Publications by authors named "Malgorzata Stanczyk"

34 Publications

Interfamilial clinical variability in four Polish families with cranioectodermal dysplasia and identical compound heterozygous variants in WDR35.

Am J Med Genet A 2021 04 9;185(4):1195-1203. Epub 2021 Jan 9.

Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland.

Cranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED. Intra- and interfamilial clinical variability has been reported in a few CED studies and the findings of this study align with these observations. Here, we report on five CED patients from four Polish families with identical compound heterozygous variants [c.1922T>G p.(Leu641Ter) and c.2522A>T; p.(Asp841Val)] in WDR35. The frequent occurrence of both identified changes in Polish CED families suggests that these variants may be founder mutations. Clinical evaluation of the CED patients revealed interfamilial clinical variability among the patients. This includes differences in skeletal and ectodermal features as well as variability in development, progression, and severity of renal and liver insufficiency. This is the first report showing significant interfamilial clinical variability in a series of CED patients from unrelated families with identical compound heterozygous variants in WDR35. Our findings strongly indicate that other genetic and non-genetic factors may modulate the progression and expression of the patients' phenotypes.
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http://dx.doi.org/10.1002/ajmg.a.62067DOI Listing
April 2021

A new procedure for the determination of 21 macro- and trace elements in human fetal urine using an inductively coupled plasma mass spectrometry with dynamic reaction cell (ICP-DRC-MS) equipped with a micro-flow nebulizer.

Talanta 2021 Jan 17;222:121672. Epub 2020 Sep 17.

Department of Trace Analysis, Faculty of Chemistry, Adam Mickiewicz University, Poznań, ul. Uniwersytetu Poznańskiego 8, 61-614, Poznań, Poland.

The procedure for determination of 21 macro- and trace elements - Li, Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Cu, Zn, Se, Sr, As, Cd, Sb, Ba, Pb and U - in human fetal urine by inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated. The application of a micronebulizer and a dynamic reaction cell (DRC) allowed to perform a full analysis of small volumes (200 μL) of urine collected from human fetuses without the need for sample digestion with closed microwave systems. The procedure and ICP-MS instrument was thoroughly optimized in order to reliably determine both macroelements and ultra-trace concentrations of elements. The internal standard method (Ge, Rh and Tb) was applied in order to encompass signal drift and non-spectral interferences. The rules of metrology were used in order to ensure the quality of the results: (1) the procedure was validated, (2) the uncertainty of the measurement results was estimated and (3) the traceability of the measurement result was established by using the certified reference material with matching matrix (Seronorm Trace Elements Urine L-1). Also, the analyte addition method to the artificial urine was employed for additional confirmation of trueness of the procedure. The selected parameters of the procedure were as follows: (a) limits of detection - (0.00023-53 μg L) for U and Ca, respectively, (b) recoveries of the reference value - 81%-136% for Mn and Cd, respectively (c) linearity expressed as R - greater than 0.999, and (d) expanded relative uncertainties (k = 2) - 13%-66% for Sr and Cd, respectively. The developed and validated procedure was applied to 58 samples of urine collected from human fetuses. The samples were diluted with nitric acid and analyzed without further treatment. The procedure allowed to reliably determine both macro- and trace elements in very low volume of sample in a single analytical run.
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http://dx.doi.org/10.1016/j.talanta.2020.121672DOI Listing
January 2021

"Apple does not fall far from the tree" - subclinical atherosclerosis in children with familial hypercholesterolemia.

Lipids Health Dis 2020 Jul 14;19(1):169. Epub 2020 Jul 14.

Department of Hypertension, Medical University of Lodz, Lodz, Poland.

Background: Familial hypercholesterolemia (FH) increases the risk of atherosclerosis in children and adults. Atherosclerotic cardiovascular disease in young patients FH is usually subclinical but recognition of children with more pronounced changes is crucial for adjusting effective management. Aim of this research was to use ultrasonography with two-dimensional speckle tracking (2DST) and tonometry to evaluate atherosclerotic changes in patients with FH (parents and their offspring).

Methods: Applanation tonometry and carotid arteries sonography with evaluation of the intima-media complex thickness (IMCT) and application of the 2DST were performed in 20 families with FH (20 parents and 29 children). The same size control group (age and sex matched) was included. Results were compared between peers and between generations together with the correlation analysis.

Results: Adults with FH, in comparison with healthy peers, presented significantly more atherosclerotic plaques (9 vs. 2, p = 0.0230), had significantly thicker IMC (0.84 ± 0.19 vs. 0.56 ± 0.06 mm, p < 0.0001) and had stiffer arterial wall (for stain: 6.25 ± 2.3 vs. 8.15 ± 2.46, p = 0.0103). In children from both groups there were no atherosclerotic plaques and IMCT did not differ significantly (0.42 ± 0.07 vs. 0.39 ± 0.04, p = 0.1722). However, children with FH had significantly stiffer arterial wall according to 2DST (for strain: 9.22 ± 3.4 vs. 11.93 ± 3.11, p = 0.0057) and tonometry (for the pulse wave velocity: 4.5 ± 0.64 vs.3.96 ± 0.62, p = 0.0047). These parameters correlated with atherosclerosis surrogates in their parents (p < 0.001) but were not significantly affected by presence of presumed pathogenic gene variant.

Conclusions: Children with FH presented subclinical atherosclerosis manifested as decreased arterial wall elasticity. Degree of stiffening was associated with advancement of atherosclerosis in their parents but did not present significant association with gene variants. Sonography with application of 2DST seems to be a good candidate for comprehensive evaluation of atherosclerosis in families with FH.
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http://dx.doi.org/10.1186/s12944-020-01335-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362468PMC
July 2020

Comprehensive Evaluation of the Safety and Efficacy of BAFASAL Bacteriophage Preparation for the Reduction of in the Food Chain.

