Tehotenstvo a popôrodné obdobie sa spája s náročnými fyzickými a psychickými zmenami, ktoré neraz vedú k rozvoju psychických porúch. Depresia je diagnostikovaná u viac ako jednej zo šiestich žien po pôrode. Prevalencia popôrodnej depresie však môže byť oveľa vyššia, pretože mnohé prípady ochorenia ostávajú nediagnostikované. V prípade ťažkých foriem depresie sa pacientka nastavuje na farmakologickú liečbu, pričom najčastejšie sa u tejto diagnózy využíva sertralín. Novým liečivom používaným v terapii popôrodnej depresie je brexanolón, ktorý bol registrovaný FDA v roku 2019. Jeho výhodou oproti konvenčnej liečbe je rýchly nástup účinku. Štruktúra brexanolónu predstavuje neuroaktívny steroid – allopregnanolón, ktorý pôsobí agonisticky na δ-podjednotku GABA-A receptora a zlepšuje symptómy popôrodnej depresie. Okrem registrovaného brexanolónu sa v 3. fáze klinického skúšania nachádza aj ďalšie steroidné liečivo zuranolón v perorálnej liekovej forme. Iný syntetický analóg neuroaktívneho allopregnanolónu, známy ako ganaxolón, v druhej fáze klinického skúšania nepreukázal výrazné zlepšenie depresívnych symptómov oproti placebu. Napriek tomu má veľký terapeutický potenciál v liečbe rôznych typov epilepsie.
Pregnancy and postpartum period are associated with demanding physical and psychological changes that often lead to the development of psychological disorders. Depression is diagnosed in more than one in six women after childbirth. However, the prevalence of postpartum depression can be much higher because many cases are undiagnosed. In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis. A new drug used in the treatment of postpartum depression is brexanolone, which was registered by FDA in 2019. The advantage over conventional therapy is its rapid onset of action. The structure represents the neuroactive steroid – allopregnanolone, which acts as an agonist on the δ-subunit of the GABA receptor and improves the symptoms of postpartum depression. In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial. The steroid structure was chemically altered to improve bioavailability and create an oral dosage form. Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.
- Klíčová slova
- brexanolón, zuranolón, ganaxolón,
- MeSH
- lidé MeSH
- neurosteroidy * farmakologie terapeutické užití MeSH
- poporodní deprese * etiologie farmakoterapie psychologie MeSH
- poporodní období psychologie MeSH
- pregnanolon analogy a deriváty antagonisté a inhibitory terapeutické užití MeSH
- pregnany aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
Stem cells represent promising candidates for regenerative therapy of craniomaxillofacial bone defects, where common techniques, such as autogenous bone graft, allografts or others possess shortcomings and limitations in restoring the morphology and function in bone loss. The efficacy of regenerative therapy with mesenchymal stromal cells (MSC) depends on a combination of the interactions between transplanted MSCs and cellular and molecular components of the recipient, and any current pharmacotherapy in the recipient with effects on transplanted MSC and the bone microenvironment. In the present investigation, dental pulp stem cells (DPSC) were isolated from human impacted third molar teeth. DPSC were treated with ibuprofen in vitro at clinically relevant concentration and relative expression of selected genes were assessed. Our preliminary data suggest a significant effect of ibuprofen as indicated by upregulation of the relative expression levels of growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). While the effects of stem cell therapy in bone regeneration are being investigated in ongoing clinical trials, the effects of commonly used pharmacotherapy should be studied for its potential impact on the paracrine effects of stem cells and consequently bone regenerative processes.
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- exprese genu MeSH
- hepatocytární růstový faktor MeSH
- ibuprofen * terapeutické užití MeSH
- kmenové buňky MeSH
- lebka patologie MeSH
- lidé MeSH
- mezenchymální kmenové buňky * MeSH
- nemoci kostí farmakoterapie terapie MeSH
- parakrinní signalizace MeSH
- polymerázová řetězová reakce MeSH
- regenerativní lékařství metody MeSH
- techniky in vitro metody MeSH
- vaskulární endoteliální růstový faktor A MeSH
- Check Tag
- lidé MeSH
Metformin (MTF) is a widely used drug for the treatment of diabetes mellitus type 2 (DM2) and frequently used as an adjuvant therapy for polycystic ovarian syndrome, metabolic syndrome, and in some cases also tuberculosis. Its protective effect on the cardiovascular system has also been described. Recently, MTF was subjected to various analyzes and studies that showed its beneficial effects in cancer treatment such as reducing cancer cell proliferation, reducing tumor growth, inducing apoptosis, reducing cancer risk in diabetic patients, or reducing likelihood of relapse. One of the MTF's mechanisms of action is the activation of adenosine-monophosphate-activated protein kinase (AMPK). Several studies have shown that AMPK/mammalian target of rapamycin (mTOR) pathway has anticancer effect in vivo and in vitro. The aim of this review is to present the anticancer activity of MTF highlighting the importance of the AMPK/mTOR pathway in the cancer process.
- MeSH
- antitumorózní látky škodlivé účinky terapeutické užití MeSH
- apoptóza účinky léků MeSH
- hypoglykemika terapeutické užití MeSH
- lidé MeSH
- metformin škodlivé účinky terapeutické užití MeSH
- nádory farmakoterapie enzymologie patologie MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- proteinkinasy aktivované AMP metabolismus MeSH
- signální transdukce MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.
- MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- fyziologická neovaskularizace MeSH
- ischemie metabolismus terapie MeSH
- kinázy asociované s rho metabolismus MeSH
- lidé MeSH
- mezenchymální kmenové buňky metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- oxidační stres MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The randomized trials showed that the addition of training resistance program to androgen-deprivation therapy (ADT) had many beneficial effects for prostate cancer (PC) patients (significant protective effect on the volume of muscle mass) and the studies have revealed a panel of miRNAs, which are deregulate in PC and may serve as promising biomarkers of PC risk. The primary aim of our present study was to investigate the effect of exercise training to changes in body composition (muscle strength) and the secondary endpoint was to investigate the impact of an exercise training program on plasma levels of selected myogenic microRNAs (miRNAs) (miRNA-1, miRNA-29b, and miRNA-133) in PC patients undergoing the ADT. Effect of ADT and exercise intervention showed significant increase (experimental group vs. control group) the changes in body composition, free testosterone levels, IL-6 and plasma levels of myogenic miRNAs and significant reduced insulin serum levels. In conclusion, resistance training with ADT in the treatment of PC significantly changed the physical and metabolic function and the plasma levels of specific myogenic miRNAs. Our data support with the other publicized results.
- MeSH
- antagonisté androgenů terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA krev MeSH
- nádory prostaty krev terapie MeSH
- odporový trénink * MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
