Biotransformation of steroids by fungi has been raised as a successful, eco-friendly, and cost-effective biotechnological alternative for chemical derivatization. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes that carry out uncommon reactions. Moreover, using nanofibrous membranes as support for immobilizing fungal cells is a powerful strategy to improve their performance by enabling the combined action of adsorption and transformation processes, along with increasing the stability of the fungal cell. In the present study, we report the use of polyacrylonitrile nanofibrous membrane (PAN NFM) produced by electrospinning as supporting material for immobilizing the endophytic fungus Penicillium citrinum H7 aiming the biotransformation of progesterone. The PAN@H7 NFM displayed a high progesterone transformation efficiency (above 90%). The investigation of the biotransformation pathway of progesterone allowed the putative structural characterization of its main fungal metabolite by GC-MS analysis. The oxidative potential of P. citrinum H7 was selective for the C-17 position of the steroidal nucleus.
- MeSH
- biotransformace MeSH
- nanovlákna * chemie MeSH
- progesteron MeSH
- Publikační typ
- časopisecké články MeSH
RATIONALE: Cabergoline (CAB) is an ergot derivative typically prescribed for the treatment of hyperprolactinemia. It suppresses the release of prolactin through agonist actions on dopamine (DA) D2 receptors; however, it possesses binding affinity for other DA and 5-HT receptors. Side effects that exacerbate valvular heart disease can occur with high doses. OBJECTIVE: The present study examined the acute, subchronic, and chronic dose-response effects of CAB and a derivative dimethylcabergoline (DMC) which acts as an antagonist instead of agonist at 5-HT 2B receptors, on appetitive and consummatory sexual behaviors of male rats. METHODS: CAB (0, 0.03, 0.15, or 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 68 days. Sexual behavior was tested every 4 days during this period for a total of 16 trials. On the 17th trial, rats were administered their dose of CAB, and 4 h after were overdosed with sodium pentobarbital, perfused intracardially, and their brains processed for Fos immunohistochemistry. DMC (0, 0.03, 0.15, 0.3 mg/kg/ml) was administered daily to sexually experienced male rats (N = 10/dose) by oral gavage for a total of 36 days. Sexual behavior was tested every 4 days for a total of 9 trials. RESULTS: CAB increased anticipatory level changes, intromissions, and ejaculations significantly across all timepoints, with the medium and high doses being most potent. The medium and high doses also increased Fos protein significantly within the medial preoptic area, whereas in the nucleus accumbens shell, the low and medium doses decreased Fos protein but the high dose increased it significantly from control. Similar to CAB, the medium and high doses of DMC increased the number of ejaculations significantly. Rats in all drug dose groups appeared healthy for the duration of the experiments. CONCLUSIONS: Both CAB and DMC facilitate ejaculations, and CAB further facilitates measures of anticipatory sexual motivation and intromissions. These data suggest that both could be used as treatments for sexual arousal disorders and ejaculation/orgasm disorders with little or no untoward side effects at low doses.
- MeSH
- kabergolin farmakologie MeSH
- kopulace * MeSH
- krysa rodu rattus MeSH
- motivace MeSH
- mozek MeSH
- pohlavní steroidní hormony MeSH
- receptory dopaminu D2 MeSH
- sexuální chování zvířat * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- hormonální substituční terapie * škodlivé účinky MeSH
- hypogonadismus komplikace MeSH
- kardiovaskulární nemoci chemicky indukované epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty chemicky indukované epidemiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- senioři MeSH
- testosteron krev škodlivé účinky MeSH
- urologické nemoci chemicky indukované epidemiologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- komentáře MeSH
Perinatal testosterone, or its metabolite estradiol, organize the brain toward a male phenotype. Male rodents with insufficient testosterone during this period fail to display sexual behavior and partner preference for receptive females in adulthood. However, cohabitation with non-reproductive conspecifics under the influence of a D2 agonist facilitates the expression of conditioned partner preference via Pavlovian learning in gonadally intact male rats. In the present experiment, three groups of neonatal PD1 males (N = 12/group) were either gonadectomized (GDX), sham-GDX, or left intact and evaluated for social preferences and sexual behaviors as adults. We then examined whether the effects of GDX could be reversed by conditioning the males via cohabitation with receptive females under the effects of the D2 agonist quinpirole (QNP) or saline, along with the size of some brain regions, such as the sexually dimorphic nucleus of the preoptic area (SDN-POA), suprachiasmatic nucleus (SCN), posterior dorsal medial amygdala (MeApd) and ventromedial hypothalamus (VMH). Results indicated that neonatal GDX resulted in the elimination of male-typical sexual behavior, an increase in same-sex social preference, and a reduction of the area of the SDN-POA. However, GDX-QNP males that underwent exposure to receptive females in adulthood increased their social preference for females and recovered the size in the SDN-POA. Although neonatal GDX impairs sexual behavior and disrupts partner preference and brain dimorphism in adult male rats, Pavlovian conditioning under enhanced D2 agonism ameliorates the effects on social preference and restores brain dimorphism in the SDN-POA without testosterone.
- MeSH
- area praeoptica * metabolismus MeSH
- chinpyrol farmakologie MeSH
- kastrace MeSH
- krysa rodu rattus MeSH
- mozek MeSH
- pohlavní dimorfismus * MeSH
- těhotenství MeSH
- testosteron farmakologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Endogenous neurosteroids (NS) and their synthetic analogs, neuroactive steroids (NAS), are potentially useful drug-like compounds affecting the pathophysiology of miscellaneous central nervous system disorders (e.g. Alzheimer ́s disease, epilepsy, depression, etc.). Additionally, NS have been shown to promote neuron viability and neurite outgrowth upon injury. The molecular, structural and physicochemical basis of the NS effect on neurons is so far not fully understood, and the development of new, biologically relevant assays is essential for their comparative analysis and for assessment of their mechanism of action. Here, we report the development of a novel, plate-based, high-content in vitro assay for screening of NS and newly synthesized, 5β-reduced NAS for the promotion of postnatal neuron survival and neurite growth using fluorescent, postnatal mixed cortical neuron cultures isolated from thy1-YFP transgenic mice. The screen allows a detailed time course analysis of different parameters, such as the number of neurons or neurite lengths of 7-day, in vitro neuron cultures. Using the screen, we identify a new NAS, compound 42, that promotes the survival and growth of postnatal neurons significantly better than several endogenous NS (dehydroepiandrosterone, progesterone, and allopregnanolone). Interestingly, we demonstrate that compound 42 also promotes the proliferation of glia (in particular oligodendrocytes) and that the glial function is critical for its neuron growth support. Computational analysis of the biological data and calculated physicochemical properties of tested NS and NAS demonstrated that their biological activity is proportional to their lipophilicity. Together, the screen proves useful for the selection of neuron-active NAS and the comparative evaluation of their biologically relevant structural and physicochemical features.
- MeSH
- myši transgenní MeSH
- myši MeSH
- neurity MeSH
- neurony MeSH
- neurosteroidy * MeSH
- oligodendroglie MeSH
- progesteron farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the study was to examine the potential impacts of bisphenol A (BPA) and its analogues BPB, BPF, and BPS on mice TM3 Leydig cells, with respect to basal cell viability parameters such as metabolic activity, cell membrane integrity, and lysosomal activity after 48-h exposure. In addition, monitoring of potential bisphenol ́s actions included evaluation of ROS production and gap junctional intercellular communication (GJIC) complemented by determination of testosterone secretion. Obtained results revealed significant inhibition in mitochondrial activity started at 10 microg/ml of bisphenols after 48-h exposure. Cell membrane integrity was significantly decreased at 5 microg/ml of BPA and BPF and 10, 25, and 50 microg/ml of BPA and BPS. The lysosomal activity was significantly affected at 10, 25, and 50 microg/ml of applied bisphenols. A significant overproduction of ROS was recorded mainly at 5 and 10 microg/ml of tested compounds. In addition, significant inhibition of GJIC was observed at 5 microg/ml of BPB followed by a progressive decline at higher applied doses. In the case of testosterone production, a significant decline was confirmed at 10, 25 and 50 microg/ml.
- MeSH
- benzhydrylové sloučeniny metabolismus MeSH
- endokrinní disruptory * farmakologie MeSH
- Leydigovy buňky * MeSH
- myši MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sulfony farmakologie MeSH
- testosteron metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Microtubule dynamic is exceptionally sensitive to modulation by small-molecule ligands. Our previous work presented the preparation of microtubule-targeting estradiol dimer (ED) with anticancer activity. In the present study, we explore the effect of selected linkers on the biological activity of the dimer. The linkers were designed as five-atom chains with carbon, nitrogen or oxygen in their centre. In addition, the central nitrogen was modified by a benzyl group with hydroxy or methoxy substituents and one derivative possessed an extended linker length. Thirteen new dimers were subjected to cytotoxicity assay and cell cycle profiling. Dimers containing linker with benzyl moiety substituted with one or more methoxy groups and longer branched ones were found inactive, whereas other structures had comparable efficacy as the original ED (e.g. D1 with IC50 = 1.53 μM). Cell cycle analysis and immunofluorescence proved the interference of dimers with microtubule assembly and mitosis. The proposed in silico model and calculated binding free energy by the MM-PBSA method were closely correlated with in vitro tubulin assembly assay.
- MeSH
- antitumorózní látky * chemie farmakologie MeSH
- apoptóza MeSH
- ethinylestradiol * chemie farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- mikrotubuly MeSH
- modulátory tubulinu * chemie farmakologie MeSH
- nádorové buněčné linie MeSH
- triazoly * chemie farmakologie MeSH
- tubulin * metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prevalence a incidence malignit v České republice i celosvětově roste. Pokroky v diagnstice a léčebných modalitách aplikovaných v oblasti onkologie během poslední dekády vedly k prodlou- žení celkového přežití pacientů s mnoha různými typy nádorů. V důsledku toho je zachování kvality života další důležitý problém onkologických pacientů. Sexuální problémy u onkologických pacientů mohou pramenit z poškození libida, vzrušivosti, orgasmu a ejakulace, sexuální satisfakce a bolesti. Karcinom prostaty, močového měchýře a kolorektální karcinom představují nejčastější malignity, které jsou diagnostikovány u mužů ve středním věku, kteří na sexualitu po prodělané léčbě nerezignují. Součástí konzultace s pacientem před započetím komplexní léčby by proto mělo být seznámení s rizikem vzniku sexuálních dysfunkcí, modalitami léčby a s možností penilní rehabilitace.
The prevalence and incidence of malignancies in the Czech Republic is increasing. Advances in the diagnosis and treatment modalities applied in the field of oncology during the last decade have led to an increase in the overall survival of patients with many different types of tumors. As a result, maintaining quality of life is another important issue for oncology patients. Sexual problems in oncology patients can stem from impairment of libido, arousal, orgasm and ejaculation, sexual satisfaction and pain. Prostate, bladder and colorectal cancer are the most common malignancies that are diagnosed in middle-aged men who do not renounce their sexuality after undergoing treatment. The consultation with the patient before starting complex treatment should therefore include familiarization with the risk of sexual dysfunctions, treatment modalities and the possibility of penile rehabilitation.
- MeSH
- antagonisté androgenů škodlivé účinky terapeutické užití MeSH
- erektilní dysfunkce diagnóza etiologie terapie MeSH
- lidé MeSH
- nádory mužských pohlavních orgánů * chirurgie psychologie terapie MeSH
- sexuální dysfunkce fyziologická * etiologie patologie MeSH
- sexuální dysfunkce psychické etiologie patologie MeSH
- testosteron nedostatek MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- přehledy MeSH
The precise method of action of dienogest on the production and development of endometriosis lesions is unknown, and its controversial effect on endometrial thickness has been under investigation. In the following study the Dienogest's effects on the target animal's histology of female reproductive organs, including the tissues from the Fallopian tubes, ovaries, and uterus, as well as the impact of drug administration on the liver's enzymes and the drug's effects on triglycerides, body weight, and HbA1c, have all been studied. The findings of the following experiment indicated that there was no significant elevation of liver enzymes. The little to no elevation of the liver enzymes indicated that the drug did not induce stress on the hepatic cells and according to the subsequent experiment it is safe for clinical use. Moreover, after 10, 20, and 30 days of blood administration, the level of blood TG significantly decreased, and after 30 days of intake, the level of blood sugar significantly decreased. However, there were no appreciable changes after 10 and 20 days. After 30 days of treatment, the rats' weight also showed a very minor drop. In addition to it, the results of histological changes in the tissue in the following study represented that there were evident changes in the tissues which comprised of decline in blood circulation, fibrosis in tissues, and degeneration of follicles.
- Klíčová slova
- dienogest,
- MeSH
- histologické techniky MeSH
- jaterní testy metody přístrojové vybavení MeSH
- játra enzymologie účinky léků MeSH
- kontraceptiva * farmakologie krev metabolismus MeSH
- modely u zvířat MeSH
- potkani Sprague-Dawley MeSH
- progesteron farmakologie krev metabolismus MeSH
- statistika jako téma MeSH
- transaminasy analýza krev účinky léků MeSH
- ženské pohlavní orgány * patologie účinky léků MeSH
- Check Tag
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
Hlavní léčbou primárního hypogonadismu je substituce testosteronu. V urologické ambulantní praxi se nejčastěji setkáváme s pozdním nástupem hypogonadismu v souvislosti se stárnutím mužů. A právě s ohledem na věk pacientů a jejich komorbidity je zásadní znalost správné diagnostiky, indikace a forem léčby. Cílem je zmírnění příznaků hypogonadismu při zachování maximální bezpečnosti a omezení nežádoucích účinků léčby.
The main treatment for primary hypogonadism is testosterone replacement therapy. In urological outpatient practice, we often consult men with late onset hypogonadism due to aging. Regarding patients age and comorbidities knowledge of correct diagnostics, indications and forms of treatment is essential. The goal is torelive the symptoms of hypogonadism while maintaining maximal safety and minimalising the adverse effects of the treatment. The article summarizes knowledge about the physiological effect of testosterone, the benefits and risks of its substitution.
- Klíčová slova
- syndrom mužského stárnutí,
- MeSH
- diferenciální diagnóza MeSH
- hormonální substituční terapie * škodlivé účinky MeSH
- hypogonadismus diagnóza farmakoterapie klasifikace MeSH
- lidé MeSH
- rizikové faktory MeSH
- testosteron * nedostatek škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- přehledy MeSH
