Úvod: V důsledku metabolických dějů dochází v živých strukturách k endogenní produkci chemiluminiscence, kterou také označujeme jako biologickou autochemiluminiscenci (BAL). Generování BAL je úzce spojeno s oxidačními procesy, tvorbou volných radikálů a obecně oxidačně-redukční homeostázou zkoumaného biologického materiálu. BAL byla již dříve studována v savčích buněčných modelech a tkáních. Doposud ovšem nebyl tento jev popsán v případě struktur zubní tkáně. Kromě endogenně generované BAL lze BAL indukovat i exogenně, a to jak fyzikálními (UV záření, mechanické poškození, teplo), tak i chemickými (oxidační činidla, např. H2O2) a biotickými (patogeny) faktory. Metodika: V předložené práci byla zkoumána endogenně produkovaná i exogenně indukovaná BAL v povrchových a vnitřních strukturách semiretinovaných a retinovaných třetích molárů, které byly indikovány k extrakci zubním lékařem pro jejich nevhodné uložení v čelisti u dvou pacientů (žena, 21 let, muž, 22 let). Detekce BAL byla provedena po mechanickém odstranění zubního plaku rotačním kartáčkem. Pomocí piezoelektrické pily byly připraveny podélné řezy vedené tak, aby došlo k odhalení všech vnitřních částí zubu. Takto připravené vzorky – celého vnitřního řezu a vnější části celého zubu – byly podrobeny detekci BAL ve světlotěsné komoře za použití fotonásobičového modulu. Následně byly vzorky ošetřeny roztokem oxidačního činidla 3% H2O2 a redukčního činidla 10 mM TCEP (tris(karboxyethyl)fosfin). Výsledky: U obou vzorků zubu bylo prokázáno, že produkují BAL. Produkce endogenní chemiluminiscence byla pozorována ve vnitřních strukturách zubu (18 600 pulzů/600 s), která byla přibližně 2,7krát vyšší než BAL detekovaná na povrchových strukturách zubu (6 900 pulzů/600 s). Po ošetření H2O2 došlo k významnému (až 14násobnému) nárůstu BAL pro vnitřní struktury zubu ve srovnání s bazální intenzitou endogenně produkované BAL. Aplikace TCEP (negativní kontrola) vedla k mírnému potlačení produkce BAL. Závěr: Výsledky této pilotní studie ukazují, že BAL může být produkována nejenom měkkými tkáněmi, ale i tvrdou zubní tkání. Získané výsledky by mohly být využity k výzkumu metabolické aktivity a reaktivity vnitřních i vnějších částí zubu, a to především v kontextu výzkumu oxidačněredukční homeostázy. Detekce BAL by také mohla být aplikována pro vývoj nových zobrazovacích technik.

Introduction: As a result of metabolic processes, the endogenous production of chemiluminescence occurs in living biological structures, which we also refer to as biological autochemiluminescence (BAL). The generation of BAL is closely connected with oxidation processes, the formation of free radicals, and in general the redox homeostasis of the investigated biological material. BAL has previously been studied in mammalian cells and tissues. So far, however, this phenomenon has not been described in dental tissue structures. In addition to endogenously generated BAL, BAL can be exogenously induced by physical (UV radiation, mechanical damage, heat), chemical (oxidizing agents, e.g. H2O2) or biotic (pathogens) factors. Methods: Endogenously and exogenously induced BAL were investigated on the surface and internal structures of semi-impacted and impacted third molars, which were indicated for extraction by a dentist due to their inappropriate placement in the jaw in two patients (a 21-year-old woman and a 22-year-old man). BAL detection was performed with samples after dental plaque was mechanically removed with a rotating brush. Using a piezosurgery unit with a saw headpiece, longitudinal sections were made to reveal all internal parts of the tooth. The samples prepared in this way – the entire internal section and the external part of the entire tooth – were subjected to BAL detection in a dark chamber using H7360-01 PMT photomultiplier. Subsequently, the samples were treated with a solution of the oxidizing agent 3% H2O2 or the reducing agent 10 mM TCEP (tris(carboxyethyl)phosphine). Results: Both tooth samples were shown to produce BAL. Endogenous chemiluminescence production was observed in the internal structures of the tooth (18,600 counts/600 s), which was 2.7-fold higher than the BAL detected on the tooth outer surfaces (6,900 counts/600 s). After H2O2 treatment, there was a significant (up to 14-fold) increase in BAL for internal tooth structures compared to the basal intensity of endogenously produced BAL. The application of TCEP (negative control) resulted in a residual suppression of BAL production. Conclusion: The results of this pilot study show that BAL can be produced not only by soft tissues but also by hard dental tissue. The obtained results could be used for further research of the metabolic activity and reactivity of the inner and outer parts of the tooth, especially in the context of redox biology research. BAL detection could also be applied in the development of new imaging techniques.

