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1.
Pharmacol Rep ; 73(6): 1781-1786, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34173968

ABSTRACT

BACKGROUND: Variation in lipid changes in response to statin treatment is associated with genetic polymorphism. Sterolin-1, encoded by ABCG5, and sterolin-2, encoded by ABCG8, together form a sterol transporter. There are some reports indicating association of rs11887534 (ABCG8:c.55G > C) polymorphism with lipid concentrations, both prior to and after statin treatment. The aim of this study was to analyze both baseline plasma lipids and their concentrations in response to statin treatment with regard to ABCG8: rs11887534 polymorphism in Caucasian patients of Polish origin. METHODS: The study group consisted of 170 consecutive adult out-patients treated with atorvastatin or simvastatin for a minimum of 2 months. Concentrations of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) were measured before and after statin treatment. The ABCG8 polymorphism was identified by mini-sequencing genomic DNA extracted from peripheral blood leukocytes. RESULTS: There were no significant differences in regard to ABCG8 variants for baseline TG, TC, LDL-C and HDL-C as well as for TG, TC or LDL-C concentrations after statin treatment. However, patients carrying at least one C allele showed a decrease in post-statin HDL-C concentrations and the absolute and relative changes between post- and pre-statin HDL-C concentrations were negative in contrast to positive values in wild-type homozygotes. CONCLUSIONS: Our results suggest that the c.55C allele of the ABCG8: rs11887534 polymorphism might be associated with decrease in HDL-cholesterol in response to statin treatment in Polish patients.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Atorvastatin/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Simvastatin/pharmacology , Adult , Aged , Aged, 80 and over , Cholesterol, HDL/blood , Female , Humans , Lipids/blood , Male , Middle Aged , Poland , Polymorphism, Genetic , Retrospective Studies
2.
Physiol Res ; 68(6): 947-954, 2019 12 30.
Article in English | MEDLINE | ID: mdl-31647290

ABSTRACT

Chronic kidney disease adversely affects the structure and metabolism of bone tissue, which may be a result of disturbed biochemical processes in adipose tissue. Renal replacement therapy is a life-saving therapy but it does not restore all metabolic functions and sometimes even escalates some disturbances. The study included 126 subjects: 47 hemodialysis patients (HD), 56 patients after renal transplantation (Tx) and 23 healthy controls (K). Bone density at the femoral neck (FN) and lumbar spine (LS), as well as body composition (adipose tissue content and lean body mass) were measured in each patient using the DXA method. In addition, serum concentrations of glucose, calcium, phosphorus, parathormone, FGF23, Klotho, osteocalcin, leptin, adiponectin and 1,25-dihydroxyvitamin D3 were measured. We observed significantly higher concentrations of leptin, FGF23 and Klotho proteins in the HD patients (77.2±48.1 ng/ml, 54.7±12.4 pg/ml, 420.6±303.8 ng/ml, respectively) and the Tx group (33.2±26.5 ng/ml; 179.8±383.9 pg/ml; 585.4±565.7, respectively) compared to the control group (24.4±24.6 ng/ml, 43.3±37.3 pg/ml, 280.5±376.0 ng/ml). Significantly lower bone density at FN was observed in the HD and Tx patients in comparison to the controls and in the HD patients compared to the Tx group. There were no significant differences in body mass composition between the studied groups. The results of this study indicate that both hemodialysis and transplantation are associated with increased serum concentrations of leptin, FGF23 and Klotho proteins, as well as lower bone density at femoral neck.


Subject(s)
Bone Density/physiology , Kidney Transplantation/trends , Renal Dialysis/trends , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Adult , Aged , Bone Remodeling/physiology , Female , Femur Neck/diagnostic imaging , Femur Neck/metabolism , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Glucuronidase/blood , Humans , Kidney Transplantation/adverse effects , Klotho Proteins , Leptin/blood , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/metabolism , Male , Middle Aged , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/diagnostic imaging
3.
Folia Biol (Praha) ; 64(2): 59-64, 2018.
Article in English | MEDLINE | ID: mdl-30338757

