OBJECTIVE: To evaluate the effect of iatrogenic menopause on the physiology of the vagina of the ewe and to evaluate if vaginal changes in ewes can be translated to women with genitourinary syndrome of menopause (GSM). METHODS: Preclinical research with Dohne Merino ewes. Iatrogenic menopause was induced by bilateral ovariectomy (OVX). Animals were randomized for surgery, blinded for allocation and outcome assessment. Differences between groups were determined by linear regression analyses at 5 months after OVX. Outcome measures were vaginal epithelial thickness, pH, vaginal maturation value, vaginal maturation index, epithelial glycogen accumulation, content of elastin fibers, collagen, and vascularity. RESULTS: OVX ewes (n = 20) showed epithelial thinning of the vaginal wall from 146 μm to 47 μm (mean, P < 0.001). Furthermore, epithelial glycogen accumulation and vascularity of the vaginal wall significantly decreased (43% and 23%, respectively) as compared with the control group (no intervention; n = 5). No significant differences were found for other outcome measures. CONCLUSION: This study established the ewe as a suitable large animal model for GSM. Furthermore, the similar relevant outcomes in humans and ewes hold great value for future translational research for the evaluation and optimization of different treatment modalities for GSM.
- MeSH
- glykogen MeSH
- iatrogenní nemoci MeSH
- lidé MeSH
- menopauza * MeSH
- modely u zvířat MeSH
- ovarektomie škodlivé účinky MeSH
- ovce MeSH
- vagina * chirurgie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Niraparib,
- MeSH
- adjuvantní chemoterapie metody MeSH
- indazoly farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory vaječníků * chirurgie farmakoterapie MeSH
- neoadjuvantní terapie metody MeSH
- ovarektomie metody MeSH
- PARP inhibitory farmakologie terapeutické užití MeSH
- piperidiny farmakologie terapeutické užití MeSH
- proktektomie metody MeSH
- protokoly protinádorové léčby MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (-15.6 ± 0.48% in HFD and -37.5 ± 0.235% in HFD-OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD-OVX, p < 0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD-OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.
- MeSH
- diabetes mellitus 2. typu * komplikace MeSH
- dieta s vysokým obsahem tuků * škodlivé účinky MeSH
- estrogeny MeSH
- kosti a kostní tkáň metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita komplikace metabolismus MeSH
- ovarektomie škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Intracerebroventricular (ICV) administration of estradiol benzoate (E2B) and progesterone (P) induces intense lordosis behavior in ovariectomized rats primed peripherally with E2B. The present study tested the hypothesis that the Kisspeptin (Kiss) and melanin-concentrating hormone (MCH) pathways regulate female sexual behavior induced by these steroid hormones. In Experiment 1, we tested the relevance of the Kiss pathway by ICV infusion of its inhibitor, kiss-234, before administration of E2B or P in estrogen-primed rats. Lordosis induced by E2B alone or with the addition of P was reduced significantly at 30, 120, and 240 min. In Experiment 2, ICV infusion of MCH 30 min before E2B or P significantly reduced lordosis in rats primed with E2B alone. These data support the hypothesis that the Kiss and MCH pathways, which can release or modulate gonadotropin-releasing hormone (GnRH), are involved in E2B- and P-induced lordosis.
- MeSH
- estradiol farmakologie MeSH
- hormon uvolňující gonadotropiny farmakologie MeSH
- kisspeptiny farmakologie MeSH
- krysa rodu rattus MeSH
- lordóza * chemicky indukované MeSH
- ovarektomie MeSH
- progesteron * farmakologie MeSH
- sexuální chování zvířat fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Osteoporosis is a bone disease characterized by low bone mineral density (BMD) and impaired bone microarchitecture due to the abnormal activity of osteoclasts. Cathelicidins are antimicrobial peptides present in the lysosomes of macrophages and polymorphonuclear leukocytes. LL-37, a cathelicidin, induces various biological effects, including modulation of the immune system, angiogenesis, wound healing, cancer growth, as well as inflammation, and bone loss. A previous study reported direct involvement of LL-37 suppressing osteoclastogenesis in humans. Here, we examined the role of LL-37 in the treatment of osteoporosis using an ovariectomy (OVX) rat model. Our results showed that LL-37 significantly reduced bone loss and pathological injury in OVX rats with osteoporosis. Furthermore, we found that LL-37 significantly increased the activity of the Wnt/beta-catenin pathway in OVX rats with osteoporosis, including the increased expression of beta-catenin, Osterix (Osx), and Runt-related transcription factor 2 (Runx2), whereas XAV-939, an inhibitor of the Wnt/beta-catenin pathway, significantly blocked the effects of LL-37 on bone loss and abnormal bone metabolism. Altogether, our findings suggested that LL-37 exerted a protective role in regulating bone loss and abnormal bone metabolism in rats with osteoporosis by activating the Wnt/beta-catenin pathway.
