Implikacje leczenia farmakologicznego u kobiet w wieku rozrodczym i po menopauzie

Women have three very important physiological functions that are not observed in men – menstruation, pregnancy, and lactation. Each of these mechanisms influences pharmacokinetics and pharmacodynamics of many drugs. Individualization of pharmacotherapy is a major challenge of modern medicine. The differences in response to drug are responsible for the effectiveness of pharmacological treatment and the occurrence and severity of toxic effects and side effects. Therapeutic decision should be based not only on account of the dose-effect, but the consideration of gender, genetic and environmental differences affecting the final therapeutic effect. Many important differences between men and women like sex-based differences in normal physiology, or in the predisposition to a specific disease, can be due to genetic differences, the actions of the sex steroid hormones or an interaction between these factors. Women generally have a lower body mass, a reduced hepatic clearance, differences in activity of cytochrome P450 (CYP) enzymes (increase in CYP3A4, decrease in CYP2D6, CYP2C19 and CYP1A2) and different from men’s rate of drug metabolism. Other important factors contributing to gender differences in the pharmacokinetics of drugs are conjugation, absorption, protein binding and urinary excretion. It still remains unexplained how gender differences affect the increased risk of side effects. This review is an attempt to assess the biological, physiological and hormonal basis of women differences in the pharmacokinetics and pharmacodynamics of many drugs.Kobiety charakteryzują trzy niezwykle istotne z punktu widzenia farmakologii procesy fizjologiczne, które nie występują u mężczyzn - menstruacja, ciąża i laktacja. Każdy z tych procesów w znaczący sposób wpływa na farmakokinetykę i farmakodynamikę wielu leków. Indywidualizacja farmakoterapii, również z uwzględnieniem płci, stanowi poważne wyzwanie współczesnej medycyny. Różnice w odpowiedzi farmakologicznej odpowiadają za skuteczność leczenia oraz występowanie i nasilenie efektów toksycznych i niepożądanych. Decyzja terapeutyczna powinna opierać się nie tylko na uwzględnieniu zależności dawka-efekt, ale na rozważeniu różnic płciowych, genetycznych i środowiskowych, wpływających na końcowy efekt terapeutyczny. Szczególnie istotne wydają się różnice płciowe w farmakokinetyce leków wynikające z odmiennej fizjologii, predyspozycji do występowania chorób, uwarunkowań genetycznych czy gospodarki hormonalnej oraz wzajemnych oddziaływań pomiędzy tymi czynnikami. Kobiety charakteryzują się mniejszą masą ciała, obniżonym klirensem wątrobowym i różnicami w aktywności cytochromu P450 (CYP) (wzrost aktywności CYP3A4, obniżenie aktywności CYP2D6, CYP2C19 i CYP1A2) oraz odmienną od mężczyzn szybkością metabolizmu leków. Innymi ważnymi czynnikami wpływającymi na różnice płciowe w farmakokinetyce leków są koniugacja, wchłanianie, wiązanie z białkami i wydalanie z moczem. Nadal pozostaje niewyjaśnione w jaki sposób różnice płciowe wpływają na zwiększone ryzyko wystąpienia działań niepożądanych. Niniejsza praca stanowi przegląd biologicznych, fizjologicznych i hormonalnych podstaw występowania różnic płciowych w organizmie kobiety, które wpływają na farmakokinetykę i farmakodynamikę leków

Zastosowanie manualnych technik osteopatycznych w leczeniu bólu pleców u kobiet w ciąży

Changes in body posture, musculoskeletal disorders and somatic dysfunctions are frequently observed during pregnancy, especially ligament, joint and myofascial impairment. The aim of the paper is to present the use of osteopathic manipulative treatment (OMT) for back and pelvic pain in pregnancy on the basis of a review of the available literature. MEDLINE and Cochrane Library were searched in January 2014 for relevant reports, randomized controlled trials, clinical and case studies of OMT use in pregnant women. Each eligible source was verified and analyzed by two independent reviewers. OMT procedures appear to be effective and safe for pelvic and spinal pain management in the lumbosacral area in pregnant women.W trakcie ciąży u kobiet zachodzą zmiany w postawie ciała, układzie mięśniowo-szkieletowym oraz zaburzenia somatyczne. Najczęściej dochodzi do dysfunkcji więzadeł, stawów i powięzi. Celem pracy jest przedstawienie wykorzystania bezpiecznych osteopatycznych technik manualnych w leczeniu bólu pleców i miednicy u kobiet w ciąży, na podstawie przeglądu dostępnej literatury naukowej. Przegląd literatury przeprowadzono w bazach danych MEDLINE i Cochrane Library w styczniu 2014 roku. Do analizy wybrano prace poglądowe, randomizowane, kliniczne oraz studium przypadku dotyczące terapii manualnej u kobiet w ciąży. Każda praca była weryfikowana i analizowana przez dwóch niezależnych badaczy. Osteopatyczne techniki manualne (OMT) wydają się być skuteczną i bezpieczną terapią w bólach odcinka lędźwiowo-krzyżowego kręgosłupa i miednicy u kobiet w ciąży

Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death

Objectives: Choline and folate metabolism disturbances may be involved in the occurrence of intrauterine fetal death (IUFD). The proper activity of this metabolism could be determined by genetic variants involved in choline pathway e.g. CHKA (gene encoding choline kinase α), PCYT1A (gene encoding CCTα) and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD occurrence. Material and methods: The study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis was performed with the use of PCR/RFLP method. Results: The frequency of genotypes and alleles of studied polymorphisms was similar in both groups. The study revealed no association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women. While evaluating the co-existence of analysed polymorphisms statistically significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes was observed statistically more frequently in the study group than in the control group (p = 0,031). Conclusions: There is no correlation between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death. However, revealed statistically significant difference between co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the need of further analysis

Nowoczesna diagnostyka osteoporozy w oparciu o wykorzystanie biochemicznych markerów obrotu kostnego

Osteoporosis is a disease with low bone mass and disorganization of the internal microarchitecture of bone tissue. Determination of biochemical markers allows for early diagnosis of changes in bone tissue metabolism. The search for a marker whose biological function could be directly connected with bone metabolism, clearly indicating a connection between its concentration and risk fracture as well as response to treatment, continues. Currently, measurement of collagen-derived markers of bone resorption is used in the majority of cases. They are, first of all, telopeptides of collagen type I localized on the amino end - N-terminal telopeptide of type 1 collagen (NTX), as well as on the carboxy end - C-telopeptide of type 1 collagen (CTX) of collagen molecule. Among markers of bone synthesis, special attention is paid to the procollagen type 1 carboxy-terminal propeptide (P1CP) and procollagen type 1 amino-terminal propeptide (P1NP). Simultaneous application of bone synthesis and resorption markers allows for a full imaging of the bone remodeling process and application of biochemical markers in the diagnosis and therapy of osteoporosis.Osteoporoza jest chorobą charakteryzującą się małą masą kostną oraz dezorganizacją wewnętrznej mikroarchitektury tkanki kostnej. Oznaczanie markerów biochemicznych umożliwia wczesne zdiagnozowanie zmian w metabolizmie tkanki kostnej. Wciąż poszukuje się markera, którego biologiczną funkcję można powiązać bezpośrednio z metabolizmem kostnym, jednoznacznie wskazując na związek pomiędzy jego stężeniem a ryzykiem złamań oraz odpowiedzią na stosowane leczenie. Obecnie główne zastosowanie znajduje pomiar kolagenopochodnych markerów resorpcji kości. Są to przede wszystkim telopeptydy kolagenu typu I mające postać heliakalnych, usieciowanych fragmentów zlokalizowanych zarówno na końcu aminowym (NTX), jak i karboksylowym (CTX) cząsteczki kolagenu. Wśród markerów syntezy kości na szczególną uwagę zasługują natomiast kolagenopochodne markery kościotworzenia C-końcowy propeptyd prokolagenu typu I (P1CP) i N-końcowy propeptyd prokolagenu typu I (P1NP). Jednoczesne zastosowanie markerów syntezy i resorpcji kości pozwoli na pełne zobrazowanie przeciwstawnych procesów remodelingu kostnego oraz na szerokie wykorzystanie markerów biochemicznych w diagnostyce i terapii osteoporozy

The RANKL/RANK/OPG signal trail: significance of genetic polymorphisms in the etiology of postmenopausal osteoporosis

Objectives: Recent studies have demonstrated that disorders of bone metabolism, which is regulated by RANK/RANKL/OPG signaling pathway, are the cause of osteoporosis. The aim of the study was to investigate the distribution of genotypes of the RANK 575C>T and RANKL –643C>T polymorphisms and to analyze their relationship with bone parameters in postmenopausal women. Material and methods: A total of 310 postmenopausal Caucasian women (139 with osteoporosis, 107 with osteopenia, and 64 healthy postmenopausal controls) were included. Bone mineral density (BMD) at the lumbar region of the spine (L2–L4) was measured by dual energy X-ray absorptiometry (DXA). Genetic analysis was performed using the PCR-RFLP method. Results: Analysis of the frequency of genotypes and alleles of the RANK 575C>T and RANKL –643C>T polymorphisms did not show any statistically significant differences between the study groups (osteoporosis and osteopenia) and postmenopausal women with normal t-score value (ns). Notably, a significant association between the RANKL –643C>T polymorphism and body mass, such as BMI values in osteoporotic women (p<0.05), was observed. Conclusions: Our results suggest lack of association between the 575C>T RANK polymorphism and the development of osteoporosis. The –643C>T RANKL polymorphism, through its significant influence on body weight and BMI value, may contribute to the development of osteoporosis in postmenopausal women

