AIM: To evaluate the effects of orally administered gadolinium orthovanadate GdVO4:Eu3+ nanoparticles (VNPs) on the course of chronic carrageenan-induced intestinal inflammation. METHODS: Samples of small intestinal tissue were collected from four groups of rats (intact, after administration of VNPs, with carrageenaninduced intestinal inflammation, with carrageenan-induced intestinal inflammation orally exposed to VNPs) to assess the intestinal morphology and HSP90α expression. Levels of seromucoid, C-reactive protein, TNF-α, IL-1β and IL-10 were determined in blood serum. RESULTS: Oral exposure to VNPs was associated with neither elevation of inflammation markers in blood serum nor HSP90α overexpression in the small intestine, i.e. no toxic effects of VNPs were observed. Carrageenan-induced intestinal inflammation was accompanied by higher levels of TNF-α and IL-1β, as well as HSP90α upregulation in the intestinal mucosa, compared with controls. Administration of VNPs to rats with enteritis did not lead to statistically significant changes in concentrations of circulating pro-inflammatory cytokines with the trend towards their increase. CONCLUSION: No adverse effects were observed in rats orally exposed to VNPs at a dose of 20 μg/kg during two weeks. Using the experimental model of carrageenan-induced enteritis, it was demonstrated that VNPs at the dose used in our study did not affect the course of intestinal inflammation.

• MeSH
• C-reaktivní protein účinky léků   metabolismus   MeSH
• enterokolitida krev   chemicky indukované   patologie   MeSH
• gadolinium farmakologie   MeSH
• idiopatické střevní záněty krev   patologie   MeSH
• interleukin-10 krev   MeSH
• interleukin-1beta krev   účinky léků   MeSH
• karagenan toxicita   MeSH
• kovové nanočástice * MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• orosomukoid účinky léků   metabolismus   MeSH
• proteiny tepelného šoku HSP90 účinky léků   metabolismus   MeSH
• scavengery volných radikálů farmakologie   MeSH
• střevní sliznice účinky léků   metabolismus   patologie   MeSH
• TNF-alfa krev   účinky léků   MeSH
• vanadáty farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Type B trichothecene mycotoxins comprise deoxynivalenol ("Vomitoxin", DON) and four structually related congeners: 15-acetyl- and 3-acetyl-deoxynivalenol (15-ADON and 3-ADON), nivalenol (NIV), 4-acetyl-nivalenol (fusarenon X, FX). These foodborne mycotoxins has been linked to food poisoning leading to anorexic response in human and several animal species. However, the pathophysiological basis for anorexic effect is relatively unclear. The goal of this research was to compare anorexic effect to type B trichothecenes and relate these effects to two common cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) following oral and IP exposure. Both cytokines were increased within 1-2 h in plasma and returned to basal concentrations at 6 h following exposure to DON and ADONs. FX evoked both cytokines with initial time and duration at 1-2 h and > 6 h, respectively. Elevation of TNF-α and IL-1β induced by orally exposure to NIV did not occur until 2 h and recovered to basal concentrations at 6 h. Both cytokines were elevated at 1 h and lasted more than 6 h following IP exposure to NIV. Type B trichothecenes stimulated plasma secretion of both cytokines that were consistent with reduction of food intake. In conclusion, our findings demonstrate that TNF-α and IL-1β act critical roles in type B trichothecenes-induced anorexic response.