ABSTRACT

Periodontal disease is a common oral disease. Inflammatory and immune responses to oral microorganisms initiate the development of periodontitis. Cigarette smoking is an important environmental risk factor for periodontitis. Another important inflammatory mediator is nitric oxide (NO). NO modulates vascular tone, microvascular permeability, leukocyte migration and oxidative activity, contributing to the direct killing of microorganisms. Several polymorphisms of the NOS3 gene have been detected, which may alter gene expression and NO synthesis. The aim of this study was to examine the association between the NOS3 rs1799983 and rs2070744 polymorphisms and periodontal disease. This study enrolled 200 patients with periodontal diseases (130 were non-smokers and 70 were smokers) and 160 control subjects (126 were non-smokers and 34 were smokers). Among the patients with periodontal disease, we observed a statistically increased frequency of patients with the CT genotype (TC vs. TT; 95%CI 1.83, OR 1.16-2.88, P = 0.011). There was a statistically significant increased frequency of CT genotype carriers among non-smoking patients with periodontal disease as compared with non-smoking controls, whereas there were no statistically significant differences between smoking patients with periodontal disease and smoking control subjects. The results of our study suggest an association between the NOS3 rs2070744 polymorphism and periodontal disease.


Subject(s)
Genetic Predisposition to Disease , Nitric Oxide Synthase Type III/genetics , Periodontal Diseases/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Aged , Case-Control Studies , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Smoking/genetics
4.
Arch Pediatr ; 25(3): 177-181, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29576254

ABSTRACT

INTRODUCTION: The receptor CD36 has been reported to play an important role in atherogenicity. The aim of this study was to gain insight into the relationship between CD36 gene polymorphisms or the plasma concentration of sCD36 and clinical or biochemical parameters in children. PATIENTS AND METHODS: The study groups comprised Caucasian children with and without hypercholesterolemia. The alterations in the CD36 gene were detected by DHPLC and the plasma concentrations of sCD36 were measured by ELISA. RESULTS: The data presented suggest that the IVS4-10A allele of CD36 (rs3211892) is associated with a lower risk of hypercholesterolemia. We observed a negative correlation of the sCD36 concentration with uric acid and insulin concentrations, the HOMA-IR ratio, weight, waist and hip circumference, systolic blood pressure, body mass index, waist-hip ratio and mean arterial pressure ratio, but a positive correlation with HDL cholesterol and ApoA1 concentrations. Female gender was a significant independent predictor of a higher plasma sCD36 concentration. CONCLUSIONS: The data presented suggest a possible protective effect of a higher sCD36 concentration in relation to metabolic syndrome components.


Subject(s)
CD36 Antigens/blood , CD36 Antigens/genetics , Hyperlipoproteinemia Type II/genetics , Polymorphism, Genetic , Adolescent , Apolipoprotein A-I/blood , Blood Pressure , Body Mass Index , Child , Cholesterol, HDL/blood , Female , Humans , Insulin , Male , Sex Factors , Systole , Uric Acid , Waist-Hip Ratio , White People/genetics
5.
J Physiol Sci ; 68(3): 293-305, 2018 May.
Article in English | MEDLINE | ID: mdl-28432611

ABSTRACT

This study aimed at evaluating the concentration of erythrocyte purine nucleotides (ATP, ADP, AMP, IMP) in trained and sedentary subjects before and after maximal physical exercise together with measuring the activity of purine metabolism enzymes as well as the concentration of purine (hypoxanthine, xanthine, uric acid) and pyrimidine (uridine) degradation products in blood. The study included 15 male elite rowers [mean age 24.3 ± 2.56 years; maximal oxygen uptake (VO2max) 52.8 ± 4.54 mL/kg/min; endurance and strength training 8.2 ± 0.33 h per week for 6.4 ± 2.52 years] and 15 sedentary control subjects (mean age 23.1 ± 3.41 years; VO2max 43.2 ± 5.20 mL/kg/min). Progressive incremental exercise testing until refusal to continue exercising was conducted on a bicycle ergometer. The concentrations of ATP, ADP, AMP, IMP and the activities of adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and phosphoribosyl pyrophosphate synthetase (PRPP-S) were determined in erythrocytes. The concentrations of hypoxanthine, xanthine, uric acid and uridine were determined in the whole blood before exercise, after exercise, and 30 min after exercise testing. The study demonstrated a significantly higher concentration of ATP in the erythrocytes of trained subjects which, in part, may be explained by higher metabolic activity on the purine re-synthesis pathway (significantly higher PRPP-S, APRT and HGPRT activities). The ATP concentration, just as the ATP/ADP ratio, as well as an exercise-induced increase in this ratio, correlates with the VO2max level in these subjects which allows them to be considered as the important factors characterising physical capacity and exercise tolerance. Maximal physical exercise in the group of trained subjects results not only in a lower post-exercise increase in the concentration of hypoxanthine, xanthine and uric acid but also in that of uridine. This indicates the possibility of performing high-intensity work with a lower loss of not only purine but also pyrimidine.