The importance of polymorphic variants of collagen 1A2 gene (COL1A2) in the development of osteopenia and osteoporosis in postmenopausal women

Objectives: Collagen type I plays an important role in the bone matrix and is encoded by COL1A2 (collagen type I alpha 2) gene that may be a potential candidate for osteoporotic fracture. The aim of this study is to determine whether EcoRI, Del38 and PvuII polymorphisms of COL1A2 are associated with the development of osteoporosis and osteopenia in post­menopausal Polish women. Moreover, analysis of relationship between frequency of COL1A2 gene polymorphic variants and clinical parameters of bone turnover and degree of osteoporosis was performed. Material and methods: The study group comprised of women with osteoporosis (n = 90), osteopenia (n = 56) and healthy individuals (n = 56). The EcoRI, Del38 and PvuII polymorphisms in COL1A2 gene were detected by PCR-RFLP method. Results: In women with osteoporosis the TT genotype of EcoRI polymorphism had the lowest Z-score value compared to other genotypes (p = 0.034). In case of Del28 polymorphism, there was a statistically significant correlation between lower BMI values and the DD genotype in women with osteopenia (p = 0.041). There was no statistically significant correlation between polymorphic variants of Del28 polymorphism and clinical parameters of women with osteoporosis. The analysis of PvuII polymorphism showed that in women with osteopenia the CC genotype had the lowest body weight compared to other genotypes (p = 0.039). PvuII polymorphism and clinical parameters in the group of women with osteoporosis had no statistically significant correlations. Conclusions: The analyzed COL1A2 polymorphisms seem to be related to osteoporosis development and their particular clinical parameters. Hence, the COL1A2 polymorphism may be a genetic risk factor related to the development of osteoporosis

Low back pain in pregnant wome

Pain of lumbosacral segment of the vertebral column and the pelvis concerns about 45% of all pregnant women. The change of the body posture during pregnancy is the result of gravity centre relocation, which affects the musculosceletal system. Development of the joint, ligament and myofascial dysfunctions, as well as the pain in the lumbosacral segment and the pelvis, are the most common reasons of spine pain. The aim of this review is to present the current state of knowledge about lumbar spine pain in pregnant women with special focus on the pain connected with muscular, joint and ligament disorders. Pregnancy is a serious burden for the female osteo-skeletal system. Lumbar pain with different location and intensification is the negative consequence of the position changes during pregnancy. Pharmacotherapy could be useful only in cases of intensive low back pain, with possible application of small spectrum of drugs that are safe during pregnancy. Physical therapy, including manual therapy, exercises, massage and techniques of local anesthesia are alternative methods in case of low back pain in pregnant women

The Impact of Walking Exercises and Resistance Training upon the Walking Distance in Patients with Chronic Lower Limb Ischaemia

Objective. The objective of this paper is to compare the impact of supervised walking and resistance training upon the walking distance in PAD patients. Materials and Methods. The examination involved 50 PAD patients at the 2nd stage of the disease according to Fontaine’s scale. The participants were randomly allocated to two groups: one exercising on the treadmill (n=24) and one performing resistance exercises of lower limbs (n=26). Results. The 12-week program of supervised rehabilitation led to a significant increase in the intermittent claudication distance measured both on the treadmill and during the 6-minute walking test. The group training on the treadmill showed a statistically significant increase of the initial claudication distance (ICD) and the absolute claudication distance (ACD) measured on the treadmill, as well as of ICD and the total walking distance (TWD) measured during the 6-minute walking test. Within the group performing resistance exercises, a statistically significant improvement was observed in the case of parameters measured on the treadmill: ICD and ACD. Conclusions. The supervised rehabilitation program, in the form of both walking and resistance exercises, contributes to the increase in the intermittent claudication distance. The results obtained in both groups were similar

Low back pain in women before and after menopause

Low back pain is a massive problem in modern population, both in social and economic terms. It affects large numbers of women, especially those aged 45-60. Going through a perimenopausal period is associated with many symptoms, including low back pain. This paper is a review of published research on the association between the perimenopausal age and low back pain. PubMed databases were investigated. After the search was narrowed to “menopausal status, back pain”, 35 studies were found. Seven studies, which suited our area of research best, were thoroughly analyzed. All studies show increased pain when women enter this period of their life. There is no agreement among researchers regarding which stage of menopause is the most burdensome. Examples of possible treatments and physiotherapeutic methods targeting low back pain are also presented. Physiotherapeutic procedures used to treat low back pain include exercises in safe positions, balance exercises, manual therapy, massage and physical measures