Viruses 2020 07 10;12(7). Epub 2020 Jul 10.

Proteon Pharmaceuticals S.A., Tylna 3a, 90-364 Łódź, Poland.

Bacteriophages are bacterial predators, which are garnering much interest nowadays vis-à-vis the global phenomenon of antimicrobial resistance. Bacteriophage preparations seem to be an alternative to antibiotics, which can be used at all levels of the food production chain. Their safety and efficacy, however, are of public concern. In this study, a detailed evaluation of BAFASAL preparation was performed. BAFASAL is a bacteriophage cocktail that reduces in poultry farming. In vivo acute and sub-chronic toxicity studies on rats and tolerance study on targeted animals (chicken broiler) conducted according to GLP and OECD guidelines did not reveal any signs of toxicity, which could be associated with BAFASAL administration. In addition, no evidences of genotoxicity were observed. The tolerance study with 100-times concentrated dose also did not show any statistically significant differences in the assessed parameters. The in vitro crop assay, mimicking normal feed storage and feed application conditions showed that BAFASAL reduced the number of bacteria in experimentally contaminated feed. Moreover, reductions were observed for all examined forms (liquid, powder, spray). Furthermore, the in vivo efficacy study showed that treatment with BAFASAL significantly decreased content in caeca of birds infected with Enteritidis. Detailed examination of BAFASAL in terms of safety and efficacy, adds to the body of evidence that bacteriophages are harmless to animals and effective in the struggle against bacteria.
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http://dx.doi.org/10.3390/v12070742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412135PMC
July 2020

Anti-Salmonella Potential of New Strains with the Application in the Poultry Industry.

Pol J Microbiol 2020 Sep 28;69(1):5-18. Epub 2020 Jan 28.

Proteon Pharmaceuticals SA , Lodz , Poland.

Probiotics are considered an alternative to antibiotics in the prevention and treatment of diseases in poultry. However, to use probiotics as proposed above, it is necessary to evaluate their properties in detail and to select the most effective bacterial strains in the application targeted. In this study, probiotic properties of new sp. strains were investigated and their antimicrobial activity against 125 environmental strains of sp. was determined using the agar slab method. Furthermore, their survival in the presence of bile salts and at low pH, antibiotics susceptibility, aggregation and coaggregation ability, adherence to polystyrene and Caco-2 cells, and cytotoxicity were investigated. Each strain tested showed antagonistic activity against at least 96% of the environmental sp. strains and thus representing a highly epidemiologically differentiated collection of poultry isolates. In addition, the probiotic properties of new strains are promising. Therefore, all strains examined showed a high potential for use in poultry against salmonellosis.

Probiotics are considered an alternative to antibiotics in the prevention and treatment of diseases in poultry. However, to use probiotics as proposed above, it is necessary to evaluate their properties in detail and to select the most effective bacterial strains in the application targeted. In this study, probiotic properties of new sp. strains were investigated and their antimicrobial activity against 125 environmental strains of sp. was determined using the agar slab method. Furthermore, their survival in the presence of bile salts and at low pH, antibiotics susceptibility, aggregation and coaggregation ability, adherence to polystyrene and Caco-2 cells, and cytotoxicity were investigated. Each strain tested showed antagonistic activity against at least 96% of the environmental sp. strains and thus representing a highly epidemiologically differentiated collection of poultry isolates. In addition, the probiotic properties of new strains are promising. Therefore, all strains examined showed a high potential for use in poultry against salmonellosis.
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http://dx.doi.org/10.33073/pjm-2020-001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256722PMC
September 2020

A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves.

Pediatr Nephrol 2020 03 7;35(3):469-475. Epub 2019 Nov 7.

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.

Background: Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study.

Methods: Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m before 6 months of age or pre- or perinatal death.

Results: The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74-1.0) and an accuracy of 90% (95%CI 78-100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72-0.97) and an accuracy of 84% (95%CI 71-97).

Conclusions: This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.
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http://dx.doi.org/10.1007/s00467-019-04390-9DOI Listing
March 2020

Two-Dimensional Speckle Tracking Versus Applanation Tonometry in Evaluation of Subclinical Atherosclerosis in Children with Type 1 Diabetes Mellitus.

Med Sci Monit 2019 Sep 28;25:7289-7294. Epub 2019 Sep 28.

Department of Diagnostic Imaging, Polish Mothers' Memorial Hospital Research Institute, Łódź, Poland.

BACKGROUND Patients with type 1 diabetes mellitus (T1DM) often develop atherosclerosis at an early age. In the subclinical stage of the process, minimal/non-morphological changes can be noticed, but the arterial wall function can be impaired. Applanation tonometry allows to assess the arterial tree stiffness; however, the Two-Dimensional Speckle Tracking (2DST) is an increasingly accepted alternative. This study evaluated arterial wall stiffness using these 2 techniques in children with T1DM. MATERIAL AND METHODS We performed applanation tonometry and carotid arteries sonography with evaluation of the carotid intima-media thickness (cIMT) and use of the 2DST in 50 children with T1DM and in 50 healthy sex- and age-matched controls. We also assessed the reliability of 2DST in 10 random subjects. RESULTS Children with T1DM had increased arterial wall stiffness, which was confirmed by tonometry (PWV: p=0.0386) and 2DST (Strain: p=0.0004; Strain rate: p=0.0081). There was no significant difference in cIMT between groups (0.45±0.06 vs. 0.43±0.05, p=0.073 in children with T1DM and controls, respectively). 2DST presented good intraclass correlation coefficient between researchers and within a single researcher. CONCLUSIONS Children with T1DM presenting with subclinical stage of atherosclerosis were found to have arterial wall stiffening. The 2DST, the same as applanation tonometry, allows to recognize this condition but in a more accessible and reproducible manner.
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http://dx.doi.org/10.12659/MSM.916466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784626PMC
September 2019

Neonatal survival and kidney function after prenatal interventions for obstructive uropathies.