• MeSH
• lidé MeSH
• luminiscence * MeSH
• luminiscenční měření MeSH
• moláry MeSH
• oxidační stres MeSH
• peroxid vodíku chemie   MeSH
• pilotní projekty MeSH
• struktury zubu MeSH
• Check Tag
• lidé MeSH

Copper radioisotopes can be used for imaging as well as for therapy and, thus, can form ideal theranostic pairs. The Cu(II) complexes of cross-bridged cyclam (cb-cyclam) derivatives are considered to be highly stable in vivo. However, the complexes are mostly formed under harsh conditions not compatible with sensitive biomolecules. Here, a new class of cb-cyclam derivatives, cross-bridged bis(phosphinate)cyclams ("cb-BPC"), were investigated. Ligands with one or two methylene-bis(phosphinate) -CH2-PO2H-CH2-PO2H(R) (R = H, OH, substituted alkyl) pendant arms were synthesized. Bifunctionalization on the distant phosphorus atom was carried out by employing P-nitrobenzyl (R = CH2-Ph-4-NO2) precursors and/or, for cb-BPC with two bis(phosphinate) pendant arms, by reactions of silyl-phosphites obtained by silylation of their P(O)-H fragments. The reactive bifunctional groups include amine, carboxylate, azide, isothiocyanate, maleimide and/or tetrazine, and also their orthogonally reactive combination in a single molecule of chelator. The cb-BPCs with one bis(phosphinate) arm were not efficiently radiolabelled with 64Cu. The cb-BPCs with two pendant arms were radiolabelled even at room temperature and with only a small excess of chelator, leading to a high specific activity. Radiolabelling was fully comparable with that of analogous bis(phosphinate) derivatives of cyclam and identical radiolabelling of cyclam and cb-cyclam derivatives was observed for the first time. The cb-BPCs with two bis(phosphinate) pendant arms represent a new class of rigid chelators for copper radioisotopes that are easily synthetically modifiable, highly hydrophilic and radiolabelled under mild conditions.

• Publikační typ
• časopisecké články MeSH

Background/Objectives: Dual-modality probes, combining positron emission tomography (PET) with fluorescence imaging (FI) capabilities in a single molecule, are of high relevance for the accurate staging and guided resection of tumours. We herein present a pair of candidates targeting the cholecystokinin-2 receptor (CCK2R), namely [68Ga]Ga-CyTMG and [68Ga]Ga-CyFMG. In these probes, the SulfoCy5.5 fluorophore and two units of a CCK2R-binding motif are coupled to the chelator acting as a core scaffold, triazacyclononane-phosphinic acid (TRAP), and Fusarinine C (FSC), respectively. Using this approach, we investigated the influence of these chelators on the final properties. Methods: The synthetic strategy to both precursors was based on the stoichiometric conjugation of the components via click chemistry. The characterization in vitro included the evaluation of the CCK2R affinity and internalization in A431-CCK2R cells. Ex vivo biodistribution as well as PET and FI studies were performed in xenografted mice. Results: 68Ga labelling was accomplished with high radiochemical yield and purity for both precursors. A CCK2R affinity in the subnanomolar range of the conjugates and a receptor-specific uptake of the radioligands in cells were observed. In A431-CCK2R/A431-mock xenografted mice, the investigated compounds showed specific accumulation in the tumours and reduced off-target uptake compared to a previously developed compound. Higher accumulation and prolonged retention in the kidneys were observed for [68Ga]Ga-CyTMG when compared to [68Ga]Ga-CyFMG. Conclusions: Despite the promising targeting properties observed, further probe optimization is required to achieve enhanced imaging contrast at early timepoints. Additionally, the results indicate a distinct influence of the chelators in terms of renal accumulation and retention.

