivalenol (DON) are toxic fungal secondary metabolites, found mainly in contaminated food, that are associated with serious health problems. It is important to identify undesirable toxins and metabolites that may be present in human milk. The aim of this study was to evaluate human milk ZEA and DON levels, total daily intake of ZEA and DON; and their possible relationship with maternal dietary habits. METHODS: We enrolled 90 lactating mothers who had 7- to 90-day-old babies. A dietary questionnaire was completed by each of the mothers. Human milk samples were obtained from 90 mothers, and human milk ZEA and DON levels were evaluated with the solid-phase direct enzyme immunoassay. The total daily intake (TDI) was calculated for the 63 exclusively breastfed infants. RESULTS: ZEA was detected in all human milk samples; median was 173.8 ng/L (35.7-682 ng/L). The calculated median TDI for ZEA was 33.0 ng/kg body weight (bw) (10.4-120.5 ng/kg) among exclusively breast-fed infants, none of them had a TDI that was above the previously defined threshold levels. Human milk ZEA levels were associated with the maternal consumption of meat, fish, dry fig, dried apricot, flaked red spice and spice. The median DON levels was 3924 ng/L (400-14997 ng/L). The median TDI of DON was 750 ng/kg (240-2774 ng/kg) among exclusively breastfed infants and 36% out of them, the TDI for DON was above the previously defined threshold level. Human milk DON levels were associated with the maternal meat consumption. CONCLUSIONS: Our findings are indicative of dietary exposure to mycotoxins during the pregnancy and lactation periods in nursing mothers. Further, the excessive TDI values for DON observed in 36% of the exclusively breastfed infants point to the need for further regulations and recommendations on the dietary habits of pregnant/nursing mothers in order to avoid exposure to potential mycotoxins....

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Journal Article 2018; 39(4): 281-287 PubMed PMID: 30531701 Citation  Keywords:  Adolescent, Adult, Aged, Aged, 80 and over, Brain Neoplasms:radiotherapy, Female, Glioblastoma:radiotherapy, Humans, Male, Middle Aged, Neoplasm Recurrence, Local:radiotherapy, Palliative Care, Radiosurgery, Retrospective Studies, Survival Rate, Treatment.   

OBJECTIVE: Local recurrence of glioblastoma is observed in most patients after standard oncologic treatment (surgery, chemotherapy and radiotherapy). Stereotactic radiosurgery with the Leksell Gamma Knife (SRS with LGK) was used to treat recurrent tumors in selected cases, and retrospective analysis of treatment outcome was performed. METHODS: Altogether 126 patients were treated for glioblastoma at our center from 1992-2014. Sixty-nine patients (55%) were male and 57 (45%) female, with a median age of 56 years (range 17-80 years). Prior to LGK radiosurgery, 123 (98%) underwent surgery, 126 (100%) radiotherapy and 116 (92%) chemotherapy. The median Karnofsky score before LGK radiosurgery was 90% (range 50-100), and the median time from GBM diagnosis to LGK radiosurgery was 12 months (range 1-96 months). The median tumor volume was 3.75 cm3 (range 0.04-37.10 cm3). LGK radiosurgery was performed in a single fraction with a median minimal tumor dose of 12 Gy (range 10-25 Gy) on a median 50% (range 40-86%) isodose line. Two and more LGK radiosurgeries were performed in 19 (15%) cases, a median interval of 9.6 months (range 2-45 months) from the initial LGK radiosurgery. The median prescribed dose in these patients was 12.6 Gy (range 10-15 Gy), and the median volume 5.8 cm3 (range 0.1-13.7 cm3). RESULTS: The median survival from GBM diagnosis was 20 months (range 6-237 months). The median survival after LGK radiosurgery was 7 months (range 1-223 months). The one year survival after LGK radiosurgery was 27%, 2 years 8%, and more than 3 years 4%. Tumor regression on MR images was observed in 17% of patients at a median interval of 7 months. The median interval to tumor progression on MR images after LGK treatment was 8.5 months. No treatment-related radionecrosis with expansive behaviour was detected after radiosurgery. CONCLUSION: We show that LGK radiosurgery is a safe palliative treatment modality in patients with recurrent GBM....

