Genetic Architecture of Pregnancy Loss: Co-inheritance of Risk Factors in Bosnian Women.

Pregnancy-related complications (PRC) re-present a serious public health and healthcare challenge. In European countries, infertility among couples varies from 5 to 24 %. The cause of PRC may include autoimmune and metabolic factors, correctness of the karyotype and variants of selected genes. The impact magnitude of genetic variants in one of PRC, pregnancy loss (PL), is still unexplored. Therefore, in this study, raw data on 12 single-nucleotide polymorphisms (SNPs) that were published separately in 2017-2019 were re-examined. We analysed the co-inheritance of 12 SNPs: rs6025 FV, rs429358 and rs7412 ApoE, rs1799752 ACE, rs1799889 PAI-1, rs1799963 PT, rs1801133 MTHFR, rs9468 and rs1800547 INV 17q21.31, rs731236 and rs1544410 VDR, and rs10421768 HAMP. Each time, the same study group of 154 women with PL, mean age 33 (± 5.4) years, and 154 mothers without PL, mean age 31.4 (± 6.7) years, with at least one live-born child, a control group, was investigated. In Bosnian women, no relationship of the co-inheritance pattern of any of the studied variants with PL was confirmed: P was in the range 0.248-1.0. In conclusion, the role of co-inheritance of heterozygotes and homozygotes or homozygotes of selected genes in PL has not been fully confirmed.

FCN1 polymorphisms are not the markers of dental caries susceptibility in Polish children: A case-control study.

OBJECTIVE: To examine the association of four FCN1 SNPs: -542G>A (rs10120023), -144C>A (rs10117466), +6658C>T (rs148649884), and +7895A>G (rs150625869) with dental caries in Polish children. SUBJECTS AND METHODS: The study group consisted of 261 15-year-old Polish teenagers: 82 children with "higher" caries experience (having Decayed Missing Filled Teeth, DMFT >5) and 179 children with "lower" caries experience (having DMFT ≤5). Moreover, in additional comparison, a group of 229 children with caries experience (DMFT ≥1) was compared to a caries-free (DMFT =0) group of 32 children. Extraction of genomic DNA was performed from buccal swabs, and genotyping was performed by Real-Time PCR. RESULTS: FCN1 SNPs +6658C>T and +7895A>G appeared to be monomorphic in our sample. The genotype, allele, or haplotype distributions in FCN1 SNPs -542G>A and -144C>A in children with "higher" caries experience did not differ significantly from those in "lower" caries experience group. Similar results with no significant differences were demonstrated for subjects with DMFT ≥1 compared to subjects with DMFT =0. CONCLUSION: FCN1 SNPs are not the markers of dental caries susceptibility in Polish children.

Genetic diversity of CYP3A5 and ABCB1 variants in East-Central and South European populations.

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. AIM: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. SUBJECTS AND METHODS: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. RESULTS: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively. CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

Bosnian study of APOE distribution (BOSAD): a comparison with other European populations.

BACKGROUND: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. AIM: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations. SUBJECTS AND METHODS: Overall, 170 unrelated Bosnian subjects (108 female and 62 male), aged 53.0 (±5.0) years were included in this study. Genotypes were determined by real-time PCR. RESULTS: In our group the prevalence of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively, while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 12.6%, 78.0% and 9.4%, respectively. CONCLUSIONS: In studied European populations we observed a linear, gradually increasing trend in the frequency of ε4 allele from South to North (Pearson's test 0,7656, p value <0.00001), and the Bosnian population fits into this pattern perfectly.

The Prevalence of Autism Spectrum Disorders in West Pomeranian and Pomeranian Regions of Poland.

BACKGROUND: The prevalence of autism spectrum disorders (ASD) varies worldwide from 1.4/10 000 children in the Arabian Peninsula to 185/10 000 children of Asian population. In Europe, the highest prevalence has been observed in Sweden, while the lowest in Croatia (115/10 000 and 2-3/10 000, respectively). There have been no epidemiological studies on the prevalence of ASD in Polish population. The aim of our study was to assess the prevalence of ASD in children aged 0-16 years, inhabitants of West Pomeranian and Pomeranian regions. MATERIAL AND METHODS: In total, 2514 children (2038 males, 81.1%) were included. The estimates were based on the government registries, whereas data were obtained from Provincial Disability Services Commissions. RESULTS: The prevalence of ASD in children aged 0-16 years varies between two regions of Poland - 32/10 000 in West Pomeranian and 38/10 000 in Pomeranian region. CONCLUSIONS: The average prevalence of ASD was 35/10 000 children and was about 4-fold higher in males (P < 0.05). More studies are necessary.