Subject(s)
Erythrocytes/metabolism , Exercise/physiology , Purine Nucleotides/metabolism , Purines/blood , Pyrimidines/blood , Adult , Humans , Hypoxanthine/metabolism , Hypoxanthine Phosphoribosyltransferase/metabolism , Male , Purines/metabolism , Pyrimidines/metabolism , Uric Acid/metabolism , Xanthine/metabolism , Young Adult
6.
Folia Biol (Praha) ; 63(3): 115-119, 2017.
Article in English | MEDLINE | ID: mdl-28805561

ABSTRACT

Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by ß cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus. The study included 201 patients who received kidney transplants. The patients were subdivided into two subgroups: patients with PTDM (N = 35) and patients without PTDM (N = 166). The association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes was studied in three models of univariate Cox regression analysis, i.e., additive, dominant and recessive. In these three models there were no statistically significant associations between KCNJ11 and KCNQ1 gene polymorphisms and PTDM. The results of this study suggest lack of association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes mellitus in kidney allograft recipients treated with tacrolimus in the Polish population.


Subject(s)
KCNQ1 Potassium Channel/genetics , Kidney Transplantation/methods , Polymorphism, Genetic/genetics , Potassium Channels, Inwardly Rectifying/genetics , Tacrolimus/therapeutic use , Adult , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/surgery , Female , Humans , Male , Middle Aged
7.
J Perinatol ; 37(4): 345-348, 2017 04.
Article in English | MEDLINE | ID: mdl-28079868

ABSTRACT

OBJECTIVE: Gestational diabetes mellitus (GDM) is carbohydrate intolerance occurring in pregnant women. CDC123/CAMK1D and CDKN2A/2B are associated with increased risk of type 2 diabetes and may affect pancreatic beta cell function. The aim of this study was to examine the association between CDKN2A/2B rs10811661 and CDC123/CAMK1D rs12779790 gene polymorphisms and GDM. STUDY DESIGN: This study included 411 pregnant women. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups criteria. According to the results of their oral glucose tolerance test, the women were divided into two groups: 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. RESULTS: There were no statistically significant differences in the distribution of CDC123/CAMK1D rs12779790 genotypes and alleles between women with GDM and healthy pregnant women. However, there was a statistically significant association between the C allele of CDKN2A/2B rs10811661 polymorphism and reduced risk of GDM (C vs T, OR 0.53, 95% CI 0.36 to 0.79, P=0.0014). In the multivariate logistic regression analysis, older age and higher body mass index before pregnancy were independent significant predictors of a higher risk of GDM, while higher number of C alleles (CDKN2A/2B rs10811661) was a protective factor against GDM. CONCLUSION: The results of this study suggest an association between CDKN2A/2B gene rs10811661 polymorphism and GDM.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p18/genetics , Diabetes, Gestational/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Body Mass Index , Calcium-Calmodulin-Dependent Protein Kinase Type 1/genetics , Case-Control Studies , Cell Cycle Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p16 , Female , Genetic Predisposition to Disease , Glucose Tolerance Test , Humans , Logistic Models , Multivariate Analysis , Poland , Pregnancy , Risk Factors
8.
Caries Res ; 51(1): 79-84, 2017.
Article in English | MEDLINE | ID: mdl-28088794

ABSTRACT

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in the gene encoding ficolin-2 protein (FCN2 gene) at positions -986 (rs17514136), -602 (rs3124953), and -4 (rs3124952) with dental caries in Polish children. Two hundred and sixty Polish Caucasian children aged 15 years were enrolled in this study: 82 with "higher" caries experience (DMFT >5) and 178 with "lower" caries experience (DMFT ≤5). In addition, subjects with caries experience (DMFT ≥1) and caries-free subjects (DMFT = 0) were compared. FCN2 SNPs were genotyped with PCR-RFLP methods. There were no significant differences in the genotype, allele, or haplotype distributions in 3 analyzed SNPs of the FCN2 gene between children with "higher" and those with "lower" caries experience as well as between children with caries experience and caries-free children. In conclusion, we did not find any association of FCN2 promoter polymorphisms at positions -986, -602, and -4 with dental caries in Polish children.


