Beata Kulik-Rechberger

The polymorphisms of the MMP-1 and the MMP-3 genes and the risk of pelvic organ prolapse

Introduction and hypothesisTo investigate the associations between single nucleotide polymorphism (SNP) type 1G/2G at position −1607/−1608 of the matrix metalloproteinase (MMP)-1 gene and SNP type 5A/6A at position −1612/-1617 of the MMP-3 gene and the development of pelvic organ prolapse (POP) in women.Methods133 patients with symptomatic POP were included in the study group. The control group consisted of 132 women with a normal pelvic floor. 1G/2G MMP-1 and 5A/6A MMP-3 SNPs were determined by polymerase chain reaction (PCR) and restriction fragments length polymorphism analysis.ResultsWhen estimated individually none of the investigated SNPs were associated with POP. The combined MMP-1/MMP-3 SNP analysis showed that the following polymorphic pairs were overrepresented in women with POP: 1G/2G −5A/6A, 2G/2G −5A/6A, 2G/2G −5A/5A, 1G/1G −6A/6A, p = 0.005.ConclusionsThe combined effect of −1607/−1608 MMP-1 and −1612/−1617 MMP-3 SNPs may contribute to the development of POP in some women.

Transvaginal Prolift(®) mesh surgery due to advanced pelvic organ prolapse does not impair female sexual function: a prospective study.

OBJECTIVES To evaluate sexual function among women with advanced pelvic organ prolapse (POP) before and after Prolift(®) vaginal reconstructive mesh surgery. STUDY DESIGN Assessments were performed preoperatively and 12-18 months after the surgery, including physical examination using the Pelvic Organ Prolapse Quantification (POP-Q) scale as well as the Female Sexual Function Index (FSFI) questionnaire. RESULTS Fifty-nine sexually active patients who underwent vaginal reconstructive surgery due to advanced POP between June 2008 and January 2010 were included in the study. Analysis of the FSFI questionnaire showed no statistically significant differences after surgery, despite proper anatomical results. When comparing the group of women who underwent additional surgical restoration of the perineal body with patients without this procedure we also did not observe any differences in FSFI scores. CONCLUSIONS Surgical treatment of advanced POP with the Prolift(®) system does not negatively influence sexual function, but patients should not expect a significant improvement after this type of operation. Additionally performed surgical restoration of perineal body does not reduce sexual function, either.

Serum leptin concentrations in women taking oral contraceptives

OBJECTIVES To investigate serum leptin concentrations in women taking oral contraceptives containing the same gestagen and different doses of ethinyl estradiol. STUDY DESIGN 30 women received tablets containing 20 microg of ethinyl estradiol (EE) and 150 microg of desogestrel (DSG) (Mercilon) whereas another group of 30 women received 30 microg of EE and 150 microg of DSG (Marvelon). Serum leptin concentrations were estimated using a Leptin RIA kit (Linco Research USA) after an overnight fast on the first day of the cycle prior to the onset of therapy as well as after the 3rd and 6th treated cycles. RESULTS In both groups a positive correlation between serum leptin and body mass index (BMI) was found (r=0.56; P<0.001 and r=0.67; P<0.001). The initial serum leptin concentration in the Mercilon group was 7.62+/-8.46 ng/ml. This value was not statistically different from values after 3 months (9.31 8.23 ng/ml) and after 6 months (10.53+/-8.03 ng/ml) of treatment. Very similar results were found in patients receiving Marvelon: 8.81+/-6.56 ng/ml initially; 11.62+/-11.16 ng/ml at 3 months, and 10.38+/-7.32 ng/ml at 6 months. The statistical analysis did not reveal any significant difference at each investigated time point in either study group. CONCLUSIONS Modern low dose OC containing third generation gestagen and low dose of ethinyl estradiol, does not have any influence on serum leptin or BMI, and therefore does not exert a significant influence on body energy metabolism.

Hepcidin and iron status in pregnant women and full-term newborns in first days of life.