The impact of the d3-growth hormone receptor (d3-GHR) polymorphism on the therapeutic effect of growth hormone replacement in children with idiopathic growth hormone deficiency in Poland.

OBJECTIVES: The human growth hormone receptor (GHR) exon 3 deletion (d3) polymorphism has been reported to be associated with the responsiveness to growth hormone (GH) therapy. This study aimed to: (a) assess the frequency of this polymorphism in a group of Polish children with idiopathic growth hormone deficiency (IGHD) and (b) analyze their response to GH therapy. METHODS: The study group consisted of 67 prepubertal children with IGHD. The control group was composed of 150 Caucasian newborns from whom umbilical cord blood samples were drawn. A genotype analysis was performed using the PCR multiplex technique in search for the existence or deletion of exon 3 of the GHR gene. RESULTS: In the study group the following genotype distribution was observed: fl/fl-GHR 64.2%; fl/d3-GHR 29.9%; d3/d3-GHR 5.9%. The total percentage of patients with d3-GHR polymorphism was 35.8% and 64.2% patients had a fl/fl-GHR. No significant differences were noted in growth rate SD before introducing therapy and growth rate after one year of recombinant human GH therapy in patients with individual genotypes. In the control group the genotype distribution was: fl/fl-GHR 63.3%; fl/d3-GHR 29.9%; d3/d3-GHR 6.8%. CONCLUSION: No differences were observed in genotype distribution between the study and the control group. Patients with IGHD did not differ among each other depending on their genotype (fl/fl-GHR or fl/d3-GHR) in terms of growth velocity before introducing therapy or growth rate after one year of recombinant human GH therapy.

DD Genotype of ACE I/D Polymorphism Might Confer Protection against Dental Caries in Polish Children.

The aim of the study was to examine the frequencies of the genotypes and alleles of ACE insertion/deletion (I/D) polymorphism and their association with dental caries in a sample of Polish children. The study subjects were 120 children with dental caries experience (cases) and 41 caries-free individuals (controls). The genotyping was performed using polymerase chain reaction. The genotype distributions of ACE I/D polymorphism were not statistically different between carious and control children. However, we found a borderline overrepresentation of the II + ID genotypes versus the DD genotype in the carious compared to the control group (69.2% and 51.2%, respectively, p = 0.057). Logistic regression analysis adjusted for age and sex revealed that I allele carriage was a significant predictor of dental caries susceptibility (OR = 2.14, 95% CI = 1.02-4.49, p = 0.041). In conclusion, the DD genotype of ACE I/D polymorphism might be protective against dental caries in Polish children.

Prevalence of genetic prothrombotic risk factors: 1691G > A FV, 20210G > A PT and 677C > T MTHFR mutations in the Bosnian population.

BACKGROUND: Venous thrombosis (VT) affects 1-2 out of 10(3) individuals each year. Mutations of 1691G > A FV gene, 20210G > A PT gene and 677C > T gene MTHFR are common in Europe and increase the risk of venous thrombosis. To the authors' knowledge, this is the first report on the prevalence of these mutations in the general population of Bosnia and Herzegovina. AIM: The aim of this study was to simultaneously analyse main VT associated polymorphisms and compare the results with those published for other European populations. DATA SOURCES: Electronic databases including Medline and Embase were searched from 1995 to December 2013. SUBJECTS AND METHODS: The subjects of the study consisted of 100 unrelated healthy people from Bosnia and Herzegovina (82 female and 18 male). The mean age of the cohort was 58.8 (± 10.7) years. PCR-RFLP was used for measurement of allele frequencies. RESULTS: All three SNPs were found to be polymorphic, with allele frequencies of 6.0%, 6.0% and 37.5% for 1691A FV, 20210A PT and 677T MTHFR, respectively. CONCLUSION: Further studies on larger cohorts with an adequate female-to-male ratio are necessary to confirm a high prevalence of hereditary thrombophilia in the Bosnian population.

Association of 1936A > G in AKAP10 (A-kinase anchoring protein 10) and blood pressure in Polish full-term newborns.