• MeSH
• interleukin-1beta krev   MeSH
• myši MeSH
• nechutenství krev   chemicky indukované   MeSH
• přijímání potravy účinky léků   MeSH
• TNF-alfa krev   MeSH
• trichotheceny toxicita   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Proveřit možnost monitorace efektu anti TNFα terapie u pacientů léčených pro revmatoidní artritidu pomocí multiplexového stanovení sérových hladin vybraných biomarkerů odrážejících základní patofyziologické mechanizmy a aktivitu onemocnění. Metody: Byla hodnocena skupina 23 pacientů s aktivní revmatoidní artritidou, z toho 20 žen, 3 muži, průměrný věk 48,6 ± 10,3 let, průměrná hmotnost 68,5 ± 13 kg před léčbou a po 14–16 týdnech léčby s inhibitorem TNFα adalimumabem 40 mg subkutánně podávaným jednou za dva týdny (N = 21) nebo etanerceptem 25 mg podávaným podkožně dvakrát týdně (N= 2). Z 23 pacientů, 16 (70 %) užívalo současně s glukokortikoidy (GC) a 19 subjektů (84 %) methotrexát. Krev byla odebrána ze žíly pomocí odběrové zkumavky Vacuette (Greiner Bio One, Rakousko). Krevní vzorky byly odstřeďeny při 640 g po dobu 10 min. Sérum bylo rozděleno na alikvoty a zamraženo do provedení analýzy při teplotě -75 °C. Sérové hladiny IL 1β, IL10, IL6, VEGF, MMP9 a adiponektinu byly stanoveny multiplexovou analýzou pomocí technologie XMAP komerčním kitem Human Cardiovascular 1, Lineo Research (USA) podle návodu výrobce k použití. Analýza byla provedena na přístroji Luminex 100 a analýza dat pomocí Luminex 100 IS software verze 2.3. Tyto parametry byly korelovány s krevními hladinami CRP, PCT, TK (stanoveno radioenzymaticky), hmotností pacienta a DAS-28. Pro všechny parametry byl vypočten průměr, medián, směrodatná odchylka, minimální a maximální hodnoty z výsledků před a po terapii. Data byla analyzována Wilcoxonovým párovým testem a koeficientem pořadové korelace. Výsledky: Potvrdili jsme statisticky signifikantní snížení hladiny CRP (p = 0,001), VEGF (p = 0,05) a adiponektinu (p = 0,05), aktivity onemocnění hodnocené pomocí DAS-28 (p = 0,001) a významné zvýšení hmotnosti po léčbě (p = 0,01). Pokles hodnot všech tří prozánětlivých interleukinů nebyl významný. Závěry: Naše pilotní studie prokázala potencionální využitelnost i limity multiplexové analýzy cytokinů a některých dalších biomarkerů v monitorování léčby revmatoidní artritidy. Ke stanovení doporučení pro rutinní klinickou praxi je nezbytné zvolit vhodnější panel a rozšířit skupinu pacientů.

Methods: A group of 23 patients with active rheumatoid arthritis, 20 female, 3 male, average age 48.6 years ± 10.3, average weight 68,5 ± 13 kg was evaluated prior therapy and after 14–16 weeks of therapy with TNFα blocking agent adalimumab 40 mg subcutaneously every two weeks (No = 21) and etanercept 25 mg subcutaneously twice weekly (No = 2). Of 23 patients, 16 (70 %) of subject were treated concomitantly with glucocorticoids (GC), and 19 subject ( 84 %) with methotrexate. The blood was collected by venipuncture using Vacuette collection tubes (Greiner Bio-One, Austria). The blood samples were centrifuged at 640 g for 10 min, serum was aliquoted and stored until analysed in freezer at -75 °C. Serum levels of six parameters: IL 1β, IL10, IL6, VEGF, MMP9 and adiponectin were assessed by multiplex immunoanalysis using xMAP technology with commercially available multiplex kits Human Cardiovascular 1 panel and Human Cytokines-Chemokines panel, both from Linco Research (USA) according to manufacturer‘s instructions for use. The analysis was performed on Luminex 100 instrument and data analysis on Luminex 100 IS software version 2.3. These parameters were correlated with blood levels of CRP, PCT, TK (assessed by traditional immunoassays), patient weight and DAS-2828. For all parameters there was counted average, median, standard deviation, minimal and maximal values from results prior and after therapy. Furthermore, data were analysed by Wilcoxon pair test and Rank-order correlation. Results: We confirmed significantly decreased CRP levels (p = 0,001), VEGF(p = 0,05) and adiponectin (p = 0,05), disease activity score DAS-28 (p = 0,001) and significant increase of weight after therapy (p = 0,01). Decrease of all of three proinflammatory interleukins were not significant. Conclusions: Our pilot study showed the usefulness and limitations of multiplex measurements of cytokines and some other biomarkers in monitoring of rheumatoid arthritis therapy. But to establish guidelines for the routine clinical practice it is necessary to select preferable panel and to enlarge a group of the patients.