OBJECTIVES The amount of iron is regulated by hepcidin. The aim of the study was to assess hepcidin concentrations in healthy pregnant women before delivery, in cord blood, and in 3-day-old newborns in relation to maternal and neonatal iron status. MATERIAL AND METHODS The study group consisted of 44 mother-newborn pairs. Serum concentrations of hepcidin, ferritin, and transferrin receptor (sTfR) were assessed. RESULTS Maternal hepcidin was significantly lower than cord blood (p < 0.001), and full-term newborn values (p < 0.001). Mothers also had the lowest ferritin and sTfR concentrations. The highest concentration of hepcidin was observed in the newborns. They had lower sTfR and higher ferritin concentrations than in cord blood (p < 0.001). Maternal ferritin correlated negatively with sTfR (R = -0.50 p = 0.005), and positively with hepcidin (R = 0.41; p = 0.005). There were no correlations between hepcidin and ferritin or sTfR concentrations in cord blood, nor between hepcidin and ferritin or sTfR concentrations in the newborns. Moreover, there were no correlations between maternal and cord blood or neonatal blood hepcidin, nor between maternal hepcidin and infant iron status. There were also no correlations between hepcidin in cord blood and hepcidin or parameters of the iron status in the children. CONCLUSIONS It may be assumed that a relatively low concentration of hepcidin in women in late pregnancy facilitates their iron accumulation. Higher levels of hepcidin in full-term newborns than in their mothers may be the result of a relatively high level of iron from the stored supplies. Neonatal iron status was independently associated with either maternal or cord blood hepcidin.

Self-perceived quality of life after pelvic organ prolapse reconstructive mesh surgery: prospective study

OBJECTIVE To assess the self-perceived quality of life in women with advanced pelvic organ prolapse before and after mesh surgery. STUDY DESIGN Women with symptomatic pelvic organ prolapse (stage III-IV according to pelvic organ prolapse quantification (POP-Q)) were invited to participate in the study. All enrolled patients underwent prolapse surgery using the transvaginal mesh technique. Success was defined as ICS POP-Q stage 0 and I. The SF36v2 questionnaire was used as a subjective outcome measure. RESULTS 113 patients were available for follow-up at 6-8 weeks and 16-18 months. Overall anatomic success rates were 87.6%. Statistically significant improvements in the self-perceived quality-of-life were found in 3 individual domains (general health (GH), vitality (V) and mental health (MH)) and in one summary domain (MCS) at 6-8 weeks post-op. In one individual and one summary domain (role - physical (RP) and physical component summary (PCS)) the scores were significantly lower. At the end of the study statistically significant improvement was observed in four out of eight individual domains (vitality (V), menthal health (MH), physical functioning (PF), social functioning (SF)) as well as in both summary scores (PCS and MCS). CONCLUSIONS Reconstructive mesh surgery improved significantly various self-perceived quality of life dimensions. Therefore, women should expect significant improvement in their general quality of life after this type of operation. The assessment of urogenital well-being should be a routine attitude when counseling menopausal women.

Height at menarche is influenced by estrogen receptor α gene polymorphisms

Background: It has been suggested that polymorphic variations in estrogen receptors (ERs) genes may have an impact on linear growth of girls during puberty. Aim: The aim of the study was to investigate whether height at menarche is influenced by PvuII and XbaI polymorphisms of the ERα gene. Subjects and methods: The study population consisted of 127 healthy girls, who were observed from premenarcheal period at six monthly intervals, until menarche occurred in all participants. Anthropometric measurements were taken at each visit and their values at menarche were calculated using centile curves drawn individually for each subject. PvuII and XbaI ERα gene polymorphisms were evaluated with RLFP-PCR. Results: The age at menarche was not related to ERα gene polymorphisms. Girls with pp genotype were at menarche on average 3.2 cm shorter than PP homozygotes and in addition xx homozygotes were shorter than subjects with XX and Xx genotypes: 3.0 cm and 3.9 cm respectively. Subjects with px haplotype were, at the onset of the first menstrual period, from 2.3 cm to 3.1 cm shorter than carriers of other haplotypes. The leg length-to-height ratio at menarche was lower in xx homozygotes than in Xx heterozygotes and lower in px haplotype in comparison to Px and pX haplotypes carriers. Corresponding associations were observed at the final visit. Conclusions: Height at menarche is influenced by the ERα gene polymorphism.

Inhibition of Rho kinase by GSK 269962 reverses both corticosterone-induced detrusor overactivity and depression-like behaviour in rats

ABSTRACT Literature data give clear evidence that upregulated RhoA/Rho‐kinase signalling is one of the factors that may lead to the development of detrusor overactivity and various disorders of the central nervous system. Therefore, the main objective of our study was to investigate whether administration of a Rho‐kinase inhibitor – GSK 269962 could reverse corticosterone‐induced depressive‐like behaviour and changes in cystometric parameters associated with detrusor overactivity, as well as undo the alterations of several biomarkers related to both disorders (i.e., pro‐inflammatory/anti‐inflammatory cytokines and neurotrophins) in serum, urinary bladder, and different brain structures. The experiments were carried out on female Wistar rats. Surgical procedures, cystometric investigations, biochemical analyses, and behavioural studies (measurement of the locomotor activity and the forced swim test) were performed according to the published literature. As expected, administration of corticosterone at a daily dose of 20mg/kg for 14 days increased the immobility time of animals in the forced swim test, induced changes in the cystometric parameters specific to bladder overactivity, reduced levels of neurotrophins, and elevated concentrations of the pro‐inflammatory cytokines. Inhibition of Rho‐kinase by 7‐day treatment with GSK 269962 (10mg/kg/day) reversed the symptoms of both detrusor overactivity and depression as well as normalized levels of the tested biomarkes. Our findings encourage the idea of Rho‐kinase inhibitors as a potential future treatment option for overactive bladder accompanied by depression.

New perspectives of the treatment of urogenital atrophy in women: intravaginal DHEA therapy

Według jednej z nowszych teorii objawy menopauzalne nie wynikają jedynie ze spowodowanego wygaśnięciem funkcji jajników niedoboru estrogenów, ale są także związane ze stopniowym, postępującym przez kilka lat zmniejszeniem stężenia dehydroepiandrosteronu (DHEA) wydzielanego przez nadnercza. Ponad 50% kobiet po menopauzie zgłasza objawy związane z atrofią nabłonka pochwy: podrażnienie, nawracające infekcje, uczucie suchości, ból podczas współżycia. Ogólnoustrojowa terapia hormonalna z użyciem samych estrogenów lub w połączeniu z progestagenami skutecznie przeciwdziała tym objawom, jednak wiąże się z możliwością wystąpienia działań niepożądanych. Poza tym u kobiet, u których jedynymi uciążliwymi objawami są te związane z atrofią pochwy, warto pomyśleć o terapii miejscowej. Do obiecujących wyników badań należą te nad dopochwowym zastosowaniem DHEA, w których założono, że terapia fizjologicznymi dawkami DHEA przyczyni się do zwiększenia stężenia androgenów i estrogenów syntetyzowanych miejscowo w tkance poprzez mechanizmy intrakrynne przy niewielkim działaniu ogólnoustrojowym. W grupie kobiet leczonych DHEA podawanym dopochwowo wykazano zmniejszenie objawów atrofii pochwy, regresję zmian dysplastycznych na szyjce macicy oraz zwiększenie libido. Słowa kluczowe: dehydroepiandrosteron, atrofia urogenitalna, menopauza.

Wiek menarche w zależności od stanu odżywienia i polimorfizmu sekwencji intronu 1 genu receptora estrogenowego alfa

Polimorfizmy dlugości fragmentow restrykcyjnych PvuII i XbaI genu receptora estrogenowego alfa (ERα) są spowodowane zmianami sekwencji DNA dotyczącymi pojedynczych nukleotydow w intronie 1 genu. Zwazywszy na genetyczne uwarunkowanie procesu pokwitania mozna przypuszczac, ze moze on takze zalezec od typu polimorficznego ERα. Celem pracy byla ocena zalezności miedzy genotypem ERα, wiekiem menarche i stanem odzywienia dziewcząt. Material i metody Badaniem dlugofalowym objeto 126 zdrowych dziewcząt. Oceniano wskaźniki masy ciala (BMI), obwody ramienia oraz grubości faldow skorno-tluszczowych na brzuchu, na ramieniu i pod lopatką. Ustalano date wystąpienia menarche. Jednorazowo, kiedy dziewczeta byly w wieku średnio 12,42 ± 0,34 lat, określano stezenie leptyny, estradiolu oraz genotyp ERα Dziewczeta podzielono na dwie grupy: pierwszą stanowily dziewczeta, ktore byly po menarche lub osiągnely menarche w ciągu roku od badania, drugą dziewczeta, ktore osiągnely menarche poźniej. Wyniki Stwierdzono dodatnie korelacje miedzy leptyną i BMI (R = 0,69; p Wnioski Wiek menarche zalezy od stanu odzywienia i stezenia leptyny we krwi dziewcząt. Wyniki naszych badan nie wskazują, aby polimorfizmy PvuII oraz XbaI ERα mialy wplyw na stan odzywienia i wiek menarche.