Chem. Listy 2022; 116: 101−109. doi: 10.54779/ chl20220101 vladimir.pliska@biol.ethz.ch, parizek@porodnice.cz Došlo 12. 10. 2021, přijato 1. 11. 2021.

Abstract: Licence agreements between the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague (IOCB), and the pharmaceutical company Ferring AB Malmö enabled the Swedish company to produce and commercialize worldwide a number of neurohypophyseal peptides designed at the IOCB. Several of them found therapeutic applications. dDAVP: 1-deamino-8-D-arginine-vasopressin was designed in one of the IOCB peptide laboratories (M. Zaoral and F. Šorm) in 1967. It displayed an extremely high antidiuretic activity (various tests indicate a 2- to 50-fold increase, as compared to arginine vasopressin) and a very low pressor activity. The peptide (covered by the U.S. Patent No. 3,497,491, 1970) has been used as a preferred drug in the substitution therapy of the central form of diabetes insipidus (Minirin®, today as Desmopressin INN). Besides, as later discovered (Mannucci et al. 1977), dDAVP increases the plasma concentration of the blood clottiing factor VIII. This fact extended its clinical use as haemostatics in cases of milder forms of haemophilia A, von Willebrand-Jürgens syndrome and some thrombocyte dysfunctions. Despite of the clinical success of dDAVP, a closer look reveals certain inadequacies in the presently available pharmacological data: several reports declare activity values and the prolongation effect (index of persistence) in very broad ranges. Triglycyl-8- -lysine-vasopressin (Terlipressin), a peptide with lysine vasopressin chain extended at the N-terminal by a triglycine residue, acts mainly as a prodrug (releasing lysine vasopressin after aminopeptidase splitting at the Na group). The analogue belongs to the so-called „synthetic hormonogens“; individual peptides carrying various acylating groups were synthesized in the midsixties at the IOCB and legally protected by U.S. Patent No. 3,558,590 (1968). It was a part of the licence agreements mentioned above. The activities of triglycyl-8-lysine-vasopressin (both antidiuretic and vasopressor) are about 100 times lower than those of lysine vasopressin, but its persistence is 5 times longer. As such, it is occasionally used in emergency medicine in cases of esophageal (and other gastroenteral) bleeding, traumatic or septic shock, in cirrhotic patients and patients with portal hypertension. Its use as an early abortion drug was discussed but not pursued. Carbetocin (deaminocarba1-2-O-methyltyrosin-oxytocin) was synthetized in the laboratory of Karel Jošt at the IOCB before 1971; its synthesis was covered by a Czechoslovak patent (CS-149,028 B1) in June 1973 (at that time, Czechoslovak patent law did not provide for the patentability of substances as such) and first published in a biophysical communication by Frič et al., 1974). As a part of the licence agreement, it was included in the production program of Ferring AB, but marketed later also by several other pharmaceutical companies due to an incomplete patent protection. The peptide is a moderately active uterotonic partial agonist and as such has been utilized in veterinary obstetrics for delivery induction in cows and (multiparous) pigs: its milder and better--controlled uterotonic action was found preferential as compared to oxytocin so far used for these purposes. In the last two decades, carbetocin has been commonly used also in the human obstetrics, especially to prevent the peri- and post-partum haemorrhage, from the maternal side the most frequent and most severe delivery complication. It became a life-saving drug in emergency obstetrics.