Subject(s)
Dental Caries/ethnology , Dental Caries/epidemiology , Genetic Predisposition to Disease/ethnology , Lectins/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Adolescent , Alleles , DMF Index , Dental Caries/genetics , Female , Gene Frequency , Genotyping Techniques , Haplotypes , Humans , Male , Poland/epidemiology , Ficolins
9.
Clin Genet ; 91(6): 843-848, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27684496

ABSTRACT

Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks' gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR = 1.40, 95% CI: 1.05-1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes, Gestational/genetics , Homeodomain Proteins/genetics , Transcription Factors/genetics , Tumor Suppressor Proteins/genetics , Adult , Body Mass Index , Diabetes Mellitus, Type 2/pathology , Diabetes, Gestational/pathology , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Glucose Tolerance Test , Humans , Insulin/genetics , Polymorphism, Single Nucleotide , Pregnancy , Risk Factors
10.
Scand J Med Sci Sports ; 27(8): 788-800, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27140937

ABSTRACT

The aim of the study was to assess whether selected genetic variants are associated with elite athlete performance in a group of 413 elite athletes and 451 sedentary controls. Polymorphisms in ACE, ACTN3, AGT, NRF-2, PGC1A, PPARG, and TFAM implicated in physical performance traits were analyzed. Additionally, polymorphisms in CHRNB3 and FAAH coding for proteins modulating activity of brain's emotion centers were included. The results of univariate analyses indicated that the elite athletic performance is associated with four polymorphisms: ACE (rs4341, P = 0.0095), NRF-2 (rs12594956, P = 0.011), TFAM (rs2306604, P = 0.049), and FAAH (rs324420, P = 0.0041). The multivariate analysis adjusted for age and gender confirmed this association. The higher number of ACE D alleles (P = 0.0021) and the presence of NRF-2 rs12594956 A allele (P = 0.0067) are positive predictors, whereas TFAM rs2306604 GG genotype (P = 0.031) and FAAH rs324420 AA genotype (P = 0.0084) negatively affect the elite athletic performance. The CHRNB3 variant (rs4950, G allele) is significantly more frequent in the endurance athletes compared with the power ones (P = 0.025). Multivariate analysis demonstrated that the presence of rs4950 G allele contributes to endurance performance (P = 0.0047). Our results suggest that genetic inheritance of psychological traits should be taken into consideration while trying to decipher a genetic profile of top athletic performance.


Subject(s)
Athletes , Athletic Performance , Polymorphism, Genetic , Adult , Alleles , Amidohydrolases/genetics , DNA-Binding Proteins/genetics , Female , Genotype , Humans , Male , Mitochondrial Proteins/genetics , NF-E2-Related Factor 2/genetics , Peptidyl-Dipeptidase A/genetics , Poland , Receptors, Nicotinic/genetics , Sports , Transcription Factors/genetics , Young Adult
11.
Transplant Proc ; 48(7): 2450-2453, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27742319

ABSTRACT

BACKGROUND: Due to demographic projections, and lack of an algorithm in the case of a prostate specific antigen (PSA)-positive donor, the loss of organ recovery may occur more frequently in the near future without approved procedures. In Poland in recent years it has been recommended to determine tumor markers in potential donors. In the first year of the recommendation 10% of potential deceased donors were disqualified in our transplantation center on the basis of the elevated PSA levels (high PSA >10 ng/mL). Histopathologic evaluation of prostate was implemented in a donor qualification procedure to prevent reduction of the actual organ donor pool. MATERIAL AND METHODS: In the period of January 2010-January 2014 each donor reported to a coordination center (n = 52; median age, 54 years) and underwent the routine histological evaluation of the whole prostate, regardless of the PSA level. RESULTS: Pathologist revealed in the study group of 52 male donors, 6 cases of carcinoma of the prostate (CaP; 12%). There was no correlation between PSA level and CaP (-)/CaP(+) (median 7.0 vs 3.9 ng/mL, respectively; P = .51) nor high-grade prostate intraepithelial neoplasia (HGPIN) (+)/HGPIN (-) (median 5.9 vs 4.3 ng/mL; P = .14). All of the recovered organs (12 kidneys and 3 livers) from donors with CaP were transplanted, resulting in a 15% increase in the organ donor pool. CONCLUSIONS: There is no association between PSA values and CaP occurrence in deceased organ donors. Histological verification allowed for an increase in the organ pool with maintenance of safety standards.


Subject(s)
Biomarkers, Tumor/blood , Pathologists/standards , Prostate-Specific Antigen/blood , Tissue and Organ Procurement/methods , Adult , Aged , Algorithms , Clinical Competence/standards , Humans , Male , Middle Aged , Poland , Prostate/pathology , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/pathology , Tissue Donors/supply & distribution , Young Adult
12.
Transplant Proc ; 48(5): 1374-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27496408

ABSTRACT

Currently, there is no clear position regarding the donation of organs from donors with prostate carcinoma (CaP) in European countries, except Italy. The lengthening of life expectancy increases the probability of prostate cancer among potential organ donors. The concentration of prostate-specific antigen (PSA) >2 ng/mL at 60 years of age is related to the increasing possibility of identifying an advanced form of CaP. In recent years in Poland, the recommendation has been to determine tumor markers in potential donors. In the first year of the recommendation, 10% of potential male cadaveric donors were disqualified in West Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid reduction of the actual donor pool, each potential male donor reported to the center since January 2010 undergoes a routine histologic evaluation of the whole prostate, regardless of the PSA level, before organ implantation. In the study group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between histologically confirmed CaP and the PSA level.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma/blood , Donor Selection/methods , Prostate-Specific Antigen/blood , Prostatic Hyperplasia/blood , Prostatic Intraepithelial Neoplasia/blood , Prostatic Neoplasms/blood , Tissue Donors , Adult , Aged , Carcinoma/diagnosis , Carcinoma/pathology , Death , Europe , Humans , Italy , Male , Middle Aged , Poland , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/pathology , Prostatic Intraepithelial Neoplasia/diagnosis , Prostatic Intraepithelial Neoplasia/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Risk Factors , Time Factors , Urinary Catheterization , Young Adult
13.
Transplant Proc ; 48(5): 1451-5, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27496426

ABSTRACT

BACKGROUND: Reports regarding recipient's nonmodifiable genetic factors affecting telomerase activity and thus allograft function are lacking. Therefore the aim of this study was to analyze the associations between recipients' rs2735940 hTERT, rs2630578 BICD1, and rs7235755 chromosome 18 polymorphisms and kidney function after transplantation. METHODS: The study enrolled 119 white Polish kidney allograft recipients (64 men, 55 women; overall mean age, 47.3 ± 14.0 y). To identify genotypes of the studied polymorphisms, real-time polymerase chain reaction was performed. RESULTS: There were statistically significant differences in distribution of rs7235755 chromosome 18 polymorphism genotypes and alleles between recipients with delayed graft function (DGF) and without DGF (P = .03). The presence of A allele was significantly associated with higher risk of DGF occurrence (AA + GA vs GG: OR, 3.25 [95% CI, 1.16-9.14]; P = .02; GA vs GG: OR, 4.00 [1.35-11.82]; P = .01). Analysis of the rs2630578 BICD1 gene polymorphism genotypes revealed statistically significant differences in long-term creatinine concentrations. The presence of C allele of this polymorphism was significantly associated with higher creatinine concentrations 24, 36, and 18-48 months after transplantation (GC + CC vs GG: P = .008, P = .008, and P = .01, respectively). CONCLUSIONS: Recipients' polymorphisms of genes associated with telomere length, BICD1 and chromosome 18, but not hTERT, affect kidney allograft early and long-term function after transplantation. There is an urgent need for explanation of these observations in genome-wide association studies.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Allografts/physiopathology , Chromosomes, Human, Pair 18/genetics , Cytoskeletal Proteins/genetics , Delayed Graft Function/genetics , Kidney Transplantation , Adult , Alleles , Creatinine/blood , Female , Genotype , Humans , Male , Middle Aged , Poland , Polymorphism, Genetic , Real-Time Polymerase Chain Reaction , Telomerase/genetics , Telomere
14.
Scand J Immunol ; 83(6): 418-26, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27007325

ABSTRACT

This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner.


Subject(s)
Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Killer Cells, Natural/immunology , Pregnancy/drug effects , Spleen/drug effects , Thymus Gland/drug effects , Administration, Oral , Animals , Female , Humans , Immunosuppression Therapy , Interleukin-17/metabolism , Pregnancy/immunology , Rats , Rats, Wistar , Spleen/immunology , Thymus Gland/immunology
15.
Genetika ; 52(5): 616-20, 2016 May.
Article in English | MEDLINE | ID: mdl-29368490

ABSTRACT

Pain in patients with hip osteoarthritis appears long before surgery, and requires effective management as it affects patient comfort and daily activities. Therefore, the search for factors influencing response rate to analgesics is mandatory. In recent years, increasing attention has been paid to genetic factors underlying pain threshold and treatment efficacy. Polymorphic gene of catechol-oxide-methyltransferase (COMT) is a candidate gene associated with pain pathology and treatment response. The aim of the study was to evaluate association between the COMT rs4680:G>A polymorphism and demand for analgesics in patients subjected to elective hip replacement. The study included 196 patients after hip replacement surgery. Opioid demand was recorded and analgesic efficacy was scored using a four-level verbal pain intensity scale. COMT rs4680:G>A polymorphism was analysed by PCR-RFLP method. The studied COMT genotypes did not influence opioid administration in the studied patients from the day of surgery till day 6 afterwards. The distribution of the COMT rs4680:G>A in the studied subjects was as follows: GA­52.04%, AA­23.98% and GG­23.98%. It can be concluded that the COMT rs4680:G>A polymorphism is not associated with opioid demand in patients after elective hip replacement.


Subject(s)
Analgesics/administration & dosage , Catechol O-Methyltransferase/genetics , Elective Surgical Procedures , Pain Management , Pain , Polymorphism, Genetic , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Female , Genotype , Humans , Male , Middle Aged , Pain/drug therapy , Pain/genetics
16.
Eur Rev Med Pharmacol Sci ; 19(16): 3037-40, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26367725

ABSTRACT

OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid arthritis (RA). The aim of many studies is to identify factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX in RA is associated with the inhibition of inflammatory mediators synthesis. CXCL9 and CXCL10 chemokines play the important role in inflammatory response in RA patients. The aim of this study was to examine the association between CXCL9/10 gene polymorphisms and response to therapy of RA patients with MTX. PATIENTS AND METHODS: The study included 422 patients diagnosed with rheumatoid arthritis, treated with MTX in doses 20 mg weekly. Good responders were defined as patients who were receiving MTX and had a DAS28 of ≤ 2.5 at 6 months of therapy. Poor-responders were defined as patients who were receiving MTX and had a DAS28 of > 2.5. RESULTS: There were not statistically significant associations between studied polymorphisms and the outcome of rheumatoid arthritis treatment with methotrexate. CONCLUSIONS: The results of this study suggest lack of associations between the polymorphisms in CXCL9 and CXCL10 genes and the response to MTX in RA patients.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Chemokine CXCL10/genetics , Chemokine CXCL9/genetics , Methotrexate/therapeutic use , Antirheumatic Agents/adverse effects , Drug Therapy, Combination , Female , Genotype , Humans , Male , Methotrexate/adverse effects , Middle Aged , Polymorphism, Genetic , Treatment Outcome
17.
Eur Rev Med Pharmacol Sci ; 19(17): 3152-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26400516

