Optimization of antibiotic therapy in pregnancy – clinical implications

The aim of the antibacterial therapy during pregnancy is to select a proper antibiotic and determine its effective dose, at the same time excluding the risk of potential teratogenic effect. Pregnancy is characterized by many physiological, disease-predisposing changes, particularly of bacterial etiology, that have an influence on different pharmacokinetic of drugs. When determining an effective dose of an antibiotic, one should take into account changes in the pharmacokinetics (PK) of drugs in pregnant women, involving mainly the phase of distribution(increased volume of body fluids, cardiac output, reduced concentration of albumins), metabolism (induction of hepatic enzymes: CYP3A4, CYP2D6, CYP2C9, UGT1A4, UGT2B7, inhibition of CYP1A2, CYP2C19), and excretion (increased glomerular filtration rate). Results of few pharmacokinetic studies on pregnant patients point to the need of increasing the dose or reducing dosage intervals for some antibiotics (e.g. penicillin V, ampicillin, piperacillin, imipenem, clindamycin). The aim of this study was to summarize current knowledge regarding the PK of antibiotics during pregnancy

Znaczenie polimorfizmu CYP1A1 i regulacji jego transkrypcji w podatności na raka jajnika i endometrium

Abstract Human cytochrome P450 1A1 is one of the most important enzymes participating in human carcinogenesis because it metabolites several procarcinogens to active carcinogenic metabolites. Additionally, enzymes of CYP450 family play an important role in estrogenes catabolization (17-β-estradiol and estron) to intermediate products (2-, 4-hydroxyestradiol and 2-, 4-hydroxyestrone) including CYP1A1 that catalyses hydroxylation to 2-hydroxyestrogens in the endometrium. Derivates of these compounds (4-hydroxyestrogens) are carcinogenic and could induce DNA damage leading to tumour transformation. The presence of CYP1A1 enzyme in genital tract tissues could induce chemical carcinogenesis initiating cancer development. Recent studies also confirmed the role of CYP1A1 in the development of ovarian and endometrial cancer in humans. The presence of mutated CYP1A1 polymorphic variants influencing the CYP1A1 activity could be responsible for different interindividual susceptibility to genital cancers in women.Streszczenie Ludzki cytochrom CYP4501A1 jest jednym z najważniejszych enzymów uczestniczących w procesie kancerogenezy, ponieważ metabolizuje wiele pro-kancerogenów do ich aktywnych kancerogennych metabolitów. Dodatkowo, enzymy z rodziny CYP450 odgrywają ważną rolę w katabolizmie estrogenów (17-β-estradiol i estron) do produktów pośrednich (2-, 4-hydroksyestradiol oraz 2-, 4-hydroksyestron) uwzględniając CYP1A1, który katalizuje hydroksylację do 2-hydroksyestrogenu w endometrium. Pochodne tych związków (4-hydroksyestrogeny) są kancerogenne i mogą indukować uszkodzenia DNA prowadząc do transformacji nowotworowej komórki. Obecność enzymu CYP1A1 w tkankach narządów płciowych może indukować chemiczną kancerogenezę inicjując rozwój nowotworu. Najnowsze badania potwierdziły rolę CYP1A1 w rozwoju raka jajnika i endometrium. Obecność zmutowanych wariantów polimorficznych genu CYP1A1 wpływających na aktywność CYP1A1 może być związana ze zróżnicowaniem osobniczym w podatności na nowotwory narządów płciowych u kobiet

The influence of soybean extract on the expression level of selected drug transporters, transcription factors and cytochrome P450 genes encoding phase I drug-metabolizing enzymes

Objective: Soybean phytoestrogens, such as genistein and daidzein, reduce climacteric symptoms and the risk of certain chronic diseases such as cancer and cardiovascular diseases. Despite their widespread use in functional foods and dietary supplements, there is very little data available on their safety and herb-drug interactions, especially with antineoplastic agents. Hence, the aim of our study was to assess the effects of soybean extracts on the expression level of CYP genes and their transcriptional factors. We also investigated the effect of soybean on the mRNA level of transporters, such as P-glycoprotein (MDR1) and multidrug resistance-associated proteins (MRP1, MRP2). Materials and methods: Wistar rats were fed a standardized soybean extract (100 mg/kg, p.o.). cDNA was synthesized from total RNA isolated from different tissues (liver and intestinal epithelium) using reverse transcription. Gene expression level was analyzed by RT-PCR method. Results: We demonstrated a significant increase of CYP1A1 mRNA level (by 89%, p=0.002 and 125%, p=0.004) as compared with the control group. An increase of AHR and CAR expression after 10 days was also observed (by 60%, p0.05, respectively). Additionally, an inductive effect for CYP2D1 by 22% (p=0.008), Mdr1a by 267% (

Znaczenie polimorfizmów rs1021737 i rs482843 gamma-liazy cystationinowej w etiologii stanu przedrzucawkowego w populacji kaukaskiej