Cíl: Cílem studie byla analýza vlivu pandemie covidu-19 na epidemiologickou situaci invazivního meningokokového onemocnění (IMO) a na molekulární charakteristiky izolátů Neisseria meningitidis způsobujících IMO v České republice. Materiál a metody: Studie vycházela z dat surveillance IMO za období 2018–2024 (k 27. 5. 2024) a analyzovány celogenomovou sekvenací (WGS) byly všechny dostupné izoláty N. meningitidis z IMO z těchto let. Pro analýzu vlivu pandemie covidu-19 bylo sledované období rozděleno na tři srovnávané etapy: pre-covidové období (2018–2019), období pandemie covidu-19 (2020–2022) a post-covidové období (2023–2024). Výsledky: V důsledku zavedení epidemiologických opatření proti pandemii covidu-19 došlo v České republice, podobně jako v ostatních zemích, k poklesu počtu infekčních onemocnění přenášených vzdušnou cestou, včetně IMO. Po uvolnění těchto epidemiologických opatření však nedošlo v České republice k opětnému vzestupu počtu IMO, na rozdíl od řady jiných zemí. Charakterizace izolátů z IMO metodou WGS prokázala, že v průběhu covidového a post-covidového období došlo k postupné změně populace meningokoků, které v České republice působí IMO. U izolátů N. meningitidis séroskupin C, W a Y lze sledovat postupný a výrazný pokles celkové heterogenity – z deseti různých klonálních komplexů zachycených v pre-covidovém období na pouhé tři v post-covidových letech (cc11, cc23 a cc103). Zároveň byla zjištěna významná redukce izolátů N. meningitidis C; cc11. U izolátů N. meningitidis B lze naopak pozorovat nárůst celkové heterogenity během období pandemie covidu-19 a její opětovnou redukci na celkově nejnižší hodnoty v post-covidovém období. Závěr: V přetrvávajícím poklesu počtu IMO v České republice má roli i zavedení úhrady očkování MenB vakcínou a konjugovanou vakcínou A, C, W, Y pro malé děti (v květnu 2020) a pro adolescenty (v lednu 2022). K udržení nízkých počtů IMO v České republice je žádoucí pokračovat v očkování MenB vakcínou a konjugovanou vakcínou A, C, W, Y dle doporučení České vakcinologické společnosti ČLS JEP.

Objective: To analyse the impact of the COVID-19 pandemic on the epidemiological situation of invasive meningococcal disease (IMD) and molecular characteristics of Neisseria meningitidis isolates causing IMD in the Czech Republic. Material and Methods: The study was based on IMD surveillance data for 2018–2024 (as of 27 May 2024), and all available N. meningitidis isolates from IMD of these years were subjected to whole genome sequencing (WGS). To analyse the impact of the COVID-19 pandemic, the study period was divided into three parts: the pre-COVID period (2018–2019), the COVID-19 pandemic period (2020–2022), and the post-COVID period (2023–2024). Results: As a result of the implementation of the COVID-19 control measures, similar to other countries, there has been a decline in the incidence of air-borne infections including IMD in the Czech Republic. However, unlike many other countries, there has not been a resurgence of IMD in the Czech Republic following the release of these epidemiological measures. WGS characterisation of IMD isolates showed a gradual change in the population of meningococci causing IMD in the Czech Republic during the COVID-19 and post-COVID periods. For N. meningitidis isolates of serogroups C, W, and Y, a gradual and significant decline in overall heterogeneity can be observed – from ten different clonal complexes detected in the pre-COVID period to only three in the post-COVID years (cc11, cc23, and cc103). At the same time, a significant reduction was observed in N. meningitidis C isolates; cc11. In contrast, an increase in overall heterogeneity can be observed for N. meningitidis B isolates during the COVID-19 pandemic period, followed by its decline again to overall lowest values in the post-COVID period. Conclusion: The fact that MenB vaccine and conjugate vaccine A, C, W, Y started to be covered by health insurance for young children (in May 2020) and adolescents (in January 2022) also appears to play a role in the persistent decline of IMD in the Czech Republic. In order to maintain the low incidence of IMD in the Czech Republic, it is desirable to continue vaccination with MenB vaccine and conjugated vaccine A, C, W, Y in accordance with the recommendations of the Czech Society of Vaccinology of the Czech Medical Association of Jan Evangelista Purkyně.