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Journal Article 2018; 39(4): 288-293 PubMed PMID: 30531699 Citation  Keywords:  Adult, Chile, Circadian Rhythm, Depression:blood, Female, Humans, Hydrocortisone:blood, Male, Middle Aged, Primary Health Care,.   

BACKGROUND: Cortisol dysregulation has a potential role in depression. AIM AND METHODS: We evaluated depressive symptoms using the Hamilton Rating Scale for Depression in 48 primary care subjects without history of previous or current depression and its association with cortisol dysregulation (morning plasma cortisol, 24-hour urinary free cortisol and cortisol metabolites). Presence of metabolic syndrome and inflammatory parameters were also assessed. RESULTS: Hamilton Rating Scale for Depression correlated significantly with morning cortisol, but not with urinary free cortisol or metabolites. A significant increase in morning cortisol by Hamilton groups (asymptomatic ≤8; mild to moderate: 9-18; moderate to severe: ≥19) was observed even when adjusted by age/gender. We observed no association of depressive symptoms with metabolic or inflammatory parameters. CONCLUSION: Depressive symptoms in primary care subjects not consulting for their mood are associated with higher morning plasma cortisol, but not urinary cortisol or its metabolites. These observations suggest that systemic hypercortisolism and related metabolic disorders are not observed in mild/initial states of depressive disorders....

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Journal Article 2019; 39(7): 525-531 PubMed PMID: 30860684 Citation  Keywords:  5-Aminolevulinate Synthetase:biosynthesis, Animals, Arachidonate 15-Lipoxygenase:biosynthesis, Female, Gene Expression:drug effects, Growth Hormone:pharmacology, Hippocampus:metabolism, Hypophysectomy, Insulin-Like Growth Factor I:metabolism, Rats, Weight.   

OBJECTIVE: Growth hormone (GH) increases insulin-like growth factor I (IGF-I) production and both hormones affect hippocampal plasticity. We have previously shown that Hbb and Alas2 in the rat hippocampus were robustly regulated by GH-infusions for six days, whereas other transcripts were weakly affected. Here, we explored the effects of prolonged GH administration on transcripts linked to neuroprotection and investigated whether serum IGF-I administration may exert similar effects. DESIGN: Hypophysectomised female rats were infused with GH or IGF-I for 19 days. Hbb, Alas2 and seven additional GH- and IGF-I-related transcripts were quantified by Q-RT-PCR in rat hippocampus. RESULTS: Three transcripts, Hbb, Alas2, and Alox15 were increased by both GH and IGF-I administration. The other transcripts were marginally affected. CONCLUSION: The 19-day GH-infusion induced similar effects as those reported after 6-day GH treatment, with the addition of the regulation of transcript Alox15. IGF-I induced altered gene expression in relation to its effect on weight gain. This study underlines that there is an entity of transcripts involved in neuroprotection and vascular tone that is regulated by both systemic GH and IGF-I. For other transcripts, the longer duration of this study did not significantly enhance the marginal effects of GH administration seen previously....

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Journal Article 2019; 39(7): 515-524 PubMed PMID: 30860683 Citation  Keywords:  Anilides:pharmacology, Animals, Cytochrome P-450 Enzyme Inhibitors:pharmacology, Ellipticines:pharmacokinetics, Humans, Microsomes, Liver:drug effects, Oxidation-Reduction:drug effects, Peroxidases:antagonists & inhibitors, Phenylurea Compounds:pharmacolo.   

OBJECTIVES: Vandetanib¸ lenvatinib, and cabozantinib are tyrosine kinase inhibitors (TKIs) targeting VEGFR subtypes 1 and 2, EGFR and the RET-tyrosine kinase, thus considered as multiple TKIs. These TKIs have already been approved for treating patients suffering from thyroid cancer and renal cell carcinoma. Ellipticine, a DNA-damaging drug, is another anticancer agent that is effective against certain tumors of the thyroid gland, ovarian carcinoma, breast cancer and osteolytic breast cancer metastasis. Its anticancer efficiency is dictated by its oxidation with cytochrome P450 (CYP) and peroxidase enzymes. A number of studies testing the effectiveness of individual anticancer drugs, the pharmacological efficiencies of which are affected by their metabolism, alone or in a combination with other cytostatics demonstrated that such combination can have both positive and negative effects on treatment regimen. The aim of this study was to study the effect of vandetanib, lenvatinib and cabozantinib on oxidation of ellipticine which dictates its pharmacological efficiency. METHODS: Ellipticine oxidation catalyzed by hepatic microsomes, recombinant CYP enzymes and peroxidases (horseradish peroxidase, lactoperoxidase and myeloperoxidase) and the effect of TKIs (vandetanib, lenvatinib and cabozantinib) on this oxidation were analyzed by HPLC used for separation of ellipticine metabolites and quantification of their amounts formed during oxidation. RESULTS: The CYP enzymatic system oxidizes ellipticine up to five metabolites (9-hydroxy-, 12-hydroxy-, 13-hydroxy-, 7-hydroxyellipticine, and ellipticine N2- oxide), while peroxidases form predominantly ellipticine dimer. Ellipticine oxidation catalyzed by rat and human hepatic microsomes was inhibited by vandetanib and cabozantinib, but essentially no inhibition was caused by lenvatinib. Of individual CYP enzymes catalyzing oxidation of ellipticine, TKIs inhibited oxidation of ellipticine catalyzed by CYP2D6 > 2D1 > 2C9 > 3A1 > 3A4, the CYP enzymes participating in ellipticine oxidation to metabolites increasing the ellipticine anticancer efficiency. On the contrary, they have essentially no inhibition effect on ellipticine oxidation catalyzed by CYP1A1 and 1A2, which are the enzymes that predominantly detoxify this drug. All tested TKIs had essentially no effect on oxidation of ellipticine by used peroxidases. CONCLUSION: The results found demonstrate that TKIs vandetanib, lenvatinib and cabozantinib cause a decrease in oxidative activation of DNA-damaging drug ellipticine by several CYP enzymes in vitro which might lead to a decrease in its pharmacological efficiency. In contrast, they practically do not influence its detoxification catalyzed by CYP1A1, 1A2 and peroxidases. The present study indicates that tested TKIs seem not to have a potency to increase ellipticine anticancer efficiency....

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Journal Article 2019; 39(7): 501-514 PubMed PMID: 30860682 Citation  Keywords:  Biomarkers:blood, Dietary Supplements:adverse effects, Double-Blind Method, Female, Ferritins:blood, Folic Acid:blood, Glycated Hemoglobin A, Homocysteine:blood, Humans, Iron:blood, Male, Prospective Studies, Sex Factors, Time Factors, Vitamin B 12:blood,.   

OBJECTIVES: Pregnancy is a period in life with a high demand of micronutrients. A prophylactic supplementation of folic acid to reduce the risk of neurological malformations in the newborn is common practice. The array of essential micronutrients during pregnancy includes neurotropic vitamins (Vitamin B6, B12 and folic acid), minerals like iron, and trace elements like zinc. As the serum level of most micronutritients is actively regulated by the organism, a prophylactic broad supplementation with a mild, but effective supplementation typically does not pose any risk for exaggerated serum levels, therefore prophylactic intake may be prefered to blood screening and specific interventions. METHODS: To investigate the ingredients' bioavailability of the complex vitamin-mineral-trace element composition LaVita® we recruited healthy volunteers for six months and observed the changes of pregnancy relevant parameters by means of laboratory measures. The study design was prospective, double blind, placebo controlled, and included a "male group control". We determined baseline parameters of folate, vitamin B6 and vitamin B12, iron, zinc, homocysteine and Hb-alpha-1c. After three and six months of daily intake of the study substance the blood tests were repeated and compared to the baseline levels. RESULTS: The regular intake resulted in an increase of the supplemented substances' serum levels. The metabolic parameter homocysteine decreased significantly, Hb-alpha-1c was slightly lowered. CONCLUSION: The regular intake filled up the respective storage compartments and reservoirs in the tissues, and improved the metabolic status. Female participants tended to benefit more than male. We conclude that the composition is safe, and warrants optimized micronutrient supply during pregnancy or postnatal breastfeeding....

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Journal Article 2019; 39(7): 489-495 PubMed PMID: 30860680 Citation  Keywords:  Adult, Aged, Antibodies:immunology, Comorbidity:trends, Female, Fever:epidemiology, Hematuria:epidemiology, Humans, Iodide Peroxidase:immunology, Male, Middle Aged, Pain:epidemiology, Poland:epidemiology, Receptors, Thyrotropin:immunology, Retrospective S.   

INTRODUCTION: The clinical characteristics of subacute thyroiditis (SAT) has been changing in recent years. There are more and more patients with painless SAT, and more cases of SAT with elevated levels of anti-thyroid antibodies were reported. The aim of the study was to evaluate the clinical characteristics of SAT patients with special regard to the differences between the previously described and currently observed features of the disease. MATERIAL AND METHODS: Clinical and laboratory data were retrospectively reviewed for 64 patients with confirmed SAT. RESULTS: Mean age of the patients was 42.67 years. The male to female ratio was 1:7. Neck or ear pain was reported by 93.75% of patients, while fever occurred in 65.63% of patients. The aTPO and aTg levels were increased in 15.5% and 33.3% of patients, respectively. TRAb level was increased in 6% of patients. Transient microhaematuria was present in 63% of analyzed cases. No statistically significant differences in clinical characteristics or laboratory results were found between the groups with- and without neck/ear pain, with- and without elevated TRAb, and with- and without elevated aTPO and/or aTg. CONCLUSION: In our study, several new features of current SAT course, different from what we used to know about the disease, were reported. Higher frequency of painless SAT than it was ever described, was observed. Moreover, in as much as one third of the patients aTPO and/or aTg were present, and in 6% of SAT cases the coexistence of TRAb was demonstrated. Transient microhaematuria was typical for the acute SAT phase....

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Journal Article 2019; 39(7): 481-488 PubMed PMID: 30860679 Citation  Keywords:  Accidental Falls:statistics & numerical data, Adult, Aged, Aged, 80 and over, Case-Control Studies, Czech Republic:epidemiology, Female, Hospitals:statistics & numerical data, Humans, Male, Middle Aged, Prevalence, Risk Factors, Young Adult,.   

THEORY: Patients falls have a multifactorial character and typically have multiple causalities. GOAL: The goal of the study was to identify risk factors for falls of hospitalized patients. METHODOLOGY: This was a case-control study. The study included 222 patients who experienced a fall during their hospitalization (cases) and 1,076 patients who did not fall during their hospitalization (controls). The study involved four hospitals in the South Bohemian Region of the Czech Republic. The study took place during the 2017 calendar year. RESULTS: The average age of patients who experienced a fall was 77.9 years. The group of cases included 5-times more patients with a history of falls than the controls. Patients who fell were in higher risk of falls than patients in the control group at hospital admission. The group of cases also had a higher prevalence of confused and restless patients; however, the group did not include a statistically significantly higher number of incontinent patients, patients with eating and drinking disorders, or patients with intravenous therapy than the control group. CONCLUSION: Interventions aimed at prevention of falls should be included in care plans, especially for older patients, patients who have fallen in the past, patients who have movement restriction, patients with cognitive dysfunction, and patients with increased need of assistance with basic daily activities....

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