OBJECTIVE: The 1936G AKAP10 allele is associated with increased adult basal heart rate (HR) and decreased variability, markers of low cholinergic/vagus sensitivity associated with hypertension. Blood pressure (BP) values in newborns are important measurable markers of cardiovascular risk later in life. The question was whether decreased vagal function-related 1936A > G AKAP10 is associated with newborn BP. STUDY DESIGN: 114 healthy Polish newborns born after 37th gestational week to healthy women with uncomplicated pregnancies. At birth, newborn cord blood obtained for isolation of genomic DNA. BP and HR measured on days 1 and 3 after delivery. RESULTS: Diastolic BP on day 3 and absolute and relative differences between diastolic BP values, as well as between mean BP values on day 3 and on day 1 after birth, in carriers of 1936G AKAP10 allele, were significantly higher as compared with wild-type homozygotes. CONCLUSION: Results demonstrate possible association between 1936G AKAP10 variant and BP in Polish newborns.

1936A→G (I646 V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10 in very long-lived poles is similar to that in newborns.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The common 1936A→G transition (rs203462) in the AKAP10 gene encoding the A-kinase-anchoring protein 10 has been recently associated with negative prognosis in the aging European American population (60 to 79 years old). The aim of this study was to see the effects of this transition on allele frequency in very long-lived Poles. METHODS: AKAP10 genotype and allele distributions were analyzed in Polish subjects: 148 nonagenarians (95 to 103 years old) and 200 healthy newborn controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Distributions were separated according to gender and χ(2) tests used to analyze possible differences. RESULTS: No significant differences were found in genotype or allele distribution between the age groups, for either gender. Percentages of GG AKAP10 homozygotes were slightly greater in the very old subjects than in the newborns (12.2% vs. 9.0%, respectively), and the G allele percentages were very similar (males, 30.7% and 33.0%; females, 34.1% and 35.8%; respectively). CONCLUSION: The authors conclude that differences in study results between European Americans (60 to 79 years old) and Poles (≥95 years old) result from either (1) geographical location; or (2) the influence of this polymorphism on groups of people differing in genetic background or environmental history; or (3) the time window affected, including extreme age. Further studies with full age-frequency distributions are needed to clarify these results.

Effect of preservation solutions UW and EC on the expression of matrix metalloproteinase II and tissue inhibitor of metalloproteinase II genes in rat kidney.

Matrix metalloproteinases and tissue inhibitor of metalloproteinases play an important role in the regulation of mesangial cell proliferation and may be involved in ischemia-reperfusion injuries. Preservation solutions are thought to diminish the ischemic injury and appropriate choice of the solution should guarantee a better graft function and good prognosis for graft survival. The aim of the study was to examine the effect of preservation solutions UW and EC on the expression of matrix metalloproteinase II and tissue inhibitor of metalloproteinase II genes in rat kidney. The study was carried out on Wistar rat kidneys divided into 3 groups: kidneys perfused with 0.9% NaCl (control group), with UW, and with EC preservation solution. The results show an enhancement of MMP-2 and TIMP-2 gene expression after 12 min of cold ischemia. This increase was more expressed in kidneys preserved with UW solution in comparison with kidneys perfused with EC solution and 0.9% NaCl. After 24 h of cold ischemia the expression of MMP-2 and TIMP-2 genes in kidney perfused with UW solution decreased, while in kidneys perfused with EC it was increased. After warm ischemia the MMP-2 and TIMP-2 gene expression increased, whereas it was significantly lower in kidneys perfused with EC solution.

Diverse ß subunits of heterotrimeric G proteins are present in thyroid plasma membranes.

The functioning of heterotrimeric G protein α subunits in the transduction of hormonal signals to appropriate intracellular responses is well recognized. Much less is known about the distribution of isoforms and functions of G protein ß subunits. Here, using specific antibodies, we documented that in plasma membranes of the thyroid cell line Nthy-ori 3-1 all Gß isoforms-Gß(1), Gß(2), Gß(3), Gß(4) and Gß(5) are present, while the Gß(3) occurs in minute amount. In plasma membrane fraction isolated from pooled postoperative thyroids of patients with nodular goiter and Graves' disease, the Gß(1), Gß(2), Gß(4) and Gß(5) subunits were found, whereas Gß(3) could not be detected. Competition studies revealed that the Gß(2) is the principal Gß subunit in membranes from cultured thyroid cells, originated from normal thyroid, as well as in membranes from patients' thyroids. This suggests that Gß(2) subunit cooperates with Gα(s) subunit, the most active of the Gα variants, during stimulation of adenylate cyclase which constitutes the main route of physiological thyroid stimulation.