• MeSH
• COVID-19 epidemiologie   MeSH
• lidé MeSH
• meningokokové infekce epidemiologie   MeSH
• Neisseria meningitidis * genetika   MeSH
• pandemie MeSH
• sekvenční analýza * MeSH
• vakcinace statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Akromegália je raritné endokrinologické ochorenie charakterizované nadprodukciou rastového hormónu (RH), najčastej- šie na podklade adenómu hypofýzy s následnou zvýšenou produkciou inzulínu podobného rastového faktora 1 (IGF-1) v pečeni. Účinky RH a IGF-1 na metabolizmus glukózy sú antagonistické; RH vyvoláva inzulínovú rezistenciu, zatiaľ čo IGF-1 zvyšuje inzulínovú citlivosť. Avšak inzulín-antagonizujúci účinok RH prevyšuje inzulín-senzitizujúci účinok IGF-1 v cieľových tkanivách, čo vedie k vzniku diabetes mellitus (DM) pri akromegálii. Sekundárny DM je častou komplikáciou u pacientov s akromegáliou. DM môže byť prvým prejavom ochorenia, pretože hyperglykémia spôsobená inzulínovou rezistenciou býva často významná. Diagnostika a liečba DM u pacientov s akromegáliou je komplexná a vyžaduje multidisciplinárny prístup, ktorý zahŕňa endokrinológov, diabetológov a ďalších špecialistov. Účinná kontrola akromegálie prostredníctvom chirurgického zákroku, farmakoterapie alebo rádioterapie môže zlepšiť glukózovú homeostázu a znížiť riziko komplikácií spojených s DM. Uvedený prehľadový článok sa zaoberá patofyziologickými a klinickými zvláštnosťami DM u pacientov s akromegáliou, ako aj potenciálnymi účinkami špecifickej liečby akromegálie na glukózovú homeostázu.

Acromegaly is a rare endocrine disorder characterized by the overproduction of growth hormone (GH), most commonly due to a pituitary adenoma, leading to increased production of insulin-like growth factor 1 (IGF-1) in the liver. The effects of GH and IGF-1 on glucose metabolism are antagonistic; GH induces insulin resistance, while IGF-1 enhances insulin sensitivity. However, the insulin-antagonizing effect of GH outweighs the insulin-sensitizing effect of IGF-1 in target tissues, leading to the development of diabetes mellitus (DM) in acromegaly.Secondary DM is a frequent complication in patients with acromegaly. In fact, DM may be the first manifestation of the disease, because hyperglycemia caused by insulin resistance is often significant. The diagnosis and management of DM in patients with acromegaly are complex and require a multidisciplinary approach involving endocrinologists, diabetologists, and other specialists. Effective control of acromegaly through surgery, pharmacotherapy, or radiotherapy can improve glucose homeostasis and reduce the risk of complications associated with DM. This review article discusses the pathophysiological and clinical characteristics of DM in patients with acromegaly, as well as the potential effects of specific acromegaly treatments on glucose homeostasis.

• MeSH
• akromegalie * diagnóza   etiologie   farmakoterapie   MeSH
• diabetes mellitus etiologie   MeSH
• dopamin analogy a deriváty   MeSH
• glukosa metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• růstový hormon analogy a deriváty   krev   MeSH
• selfmonitoring glykemie MeSH
• somatostatin analogy a deriváty   MeSH
• Check Tag
• lidé MeSH