• MeSH
• adalimumab terapeutické užití   MeSH
• adiponektin krev   MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• etanercept terapeutické užití   MeSH
• interleukin-10 krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• neparametrická statistika MeSH
• pilotní projekty MeSH
• revmatoidní artritida * farmakoterapie   krev   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• vaskulární endoteliální růstové faktory krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Rapid diagnosis of acute pyelonephritis is important because of its association with long-standing complications. This study was conducted to compare the reliability of serum procalcitonin (PCT) and interleukin-1 beta (IL-1β) with conventional laboratory parameters for diagnosis of acute pyelonephritis in children. Seventy nine children with urinary tract infection were divided into two groups based on the result of Tc-99m dimercaptosuccinic acid renal scan: acute pyelonephritis (n=33) and lower UTI (urinary tract infection) (n=46) groups. White blood cell (WBC) count, neutrophil count, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), PCT and IL-1β concentrations of both groups were measured and compared. WBC count, neutrophil count, ESR, serum CRP, PCT and IL-1β concentrations were higher in acute pyelonephritis patients than in the lower UTI group (P<0.05). The sensitivity and specificity of serum PCT and IL-1β for diagnosis of acute pyelonephritis were 31, 84.7% and 27.2, 90% respectively (using a cut-point value of 0.5 ng/ml for PCT and 6.9 pg/ml for IL-1β). The sensitivity of PCT and IL-1β for diagnosis of acute pyelonephritis was less than that of conventional markers such as ESR and CRP. This study revealed that serum PCT and IL-1β are not good biologic markers for differentiating acute pyelonephritis from lower UTI. It seems that conventional inflammatory markers such as ESR and CRP besides the clinical findings are more reliable for the diagnosis of acute pyelonephritis in children.

• MeSH
• akutní nemoc MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• infekce močového ústrojí krev   diagnóza   MeSH
• interleukin-1beta krev   MeSH
• kalcitonin krev   MeSH
• kojenec MeSH
• krevní sedimentace MeSH
• lidé MeSH
• neutrofily * MeSH
• počet leukocytů MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• proteinové prekurzory krev   MeSH
• průřezové studie MeSH
• pyelonefritida krev   diagnóza   MeSH
• senzitivita a specificita MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• srovnávací studie MeSH

Aprotinin, a nonspecific serine protease inhibitor, has been primarily used as a haemostatic drug in cardiac surgery with cardio-pulmonary bypass (CPB). This study investigated the effect of aprotinin on the post-operative levels of procalcitonin (PCT) and a set of cytokines in patients undergoing pulmonary artery endarterectomy (PEA). We analyzed 60 patients with chronic thromboembolic pulmonary hypertension undergoing PEA. 30 patients (Group A) were treated with aprotinin (2,00,00 IU prior anesthesia, then 2,00,00 IU in CPB prime and 50,00 IU per hour continuously); a further 30 patients (Group B) received tranexamic Acid (1 g before anesthesia, 1 g after full heparin dose and 2 g in CPB prime). PCT, TNFalpha, IL-1beta, IL-6, and IL-8 arterial concentrations were measured from before until 72 hours after surgery. Aprotinin significantly affected early post-PEA plasma PCT. Patients treated with aprotinin (Group A) had lower peak PCT levels compared to patients in Group B (1.52 ng/ml versus 2.18, p=0.024). Postoperative peak values of PCT and IL-6 correlated closely in both groups (r=0.78, r=0.83 respectively). Aprotinin attenuates the post-PEA increase of PCT in the same manner as other pro-inflammatory cytokines. Significant correlation between PCT and IL-6 post-surgery may be indicative of an indirect IL-6-mediated pathway of PCT alteration.