Association between ER-α polymorphisms and bone mineral density in patients with Turner syndrome subjected to estroprogestagen treatment--a pilot study.

Reduced bone mineral density (BMD) is present in many women with Turner syndrome (TS), and hypo-estrogenism is known to play a vital role in bone mineralization disturbances. It has been suggested that genetic factors play an important role in the regulation of BMD. The aim of this study was to analyze the association between Pvu II and XbaI ER-α polymorphisms and BMD in TS patients subjected to estroprogestagen (EP) treatment. Thirty-two TS patients aged 17-38 (mean age 22.7 ± 8.2) along with 82 healthy controls were the subjects for this study. Baseline values of hormonal parameters, BMD and bone density markers were measured in the subjects. Subsequently, TS patients underwent 4 years of EP therapy. The results of laboratory parameters and BMD were analyzed in regard to PvuII and XbaI polymorphic variants of the ER-α gene. The increase in BMD of TS subjects was the highest in the 1st (7.5%, p = 0.013) and 2nd (6.6%, p = 0.008) years of treatment. Four years of EP therapy was reflected by a significant increase in BMD z-scores in patients with xx and Xx genotypes of the XbaI gene and in those with with the pp and Pp genotypes of PvuII. In patients with haplotypes other than XXPP, BMD z-scores were significantly higher compared to their baseline after 2 (p = 0.002), 3 (p < 0.001) and 4 (p < 0.001) years of treatment. In conclusion, genotypes xx and pp were shown to be prognostic markers of a good response to EP treatment, whereas the XXPP haplotype carriers were revealed to have the risk factors for insufficient responsiveness against EP treatment in BMD control.

Prevalence of 845G>A HFE mutation in Slavic populations: an east-west linear gradient in South Slavs.

AIM: To compare A allele frequencies of the 845G>A mutation of 10 Slavic populations in central, eastern, and southern Europe between each other and with other European populations. METHODS: The 845G>A mutation from the DNA of 400 Polish neonates collected in 2005-2006 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. The data were compared with reports from other countries. RESULTS: We identified 381 GG homozygotes, 18 GA heterozygotes, and 1 AA homozygote. The 845A allele frequency was 2.5%, which makes the summary figure for Poland from this and previous studies 3.5%. The average prevalence for Poland and other West Slavic countries was 3.6%, similar to Russia (inhabited by the East Slavs, 3.5%). The average prevalence in South Slavic countries was 2.2%, gradually decreasing from 3.6% in Slovenia to 0% in Bulgaria, with a longitudinal linear gradient (adjusted R(2)=0.976, P<0.001). CONCLUSIONS: The West and East Slavs, together with Finland, Estonia, Germany, Austria, Hungary, Slovenia, and Croatia, form a group with 845A allele frequencies between 3% and 4%. In the South Slavs, there is a gradual decline in the prevalence of 845A allele from northwest to southeast, with a surprisingly exact east-west linear gradient.

Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study.

Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: "Closure of the intestines" is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).

Concentrations of Selected Metals (NA, K, CA, MG, FE, CU, ZN, AL, NI, PB, CD) in Coffee.

INTRODUCTION: The health benefits and detrimental effects of coffee consumption may be linked to chemical compounds contained in coffee beans. The aim of our study was to evaluate the concentration of sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), iron (Fe), copper (Cu), zinc (Zn), aluminum (Al), nickel (Ni), lead (Pb) and cadmium (Cd) in green and roasted samples of coffee beans purchased in Bosnia and Herzegovina, and to determine the potential health implications at current consumption level. METHODS: The concentrations were determined using a microwave high-pressure mineralization and atomic absorption spectrometer that measures total metal (ionic and non-ionic) content. RESULTS: The average metal concentrations (µg element/g coffee) in the green coffee beans were; Na: 18.6, K: 19898, Ca: 789, Mg: 1758, Fe: 60, Cu: 14, Zn: 3.6, Al: 4.2, Ni: 0.415, Pb: 0.076, and Cd: 0.015, while, in the roasted; Na: 23, K: 23817, Ca: 869, Mg: 1992, Fe: 41.1, Cu: 11.4, Zn: 5.41, Al: 4.19, Ni: 0.88, Pb: 0.0169, and Cd: 0.0140. CONCLUSION: The level of investigated metals at the present level of consumption of coffee in Bosnia falls within the limits recommended as safe for health.

