The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.

Osteoarthritis (OA) is progressive disease characterised by cartilage degradation, subchondral bone remodelling and inflammation of the synovium. The disease is associated with obesity, mechanical load and age. However, multiple pro-inflammatory immune mediators regulate the expression of metalloproteinases, which take part in cartilage degradation. Furthermore, genetic factors also contribute to OA susceptibility. Recent studies have highlighted that epigenetic mechanisms may regulate the expression of OA-associated genes. This review aims to present the mechanisms of OA pathogenesis and summarise current evidence regarding the role of genetics and epigenetics in this process.

Association Study of SLCO1B3 and ABCC3 Genetic Variants in Gallstone Disease.

There is growing evidence that gallstone formation may be genetically determined. Recent studies have shown that polymorphism of genes encoding proteins involved in bile acid transport may be associated with the risk of gallstone disease. The aim of this study was to investigate the association between SLCO1B3 (rs4149117:G>T, rs7311358:A>G) and ABCC3 (rs4793665:T>C, rs11568591:G>A) genetic variants and susceptibility to cholesterol gallstone disease, as well as gallstone composition. The study included 317 patients suffering from cholelithiasis who underwent cholecystostomy and 249 controls with no evidence of stones, confirmed by ultrasound examination. There were no statistically significant differences in the distribution of studied gene polymorphisms between patients with gallstone disease and healthy controls. No significant associations were observed between studied genotypes and the content of analyzed gallstone components: total cholesterol, bilirubin, CaCO3, nor the total bile acids. There was also no association between bile acid content in gallstones and the polymorphisms studied. The results of this study suggest that polymorphisms of SLCO1B3 and ABCC3 genes are not a valuable marker of gallstone disease susceptibility and do not influence gallstone composition.

VAV1 Gene Polymorphism is Associated With Kidney Allograft Rejection.

BACKGROUND: VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function. METHODS: The study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction. RESULTS: There were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P = .03) and T allele (P = .02), as well as VAV1 rs2617822 GG and AG genotypes (P = .05) and G allele (P = 0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients. CONCLUSIONS: The results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection.

TNF-α and IL10 gene polymorphisms in women with postmenopausal osteoporosis.

OBJECTIVE: Postmenopausal osteoporosis is a common disorder characterized by decreased bone mineral density (BMD). Proinflammatory cytokines are among the significant factors involved in bone turnover. They are the stimulants of bone resorption, acting directly on osteoclasts and osteoclast precursors. In this study, we examined the TNF-α (-308G>A) (rs1800629) and IL10 (-1082G>A) (rs1800896), (-592C>A) (rs1800872) polymorphisms in postmenopausal women with BMD T-scores less than and greater than or equal to -2.5 SD. STUDY DESIGN: This study included 224 postmenopausal women with BMD T-scores lower than -2.5 SD (mean: -3.02±0.53) and 238 postmenopausal women with BMD T-scores -2.5 SD and greater (mean: -1.33±0.51). RESULTS: There was a decrease in the frequency of IL10 1082 G allele carriers (GG and GA genotypes) in women with T-scores below -2.5 SD (GG+GA vs AA: OR=0.65, 95% CI=0.44-0.97, p=0.037). With regard to the TNF-α -308 G>A polymorphism, in the women with T-scores below -2.5 SD, the increased frequency of GG homozygotes and G allele carriers was detected (AA+GA vs GG: OR=0.54, 95% CI=0.35-0.82, p=0.004). CONCLUSIONS: The results of our study suggest an association between TNF-α -308G>A and IL10 -1082G>A polymorphisms and postmenopausal osteoporosis.

[Pregnancy in a rudimentary horn of the uterus]. / Ciaza w rogu szczatkowym macicy.

Pregnancy in a rudimentary horn of the uterus, a rare form of ectopic pregnancy, develops in women affected by developmental abnormalities of the growth and fusion of the Müllerian paramesonephric ducts. In the Polish population, this problem affects 4-8 women per year. The paper analyzes the problems that are associated with pregnancy developing in the rudimentary horn. Due to the continuous progress in medical sciences, maternal mortality has been almost completely eliminated in this form of ectopic pregnancy, while neonatal survival has risen to about 20%. Further devel- opments in medicine allow us to be moderately optimis- tic about further improvement of the treatment's statistics.

Causes of respiratory ailments in pregnancy.

OBJECTIVE: During pregnancy, especially during its third trimester, most pregnant women reported respiratory discomfort (dyspnea), despite the absence of previously coexisting respiratory illnesses. The aim of this study was to determine the reason for this discomfort. MATERIAL AND METHODS: The study included 24 women examined before and after childbirth. Evaluation of respiratory complains was made on the basis of the respiratory questionnaire of St. George's Hospital. The data were correlated with the results of static and dynamic spirometric tests performed before and after childbirth. RESULTS: Pregnancy did not affect vital capacity (VC). Frequency of perceived symptoms correlated positively with IRV and the ratio IC/VC. A negative correlation was found between ERV and its derivative ERV/VC. There was no relationship between perceived discomfort and parameters of the flow-volume loop. CONCLUSIONS: The extent of perceived respiratory discomfort (dyspnea) during pregnancy was primarily associated with a reduction in expiratory reserve (ERV).

Ionic support of the cough reflex.

INTRODUCTION: The aim of this study was to determine the role ofintra-wall nervous and neurohormonal system in the control of airway transport of sodium and chloride ions, as well as to identify regulating mechanisms having an effect on the permanent electric potential of airway tissue, named the transepithelial electric potential (PD) and on reversible changes of this potential (dPD). Using amiloride, a sodium ion blocker, and bumetanide, a blocker of the chloride ion co-transport system, the importance oftransepithelial sodium and chloride ion transport for support of the cough reflex was determined. The conditions were identified for examination of chloride secretion in the airways presented as the chemical isolation of chloride currents with the use of amiloride. MATERIAL AND METHODS: The experimental material consisted of 135 fragments of trachea wall obtained from 45 animals. The experiments were directed at measurements of PD of the isolated tracheal wall placed in Ussing chamber where this tissue formed an interface between two half-chambers filled with an isoosmotic polyelectrolyte solution. The main procedure for irritation of sensory receptors in the airways utilized ajet from a peristaltic pump directed to the mucous surface of the isolated trachea. The jet fluid was analogous to the one in the chamber or it was modified as the experimental conditions required. RESULTS: Transepithelial transport of sodium ions in the trachea exerted a regulatory effect modulating the transepi- thelial difference of electric potentials, as well as inducing hyperpolarisation after mechanical stimulation when at 40% the sodium transport is the exclusive carrier of the hyperpolarisation reaction.

[Evaluation of respiratory tract function in healthy women in the last month of uncomplicated pregnancy]. / Ocena czynnosci ukladu oddechowego zdrowych kobiet w ostatnim miesiacu ciazy niepowiklanej.

UNLABELLED: The aim of this work was to examine the function of the respiratory system in pregnant women in the last month of non-complicated pregnancy. Spirometry with Lungtest 1000 was performed in 31 pregnant women at a mean gestational age of 37.72 weeks. In 24 of them the test was repeated after delivery (mean time from delivery = 39.40 days). The results were compared with a control group of 31 healthy non-pregnant resident of Szczecin. Prior to spirometry, all women underwent a physical examination with measurement of blood pressure, heart rate, body weight and height, chest and abdominal circumference, symphysis-fundus distance and blood analysis. Dyspneic symptoms characteristic of pregnancy were assessed with the St. George Hospital questionnaire. Spirometric parameters were recorded during three stages of the examination: 1. Components of vital capacity (IRV, ERV, TV, IC), breathing rate and minute ventilation. 2. Forced respiratory parameters (FEV0.5, FEV1, FEV1/FVCEX, FEV1/FVCIN, FEV2, FEV3, FVCEX, VPEF, FIV1, PIF, MIF50, FVCIN, VPIF, PEF, MEF25, MEF50, MEF75, FEF25/75, FEF75/85, MEF25/FVCIN, MEF50/FVCEX, MEF50/FVCIN, MEF75/FVCIN, FET, FET/FIT, FIT, TTOT, TMEF25, TMEF50, TMEF75, TPEF, TPIF, TPEF/FET, TPIF/FIT, MTT, AEX). 3. Maximum voluntary ventilation, maximum breathing frequency and breathing reserve. The results in all groups were compared with reference values. Furthermore, comparative analysis was performed in the same women before and after delivery. Data from questionnaires were related to results of spirometry. Parametric and nonparametric tests were applied. Spearman's rank test was used to study relations between respiratory symptoms and spirometric parameters. Most spirometric parameters deviated from reference values. Vital capacity was greater than expected. FEV0.5, FEV3, FEV1/FVCEX were reduced. FEV1/FVCIN were reduced in pregnant women only. Parameters of forced expiratory flow: FEF25/75, FEF75/85, MEF25, MEF25/FVCIN, MEF50/FVCEX were lower than expected. Significant difference were disclosed for MTT, AEX and MVV. MTT and MVV were increased and AEX was reduced. PEF and MEF75 were decreased in pregnant women. Other parameters did not differ significantly. Detailed analysis performed in 24 women before and after delivery revealed differences in components of vital capacity. Additionally, FEV0.5, FEV1/FVCEX, FEF25/75, MEF25, MEF50, MEF25/FVCIN, MEF50/FVCEX were increased in pregnancy. Time parameters of forced expiration--FET and TMEF25 were shorter. Minute ventilation was increased in pregnancy although the breathing rate was decreased. Values of maximum voluntary ventilation and breathing reserve were decreased in pregnancy. Correlation analysis revealed that respiratory symptoms in pregnant women depended on changes in proportions among static components of vital capacity and abnormalities in forced inspiration (FIT, TPIF/FIT). Intensity of symptoms was related to increased heart rate and diastolic pressure. CONCLUSIONS: 1. Chief spirometric parameters in the examined women differed significantly from reference values. Reliable information about respiratory function in pregnant women requires comparison of findings during and after pregnancy. 2. Vital capacity in the last month of pregnancy did not differ from values after delivery and in the control group. Component volumes changed: tidal volume was increased, expiratory reserve volume was decreased, inspiratory reserve volume remained unchanged. 3. Minute ventilation recorded at rest in pregnancy increased despite decreased breathing rate, whereas maximum voluntary ventilation was lower than after delivery and in the control group, evidencing reduced breathing reserve. 4. Chief forced expiratory parameters remained unchanged in pregnancy. Parameters characterizing bronchioles revealed increased air flow (bronchodilation). 5. Dyspneic symptoms found in pregnant women correlated with changes in vital capacity components. Symptoms depended on the mechanics of ventilation and not on the status of bronchi.