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Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated.. [ABSTRACT FROM AUTHOR]

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance of normal estrogen and androgen levels in the blood. Androgens play an important role in the female body because they influence bone mineral density (BMD), body mass composition, muscle mass, mental state, and the regulation of sexual function. The reduced activity of aromatase, due to mutations in the CYP19A1 gene, reduces the estrogen pool in favor of androgens. Clinically, aromatase deficiency causes hyperandrogenism in women. Therefore, the aim of the study was to assess the effect of the CYP19A1 gene polymorphism on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group was comprised of 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, total sRANKL (free and bound RANKL), osteoprotegerin, and total 25-OH Vitamin D. An analysis of the CYP19A1 gene polymorphisms was performed using the real-time PCR method. The GG genotype of the CYP19A1 rs700518 polymorphism turned out to be associated with: FEI (Free Estradiol Index), SHGB concentration, estradiol concentration, and insulin concentration determined in the glucose tolerance test 60' compared to AG and AA genotypes. Patients with the AG genotype had a higher ratio of android to gynoid fat and a greater content of visceral adipose tissue. Higher visceral tissue content may reduce BMD. In conclusion, the study showed that the CYP19A1 rs700518 polymorphism may be associated with the distribution of adipose tissue in young women with hyperandrogenism. These results suggest that patients with the AG genotype may develop osteoporosis. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objective: Osteoporosis is a civilization disease, in which the dominant symptoms are the loss of bone mass and disturbances in bone structure. Gremlin-2 is one of the BMP (bone morphogenetic proteins) antagonists and participate in osteogenesis and osteoblast differentiation. The aim of the study was to analyze whether the GREM2 gene polymorphism is significantly more common in postmenopausal women than in healthy women and whether it is a predisposing factor for the osteoporosis development.Study Design: The study consisted of 675 unrelated Polish postmenopausal women, including 109 with osteopenia, 333 with osteoporosis and 233 healthy women. The effect of the GREM2 polymorphism on T-score, Z-score, L2L4AM, L2L4YA, L2L4BMD, body mass, BMI, birth weight was statistically evaluated.Results: Statistical significance was observed between the TT and TC genotypes and also between TT and CC genotypes in the case of birth weight in the control group and the group of women with osteoporosis. Analysis of body mass in women with osteoporosis showed the statistical significance between genotypes TT and CC, TT and TC. Analysis of the frequencies of TT, TC and CC genotypes of the rs4454537 polymorphism of the GREM2 gene showed no statistical significance between studied groups.Conclusion: Our study found that the most frequent genotype in the group of women with osteopenia and osteoporosis was TC while in the group of healthy women the protective TT genotype was dominant. Hence, it can be postulated that the TT genotype is a protective factor against the development of osteoporosis. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the effect of baicalein or Scutellaria baicalensis root extract interaction with methyldopa in pregnant spontaneously hypertensive rats (SHR) at the pharmacodynamic, molecular, and biochemical levels. The rats, after confirming pregnancy, received baicalein (200 mg/kg/day, p.o.) and extract (1000 mg/kg/day, p.o.), in combination with methyldopa (400 mg/kg/day; p.o.), for 14 consecutive days, 1 h before blood pressure and heart rate measurements. In the heart and placenta from mothers after giving birth to their offspring, mRNA expression of factors related to inflammatory processes (TNF-α, Il-1β, IL-6) and vascular diseases (TGF-β, HIF-1α, VEGF, PlGF) was measured. Levels of markers of oxidative stress (superoxide dismutase and malondialdehyde) in the placenta and indicators of myocardial damage (troponin cTnC and cTnI, creatine kinase, myoglobin, and lactate dehydrogenase) in the heart were also assessed. Baicalein co-administered with methyldopa was associated with reduced blood pressure, especially during the first three days. The interactions were more pronounced for such factors as TGF-β, HIF-1α, VEGF, and PlGF than TNF-α, Il-1β, and IL-6. Combined application of baicalein and extract with methyldopa may be of value in the development of a new antihypertensive medication intended for patients suffering from preeclampsia or pregnancy-induced hypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies in Poland. Based on the findings of clinical trials, it is safe to conclude that genetic predisposition and environmental factors are the main factors responsible for the formation of colorectal cancer.The NQO1 gene plays an important role in reducing endogenous and exogenous quinones as well as quinone compounds to hydroquinones. It is an enzyme which is a part of the body's antioxidant defense system. The aim of the study was to evaluate the correlation between the 609C > T polymorphism of the NQO1 gene and colorectal cancer risk in the Polish population. A total of 512 people were recruited for the study, including 279 patients with colorectal cancer, diagnosed at the University Hospital, Pomeranian Medical University in Szczecin. Genomic DNA was isolated from peripheral blood and the analyzed polymorphism was determined by PCR-RFLP. In the present study, we analyzed the clinical valuesand frequency of NQO1 609C > T polymorphism in patients diagnosed with colorectal cancer and controls. In case of the carriers of the TT genotype of the NQO1 polymorphism, an elevated risk for colorectal cancer was observed (OR = 2.96; 95% CI: 1.02–10.40). The analysis of the clinical parameters concerning the location and characteristics of the tumor stage revealed a statistically significant increase in the risk for colorectal cancer in the carriers of the TT genotype of the NQO1 polymorphism. [ABSTRACT FROM AUTHOR]

The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (− 1.966 ± 0.242 vs. − 1.577 ± 0.125 and − 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]