• Publikační typ
• časopisecké články MeSH

The most common pesticide agents are organophosphates and phosphides, aluminum phosphide (ALP) in particular. ALP is a major cause of suicidal poisoning in many countries. In other countries, the problem of accidental, mainly occupational-related, poisoning is also real and actual. Almost two thirds of individuals in poisoning cases have died. This case report describes a case of a patient with accidental ALP intoxication. The origin of the poisoning was the fumigation of stored grain in an agricultural building adjacent to the building in which patient was temporarily housed, while both buildings were connected by an underground corridor, through which the released poison gas penetrated. The case was originally presented by the rescuers as well as healthcare professionals of the local hospital as carbon monoxide intoxication, which has a similar symptomatology as ALP intoxication. The patient was treated comprehensively, including using the HBOT method, which is very unique in the case of phosphine intoxication in human medicine, with an excellent final clinical outcome. This was the first described case of HBOT for ALP intoxication in clinical medicine, although the HBOT indication itself became a coincidence in this case. Further studies must be undertaken to demonstrate the effectiveness of HBOT in treating patients with ALP poisoning.

• Publikační typ
• kazuistiky MeSH

Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged <4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: <0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade >1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.

• MeSH
• akutní lymfatická leukemie * etiologie   MeSH
• busulfan * analogy a deriváty   MeSH
• dítě MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * etiologie   MeSH
• předškolní dítě MeSH
• příprava pacienta k transplantaci škodlivé účinky   MeSH
• recidiva MeSH
• thiotepa terapeutické užití   MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• Acidum phosphoricum,
• MeSH
• dítě MeSH
• kyseliny fosforu * aplikace a dávkování   MeSH
• lidé MeSH
• materia medica aplikace a dávkování   MeSH
• nemoci nosu farmakoterapie   MeSH
• pruritus farmakoterapie   MeSH
• únava * farmakoterapie   patologie   psychologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• populární práce MeSH

Jako standardní přípravný režim se před podáním autologní transplantace krvetvorných buněk (ASCT) u relabujících či refrakterních lymfomů používal BEAM, tedy carmustine (BCNU) v kombinaci s etoposidem, cytarabinem a melfalanem. Recentní nedostatek BCNU však vedl k nutnosti přechodu na alternativní režim, kterým se v našem centru stal od července 2018 režim obsahující thiotepu, tzv. TEAM. Rozhodli jsme se retrospektivně srovnat gastrointestinální (GIT) toxicitu obou přípravných režimů. Zahrnuli jsme 142 konsekutivně autologně transplantovaných pacientů (BEAM = 82, TEAM = 60), z nichž 31 % mělo difuzní velkobuněčný B-lymfom (DLBCL), 20 % Hodgkinův lymfom (HL), 15 % lymfom z plášťových buněk (MCL), 14 % T-buněčné lymfomy (T-NHL) a zbylých 20 % ostatní druhy non-Hodgkinových lymfomů (NHL). Obě kohorty byly srovnatelné stran věku pacientů, zastoupení diagnóz a stavu nemoci v době ASCT. V distribuci jednotlivých stupňů GIT toxicity nebyl mezi dvěma přípravnými režimy nalezen statisticky signifikantní rozdíl, a to ani po seskupení všech stupňů do dvou hlavních skupin pacientů (grade 0 + 1 vs. grade 2–4). Pacienti dostávající režim TEAM však častěji dospěli k potřebě parenterální výživy, a to ve 20 případech (33 %) oproti pouhým 13 případům (16 %) u režimu BEAM (p = 0,04). Nerelapsová mortalita (NRM) byla u obou režimů srovnatelně nízká, během hospitalizace byla 0 %, ve 3 měsících pak 2 % shodně pro oba přípravné režimy (p = 1,0). Nezaznamenali jsme statisticky signifikantní rozdíl v celkovém přežití (overal survival; OS) ani v přežití do známek progrese (progression free survival; PFS) (p = 0,59 pro OS, p = 0,1 pro PFS).