• MeSH
• aprotinin terapeutické užití   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• endarterektomie * MeSH
• hemostatika terapeutické užití   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• interleukin-8 krev   MeSH
• kalcitonin krev   MeSH
• kardiochirurgické výkony * MeSH
• kardiopulmonální bypass * MeSH
• kyselina tranexamová terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• plicní embolie krev   komplikace   chirurgie   MeSH
• plicní hypertenze krev   etiologie   chirurgie   MeSH
• proteinové prekurzory krev   MeSH
• senioři MeSH
• TNF-alfa krev   MeSH
• upregulace MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Disturbance of capillary perfusions due to leukocyte adhesion, disseminated intravascular coagulation, tissue edema is critical components in the pathophysiology of sepsis. Alterations in brain microcirculation during sepsis are not clearly understood. The aim of this study is to gain an improved understanding of alterations through direct visualization of brain microcirculations in an experimental endotoxemia using intravital microscopy (IVM). Endotoxemia was induced in Lewis rats with Lipopolysaccharide (LPS, 15 mg/kg i.v.). The dura mater was removed via a cranial window to expose the pial vessels on the brain surface. Using fluorescence dyes, plasma extravasation of pial venous vessels and leukocyte-endothelial interaction were visualized by intravital microscopy 4 h after LPS administration. Plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO were evaluated after IVM. A significant plasma extravasation of the pial venous vessels was found in endotoxemia rats compared to control animals. In addition, a significantly increased number of leukocytes adherent to the pial venous endothelium was observed in septic animals. Endotoxemia also induced a significant elevation of plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO. Endotoxemia increased permeability in the brain pial vessels accompanied by an increase of leukocyte-endothelium interactions and an increase of inflammatory cytokines in the plasma.

• MeSH
• buněčná adheze MeSH
• cévní endotel metabolismus   patofyziologie   MeSH
• endotoxemie metabolismus   patofyziologie   MeSH
• interferon gama krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• kapilární permeabilita MeSH
• krysa rodu rattus MeSH
• leukocyty fyziologie   MeSH
• mikrocévy metabolismus   patofyziologie   MeSH
• mikrocirkulace fyziologie   MeSH
• mozek krevní zásobení   MeSH
• mozkové žíly metabolismus   MeSH
• potkani inbrední LEW MeSH
• TNF-alfa krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

The paper examines features of balance between proinflammatory and anti-inflammatory cytokines in newborns of mothers with herpes virus infections (SHV, CMVI). This investigation included 35 newborns, of them 10 were full-term newborns of healthy mothers (group 1 - umbilical blood); 10 - full-term newborns with various pathology of perinatal period in mothers with intrauterine infections (group 2 - umbilical blood); 15 practically healthy newborns of healthy mothers (control group - peripheral blood). The paper studies production of proinflammatory IL-1b, IL-8, γ-IFN and anti-inflammatory (IL-4) cytokines in newborns in norm and with intrauterine infections. The study has shown that the level IL-4 in the umbilical blood in newborns born from the mothers with intrauterine infection did not differ from a level in peripheral blood of healthy newborns. It has found also that there was 1.5 times increase of IL-1b in newborns with intrauterine infection in the umbilical blood in comparison with umbilical blood in healthy newborns, 3.4 times increase in IL-8 and the tendency to increase IFN-gamma.

• MeSH
• cytokiny * krev   MeSH
• cytomegalovirové infekce MeSH
• fetální krev imunologie   MeSH
• herpes simplex MeSH
• infekční komplikace v těhotenství * MeSH
• interferon gama krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-4 krev   MeSH
• interleukin-8 krev   MeSH
• lidé MeSH
• novorozenec imunologie   krev   MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec imunologie   krev   MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

The study examines production of proinflammatory IL-1b, IL-8, γ -IFN and anti-inflammatory (IL-4) cytokines in newborns from mothers with healthy pregnancy and with the intrauterine infections. Under supervision there were 55 children, newborn from the mothers with herpes virus infections: from them 21 in the early neonatal period, 19 - in the late neonatal period. The control group included 15 healthy children newborn from healthy mothers with favourable course of pregnancy. The analysis has shown that γ-IFN level, in the early neonatal period in children with intrauterine infection, was in the average 7.0±0.73 pg/ml or 3.6 times lower (P<0.05) than control. In the late neonatal period production of γ-IFN increased up to 11.2±0.74 pg/ml (Р<0.05), but without reaching of control meanings. The reduced production of γ-IFN results, apparently, to long recurrent disease. The performed examinations have shown that the development of pathological process at herpes virus infection is accompanied by significant balance disturbance of proinflammatory and anti-inflammatory cytokines during all neonatal period. The revealed cytokine profile changes in the newborns in the short age periods and their severity degree show important pathogenic role of immune mechanisms in the development and progressing of herpes virus infections.

• MeSH
• cytokiny * imunologie   krev   MeSH
• herpetické infekce * imunologie   krev   vrozené   MeSH
• infekční komplikace v těhotenství * MeSH
• interleukin-18 krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-4 krev   MeSH
• interleukin-8 krev   MeSH
• lidé MeSH
• novorozenec imunologie   krev   MeSH
• poporodní období imunologie   krev   MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec imunologie   krev   MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infections and sepsis. PCT levels are usually low in viral infections, chronic inflammation or postsurgical states. The purpose of this study was to characterize PCT plasma levels in patients with various types of ileus at preoperative stage, where the other inducing factors such as a surgical stress are excluded. The prospective study was performed on 54 patients admitted to in-patient surgical department with a proven diagnosis of ileus. Patients were divided to three groups--obstructive, vascular and paralytic ileus. Plasma levels of PCT (Kryptor analysis), TNFalpha, IL-1beta, IL-6, cortisol (ELISA) and CRP (Kryptor ultrasensitive analysis) were estimated before any invasive procedure was realized. We demonstrated significant elevation of PCT in both obstructive ileus in adhesions and vascular ileus compared with healthy subjects (p 0.01). PCT levels were not elevated in paralytic ileus. The regression coefficient was the highest for PCT and CRP (r=0.78, p 0.01), for TNFalpha and IL-8 (r=0.76, p 0.01) in vascular ileus. There was no significant correlation between PCT and other inflammatory parameters. The different types of ileus induce an elevation of plasma PCT levels and PCT shows itself as an acute phase reactant. The highest PCT concentrations were presented in patients with vascular ileus, whereas paralytic ileus revealed similar cytokine and PCT pattern as in healthy subjects. Plasma PCT estimation extended to a measurement of CRP and IL-6 may become a useful complementary examination for diagnostics of acute abdomen in patients.

• MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• ELISA MeSH
• financování organizované MeSH
• hydrokortison krev   MeSH
• ileus komplikace   krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• kalcitonin MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• prospektivní studie MeSH
• proteinové prekurzory krev   MeSH
• senioři MeSH
• střevní obstrukce etiologie   krev   MeSH
• střevní pseudoobstrukce krev   MeSH
• TNF-alfa krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: The aim of the prospective study was to characterize the disturbance of gastric electrical control activity in different types of ileus and to correlate surface electrogastrography (EGG) findings with a set of inflammatory markers. PATIENTS AND METHODS: Fifty-four adult patients with mechanic, vascular and paralytic ileus proven on clinical and radiological exams and 14 age- and sex-matched controls were examined. Gastric myoelectrical activity was recorded using 3 Ag-AgCl disposable skin electrodes connected in pseudo-unipolar mode by Microdigitrapper device. The captured signal was amplified and digitalized. The dominant frequency was calculated using computerized algorithms (Fast Fourier transform and running spectrum analysis). The results were correlated with the known pathological diagnoses and 4 inflammatory parameters--interleukin (IL)-1beta, IL-6, procalcitonin (PCT) and C-reactive protein. RESULTS: Irregular EGG activity without a dominant frequency or bradygastria (electrical control activity frequency <2.4 cycles/min) was seen in all patients with both vascular and parayltic ileus and in 67.86% of the patients with obstructive ileus. Normogastria (2.4-3.7 cycles/min) was found in 32.14% of the patients with obstructive ileus. Among the patients with obstructive ileus and bradygastria, higher concentrations of IL-6 (642.0 +/- 214.7 ng/l) and PCT (0.93 +/- 0.22 microg/l) were observed compared with the patients with normogastria--IL-6 (354.5 +/- 109.2 ng/l), PCT (0.69 +/- 0.11 microg/l); p < 0.05 for both. The C-reactive protein concentration did not differ in both subgroups on p < 0.05. CONCLUSIONS: EGG examination confirmed a high sensitivity in the evaluation of gastric electrical control activity in both vascular and paralytic ileus. Significant correlation of EGG findings and both IL-6 and PCT plasma levels supports a role of the inflammatory milieu in the pathogenesis of impaired gastric electrical activity in patients with ileus.

• MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• elektrodiagnostika metody   přístrojové vybavení   MeSH
• elektrody MeSH
• financování organizované MeSH
• ileus diagnóza   imunologie   patofyziologie   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• kalcitonin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• proteinové prekurzory krev   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• transkutánní elektrická neurostimulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky kontrolované MeSH