Ginekol Pol 2019 ;90(7):416-422

Department of Gynecology, Fertility and Fetal Therapy, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.

Objectives: Prenatal interventions in LUTO (lower urinary tract obstruction) usually are still question of a debate between gynaecologist and paediatric nephrologist. We aimed the study to assess the early survival rate and renal outcome in LUTO foetuses.

Material And Methods: The study was a prospective data analysis of 39 foetuses from singleton pregnancies. All pregnant women with LUTO in the foetus were qualified for VAS based on a local practice. The mean time of first urine analysis ranged between 13-30 weeks of pregnancy. Primary end-point analysis included live birth, 28d-survival, pulmonary and renal function assessment in neonatal period.

Results: From initial number of 39, six patients miscarried before the procedure was performed. Overall, 33 VAS were performer at the mean 21 week of pregnancy (range 14-30 weeks). 25/39 foetuses survived until delivery. Three neonates died in first 3 days of life. In the first month 3 children required peritoneal dialysis, but at 28 day all children were dialysis-free. Overall survival rate at 28 day was 56%. Renal function preservation of the initial group (39) turned out to be low - 18% (7/39).

Conclusions: Our study showed average survival curves and complications. LUTO in the foetus had mostly unfavourable outcome in the neonatal period. The prenatal intervention did not increase it significantly and did not guarantee the preservation of normal kidney function.
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http://dx.doi.org/10.5603/GP.2019.0071DOI Listing
March 2020

Complete genome sequences of Aeromonas and Pseudomonas phages as a supportive tool for development of antibacterial treatment in aquaculture.

Virol J 2019 01 8;16(1). Epub 2019 Jan 8.

Proteon Pharmaceuticals, Lodz, Poland.

Background: Aquaculture is the fastest growing sector of food production worldwide. However, one of the major reasons limiting its effectiveness are infectious diseases among aquatic organisms resulting in vast economic losses. Fighting such infections with chemotherapy is normally used as a rapid and effective treatment. The rise of antibiotic resistance, however, is limiting the efficacy of antibiotics and creates environmental and human safety concerns due to their massive application in the aquatic environment. Bacteriophages are an alternative solution that could be considered in order to protect fish against pathogens while minimizing the side-effects for the environment and humans. Bacteriophages kill bacteria via different mechanisms than antibiotics, and so fit nicely into the 'novel mode of action' concept desired for all new antibacterial agents.

Methods: The bacteriophages were isolated from sewage water and characterized by RFLP, spectrum of specificity, transmission electron microscopy (TEM) and sequencing (WGS). Bioinformatics analysis of genomic data enables an in-depth characterization of phages and the choice of phages. This allows an optimised choice of phage for therapy, excluding those with toxin genes, virulence factor genes, and genes responsible for lysogeny.

Results: In this study, we isolated eleven new bacteriophages: seven infecting Aeromonas and four infecting Pseudomonas, which significantly increases the genomic information of Aeromonas and Pseudomonas phages. Bioinformatics analysis of genomic data, assessing the likelihood of these phages to enter the lysogenic cycle with experimental data on their specificity towards large number of bacterial field isolates representing different locations.

Conclusions: From 11 newly isolated bacteriophages only 6 (25AhydR2PP, 50AhydR13PP, 60AhydR15PP, 22PfluR64PP, 67PfluR64PP, 71PfluR64PP) have a potential to be used in phage therapy due to confirmed lytic lifestyle and absence of virulence or resistance genes.
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http://dx.doi.org/10.1186/s12985-018-1113-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325676PMC
January 2019

CoQ10-related sustained remission of proteinuria in a child with COQ6 glomerulopathy-a case report.

Pediatr Nephrol 2018 Dec 19;33(12):2383-2387. Epub 2018 Sep 19.

Department of Pediatrics, Immunology and Nephrology, Polish Mother's Memorial Hospital Research Institute of Lodz, Rzgowska St. 281/289, 93-338, Lodz, Poland.

Background: Treatment of steroid resistant nephrotic syndrome is still a challenge for physicians. There are a growing number of studies exploring genetic background of steroid-resistant glomerulopathies.

Case Diagnosis/treatment: We present the case of a 4-year-old girl with steroid-resistant glomerulopathy due to a COQ6 defect with no additional systemic symptoms. The disease did not respond for second-line therapy with calcineurin inhibitor, but it remitted completely after oral treatment with 30 mg/kg/d of coenzyme Q10 (CoQ10). The patient was identified to be a compound heterozygote for two pathogenic variants in COQ6 gene: a known missense substitution c.1078C > T (p.R360W) and a novel frameshift c.804delC mutation. After 12 months of CoQ10 therapy, the child remains in full remission, her physical development accelerated, frequent respiratory airways diseases subsided.

Conclusions: Genetic assessment of children with steroid-resistant nephrotic proteinuria enables therapy optimization. Proteinuria caused by a COQ6 gene defect can be successfully treated with CoQ10.
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http://dx.doi.org/10.1007/s00467-018-4083-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208703PMC
December 2018

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

J Pediatr 2018 08 9;199:22-28.e6. Epub 2018 May 9.

Department of Pediatrics, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.

Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.

Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.

Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
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http://dx.doi.org/10.1016/j.jpeds.2018.03.052DOI Listing
August 2018

Antihypertensive treatment prescription in pediatric dialysis patients in Poland: A comparison between two nationwide studies 2003/2004-2013.

Adv Clin Exp Med 2017 Nov;26(8):1263-1268

Department of Pediatrics, Immunology and Nephrology, Polish Mothers Memorial Hospital Research Institute, Poland.

Background: Blood pressure in pediatric dialyzed patients is under poor control.