The BEAM regimen, i.e., carmustine (BCNU) in combination with etoposide, cytarabine, and melphalan was used as standard conditioning prior to autologous hematopoietic cell transplantation (ASCT) in relapsed or refractory lymphomas. However, the recent unavailability of BCNU necessitated the use of an alternative regimen, which in our centre became from July 2018 the so-called TEAM regimen containing thiotepa. We decided to retrospectively compare the gastrointestinal (GIT) toxicity of both conditioning regimens. We included 142 consecutive autologous transplant patients (BEAM = 82, TEAM = 60), of whom 31% had diffuse large B-cell lymphoma (DLBCL), 20% Hodgkin‘s lymphoma (HL), 15 % mantle cell lymphoma (MCL), 14% T-cell lymphomas (T-NHL) and the remaining 20% other types of non-Hodgkin lymphomas (NHL). Both cohorts were comparable in terms of patient age, prevalence of diagnoses, and disease status at the time of ASCT. There was no statistically significant difference in the distribution of the grades of GIT toxicity between the two cohorts, even after grouping all grades into two main groups of patients (grade 0+1 vs. grade 2–4). Patients receiving the TEAM regimen were more likely to require parenteral nutrition, namely in 20 cases (33%) versus only 13 cases (16%) in the BEAM regimen (P = 0.04). Non-relapse mortality (NRM) was comparably low for both regimens – 0% during hospitalization and 2% at 3 months for both conditioning regimens (P = 1.0). We also compared overall survival (OS) and progression-free survival (PFS): there was no statistically significant difference between the two cohorts (P = 0.59 for OS, P = 0.1 for PFS).

• MeSH
• autologní transplantace MeSH
• dospělí MeSH
• karmustin škodlivé účinky   terapeutické užití   MeSH
• kombinovaná farmakoterapie metody   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom * farmakoterapie   MeSH
• nežádoucí účinky léčiv epidemiologie   MeSH
• příprava pacienta k transplantaci * metody   škodlivé účinky   statistika a číselné údaje   MeSH
• protinádorové látky škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• thiotepa škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