Introduction: Recently, an increasing number of reports indicate the participation of genetic factors in the pathogenesis of preeclampsia (PE). The genes involved in the synthesis of nitric oxide that participates in the vasolidation, may play an important role in the development of this disorder. Hydrogen sulfide (H2S) which is produced by cystathionine gamma-lyase exhibits a similar effect to nitric oxide. It is suggested that certain polymorphisms of the CTH gene may participate in the development of chronic hypertension and preeclampsia. Aim of the study: To evaluate the frequency of genotypes and alleles of rs1021737 and rs482843 polymorphisms of CTH gene in women with preeclampsia from Wielkopolska region. Material and methods: The study group consisted of 60 patients with diagnosed preeclampsia, into the control group 120 healthy pregnant women were enrolled. The examined rs1021737 and rs482843 polymorphisms of CTH gene were determined using PCR-RFLP method. Results: Analysis of rs482843 polymorphism in the CTH gene showed a statistically significant difference in the prevalence of mutated GG genotype (pWstęp: W ostatnim czasie coraz więcej doniesień wskazuje na udział czynników genetycznych w etiopatogenezie stanu przedrzucawkowego (PE – preeclampsia). Istotną rolę mogą odgrywać geny uczestniczące w syntezie tlenku azotu, głównego wazodylatora naczyń. Podobne działanie wazodyletacyjne pełni także siarkowodór (H2S) syntetyzowany przy udziale gamma-liazy cystationinowej. Sugeruje się, że określone polimorfizmy genu CTH mogą mieć znaczenie w rozwoju nadciśnienia przewlekłego i stanu przedrzucawkowego. Cel pracy: Określenie częstości występowania genotypów i alleli polimorfizmów rs1021737 i rs482843 genu CTH w grupie kobiet ze stanem przedrzucawkowym z regionu Wielkopolski. Materiał i metody: Grupa badana obejmowała 60 pacjentek ze zdiagnozowanym stanem przedrzucawkowym, natomiast grupa kontrolna stanowiła 120 zdrowych kobiet ciężarnych. Analizowane polimorfizmy rs1021737 i rs482843 genu CTH oznaczono przy pomocy metody PCR-RFLP. Wyniki: Analiza polimorfizmu rs482843 genu CTH wykazała różnicę istotną statystycznie w częstości występowania genotypu zmutowanego GG (

Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women

Objective: Preeclampsia (PE) belongs to main causes of mortality rates of mothers, fetuses and new born children. Polymorphism of MDR1 gene is connected with reduction of P-glycoprotein expression in placenta and increased fetal exposure to xenobiotics. The aim of the study was to determine the frequency of C3435T and G2677T/A polymorphisms of MDR1 gene in pregnant women with preeclampsia. Materials and methods: The study consisted of 180 Polish women including 60 women with PE and 120 healthy pregnant women. Determination of C3435T and G2677T/A polymorphisms of MDR1 gene was performed using PCR-RFLP method. Results: No significant association between genotypes of the examined polymorphisms and the clinical parameters of pregnant women with PE was observed. However the interesting tendency to higher prevalence of mutated 2677A allele of G2677T/A MDR1 polymorphism in PE group has been shown (2,50 vs. 0,83% in controls, OR=3,05, ns). Conclusions: The results of this study suggest no significant effect of examined C3435T and G2677T/A MDR1 polymorphisms in PE pathogenesis. However given the noteworthy results related to mutated 2677A allele of G2677T/A MDR1 polymorphism in preeclamptic women further studies seem to be needed. Nevertheless, the frequency of investigated polymorphisms was consistent with the distribution in other Caucasian populations

Effect of Epilobium angustifolium and Serenoa repens extracts on regulation of non-genomic signaling pathway of kinases

Objectives: Changes of kinase activity of non-genomic cellular signaling pathway may influence the effectiveness of pharmacotherapy in case of hormone-dependent tumors. Our study investigated a possible interaction at the molecular level between an aqueous herbal extract of Epilobium angustifolium as well as a lipid-sterolic fruit extract of Serenoa repens and synthetic drugs used in the treatment of hormone-dependent cancers. Material and methods: E. angustifolium and Serenoa repens extracts were orally administered to testosteroneinduced rats for 21 days. Changes of RafA/Mapk3/Mapk1 mRNA levels were analyzed by real-time quantitative PCR using target specific primers. Results: The level of RafA mRNA slightly increased in rats receiving Epilobium angustifolium (p=0.076) and Serenoa repens (p=0.016) extracts. Administration of these extracts resulted in significantly elevated Mapk1 and Mapk3 transcripts in the investigated animals (

The role of phytoestrogen therapy in relieving postmenopausal symptoms

Summary Side effects and contraindications connected with hormonal replacement therapy in climacterium resulted in search for new methods of softening menopausal symptoms. The aim of the following study was to evaluate, based on literature analysis, the effectiveness of phytohormonal therapy as an alternative method of relieving the symptoms of menopausal period and preventing the diseases connected with deficiency of estrogens after menopause. Phytoestrogens therapy reduces the number and strength of the vasomotor symptoms and improves serum lipid profile. Moreover, phytoestrogens show beneficial effects on bone tissue metabolism, skin and mucous membranes condition and are applicable in chemoprevention. This therapy is an effective method, allowing to avoid further changes in blood and urogenital systems, which result from estrogen stimulation deficiency. Phytoestrogens administration is an efficient method of relieving postmenopausal symptoms, facilitating the difficult menopausal period and keeping good health condition

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

Influence of standardized extract of Epilobium angustifolium on estrogen receptor α and β expression in in vivo model

Abstract Objective: Evaluation of the influence of the standardized extract from the herb of Epilobium angustifolium on ERα and ERβ mRNA expression in rat ventral prostate tissue and free serum estradiol level. Materials and methods: Rats were divided into 6 groups with 10 animals. ERα and ERβ mRNA expression in rat ventral prostate tissue level was performed using real-time PCR method in Light Cycler system. Serum-free estradiol was evaluated using immunoenzymatic technique. Results: In our experimental model there was an increase of ERα mRNA level by 9% and decrease by 36% of ERβ mRNA level in ventral prostate tissue in rats administrated with testosterone and E. angustifolium extract, in comparison with testosterone alone administrated animals. Conclusions: E. angustifolium standardized extract influenced the expression of estrogen receptor α and β mRNAs in differential manner which may suggest its potentially therapeutic properties or causing of adverse effects in pharmacotherapy of estrogen-related disorders. More complex studies should be undertaken to evaluate safety and to improve the efficacy of using this herbal extract