Objectives: The aim of the study was to assess the strategy and efficacy of antihypertensive drugs used for the treatment of hypertension in pediatric dialyzed patients in 2013 in comparison with the data collected in 2003/2004. The results have been viewed against present strategies of antihypertensive treatment in children. There is still limited data concerning the treatment of hypertension in dialyzed pediatric patients.

Material And Methods: The study embraced 10 of 12 pediatric dialysis units in Poland treating 59 pediatric patients (mean age - 132 months). Collected information included present antihypertensive treatment with regard to drug classes and the dose of antihypertensive agent. The treatment was regarded as effective if both systolic and diastolic values of blood pressure were below 1.64 SDS. The results from 2013 were juxtaposed with previously analyzed data from a similar study on hypertension in dialyzed children conducted in 2003/2004.

Results: Forty subjects have been provided with antihypertensive treatment. In monotherapy and polytherapy 50% of the subjects were treated with ACEI (enalapril and ramipril), 67.5% with amlodipine, 50% with beta-blockers. Only 10% of the subjects were treated with angiotensin II receptor blocker (losartan). Thirty percent of the subjects received furosemide, whereas 5% were given doxazosin. Antihypertensive drugs regarded as the 2nd and 3rd choice in treating high blood pressure (doxazosin, beta-blockers and furosemide) were applied as monotherapy in 46% of the patients. Satisfactory control of treated blood pressure was reached in 45% of them.

Conclusions: Antihypertensive treatment in dialyzed children did not change significantly during the last decade with regard to the groups of drugs being used. Despite a wider feasibility of antihypertensive substances, the effectiveness of this therapy was still unsatisfactory.
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http://dx.doi.org/10.17219/acem/65823DOI Listing
November 2017

What has changed in the prevalence of hypertension in dialyzed children during the last decade?

Ren Fail 2017 Nov 24;39(1):283-289. Epub 2016 Nov 24.

l Department of Pediatrics, Hematology, Oncology and Diabetology , Medical University of Lodz , Lodz , Poland.

Background: Hypertension very often accompanies progression of chronic kidney disease (CKD) in children. A cross-sectional analysis of hypertension prevalence in dialyzed children in Poland was designed with a comparison with the data previously recorded 10 years earlier.

Methods: Two cohorts of children were analyzed: 59 subjects dialyzed in 2013, and 134 children from the previous study performed in 2003 that were reevaluated according to the current methodology. The incidence of hypertension (defined by SDS of sBP or dBP >1.64), clinical data, medical history, dialysis modalities and selected biochemical parameters of dialysis adequacy were analyzed.

Results: The prevalence of hypertension increased from 64% in 2003 to 78% in 2013. The efficacy of antihypertensive treatment remained unsatisfactory (61% proper BP control). Preservation of residual urine output and strict fluid balance may prevent development of hypertension in children on dialysis.

Conclusions: Despite the higher awareness of hypertension and its complications in dialyzed children, the incidence of this entity has increased during the last decade, with the percentage of undertreated patients comparable to that observed 10 years ago. Thus, more attention should be paid to therapy efficacy in this population to prevent further damage to the cardiovascular system and to decrease morbidity.
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http://dx.doi.org/10.1080/0886022X.2016.1260033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014511PMC
November 2017

Growth and nutritional status in children with chronic kidney disease on maintenance dialysis in Poland.

Adv Med Sci 2016 Mar 1;61(1):46-51. Epub 2015 Oct 1.

Department of Pediatrics, Immunology and Nephrology, Polish Mother's Memorial Research Institute, Lodz, Poland; Division of Didactics in Pediatrics, Medical University of Lodz, Lodz, Poland.

Purpose: Despite vast availability of modern methods of treatment of chronic kidney disease and its complications, the short stature still is a major point of concern in adolescents with chronic kidney disease. The aim of the study was to assess changes in growth and nutritional status of Polish children on renal replacement therapy in the decade, 2004-2013.

Material And Methods: The study was designed as a cross-sectional analysis of anthropometric values and selected indices of growth status amongst children receiving dialysis in Poland between the years 2004 and 2013. Data were acquired during two different multicentre studies on hypertension in dialyzed children in Poland. Basic anthropometric parameters (body weight, body height/length, body mass index - BMI), dialysis adequacy and duration of RRT were assessed.

Results: The study showed that anthropometric parameters of children undergoing renal replacement therapy had not significantly changed in the last 10 years of observation. Children on RRT were still of short stature despite availability of modern methods of hormonal therapy and nutrition. Median of height z-score was -2.10 in 2004 and -2.19 in 2013. Expected clinical improvement in these measures was not proven.

Conclusions: The cause of chronic kidney disease, method of dialysis, time on dialysis or dialysis adequacy did not influence the anthropometric parameters significantly in dialyzed children in Poland.
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http://dx.doi.org/10.1016/j.advms.2015.09.004DOI Listing
March 2016

Protective activity of probiotic bacteria against 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP) - an in vitro study.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2015 18;32(11):1927-38. Epub 2015 Sep 18.

b Department of Molecular Genetics , University of Lodz , Lodz , Poland.

Heterocyclic aromatic amines (HAAs) are carcinogenic compounds present in a typical Western diet rich in thermally processed meat. These nutritional factors can modulate the cytotoxicity of faecal water (FW) and induce tumours in the human gastrointestinal tract. Supplementation with probiotics is promising in terms of reducing the harmful effects of HAAs in the human body. The aim of the study was in vitro assessment of the protective activity of the probiotic strains Lb. rhamnosus 0900, Lb. rhamnosus 0908, Lb. casei 0919 and Lb. casei DN 114001 against IQ (2-amino-3-methyl-3H-imidazo[4,5-f]quinoline) and PhIP (2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine) after incubation with faeces from 15 persons aged 4 months to 82 years (children, adults and the elderly). The highest mean cytotoxicity of FW was observed for the elderly (63.2% ± 3.7%) and the lowest for children (28.0% ± 9.5%), as estimated by a neutral red uptake assay. The probiotics lowered the average cytotoxicity of FW exposed to IQ or PhIP. The concentration of IQ and PhIP in FW was most effectively reduced by Lb. rhamnosus 0900 (47.5%) and Lb. casei 0919 (45.8%), respectively, as determined by high -performance liquid chromatography. All the tested strains bound PhIP to a higher extent than IQ. In an alkaline comet assay, Lb. casei 0919 and Lb. rhamnosus 0908 displayed the strongest protective effect against IQ and PhIP (up to 80% reduction of DNA damage). Also in a comet assay, Lb. rhamnosus 0908 exhibited antioxidative activity toward H2O2 and PhIP (up to 63% and 69.5% reduction of oxidative DNA damage, respectively). The protective activity of the probiotic strains was specific to a given person's FW, which implies the involvement of intestinal microbiota in the process.
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http://dx.doi.org/10.1080/19440049.2015.1084651DOI Listing
October 2016

Association of the Arg194Trp and the Arg399Gln polymorphisms of the XRCC1 gene with risk occurrence and the response to adjuvant therapy among Polish women with breast cancer.

Clin Breast Cancer 2013 Feb 26;13(1):61-8. Epub 2012 Oct 26.

Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.

Background: The XRCC1 gene encoding the X-ray cross-complementing group 1 protein (XRCC1) is involved in the base excision repair (BER) pathway.

Methods: The aim of this study was to investigate an association of the Arg194Trp and Arg399Gln polymorphisms of the XRCC1 gene with a risk of breast cancer occurrence and the response to adjuvant treatment among Polish women. Overall survival (OS) and disease-free survival (DFS) were investigated in groups of patients with breast cancer treated with (1) all types of adjuvant therapy, (2) concomitant radiotherapy and chemotherapy, (3) chemotherapy alone, or (4) radiotherapy alone. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to evaluate the genotype distribution of the XRCC1 gene among 185 patients with breast cancer and 205 female controls.

Results: We showed a higher risk of breast cancer occurrence for the Trp allele and the Arg194Trp genotype of the XRCC1 gene. However there was no significant difference in distribution of the Arg399Gln genotype of XRCC1 between patients and the control group. In the patient subgroup treated with adjuvant therapy, Kaplan-Meier survival analysis showed a significantly higher OS as well as DFS for carriers of the Gln399Gln genotype when compared with carriers of the Arg399Gln and Arg399Arg genotypes. The Gln399Gln genotype was associated with a significantly higher DFS in the subgroup of patients treated with chemotherapy alone or with concomitant radiotherapy and chemotherapy.

Conclusion: We suggest that the polymorphism of the XRCC1 gene may be considered a predictive factor associated with the risk of occurrence and the survival outcome in breast cancer among Polish women.
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http://dx.doi.org/10.1016/j.clbc.2012.09.019DOI Listing
February 2013

Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy.

Mol Biol Rep 2012 Sep 21;39(9):8669-78. Epub 2012 Jun 21.

Department of Internal Medicine, Diabetology and Clinical Pharmacology, Medical University of Lodz, ul. Parzeczewska 35, 95-100 Zgierz, Poland.

Experimental evidences suggest that hyperglycaemia-induced overproduction of reactive oxygen species and subsequent damage to proteins, lipids and DNA may play a key role in the development of distal symmetric polyneuropathy (DSPN)-the most common complication of diabetes mellitus. The study population consisted of 51 individuals aged 52-82 years classified into 3 groups: 16 patients diagnosed with type 2 diabetes mellitus (T2DM) with DSPN, 16 T2DM patients without DSPN and 19 control subjects without diabetes and neuropathy. The study was conducted to determine the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant status (TAS) in the examined groups. An alkaline comet assay was used to determine the extent of DNA damage of oxidized purines as glicosylo-formamidoglicosylase (Fpg) sites, and oxidized pyrimidines as endonuclease III (Nth) sites. A significant decrease of SOD (P < 0.05), GPX (P < 0.05) and nonsignificant decrease of CAT (P > 0.05), and TAS status (P > 0.05) were seen in T2DM patients with neuropathy compared to T2DM patients as well as controls. T2DM patients with or without neuropathy revealed significantly lower (P < 0.05) plasma concentration of nitrous oxide compared to the control subjects. Endogenous level of oxidative DNA damage in T2DM patients with DSPN was significantly higher compared both to the controls and T2DM patients without DSPN (P < 0.001). Moreover, lymphocytes isolated from T2DM patients with DSPN were more susceptible to oxidative DNA lesions induced by hydrogen peroxide than from T2DM patients without DSPN (P < 0.001). Our results confirm hypothesis that oxidative stress may play a substantial role in the development and progression of diabetic distal symmetric polyneuropathy.
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http://dx.doi.org/10.1007/s11033-012-1722-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404273PMC
September 2012

Evaluation of biological effects of nanomaterials. Part I. Cyto- and genotoxicity of nanosilver composites applied in textile technologies.

Int J Occup Med Environ Health 2011 Dec 24;24(4):348-58. Epub 2011 Oct 24.

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Łódź, Poland.

Objectives: The aim of this study was to investigate the cyto- and genotoxicity of nanocomposites (NCs) and generation of reactive oxygen species (ROS) as a result of particle-cell interactions.

Materials And Methods: Titanium dioxide (TiO(2)-Ag) and ion-exchange resin (Res-Ag), both coated with silver (Ag), were examined. The murine macrophage J774A.1 cells were incubated in vitro with NC at different concentrations for 24 h. Cytotoxicity was analyzed by the methylthiazolyldiphenyl-tetrazolium bromide reduction test (MTT reduction test). ROS generation was assessed by incubation of cells with dichlorodihydrofluorescein diacetate (DCF) and flow cytometry. DNA damage was detected by comet assay and included single-strand breaks (SSB), alkali-labile sites (ALS) and oxidative DNA damage after formamidopyrimidine glycosylase (FPG) treatment. The tail moment was used as an indicator of DNA damage.