ABSTRACT

OBJECTIVE: Post-transplant diabetes mellitus (PTDM) is a common complication after organ transplantation which leads to impaired graft function. Various factors may increase the risk of the development of PTDM. It has been reported that cytokines and genetic variations of inflammatory cytokines were associated with glucose homeostasis or diabetes. The pro-inflammatory cytokine IL-17, which is produced by T-helper 17 (Th17) cells, has been reported to be involved in the glucose metabolism and pathogenesis of diabetes via the induction of low-grade inflammation. The aim of this study was to examine the association between polymorphisms in the IL17A (rs2275913) and IL17F (rs11465553, rs2397084, rs763780) genes with post-transplant diabetes mellitus. PATIENTS AND METHODS: The study included 169 patients of Caucasian origin who received kidney transplants. For the purpose of the study, the patients were subdivided into two subgroups: patients with PTDM (n = 23) and patients without PTDM (n = 146). Standard immunosuppression consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: Post-transplant diabetes was diagnosed in 10.97% of the carriers of the IL17F rs763780 TT genotype and 42.86% of those with the TC genotype (TC vs TT: OR = 6.09, 95% CI 1.89-19.66, p = 0.0048). In multivariate analysis, older recipient age and the presence of the TC genotype were independent significant predictors of higher risk of post-transplant diabetes. CONCLUSIONS: The results of this study suggest an association between the IL17F rs763780 polymorphism and post-transplant diabetes.


Subject(s)
Diabetes Mellitus/etiology , Interleukin-17/genetics , Kidney Transplantation/adverse effects , Polymorphism, Genetic/genetics , Adult , Aged , Diabetes Mellitus/genetics , Female , Genotype , Humans , Male , Middle Aged , Risk Factors , Tacrolimus
18.
Eur J Phys Rehabil Med ; 51(3): 245-52, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25230888

ABSTRACT

BACKGROUND: Earlier and more intensive physiotherapy exercise after total knee arthroplasty (TKA) enhance recovery, but the best combination of intensity and duration has not been determined. AIM: To determine whether adding a single, 15-minute walk on the day of surgery to a fast-track rehabilitation protocol would reduce knee pain and improve knee function after TKA. DESIGN: A randomized single-blind study. SETTING: Inpatient. POPULATION: Patients with primary osteoarthrosis after TKA. METHODS: Patients undergoing TKA were randomly assigned to a standard, fast-track rehabilitation protocol consisting of a single, 15-minute walk with a high-rolling walker 4 to 6 hours after recovery from spinal anesthesia or to an intensive protocol, in which patients took a second 15-minute walk at least 3 hours after the first, only on the day of surgery. Outcomes were pain measured on a visual analog scale, Knee Society's (KSS) clinical and functional scores, Oxford knee scores, and Spielberger State-Trait Anxiety Inventory scores. Patients were blinded to group assignment. Since most data were non-normally distributed non-parametric tests were used. Groups were compared with Mann-Whitney U test (for continuous variables). Association between continuous variables was evaluated with Spearman`s rank correlation coefficient. Chi-square or Fisher's exact test was used to assess differences in categorical variables. RESULTS: Of 86 patients assessed for eligibility, 66 were randomly assigned. The 31 evaluable patients on the intensive protocol (mean age, 68 years; 18 women) did not differ significantly from the 31 (mean age, 70 years; 20 women) on the standard protocol on any baseline characteristic or on any outcome measure on any day. On the second postoperative day, pain while walking dropped from a mean of 6.1 to a mean of 4.9 in the intensive group and from 6.4 to 5.4 in the standard group. Results for pain at rest were 3.3 to 2.2, respectively, for the intensive group and 4.0 to 3.0 for the standard group. At 2 weeks, pain at rest was 2.8 in both groups, and pain while walking was 3.0, respectively, for the intensive group and 3.4 for the standard group. At 2 weeks, mean (SD) KSS clinical and KSS function scores were, respectively, 74.9 (12.5) and 51.6 (16.2) in the intensive group and 71.2 (14.3) and 46.3 (16.1) in the standard group. Older age correlated with decreasing knee function (rS=-0.43, P<0.001), and less knee flexion correlated with preoperatively higher state anxiety (rS=-0.37, P=0.005) and trait anxiety (rS=-0.29, P=0.027). The study is limited by its small sample. The fast-track program was not in line with the best available evidence following knee arthroplasty, because patients did not undergo such treatment as NMES. Finally, the intervention itself was modest. CONCLUSION: Adding an additional 15-minute walk to a fast-track rehabilitation protocol did not increase pain, but neither did it improve functional recovery. CLINICAL REHABILITATION IMPACT: A 15-minute walk immediately after recovery from spinal anesthesia did not increase pain in patients with TKA. More intense exercise during this period might improve functional recovery without increasing pain.


Subject(s)
Arthroplasty, Replacement, Knee/rehabilitation , Exercise Therapy/methods , Knee Joint/physiopathology , Osteoarthritis, Knee/rehabilitation , Range of Motion, Articular/physiology , Recovery of Function , Aged , Female , Humans , Male , Osteoarthritis, Knee/physiopathology , Postoperative Period , Single-Blind Method , Treatment Outcome , Walking
19.
Neuroradiology ; 56(8): 609-20, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24801451

ABSTRACT

INTRODUCTION: The standardized diagnostic criteria for computed tomographic angiography (CTA) in diagnosis of brain death (BD) are not yet established. The aim of the study was to compare the sensitivity and interobserver agreement of the three previously used scales of CTA for the diagnosis of BD. METHODS: Eighty-two clinically brain-dead patients underwent CTA with a delay of 40 s after contrast injection. Catheter angiography was used as the reference standard. CTA results were assessed by two radiologists, and the diagnosis of BD was established according to 10-, 7-, and 4-point scales. RESULTS: Catheter angiography confirmed the diagnosis of BD in all cases. Opacification of certain cerebral vessels as indicator of BD was highly sensitive: cortical segments of the middle cerebral artery (96.3 %), the internal cerebral vein (98.8 %), and the great cerebral vein (98.8 %). Other vessels were less sensitive: the pericallosal artery (74.4 %), cortical segments of the posterior cerebral artery (79.3 %), and the basilar artery (82.9 %). The sensitivities of the 10-, 7-, and 4-point scales were 67.1, 74.4, and 96.3 %, respectively (p<0.001). Percentage interobserver agreement in diagnosis of BD reached 93 % for the 10-point scale, 89 % for the 7-point scale, and 95 % for the 4-point scale (p=0.37). CONCLUSIONS: In the application of CTA to the diagnosis of BD, reducing the assessment of vascular opacification scale from a 10- to a 4-point scale significantly increases the sensitivity and maintains high interobserver reliability.


Subject(s)
Brain Death/diagnosis , Cerebral Angiography , Tomography, X-Ray Computed , Adult , Aged , Brain Death/physiopathology , Cerebrovascular Circulation , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Young Adult
20.
Transplant Proc ; 45(6): 2244-7, 2013.
Article in English | MEDLINE | ID: mdl-23953534

ABSTRACT

ICAM-1 and VCAM-1 adhesion molecules play important roles in the immune response and emergence of chronic allograft nephropathy (CAN). The several polymorphisms of ICAM1 and VCAM1 genes are associated with changes in molecular expression therefore affecting allograft function and immune responses after kidney transplantation. The aim of this study was to examine the impact of polymorphisms in ICAM1 and VCAM1 genes on biopsy-proven CAN and renal allograft function. The 270 Caucasian renal transplant recipients (166 men and 104 women) were genotyped for the rs5498 ICAM1 and rs1041163 and rs3170794 VCAM1 gene polymorphisms using real-time polymerase chain reaction. There was no correlation between polymorphisms and CAN. Creatinine concentrations in the first month after transplantation differed between the rs5498 ICAM1 genotypes (P = .095), being higher for GG carriers (AA + AG vs GG, P =.07) albeit not with statistical significance. Creatinine concentrations at 12, 24, and 36 months after transplantation differed significantly among rs5498 ICAM1 genotypes (P = .0046, P =.016, and P = .02) and were higher among GG carriers (AA + AG vs GG, P = .001, P = .004, and P = .006). Rs5498 ICAM1 GG genotype and receipient male gender were independent factors associated with higher creatinine concentrations. These results suggest that the rs5498 ICAM1 GG genotype may be associated with long-term allograft function.


Subject(s)
Intercellular Adhesion Molecule-1/genetics , Kidney Diseases/genetics , Kidney Transplantation/adverse effects , Kidney/physiopathology , Polymorphism, Genetic , Vascular Cell Adhesion Molecule-1/genetics , Adult , Biomarkers/blood , Biopsy , Chi-Square Distribution , Chronic Disease , Creatinine/blood , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Kidney/metabolism , Kidney/pathology , Kidney Diseases/blood , Kidney Diseases/ethnology , Kidney Diseases/pathology , Kidney Diseases/physiopathology , Male , Middle Aged , Odds Ratio , Phenotype , Poland/epidemiology , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , White People/genetics
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