Glycoconjugation is a powerful tool to improve the anticancer activity of metal complexes. Herein, we modified commercial arylphosphanes with carbohydrate-derived fragments for the preparation of novel glycoconjugated ruthenium(II) p-cymene complexes. Specifically, d-galactal and d-allal-derived vinyl epoxides (VEβ and VEα) were coupled with (2-hydroxyphenyl)diphenylphosphane, affording the 2,3-unsaturated glycophosphanes 1β and 1α. Ligand exchange with [Ru(C2O4)(η6-p-cymene)(H2O)] gave the glycoconjugated complexes Ru1β and Ru1α which were subsequently dihydroxylated with OsO4/N-methylmorpholine N-oxide to Ru2β and Ru2α containing O-benzyl d-mannose and d-gulose units respectively. Besides, aminoethyl tetra-O-acetyl-β-d-glucopyranoside was condensed with borane-protected (4-diphenylphosphanyl)benzoic acid by HATU/DIPEA under MW heating, to afford the amide 3∙BH3. Zemplén deacylation with MeONa/MeOH gave the deprotected d-glucopyranoside derivative 4∙BH3. The glycoconjugated phosphane complexes Ru3 and Ru4 were obtained by reaction of the phosphane-boranes 3∙BH3 and 4∙BH3 with [Ru(C2O4)(η6-p-cymene)(H2O)]. The employed synthetic strategies were devised to circumvent unwanted phosphine oxidation. The compounds were purified by silica chromatography, isolated in high yield and purity and characterized by analytical and spectroscopic (IR and multinuclear NMR) techniques. The behaviour of the six glycoconjugated Ru complexes in aqueous solutions was assessed by NMR and MS measurements. All compounds were screened for their in vitro cytotoxicity against A2780/A2780R human ovarian and MCF7 breast cancer cell lines, revealing a significant cytotoxicity for complexes containing the 2,3-unsaturated glycosyl unit (Ru1β, Ru1α). Additional studies on five other human cancer cells, as well as time-dependent toxicity and cell-uptake analyses on ovarian cancer cells, confirmed the prominent activity of these two compounds - higher than cisplatin - and the better performance of the β anomer. However, Ru1β, Ru1α did not show preferential activity against cancer cells with respect to fetal lung fibroblast and human embryonic kidney cells as models of normal cells. The effects of the two ruthenium glycoconjugated compounds in A2780 ovarian cancer cells were further investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The latter is a relevant factor in the mechanism of action of the highly cytotoxic Ru1β, inducing cell death by apoptosis.

• MeSH
• fosfiny MeSH
• komplexní sloučeniny * chemie   farmakologie   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků * MeSH
• protinádorové látky * chemie   MeSH
• ruthenium * chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Optimal conditioning for adults with acute lymphoblastic leukemia (ALL) treated with haploidentical hematopoietic cell transplantation (haplo-HCT) and post-transplant cyclophosphamide has not been established so far. We retrospectively compared outcomes for two myeloablative regimens: fludarabine + total body irradiation (Flu-TBI, n = 117) and thiotepa + iv. busulfan + fludarabine (TBF, n = 119). Patients transplanted either in complete remission (CR) or with active disease were included in the analysis. The characteristics of both groups were comparable except for patients treated with TBF were older. In univariate analysis the incidence of non-relapse mortality (NRM) at 2 years was increased for TBF compared to Flu-TBI (31% vs. 19.5%, p = 0.03). There was a tendency towards reduced incidence of relapse after TBF (p = 0.11). Results of multivariate analysis confirmed a reduced risk of NRM using Flu-TBI (HR = 0.49, p = 0.03). In the analysis restricted to patients treated in CR1 or CR2, the use of Flu-TBI was associated with a decreased risk of NRM (HR = 0.34, p = 0.009) but an increased risk of relapse (HR = 2.59, p = 0.01) without significant effect on survival and graft-versus-host disease. We conclude that for haplo-HCT recipients with ALL, Flu-TBI may be preferable for individuals at high risk of NRM while TBF should be considered in cases at high risk of relapse.

• MeSH
• akutní lymfatická leukemie * komplikace   terapie   MeSH
• akutní myeloidní leukemie * terapie   MeSH
• busulfan škodlivé účinky   MeSH
• celotělové ozáření škodlivé účinky   MeSH
• dospělí MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * etiologie   MeSH
• příprava pacienta k transplantaci metody   MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• thiotepa škodlivé účinky   MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• vidarabin analogy a deriváty   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS: FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). RESULTS: Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P < .0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P < .0001) and 0.02 (95% CI, < 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION: Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.

• MeSH
• akutní lymfatická leukemie patologie   terapie   MeSH
• busulfan aplikace a dávkování   analogy a deriváty   MeSH
• celotělové ozáření mortalita   MeSH
• chemoradioterapie mortalita   MeSH
• dítě MeSH
• etoposid aplikace a dávkování   MeSH
• hodnocení ekvivalence jako téma MeSH
• lidé MeSH
• mezinárodní agentury MeSH
• míra přežití MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• thiotepa aplikace a dávkování   MeSH
• vidarabin aplikace a dávkování   analogy a deriváty   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH