Crude oil contamination has been shown to impair reproduction in aquatic animals through carcinogenic and genotoxic properties. Here, we assessed the endocrine-disrupting function of crude oil on male reproductive system based on testicular histology, sex steroid hormones, and fertility endpoints in adult male goldfish (Carassius auratus), which were exposed to 0.02- to 2-mg/L crude oil for 21 days (Experiment #1) or to 5- to 250-mg/L crude oil for 9 days (Experiment #2). The crude oil contained 0.22-mg/L nickel (Ni), 1.10-mg/L vanadium (V), and 12.87-mg/L polycyclic aromatic hydrocarbons (PAHs). Twenty-four hours after adding crude oil, the sum of PAHs ranged from 0.30 to 2.28 μg/L in the aquaria containing 0.02- and 250-mg/L crude oil, respectively. Water analyses for heavy metals in Experiment #2 showed high concentrations (mg/L) of Ni (0.07-0-09) and V (0.10-0.21). For both experiments, exposure to crude oil did not impact gonadosomatic index; however, testes showed histopathological defects including hyperplasia or hypertrophy of Sertoli cells, depletion of the Leydig cells, necrosis of germ cells, and fibrosis of lobular wall. In Experiment #1, sperm production and motility, testosterone (T), and 17β-estradiol (E2) were not significantly different among treatments. In Experiment #2, the number of spermiating males decreased by ~50% following exposure to 250-mg/L crude oil. Sperm production, motility kinematics, T, and the T/E2 ratio significantly decreased in males exposed to ≥ 50-mg/L crude oil; however, E2 remained unchanged. Results show crude oil-induced imbalance of sex steroid hormones disrupts spermatogenesis resulting in diminished sperm production and motility.
- MeSH
- Water Pollutants, Chemical * toxicity MeSH
- Endocrine Disruptors * toxicity MeSH
- Goldfish * physiology MeSH
- Sperm Motility * drug effects MeSH
- Gonadal Steroid Hormones * metabolism blood MeSH
- Petroleum * toxicity MeSH
- Reproduction drug effects MeSH
- Spermatozoa * drug effects pathology MeSH
- Testis * drug effects pathology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
- MeSH
- Antioxidants metabolism MeSH
- Bioaccumulation MeSH
- Environmental Pollutants toxicity MeSH
- Humans MeSH
- Oxidative Stress * drug effects MeSH
- Metals, Heavy * toxicity MeSH
- Environmental Exposure adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
OBJECTIVES: Treponema pallidum subsp. pallidum (T. pallidum) is the etiological agent of syphilis, a sexually transmitted disease of global public health importance. The objective of this study was to introduce a novel in vitro protocol for isolation of T. pallidum directly from patients' clinical samples, eliminating the need for rabbit propagation. METHODS: Four oral and five genital swabs were collected from nine epidemiologically unrelated patients at two hospitals in Brno, Czech Republic. Swabs were submerged in TpCM-2 medium for transport. Samples were then placed on a 0.4 μm filters and incubated for 2.5 hours. During this period, spiral T. pallidum cells passed through the filter pores to the well containing TpCM-2 medium and rabbit feeder cells (Sf1Ep). Stable T. pallidum cultures (containing >1 × 107 treponemes) were achieved by subculturing every 7 days into fresh well. RESULTS: A successful protocol for in vitro isolation of T. pallidum was established. From the nine clinical specimens processed, six T. pallidum cultures (MU1-MU6) were derived after 14 to 112 days of cultivation. Five of these strains (MU1-MU5) belonged to SS14-like cluster and shared the same allelic profile 1.3.1. The remaining strain (MU6) was identified as a Nichols-like strain with an allelic profile 9.16.3. DISCUSSION: The introduced in vitro protocol enables isolation of T. pallidum from clinical material, including frozen samples, without the need for experimental rabbits. This method facilitates the isolation of contemporary, clinically relevant treponemal strains.
- MeSH
- Bacteriological Techniques * methods MeSH
- Rabbits MeSH
- Humans MeSH
- Genitalia microbiology MeSH
- Syphilis * microbiology diagnosis MeSH
- Treponema pallidum * isolation & purification genetics classification MeSH
- Mouth microbiology MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Příspěvek se zaměřuje na spektrum terapeutických materiálů, které jsou vhodné k léčbě ran, ulcerací a lézí v genitoanální oblasti u žen. Přestože obsah článku se věnuje genitoanální oblasti u žen, předložená lokální terapie se používá ve stejné oblasti rovněž u mužů. Histologicky ženský a mužský genitál má shodné tkáně, které se rozlišují pouze anatomickými rysy. Poškození v genitoanální oblasti vyžadují materiály k opakované aplikaci během dne, cenově přijatelné, zmírňující bolest a zlepšující komfort pacientů. Názorné schéma v tabulce s terapeutickými materiály je rozděleno do tří oddílů, zahrnujících fázi zánětu s vysoušením spodiny rány, fázi podporující čištění ran a fázi regenerační. Do poškození v této oblasti lze zahrnout i iritační a postradiační dermatitis. Předložená kazuistika popisuje komplikovanou léčbu lézí v genitoanální oblasti u nespolupracující pacientky.
This article deals with the issue of the spectrum of therapeutic materials suitable for the treatment of wounds, ulcerations and lesions in the genitoanal area in women. Despite the fact that the content of the article is primarily dedicated to the female genitoanal area, the described local therapy is also applicable to men in the same region. Histologically, the female and male genitalia consist of identical tissues, which are distinguished only by anatomical features. Damage to the genitoanal area requires materials for repeated application during the day, are affordable, relieve pain and improve comfort of patients. The illustrative scheme in the table with therapeutic materials is divided into three sections, including the inflammation phase with drying of the wound bed, the phase supporting wound cleansing and the regeneration phase. Damage in this area may also involve irritant and post-radiation dermatitis. The presented case describes the complicated treatment of lesions in the genitoanal area of an uncooperative patient.
- MeSH
- Wound Healing * drug effects MeSH
- Hydrogels administration & dosage MeSH
- Urinary Incontinence pathology MeSH
- Dermatitis, Contact therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Ointments administration & dosage MeSH
- Radiodermatitis therapy MeSH
- Solutions administration & dosage MeSH
- Vascular Surgical Procedures methods MeSH
- Genitalia, Female * pathology injuries MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
International comparisons highlight differences in healthcare practices, raising questions about the application of evidence-based care when wide variations exist between countries with similar populations and income levels. Caesarean section (CS) rates show significant variation, with national and regional averages differing widely. As a common surgical procedure, this variation affects a large number of people and may have major consequences for maternal and newborn health. Comparable health indicators are essential to analyse CS rates and understand the reasons for this variability. A review of data on CS rates in Europe in international databases, such as those maintained by Eurostat, OECD and WHO, confirmed wide variation in CS rates in Europe, from 16% to over 50%, but showed very limited data available to understand these differences. In contrast, many European countries collect a wide array of data in national health information systems which can be used to investigate variations in CS, including on the timing and indication of the CS, and key population and health system characteristics that affect risks of CS. Based on the published literature, work in the Euro-Peristat network and within the EBCOG advisory board, we propose a list of data items that should be available at the national and international levels to allow comprehensive international surveillance and evaluation of CS practices.
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol). The changes were assessed using steroid levels and steroid molar ratios (SMRs) that may reflect the activities of steroidogenic enzymes (SMRs). A repeated measures ANOVA, followed by multiple comparisons and OPLS models, were used for statistical analyses. The anti-MS treatment decreased steroid levels in the follicular phase. Anti-CD20 monoclonal antibodies (mAb), such as ofatumumab and ocrelizumab; inhibitors of the sphingosine-1-phosphate receptor (S1PRI); and IFNβ-1a decreased circulating 17-hydroxy-pregnanes and shifted the CYP17A1 functioning from the hydroxylase- toward the lyase step. Decreased conjugated/unconjugated steroid ratios were found after treatment with anti-MS drugs, especially for glatiramer acetate and anti-CD20 mAb. In the luteal phase, IFN-β1a treatment increased steroidogenesis; both IFN-β1a and ocrelizumab increased AKR1D1, and S1PRI increased SRD5A functioning. Anti-CD20 mAb reduced the functioning of enzymes catalyzing the synthesis of immunomodulatory 7α/β and 16α-hydroxy-androgens, which may affect the severity of MS. The above findings may be important concerning the alterations in bioactive steroids, such as cortisol; active androgens and estrogens; and neuroactive, neuroprotective, and immunomodulatory steroids in terms of optimization of anti-MS treatment.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Sclerosis * drug therapy metabolism MeSH
- Steroids therapeutic use MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Estrogeny jsou klíčové hormony, které hrají zásadní roli ve fyziologii reprodukčního systému u žen. Jejich terapeutické využití v hormonální léčbě, antikoncepci a léčbě hormonálně závislých onemocnění však může být spojeno s řadou nežádoucích účinků, zejména na játra. Tento článek se zaměřuje na mechanismy působení estrogenů a jejich potenciální hepatotoxické účinky, stejně jako na rizikové faktory a možné rozdíly mezi jednotlivými představiteli.
Estrogens are key hormones that play a vital role in the physiology of the reproductive system in women. However, their therapeutic use in hormonal treatment, contraception and the treatment of hormone-dependent diseases may be associated with a number of side effects, especially on the liver. This article focuses on the mechanisms of action of estrogens and their potential hepatotoxic effects, as well as risk factors and possible differences between representatives.
- MeSH
- Estrogens * pharmacokinetics metabolism adverse effects MeSH
- Sex Hormone-Binding Globulin drug effects MeSH
- Liver * drug effects MeSH
- Drug Interactions MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
Estrogeny jsou klíčové hormony, které hrají zásadní roli ve fyziologii reprodukčního systému u žen. Jejich terapeutické využití v hormonální léčbě, antikoncepci a léčbě hormonálně závislých onemocnění však může být spojeno s řadou nežádoucích účinků, zejména na játra. Tento článek se zaměřuje na mechanismy působení estrogenů a jejich potenciální hepatotoxické účinky, stejně jako na rizikové faktory a možné rozdíly mezi jednotlivými představiteli.
Estrogens are key hormones that play a vital role in the physiology of the reproductive system in women. However, their therapeutic use in hormonal treatment, contraception and the treatment of hormone-dependent diseases may be associated with a number of side effects, especially on the liver. This article focuses on the mechanisms of action of estrogens and their potential hepatotoxic effects, as well as risk factors and possible differences between representatives.
- MeSH
- Estetrol pharmacology MeSH
- Estrogens * pharmacology adverse effects therapeutic use MeSH
- Sex Hormone-Binding Globulin MeSH
- Liver pathology drug effects MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs. In this study, we report a significant defect in mammary epithelial development in EKAREV-NLS C57BL/6J female mice. Our findings reveal that these mice exhibit severely impaired mammary epithelial outgrowth, linked to systemic defects including disrupted estrous cycling, impaired ovarian follicle maturation, anovulation, and reduced reproductive fitness. Notably, estrogen supplementation was sufficient to enhance mammary epithelial growth in the EKAREV-NLS C57BL/6J females. Furthermore, outcrossing to the ICR genetic background fully restored normal mammary epithelial outgrowth, indicating that the observed phenotype is dependent on genetic background. We also confirmed the functional performance of the biosensor in hormone-supplemented and outcrossed tissues through time-lapse imaging of primary mammary epithelial cells. Our results underscore the critical need for thorough characterization of biosensor-carrying models before their application in specific research contexts. Additionally, this work highlights the influence of hormonal and genetic factors on mammary gland development and emphasizes the importance of careful consideration when selecting biosensor strains for mammary studies.
- MeSH
- Biosensing Techniques * methods MeSH
- Epithelial Cells metabolism drug effects MeSH
- Estrogens * metabolism MeSH
- Extracellular Signal-Regulated MAP Kinases metabolism MeSH
- Genetic Background MeSH
- Mammary Glands, Animal * growth & development drug effects MeSH
- Mice, Inbred C57BL * MeSH
- Mice, Inbred ICR MeSH
- Mice, Transgenic * MeSH
- Mice MeSH
- Fluorescence Resonance Energy Transfer methods MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Mounting an immune response is a nutritionally demanding process that requires the systemic redistribution of energy stores towards the immune system. This is facilitated by cytokine-induced insulin resistance, which simultaneously promotes the mobilization of lipids and carbohydrates while limiting their consumption in immune-unrelated processes, such as development, growth, and reproduction. However, this adaptation also restricts the availability of nutrients to vital organs, which must then be sustained by alternative fuels. Here, we employed an experimental model of severe bacterial infection in Drosophila melanogaster to investigate whether ketogenesis may represent a metabolic adaptation for overcoming periods of nutritional scarcity during the immune response. We found that the immune response to severe bacterial infection is accompained by increased ketogenesis in the fat body and macrophages, leading to elevated levels of β-hydroxybutyrate in circulation. Although this metabolic adaptation is essential for survival during infection, it is not required for the elimination of the pathogen itself. Instead, ketone bodies predominately serve as an energy source for the brain neurons during this period of nutrient scarcity.
- MeSH
- Bacterial Infections metabolism immunology MeSH
- Drosophila melanogaster * metabolism microbiology MeSH
- Energy Metabolism physiology MeSH
- Ketone Bodies * metabolism MeSH
- 3-Hydroxybutyric Acid metabolism MeSH
- Macrophages metabolism MeSH
- Brain * metabolism MeSH
- Neurons metabolism MeSH
- Fat Body metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