Aim: To present on video our current most used technique of robot-assisted resection of renal tumour (RR). Material: We performed 274 RRs between June 2020 and November 2024. Our technique is based on a modification of conventional laparoscopic renal resection, of which we performed 599 between August 2004 and May 2020. RRs currently account for over one third of the surgical procedures for kidney cancer at our institution. Laparoscopic (rarely robotic assisted) nephrectomy is almost as frequent. Open resection accounts for about 17% and open nephrectomy for slightly less. Open resections are mainly indicated for more complex tumours, for tumors with significant \"toxic\" fat capsule, and when combined with other procedures, mostly for intestinal malignancies. RR is routinely performed by two console surgeons, occasionally by two additional ones. Operation technique: General anaesthesia. Optional urinary catheter inserted. Lateral position 60-70°. Upper limbs extended in front, close together. Operative field prepared for eventual lumbotomy. Transperitoneal approach. The capnoperitoneum is created with a Veres needle, CO2 pressure 12 mmHg. Assist port 12 mm slightly lateral to the umbilicus. Four 8-mm robotic ports are inserted pararectally under visual control. Four-arm daVinci Xi robotic system is inserted. Ports craniocaudally: 1. ProGrasp, 2. bipolar grasper (bipolar forceps Maryland or more often fenestrated) or monopolar curved scissors (Hot shears) according to the operated side and the dominant hand of the operator, 3. camera 30°, 4. the second of the mentioned instruments from port 2. The scissors are alternated with a needle driver, usually the Large SutureCut needle driver. In the Toldt line, the peritoneum is opened, the colon is retracted medially, and the Gerota fascia is opened medially from the kidney. The necessary part of the kidney is dissected from the fat capsule for good access to the tumour. The tumour is verified sonographically with a drop-in probe inserted through the assistant port. Scissors can be used to mark the line of resection on the kidney. The ureter is verified and the hilar vessels are released. The artery(s) or necessary branch is bypassed with tubing and clamped with the SCANLAN® robotic endo-bulldog. Only in central tumours is the vein also clamped. Knowledge of the topographic anatomy of the vessels from two-phase CT angiography is very helpful at this stage. The effectiveness of ischemia is verified by Doppler; exceptionally (especially in selective clamping of the artery branches) by NIR imaging with FireFly® with administration of indocyanine green - Verdye® 1.25-2.5 mg. The tumour is resected with cold scissors with a rim of healthy tissue. Suturing of the base is performed with an absorbable self-anchoring barbed suture (V-Loc® 90, size 3-0, 1/2 needle 26 mm). The edges of the kidney are mattress sutured with another suture, tightened with Absolok® AP300 absorbable clips (polydioxanone PDS, size ML) - \"sliding clips\" technique. The second layer of the parenchyma is sewn with simple continuation stitches, mostly without continuous anchoring. For more superficial tumours, a straight suture of the parenchyma is

• MeSH
• laparoskopie MeSH
• lidé MeSH
• nádory ledvin * chirurgie   MeSH
• nefrektomie MeSH
• roboticky asistované výkony metody   MeSH
• Check Tag
• lidé MeSH

Screening for tuberculosis infections (TBI) using the tuberculin skin test or interferon-gamma release assays (IGRA) is crucial in controlling the global TB burden. This study evaluates the performance of a new IGRA for the detection of T-cell responses against Mycobacterium tuberculosis. Blood samples from 34 adults with tuberculosis disease (TB) and from 30 children with TB, TBI or without TB were analyzed using the prototype Quan-T-Cell TB (EUROIMMUN). The pediatric samples were additionally measured using the established QuantiFERON-TB Gold Plus assay (Qiagen). Clinical performance and inter-assay concordance were analyzed. The prototype Quan-T-Cell TB yielded positivity rates of 88.2% and 100% in adults with TB and children with TBI, respectively, at a specificity of 93.8%. Comparison between the two IGRAs showed positive, negative and overall agreement rates of 100%, 93.8% and 96.3%, respectively, with a kappa score of 0.924 indicating almost perfect agreement. Our study shows promising results of the new prototype Quan-T-Cell TB, as reflected by high concordance with the final diagnosis in adults and children and performance comparable to that of the QuantiFERON IGRA. In individual cases, the data suggest that the prototype Quan-T-Cell TB may be even more consistent with TBI-related clinical findings. Unlike the QuantiFERON assay, the Quan-T-Cell TB has a predefined borderline range, which is advantageous as it may help to differentiate non-specific variation near the cut-off, and fewer sample tubes are required per analysis. The new Quan-T-Cell TB may therefore be a good alternative to the established QuantiFERON IGRA for TBI screening. Further assay optimization is underway, including evaluation studies based on larger patient and control cohorts.

• MeSH
• dítě MeSH
• dospělí MeSH
• interferon gama MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Mycobacterium tuberculosis * imunologie   MeSH
• předškolní dítě MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• T-lymfocyty * imunologie   MeSH
• test pomocí interferonu gama * metody   MeSH
• tuberkulóza * diagnóza   imunologie   mikrobiologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Miera obezity sa z roka na rok alarmujúco zvyšuje. Je veľmi dobre známe, že (pre)obezita jednak zhoršuje tradičné kardiovaskulárne (KV) rizikové faktory, ale je tiež aj nezávislým KV-rizikovým faktorom, čo následne nepriamo zvyšuje KV-riziko. Mechanizmy, ktoré vedú k rozvoju kardiovaskulárnych ochorení (KVO), sú mnohopočetné a nie úplne pochopené. Dôkazy však spájajú obezitu a chronický subklinický zápal, ktorý uľahčuje rozvoj aterosklerózou podmieneného kardiovaskulárneho ochorenia (ASKVO). Morbiditu a mortalitu na KVO (pre)obezita zvyšuje prostredníctvom priamych a nepriamych mechanizmov. Naopak, redukcia telesnej hmotnosti (TH) je spojená s významnými zdravotnými benefitmi a v súčasnosti máme dôkazy, že výraznejší úbytok TH vedie k výraznejším (nielen) kardiometabolickým benefitom. Manažment jedincov s (pre)obezitou sa v súčasnosti veľmi rýchlo mení vďaka novinkám prichádzajúcim do klinickej praxe. Pokiaľ chceme zlepšiť KV-morbiditu a KV- mortalitu u pacientov s (pre)obezitou, musíme si uvedomiť, že intervencia musí byť včasná, razantná a dlhodobá. Našim cieľom je dosiahnuť nielen bezpečnú, efektívnu a udržateľnú redukciu TH, ktorá bude viesť k zníženiu prevalencie komorbidít súvisiach s obezitou, ale najmä k poklesu KV-morbidity a KV-mortality.

Obesity rates are increasing alarmingly year by year. It is well known that (pre)obesity exacerbates traditional cardiovascular risk factors and is also an independent cardiovascular risk factor, which in turn indirectly increases cardiovascular risk. The mechanisms that lead to the development of cardiovascular disease are multiple and not fully understood. However, evidence links obesity and chronic subclinical inflammation, which facilitates the development of atherosclerotic cardiovascular disease. (Pre)obesity increases morbidity and mortality from cardiovascular disease through direct and indirect mechanisms. Conversely, weight reduction is associated with significant health benefits and we now have evidence that more significant weight loss leads to more significant (not only) cardiometabolic benefits. The management of individuals with (pre)obesity is currently changing very rapidly due to new pharmacotherapies coming into clinical practice. If we want to improve cardiovascular morbidity and mortality in patients with (pre)obesity, we have to realize that the intervention must be early, vigorous and long-term. Our goal is to achieve not only safe, effective and sustainable weight reduction, which will lead to a decrease in the prevalence of obesity related comorbidities, but especially to a decrease in cardiovascular morbidity and mortality.

• MeSH
• hmotnostní úbytek účinky léků   MeSH
• kardiovaskulární nemoci * komplikace   mortalita   patofyziologie   terapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• liraglutid aplikace a dávkování   MeSH
• obezita * farmakoterapie   komplikace   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• žaludeční inhibiční polypeptid terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing. Here, a functional and biocompatible wound dressing is developed to enable a controlled release of a traceable vector loaded with the antisense siRNA against MMP-9 in the wound. The dressing consists of degradable polymer nanofibers embedded with a vector nanosystem - polymer-coated fluorescent nanodiamonds optimized for the binding of siRNA and colloidal stability of nanodiamond-siRNA complexes in a physiological environment. The developed dressing is tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy, and handling. The treatment results in significant local inhibition of MMP-9 and a shortening of the wound healing time. The scar formation in treated diabetic-like mice becomes comparable with that in non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach to gene therapy of non-healing wounds.

• MeSH
• aplikace lokální MeSH
• experimentální diabetes mellitus * chemicky indukované   MeSH
• hojení ran * účinky léků   MeSH
• malá interferující RNA * chemie   MeSH
• matrixová metaloproteinasa 9 * metabolismus   MeSH
• myši MeSH
• obvazy MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The use of nanoparticles as a delivery system for a specific antigen could solve many limitations of mucosal vaccine applications, such as low immunogenicity, or antigen protection and stabilization. In this study, we tested the ability of nasally administered chitosan nanoparticles loaded with glycoprotein B of murine cytomegalovirus to induce an immune response in an animal model. The choice of chitosan nanoparticle type was made by in vitro evaluation of sorption efficiency and antigen release. Three types of chitosan nanoparticles were prepared: crosslinked with tripolyphosphate, coated with hyaluronic acid, and in complex with polycaprolactone. The hydrodynamic size of the nanoparticles by dynamic light scattering, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, stability, loading efficiency, and release kinetics with ovalbumin were evaluated. Balb/c mice were immunized intranasally using the three-dose protocol with nanoparticles, gB, and adjuvants Poly(I:C) and CpG ODN. Subsequently, the humoral and cell-mediated antigen-specific immune response was determined. On the basis of the properties of the tested nanoparticles, the cross-linked nanoparticles were considered optimal for further investigation. The results show that nanoparticles with Poly(I:C) and with gB alone raised IgG antibody levels above the negative control. In the case of mucosal IgA, only gB alone weakly induced the production of IgA antibodies compared to saline-immunized mice. The number of activated cells increased slightly in mice immunized with nanoparticles and gB compared to those immunized with gB alone or to negative control. The results demonstrated that chitosan nanoparticles could have potential in the development of mucosal vaccines.

• MeSH
• adjuvancia imunologická MeSH
• aplikace intranazální MeSH
• chitosan * chemie   MeSH
• glykoproteiny MeSH
• imunizace MeSH
• imunoglobulin A MeSH
• Muromegalovirus * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• slizniční imunita MeSH
• vakcíny * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• akrylové pryskyřice * chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• hydrogely * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• lékové transportní systémy MeSH
• léky s prodlouženým účinkem chemie   farmakokinetika   MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• poloxamer * chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• termogravimetrie MeSH
• timolol * aplikace a dávkování   farmakokinetika   chemie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hypothalamic Adult Neurogenesis (hAN) has been implicated in regulating energy homeostasis. Adult-generated neurons and adult Neural Stem Cells (aNSCs) in the hypothalamus control food intake and body weight. Conversely, diet-induced obesity (DIO) by high fat diets (HFD) exerts adverse influence on hAN. However, the effects of anti-obesity compounds on hAN are not known. To address this, we administered a lipidized analogue of an anti-obesity neuropeptide, Prolactin Releasing Peptide (PrRP), so-called LiPR, to mice. In the HFD context, LiPR rescued the survival of adult-born hypothalamic neurons and increased the number of aNSCs by reducing their activation. LiPR also rescued the reduction of immature hippocampal neurons and modulated calcium dynamics in iPSC-derived human neurons. In addition, some of these neurogenic effects were exerted by another anti-obesity compound, Liraglutide. These results show for the first time that anti-obesity neuropeptides influence adult neurogenesis and suggest that the neurogenic process can serve as a target of anti-obesity pharmacotherapy.

• MeSH
• hormon uvolňující prolaktin farmakologie   terapeutické užití   MeSH
• hypothalamus MeSH
• lidé MeSH
• myši MeSH
• neurogeneze MeSH
• neuropeptidy * MeSH
• obezita * farmakoterapie   MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH