INTRODUCTION: Sepsis-induced acute kidney injury (AKI) remains a major challenge in intensive care, contributing significantly to morbidity and mortality. Tibolone, known for its neuroprotective and hormonal properties, has not been explored for its potential in AKI management. This study investigates the protective effects of Tibolone and its underlying mechanisms involving Sirtuin-1 (SIRT1) and Yes-Associated Protein (YAP) in a rat sepsis model. MATERIALS AND METHODS: Thirty-six female Wistar albino rats underwent cecal ligation and puncture (CLP) to induce sepsis. They were randomly assigned to control, CLP+Saline, and CLP+Tibolone groups. Tibolone was administered intraperitoneally. Biomarkers, including Sirtuin (SIRT1), Yes-associated protein (YAP), Tumor necrosis factor (TNF-α), High mobility group box 1 (HMGB1), malondialdehyde (MDA), creatinine, and urea, were assessed. Histopathological examination evaluated renal damage. RESULTS: Tibolone administration significantly reduced plasma TNF-α, HMGB1, MDA, creatinine, and urea levels compared to the CLP+Saline group. Moreover, Tibolone elevated SIRT1 and YAP levels in kidney tissues. Histopathological examination demonstrated a significant decrease in tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and interstitial inflammation in Tibolone-treated rats. CONCLUSION: This study unveils the protective role of Tibolone against sepsis-induced AKI in rats. The improvements in inflammatory and oxidative biomarkers and histological evidence suggest Tibolone's potential as a therapeutic intervention in sepsis-associated kidney injury. The upregulation of SIRT1 and YAP indicates their involvement in Tibolone's renoprotective mechanisms. Further investigations are warranted to explore Tibolone's translational potential in human sepsis-induced AKI.
- MeSH
- Acute Kidney Injury * etiology prevention & control drug therapy MeSH
- Biomarkers MeSH
- Rats MeSH
- Kidney drug effects metabolism MeSH
- Disease Models, Animal MeSH
- Norpregnenes * therapeutic use pharmacology MeSH
- Rats, Wistar * MeSH
- HMGB1 Protein metabolism MeSH
- Sepsis * complications drug therapy MeSH
- Sirtuin 1 * metabolism MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Nitroděložní systém s levonorgestrelem má vynikající antikoncepční účinnost za současného snížení menstruační krevní ztráty. V perimenopauze jej lze s výhodou využít k léčbě hyperplazie endometria. Jako gestagenní složka hormonální substituční terapie vykazuje výbornou kontrolu proliferace endometria. V kombinaci s transdermální aplikací estrogenu má výhodu nulového zvýšení rizika tromboembolické nemoci.
Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation’s blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen’s application.
- MeSH
- Administration, Cutaneous MeSH
- Endometrium drug effects MeSH
- Hormone Replacement Therapy * methods MeSH
- Endometrial Hyperplasia prevention & control MeSH
- Levonorgestrel administration & dosage pharmacology therapeutic use MeSH
- Humans MeSH
- Menopause * drug effects MeSH
- Intrauterine Devices, Medicated MeSH
- Thromboembolism chemically induced MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- MeSH
- Dydrogesterone administration & dosage therapeutic use MeSH
- Estrogens administration & dosage therapeutic use MeSH
- Hormone Replacement Therapy MeSH
- Climacteric * psychology drug effects MeSH
- Levonorgestrel administration & dosage therapeutic use MeSH
- Humans MeSH
- Medroxyprogesterone Acetate administration & dosage therapeutic use MeSH
- Hot Flashes drug therapy MeSH
- Perimenopause MeSH
- Progesterone administration & dosage therapeutic use MeSH
- Receptors, Estrogen MeSH
- Selective Serotonin Reuptake Inhibitors administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Keywords
- relugolix, Reygo, studie LIBERTY 1, studie LIBERTY 2,
- MeSH
- Hormone Antagonists administration & dosage therapeutic use MeSH
- Adult MeSH
- Estradiol administration & dosage therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Leiomyomatosis * diagnosis complications MeSH
- Humans MeSH
- Norethindrone Acetate administration & dosage therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Geographicals
- Czech Republic MeSH
Cíl: Navzdory značným pokrokům s nedávno vyvinutými formami kombinované perorální antikoncepce (COC – combined oral contraceptive), které vedly ke sníženému výskytu nežádoucích příhod při plném zachování antikoncepční účinnosti, zájem o další inovace přetrvává. Materiály a metody: Nový typ COC kombinuje přirozený estrogen estetrol (E4) a gestagen drospirenon (DRSP). Evropský panel odborníků hodnotil farmakologické vlastnosti, účinnost, bezpečnost a snášenlivost této kombinace. Zjištění jsou prezentována formou přehledového článku. Výsledky: Kombinace 15 mg E4/3 mg DRSP v režimu 24+4 představuje účinnou antikoncepci s dobrou regulací cyklu, charakterizovanou pravidelným krvácením a minimálním neplánovaným krvácením, a stejně tak i dobrým bezpečnostním profilem. Spojován je s vysokou spokojeností uživatelek, dobrým zdravotním stavem a minimálními změnami tělesné hmotnosti. Účinky na endokrinní a metabolické parametry jsou omezeny a kombinace má též omezený vliv na jaterní funkce a metabolizmus lipidů a sacharidů. Na hemostatické parametry má menší vliv než porovnatelná léčiva s obsahem 20 μg etinylestradiolu (EE) /3 mg DRSP a 30 μg EE/150 μg levonorgestrelu. Závěr: Kombinace 15 mg E4/3 mg DRSP poskytuje bezpečnou a účinnou antikoncepci s vysokou mírou spokojenosti uživatelek a předvídatelným krvácením. Další výzkum se bude věnovat hodnocení dlouhodobé bezpečnosti COC.
Purpose: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation. Materials and Methods: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review. Results: E4 15mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, wellbeing, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 mg/DRSP 3 mg and EE 30 mg/levonorgestrel 150 mg. Conclusion: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.
- Keywords
- relugolix,
- MeSH
- Androgen Antagonists pharmacology therapeutic use MeSH
- Adult MeSH
- Estradiol pharmacology therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Leiomyoma * surgery drug therapy MeSH
- Humans MeSH
- Norethindrone Acetate pharmacology therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
INTRODUCTION: This study was designed to evaluate the feasibility and effectiveness of hysteroscopy in the management of symptoms related to endometrial polyps and submucous leiomyomas in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: Twenty-three LNG-IUS users presenting with endometrial polyps and/or submucous leiomyomas and irregular uterine bleeding were recruited for hysteroscopic examination and surgery. Intrauterine pathology was investigated and treated by hysteroscopic resection with the LNG-IUS in situ, and the effect of the procedure on symptoms was evaluated after three to six months. RESULTS: Intrauterine pathology was successfully resected by hysteroscopy in 23 (100.0%) out of 23 cases. Following hysteroscopy, 18 (78.3%) women reported amenorrhea, one (4.3%) regular spotting, three (13.0%) irregular spotting and one (4.3%) patient resumed normal menstrual cycle. We conclude that 19 (82.6%) patients were postoperatively asymptomatic. All procedures were uncomplicated and 4 (17.4%) were carried out without general anesthesia as office procedures. CONCLUSION: Endometrial polyps and submucous leiomyomas can develop in LNG-IUS users, and this can cause irregular uterine bleeding. Hysteroscopic resection of these pathologies is a feasible method in the clinical management of symptoms.
- MeSH
- Uterine Hemorrhage MeSH
- Leiomyoma * drug therapy surgery MeSH
- Levonorgestrel therapeutic use MeSH
- Humans MeSH
- Uterine Neoplasms * drug therapy surgery MeSH
- Intrauterine Devices, Medicated * MeSH
- Polyps * drug therapy surgery MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Endometrium * diagnostic imaging pathology drug effects MeSH
- Estrogen Replacement Therapy MeSH
- Hysteroscopy MeSH
- Aromatase Inhibitors pharmacology adverse effects therapeutic use MeSH
- Clomiphene pharmacology adverse effects therapeutic use MeSH
- Contraceptive Agents, Hormonal pharmacology classification adverse effects MeSH
- Levonorgestrel adverse effects therapeutic use MeSH
- Humans MeSH
- Metformin pharmacology adverse effects therapeutic use MeSH
- Uterine Diseases chemically induced diagnostic imaging pathology MeSH
- Drug-Related Side Effects and Adverse Reactions * diagnostic imaging epidemiology pathology MeSH
- Receptors, Progesterone therapeutic use MeSH
- Tamoxifen adverse effects therapeutic use MeSH
- Testosterone history adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.
- MeSH
- Androstenes toxicity MeSH
- Water Pollutants, Chemical toxicity MeSH
- Endocrine Disruptors toxicity MeSH
- Gonads drug effects MeSH
- Hepatopancreas drug effects MeSH
- Pituitary Gland drug effects MeSH
- Hypothalamus drug effects MeSH
- Carps growth & development MeSH
- Norpregnenes toxicity MeSH
- Sex Differentiation drug effects genetics MeSH
- Gene Expression Regulation, Developmental drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