Results: TiO(2)-Ag was not cytotoxic up to 200 μg/ml, whereas IC(50) for Res-Ag was found to be 23 μg/ml. Intracellular ROS levels were elevated after 4 h of exposure to Res-Ag at the concentration of 50 μg/ml. Both types of NC induced fragmentation of DNA strands, but only one of the composites caused damage to purine bases. TiO(2)-Ag induced SSB of DNA at concentrations of 10 and 5 μg/ml. For Res-Ag, a concentration-dependent increase in tail moments was observed.

Conclusions: Silver-coated nanocomposites (both TiO(2)-Ag and Res-Ag) may cause genotoxic effects in murine macrophages J774A.1. Res-Ag increased generation of ROS which suggested that toxicity of Res-Ag in murine macrophages is likely to be mediated through oxidative stress. This paper will support industry and regulators alike in the assessment of hazards and risks and methods for their mitigation at the earliest possible stage in material and product development.
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http://dx.doi.org/10.2478/s13382-011-0041-zDOI Listing
December 2011

Sulindac and its metabolites: sulindac sulfide and sulindac sulfone enhance cytotoxic effects of arsenic trioxide on leukemic cell lines.

Toxicol In Vitro 2011 Aug 15;25(5):1075-84. Epub 2011 Apr 15.

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Sw. Teresy St., 91 348 Łódź, Poland.

The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200 μM) with SS being the most cytotoxic (72 h WST-1 reduction test). The cytotoxicity of ATO was enhanced by combination with sulindacs. The combination of ATO (1 μM) with SS or SF at concentrations over 50 μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48 h to the combinations showed smaller decrease in viability. Measurements of Jurkat, HL-60 and K562 cells exposed to ATO (1 μM) and sulindacs (100 μM or 200 μM for K562 cells) indicated apoptosis as the main cell death mechanism. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.
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http://dx.doi.org/10.1016/j.tiv.2011.04.011DOI Listing
August 2011

Evaluation of oxidative stress markers in pathogenesis of primary open-angle glaucoma.

Exp Mol Pathol 2011 Apr 15;90(2):231-7. Epub 2011 Jan 15.

Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Poland.

Primary open-angle glaucoma (POAG) is the leading cause of blindness in the industrial countries. It is reported that oxidative stress might be an important risk factor in the pathogenesis of POAG. Forty subjects including 20 patients with open-angle glaucoma (9 men and 12 women, mean age 61.8±12.1yr) and 20 controls without glaucoma symptoms (9 men and 12 women, mean age 58.1±17.7yr) were enrolled in our study. The main aim of the work was to evaluate oxidative stress markers in the pathogenesis of open-angle glaucoma. In our work the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the total antioxidant status (TAS) was estimated. An alkaline comet assay was used to measure DNA damage of strand breaks (SB), oxidized purines as glicosylo-formamido-glicosylase (Fpg) sites, and oxidized pirmidines as endonuclease III (Nth) sites. We measured endogenous as well as exogenous DNA damage after 10μM hydrogen peroxide treatment (H(2)O(2)). We did not observe any statistical changes of DNA strand break lesion in examined POAG patients according to healthy subjects (P>0.05). However, either endogenous (P<0.01) or exogenous (P<0.001) levels of oxidative DNA damage in POAG patients were found to be statistically higher than controls. A significant decrease of antioxidant enzymes: CAT (P<0.001), SOD (P<0.05), and GPX (P<0.001) and a non-statistical decrease of TAS status (P>0.05) in glaucoma patients according to controls were also indicated. In conclusion our data revealed that oxidative stress had a pathogenic role in primary open-angle glaucoma. Therefore, we suggested that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.
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http://dx.doi.org/10.1016/j.yexmp.2011.01.001DOI Listing
April 2011

Music therapy in supportive cancer care.

Rep Pract Oncol Radiother 2011 Jun 8;16(5):170-2. Epub 2011 Jun 8.

Greater Poland Cancer Centre, Garbary15 Str, 61-866 Poznan, Poland.

The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients-interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life.
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http://dx.doi.org/10.1016/j.rpor.2011.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863265PMC
June 2011

Carcinogenic effect of arsenate in C57BL/6J/Han mice and its modulation by different dietary selenium status.

Ecotoxicol Environ Saf 2009 Nov 3;72(8):2143-52. Epub 2009 Jul 3.

Nofer Institute of Occupational Medicine, 8 Sw. Teresy Street, 91-348 Łódź, Poland.

In this study, carcinogenic effects of arsenate in female C57BL/6J/Han mice exposed in drinking water to 50, 200 or 500microgAs/L for 24 months were investigated. All animals were fed low-selenium diet, however half of them were supplemented with sodium selenite in drinking water (200microgSe/L) to ensure the normal dietary level of selenium. Glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma after 3, 6, 12 and 18 months in satellite groups showed considerable decrease in animals from non-selenium supplemented groups in comparison to supplemented groups. A clear arsenic concentration-dependent increase in the number of malignant lymphoma associated with increase in the risk of death was observed (hazard ratio=0.91, 1.46, and 2.24, for 50, 200 and 500microgAs/L, respectively). No significant influence of selenium dietary status on arsenic carcinogenicity was shown. A significant association between selenium supplementation status and increased risk of death of the animals from causes other than malignant tumors was found (HR=1.79, p=0.04).
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http://dx.doi.org/10.1016/j.ecoenv.2009.06.005DOI Listing
November 2009

Potentiation of arsenic trioxide cytotoxicity by Parthenolide and buthionine sulfoximine in murine and human leukemic cells.