- MeSH
- beta-katenin metabolismus MeSH
- buněčná diferenciace MeSH
- kationické antimikrobiální peptidy * farmakologie MeSH
- kostní denzita * MeSH
- krysa rodu rattus MeSH
- osteogeneze MeSH
- osteoporóza * farmakoterapie etiologie prevence a kontrola MeSH
- ovarektomie MeSH
- signální dráha Wnt * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Autori prezentujú kazuistiku pacientky s raritným ochorením – benígnou metastázujúcou leiomyomatózou, ktorej diagnostika je náročná a liečba buď operačná, alebo založená na aplikácii antiestrogénov, eventuálne modifikácii účinku progesterónu. Dané ochorenie bolo doteraz popísané celosvetovo u menej ako 300 pacientok. Autori kladú dôraz na náročnosť rozhodovacieho procesu v liečbe tohto vzácneho ochorenia, keďže celosvetovo neexistujú jednoznačne odporúčané postupy pri jeho liečbe.
he authors present a case report of a patient with a rare diagnosis – benign metastasizing leiomyomatosis. The case report documents a difficult diagnostic and therapeutic procedure, which is either operative or based on application of antiestrogens, or alternatively on progesterone effect modification. This rare diagnosis has so far been described in less than 300 cases worldwide. The authors would like to point out the difficult decision-making process in the therapy of this disease, as there are no explicit guidelines for its treatment.
- Klíčová slova
- benigní metastazující leiomyomatóza,
- MeSH
- fatální výsledek MeSH
- leiomyom komplikace MeSH
- leiomyomatóza * diagnóza etiologie terapie MeSH
- letrozol terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic * diagnostické zobrazování sekundární terapie MeSH
- ovarektomie MeSH
- oxygenoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: If menopause is really independent risk factor for cardiovascular disease is still under debate. We studied if ovariectomy in the model of insulin resistance causes cardiovascular changes, to what extent are these changes reversible by estradiol substitution and if they are accompanied by changes in other organs and tissues. METHODS: Hereditary hypertriglyceridemic female rats were divided into three groups: ovariectomized at 8th week (n = 6), ovariectomized with 17-β estradiol substitution (n = 6), and the sham group (n = 5). The strain of abdominal aorta measured by ultrasound, expression of vascular genes, weight and content of myocardium and also non-cardiac parameters were analyzed. RESULTS: After ovariectomy, the strain of abdominal aorta, expression of nitric oxide synthase in abdominal aorta, relative weight of myocardium and of the left ventricle and circulating interleukin-6 decreased; these changes were reversed by estradiol substitution. Interestingly, the content of triglycerides in myocardium did not change after ovariectomy, but significantly increased after estradiol substitution while adiposity index did not change after ovariectomy, but significantly decreased after estradiol substitution. CONCLUSION: Vascular and cardiac parameters under study differed in their response to ovariectomy and estradiol substitution. This indicates different effects of ovariectomy and estradiol on different cardiovascular but also extracardiac structures.
- MeSH
- anastrozol terapeutické užití MeSH
- antitumorózní látky hormonální terapeutické užití MeSH
- hysterektomie MeSH
- karcinoid chirurgie diagnostické zobrazování MeSH
- lidé MeSH
- nádory prsu chirurgie patologie MeSH
- nádory vaječníků chirurgie diagnostické zobrazování patologie MeSH
- ovarektomie MeSH
- sekundární malignity * MeSH
- senioři MeSH
- stupeň nádoru MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- diseminovaná intravaskulární koagulace terapie MeSH
- dospělí MeSH
- hemoperitoneum * etiologie MeSH
- lidé MeSH
- odběr oocytu metody škodlivé účinky statistika a číselné údaje MeSH
- ovarektomie MeSH
- péče o pacienty v kritickém stavu MeSH
- pooperační komplikace MeSH
- ventilace umělá s výdechovým přetlakem MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.
- MeSH
- bílá tuková tkáň metabolismus MeSH
- dieta s vysokým obsahem tuků MeSH
- dyslipidemie metabolismus MeSH
- glukosa metabolismus MeSH
- hmotnostní přírůstek MeSH
- hnědá tuková tkáň metabolismus MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence MeSH
- játra metabolismus MeSH
- krysa rodu rattus MeSH
- lipidy krev MeSH
- lipogeneze účinky léků MeSH
- lipolýza MeSH
- menopauza metabolismus fyziologie MeSH
- metabolismus lipidů účinky léků fyziologie MeSH
- nitrobřišní tuk metabolismus MeSH
- obezita metabolismus MeSH
- ovarektomie škodlivé účinky MeSH
- poruchy metabolismu lipidů etiologie patofyziologie MeSH
- postmenopauza metabolismus fyziologie MeSH
- potkani Wistar MeSH
- systém (enzymů) cytochromů P-450 metabolismus fyziologie MeSH
- triglyceridy metabolismus MeSH
- ztučnělá játra metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