Relationship between the IL23R SNPs and Crohn's Disease Susceptibility and Phenotype in the Polish and Bosnian Populations: A Case-Control Study.

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn's disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.

The Influence of Maternal-Foetal Parameters on Concentrations of Zonulin and Calprotectin in the Blood and Stool of Healthy Newborns during the First Seven Days of Life. An Observational Prospective Cohort Study.

BACKGROUND: It can be hypothetically assumed that maternal and perinatal factors influence the intestinal barrier. METHODS: The study was conducted with 100 healthy, full-term newborns breastfed in the first week of life, with similar analyses for their mothers. Zonulin and calprotectin levels were used as intestinal permeability markers. RESULTS: The median (range) zonulin concentrations (ng/mL) were in mothers: serum, 21.39 (6.39⁻57.54); stool, 82.23 (42.52⁻225.74); and newborns: serum cord blood, 11.14 (5.82⁻52.34); meconium, 54.15 (1.36⁻700.65); and stool at age seven days, 114.41 (29.38⁻593.72). Calprotectin median (range) concentrations (µg/mL) in mothers were: stool, 74.79 (3.89⁻211.77); and newborns: meconium, 154.76 (6.93⁻8884.11); and stool at age seven days 139.12 (11.89⁻627.35). The use of antibiotics during pregnancy resulted in higher zonulin concentrations in umbilical-cord serum and calprotectin concentrations in newborn stool at seven days, while antibiotic therapy during labour resulted in higher zonulin concentrations in the stool of newborns at seven days. Zonulin concentrations in the stool of newborns (at seven days) who were born via caesarean section were higher compared to with vaginal birth. With further analyses, caesarean section was found to have a greater effect on zonulin concentrations than prophylactic administration of antibiotics in the perinatal period. Pregnancy mass gain >18 kg was associated with higher calprotectin concentrations in maternal stool. Body Mass Index (BMI) increase >5.7 during pregnancy was associated with decreased zonulin concentrations in maternal stool and increased calprotectin concentrations in stool of mothers and newborns at seven days. There was also a negative correlation between higher BMI increase in pregnancy and maternal zonulin stool concentrations and a positive correlation between BMI increase in pregnancy and maternal calprotectin stool concentrations. CONCLUSION: Maternal-foetal factors such as caesarean section, antibiotic therapy during pregnancy, as well as change in mother's BMI during pregnancy may increase intestinal permeability in newborns. Changes in body mass during pregnancy can also affect intestinal permeability in mothers. However, health consequences associated with increased intestinal permeability during the first days of life are unknown. Additionally, before the zonulin and calprotectin tests can be adopted as universal diagnostic applications to assess increased intestinal permeability, validation of these tests is necessary.

Effect of trimetazidine on xanthine oxidoreductase expression in rat kidney with ischemia--reperfusion injury.

Ischemia/reperfusion (I/R) injury is often responsible for delayed graft function after transplantation. Trimetazidine (TMZ) is an anti-ischemic and antioxidant agent used to protect grafts from I/R injury. With the supply of molecular oxygen upon reperfusion of ischemic tissues, xanthine oxidoreductase (XOR) metabolizes xanthine and hypoxanthine to uric acid and free radicals are generated. The aim of the study was to examine the effect of TMZ on XOR expression in rat kidney with I/R injury. The study was carried out on Wistar rats divided into two groups: animals treated with TMZ and control group receiving placebo. TMZ (10 mg/kg/day) was administered for 30 days. There were no significant differences in XOR expression in kidneys without ischemia between rats treated with TMZ and control group, whereas the XOR expression in kidneys with ischemia was significantly decreased in rats treated with TMZ as compared with control animals. The XOR expression in ischemic kidney was significantly lower in comparison with kidney without ischemia in the group treated with TMZ. We suggest that the decrease in xanthine oxidoreductase expression is one of the beneficial mechanisms of TMZ on I/R injury, preventing the degradation of purine nucleotides during the oxidation of hypoxanthine to xanthine and uric acid and formation of free radicals.

Association Between - 675 ID, 4G/5G PAI-1 Gene Polymorphism and Pregnancy Loss: A Systematic Review.

INTRODUCTION: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. AIM: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. RESULTS: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). CONCLUSIONS: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.