Cancer Chemother Pharmacol 2008 Apr 27;61(5):727-37. Epub 2007 Jun 27.

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Sw. Teresy Street, 91-348 Łódź, Poland.

Purpose: To possibly increase the in vitro cytotoxic activity of arsenic trioxide (ATO) by combining it with Parthenolide (PRT), a known NF-kappaB inhibitor and buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase.

Methods: Several cell lines representing various hematological malignancies were treated in vitro with the study drugs alone or in combinations. Flow cytometry was used to assess cell death rates and reative oxygen species production. Glutathione and ATP levels were determinded using a photometric and a luminometric assay, respectively. Cell death was characterised by fluorescence microscopy and DNA fragmentation analysis.

Results: PRT increased cytotoxicity of ATO in seven out of eight cell lines. Addition of buthionine sulfoximine (BSO) further potentiated cytotoxicity of the combined treatment. When combined with PRT and BSO, clinically achievable concentrations of ATO (2.5 microM) induced cytotoxicity rates of 80-98% after 24 h. Importantly, lymphocytes from healthy donors were largely unaffected by these treatment modalities, also after growth stimulation in cell culture. N-acetylcysteine inhibited the cytotoxic effects of the triple combination. Treatment of leukemic cells with ATO, PRT and BSO rapidly depleted cells from glutathione, induced oxidative stress and decreased intracellular ATP levels. Cell death showed characteristics of necrosis presumably as a result of ATP loss.

Conclusion: Based on the observed selectivity towards malignant cells this combination may offer a therapeutic option applicable to different kinds of leukemia.
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http://dx.doi.org/10.1007/s00280-007-0527-3DOI Listing
April 2008

Biomonitoring of cyanobacterial blooms in Polish water reservoir and the cytotoxicity and genotoxicity of selected cyanobacterial extracts.

Int J Occup Med Environ Health 2007 ;20(1):48-65

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, św. Teresy 8, 91-348 Łódź, Poland.

Objectives: Water pollution with toxic cyanobacterial blooms is a worldwide problem. Cyanobacteria species that mainly produce microcystins predominate in Polish water reservoirs.

Materials And Methods: In our study, cyanobacterial blooms were monitored during summer of 2004 in the Sulejów reservoir. The concentration of microcystins in water and cyanobacterial cells were determined using liquid chromatography and immunobiotests, while the biological activity of microcystic cyanobacterial extracts was assessed using bacterial tests (SOS Chromotest, UMU test), the comet assay and micronucleus test with human lymphocytes.

Results: It was revealed that cyanobacterial bloom was most intensive in mid August and lasted until the end of September. Microcystis aeruginosa and Aphanizomenon flos-aquae dominated in the blooms. The highest concentration of microcystins in cyanobacterial cells was also observed at that time. The concentration of microcystins in water did not exceed 1 microg/l. All cyanobacterial extracts showed weak genotoxicity only for Escherichia coli PQ37. The cyanobacterial extracts prepared at the beginning of September were most toxic to human lymphocytes, the effective microcystin extracts (EC50) concentration was about two or three times lower compared to the other extracts. The level of DNA damage in lymphocytes after short exposure to microcystic extracts (3 and 6 h) was significantly higher than respective levels after longer exposure. The microcystins of cyanobacterial blooms induced a slight increase in micronuclei frequencies in human lymphocytes.

Conclusion: Phytoplankton biomass and the genotoxicity of massive cyanobacterial blooms should be assessed for eucariotic cells in the Sulejów reservoir to avoid the hazard induced by cyanobacterial blooms.
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http://dx.doi.org/10.2478/v10001-007-0008-2DOI Listing
September 2007

Interleukin-1beta expression in murine J774A.1 macrophages exposed to platinum compounds: the role of p38 and ERK 1/2 mitogen-activated protein kinases.

Toxicol In Vitro 2007 Apr 29;21(3):371-9. Epub 2006 Sep 29.

Nofer Institute of Occupational Medicine, 8 Teresy St, 91-348 Lodz, Poland.

Although skin and respiratory sensitizing properties of platinum compounds have been proved in humans and mice, little is known about signal transduction pathways leading to cytokine production in the induction phase. It is generally assumed that induction of skin sensitization, but not skin irritation, is associated with a rapid increase in the IL-1beta mRNA expression. In this study, IL-1beta expression and a role of mitogen-activated protein kinases (MAPKs) in this process were investigated in murine macrophages J774A.1 exposed to four platinum compounds. Potassium tetrachloroplatinate (K(2)PtCl(4); TCPP), ammonium tetrachloroplatinate ((NH(4))(2)PtCl(4); TCPA), ammonium hexachloroplatinate ((NH(4))(2)PtCl(6); HCPA) showed a very similar range of cytotoxic concentrations (IC(50) values: 238 microM+/-30; 269 microM+/-39 and 245 microM+/-31, respectively) as assessed in the 24-h MTT reduction test. Cytotoxicity of cis-diammineplatinum dichloride (cisplatin) was considerably higher (IC(50) of 23 microM+/-4). While increased expression of IL-1beta mRNA was observed in the macrophages exposed to each test compound, IL-1beta protein production was detected in cell lysates after treatment with TCPP, TCPA and HCPA for 24h (concentration range of 150-350 microM) as well as for 2h (450-650 microM). The treatment with each compound resulted in the phosphorylation of both p38 MAPK and ERK 1/2 (p44/42). Blocking the activation of p38 MAPK as well as ERK 1/2 with specific inhibitors (SB203580 and U0126, respectively) down-regulated the IL-1beta expression. Interestingly, the skin irritant sodium dodecyl sulfate did not trigger phosphorylation of these kinases, nor induced IL-1beta production. These data suggest that p38 MAPK and ERK 1/2 play an important role in induction of IL-1beta expression in J774A.1 macrophages exposed to test platinum compounds.
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http://dx.doi.org/10.1016/j.tiv.2006.09.013DOI Listing
April 2007

Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking water and modulation of the effects by low-selenium diet.

J Toxicol Environ Health A 2006 Oct;69(20):1843-60

Nofer Institute of Occupational Medicine, Łódź, Poland.

In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 microg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.
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http://dx.doi.org/10.1080/15287390600631490DOI Listing
October 2006

Gastro-gastric fistula in the era of divided Roux-en-Y gastric bypass: strategies for prevention, diagnosis, and management.

Obes Surg 2006 Mar;16(3):359-64

Department of Surgery, Oregon Health and Science University, Portland, OR 97239, USA.

Roux-en-Y gastric bypass (RYGBP) is a mainstay of bariatric surgical therapy. Gastro-gastric fistula (GGF) is an infrequent but potentially serious complication of gastric bypass, and diagnosis may be difficult. We report two patients who underwent RYGBP complicated by development of GGF who nevertheless achieved excellent, durable weight loss. The pathogenesis, diagnosis, prevention and management of GGF after RYGBP is reviewed. GGF may not result in poor weight loss after RYGBP and is not an absolute indication for surgical revision.
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http://dx.doi.org/10.1381/096089206776116426DOI Listing
March 2006

Modulation of murine peritoneal macrophage function by chronic exposure to arsenate in drinking water.

Immunopharmacol Immunotoxicol 2005 ;27(2):315-30

Nofer Institute of Occupational Medicine, Lódź, Poland.

Exposure of humans to arsenic is associated with various adverse health effects including immunotoxicity and elevated risk of cancer development. Specific mechanisms of these effects are not well understood. In the present study we investigated some functional parameters of peritoneal macrophages isolated from mice exposed for 12 weeks to sodium arsenate in drinking water at 0.5, 5, and 50 mgAs/l. The experimental conditions were matched with the environmental conditions of arsenic exposure in humans. To characterize function of the macrophages, we assessed their ability to release nitric oxide (NO), reactive oxygen species (ROS), and tumor necrosis factor-alpha (TNF-alpha) in response to common stimulants. To this end the isolated cells were stimulated with lipopolysaccharide (1 microg/ml) to assess NO and TNF-alpha production (the WEHI-164 bioassay) or with phorbol myristate acetate (5 microg/ml) to assess superoxide production (NBT reduction test). As a result, in mice exposed to 0.5, 5, and 50 mgAs/l we observed decreased production of NO (9 +/- 2, 8 +/- 2, 11 +/- 5 microM NO2-, respectively, versus 27 +/- 7 microM in control) and superoxide (41.3 +/- 18.2%, 52.8 +/- 15.1% and 55.9 +/- 12.9%, respectively, less than in control). Despite reduced NO production, expression of iNOS mRNA in RT-PCR, showed similar levels in exposed and control animals. We did not see any significant influence of the exposure on TNF-alpha release and mRNA expression. The potential consequences of decreased production of NO and superoxide by peritoneal macrophages as observed in exposed mice may suggest impaired response of the cells against infection or developing tumor cells.
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http://dx.doi.org/10.1081/iph-200067947DOI Listing
September 2006

Roles of reactive oxygen species and selected antioxidants in regulation of cellular metabolism.

Int J Occup Med Environ Health 2005 ;18(1):15-26

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lódź, Poland.

Reactive oxygen species (ROS) are essential for life of aerobic organisms. They are produced in normal cells and formed as a result of exposure to numerous factors, both chemical and physical. In normal cells, oxygen derivatives are neutralized or eliminated owing to the presence of a natural defense mechanism that involves enzymatic antioxidants (glutathione peroxidase, superoxide dismutase, catalase) and water or fat-soluble non-enzymatic antioxidants (vitamins C and E, glutathione, selenium). Under certain conditions, however, ROS production during cellular metabolism also stimulated by external agents may exceed the natural ability of cells to eliminate them from the organism. The disturbed balance leads to the state known as oxidative stress inducing damage of DNA, proteins, and lipids. An inefficient repair mechanism may finally trigger the process of neoplastic transformation or cell death. Reactive oxygen species are also an integral part of signal transduction essential for intercellular communication. The balance between pro- and antioxidative processes determines normal cellular metabolism manifested by genes activation and/or proteins expression in response to exo- and endogenous stimuli.
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August 2005

Effect of selenium on expression of selenoproteins in mouse fibrosarcoma cells.

Biol Trace Elem Res 2005 May;104(2):165-72

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.

Selenium (Se), an essential trace element, is incorporated into selenoproteins as selenocysteine using insertion machinery, including UGA codon and selenocysteine insertion sequence (SECIS) element in the 3'-untranslated region (3'-UTR) of mRNA. To assess the biological effects of tumor cells exposed to the elevated, but nontoxic Se level on glutathione peroxidase (GPx1 [cellular] and GPx3 [extracellular]), thioredoxin reductase (TrxR), and selenoprotein P (SeP) mRNA expression, we introduced a semiquantitative reverse transcription-polymerase chain reaction technique for each selenoprotein transcript using beta-actin as a reference housekeeping gene in mouse fibroblasts (WEHI 164). Cell lines were cultured with 1.0, 2.5, and 5.0 ng of Se in 1 mL of medium for 3 and 7 d, apart from the control cell line with standard medium. It was found that Se exerts a statistically significant (p<0.05) effect only on GPx3 mRNA, referred to as the optical density (OD) ratio (GPx3/beta-actin). Moreover, the lowest Se level affected GPx3 mRNA expression more strongly than its highest concentrations. In an in vitro model applied in this study, GPx3 gene expression is most specific for Se supplementation.
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http://dx.doi.org/10.1385/BTER:104:2:165DOI Listing
May 2005