Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system.

• Klíčová slova
• HPMA polymers, cytotoxicity, penetration, pirarubicin, tumor spheroids,
• Publikační typ
• časopisecké články MeSH

The presented article demonstrates the probabilistic method based modeling of the 2D chloride ingress into reinforced concrete structures with respect to concrete heterogeneity and epoxy-coated steel reinforcement. Spatial change of concrete diffusion is assessed through the investigation of random variation of the ability of concrete to resist chloride ingress. Time-dependent chloride concentration at the reinforcement level in both homogeneous and heterogeneous models is comparatively considered taking into account of the influence of reinforcement protection as well as the defects and holidays of the coating. Expansion optimal linear estimation method is exploited to generate a random field for the structure at the mesoscale and correlation length is employed to simplify the modeling process. Preliminary analyses of the built model are conducted in both deterministic and probabilistic solutions under the scheme of the finite element method. Thus, possibility of such analyses is exploited.

• Klíčová slova
• 2D diffusion model, chloride penetration, coatings, concrete heterogeneity, random fields, reinforcement protection,
• Publikační typ
• časopisecké články MeSH

In this work, penetrometry with a sphere was employed to study the flow properties of non-consolidated pharmaceutical powder excipients: sodium chloride, sodium citrate, boric acid, and sorbitol. In order to estimate flow rate, the pressure of penetration in Pascals was used. Penetrometry measurement with a sphere requires modification of the measurement container, in particular by decreasing the diameter of the container, to prevent undesirable movement of material in a direction opposite to that in which the sphere penetrates. Thus penetrometry by a sphere seems to be similar to indentation by the Brinell hardness tester. The pressure of penetration was determined from the depth of penetration by analogy with the Brinell hardness number and an equation for the inter conversion of the two variables is presented. The penetration pressure allowed direct estimation of the flow rate only for those powder excipients with a size fraction in the range of 0.250-0.630 mm. Using the ratio of penetration pressure to bulk density, a polynomial quadratic equation was generated from which the flow rates for the group of all tested powders could be estimated. Finally, if the inverse ratio of bulk density and penetration pressure was used as an independent variable, the flow rate could be estimated by linear regression with the coefficient of determination r2 = 0.9941. In conclusion, using sphere penetrometry, the flow properties of non-consolidated powder samples could be investigated by indentation. As a result, a linear regression in which the flow rate was directly proportional to the powder bulk density and inversely proportional to the penetration pressure could be best recommended for the estimation of the flow rate of powder excipients.

• MeSH
• algoritmy MeSH
• farmaceutická chemie MeSH
• indikátory a reagencie MeSH
• kovy chemie   MeSH
• lineární modely MeSH
• pomocné látky chemie   MeSH
• prášky, zásypy, pudry * MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• indikátory a reagencie MeSH
• kovy MeSH
• pomocné látky MeSH
• prášky, zásypy, pudry * MeSH

In vivo linear penetration in total hip arthroplasty (THA) exhibits similar values for 28mm and 32mm femoral head diameter with considerable variations between and within the studies. It indicates factors other than femoral head diameter influence polyethylene wear. This study is intended to test the effect of patient׳s individual geometry of musculoskeletal system, acetabular cup orientation, and radius of femoral head on wear. Variation in patient׳s musculoskeletal geometry and acetabular cup placement is evaluated in two groups of patients implanted with 28mm and 32mm THA heads. Linear wear rate estimated by mathematical model is 0.165-0.185mm/year and 0.157-0.205mm/year for 28 and 32mm THA heads, respectively. Simulations show little influence femoral head size has on the estimated annual wear rate. Predicted annual linear wear depends mostly on the abduction angle of the acetabular cup and individual geometry of the musculoskeletal system of the hip, with the latter having the greatest affect on variation in linear wear rate.

• Klíčová slova
• Contact pressure, Design, Linear penetration, UHMWPE,
• MeSH
• acetabulum anatomie a histologie   fyziologie   MeSH
• hlavice femuru anatomie a histologie   fyziologie   MeSH
• kosterní svaly anatomie a histologie   fyziologie   MeSH
• kyčelní protézy * MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada kyčelního kloubu * MeSH
• počítačové modelování podle konkrétního pacienta MeSH
• polyethylen MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polyethylen MeSH

A new design of RF coil based on a quasi-transverse electromagnetic field is described. The coil was developed for the acquisition of MR images of the rat spinal cord at 4.7 T. Different materials for the construction of the coil were tested, and the best results were obtained with Teflon. The design of the microstrip coil enables the investigator to change the length of the coil in a longitudinal direction and yields a relatively high signal-to-noise ratio due to the restricted field of view. Low RF field penetration depth also helps in suppressing motion artifacts generated by, e.g., breathing or heartbeats.

• MeSH
• analýza selhání vybavení MeSH
• design vybavení MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční tomografie přístrojové vybavení   metody   MeSH
• magnetismus MeSH
• měniče * MeSH
• mícha cytologie   MeSH
• potkani Wistar MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• studie proveditelnosti MeSH
• vylepšení obrazu přístrojové vybavení   metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

Chop or slash wounds are produced by sharp-edged tools such as an axe, or a machete. This paper presents a case of a violent death of a 57 year-old-man. Autopsy revealed deformation of the right side of the head. A total of 23 slash, stab and cut wounds as well as contused lacerations were identified on the scalp as well as the face and the neck. In addition, superficial abrasions and bruises were identified on the skin. The immediate cause of death was due to extensive brain contusion following fragmentation of the neurocranium. The injuries resulting in the death of the victim were sustained during an assault on the head with an axe, which was used both as a slashing tool and a blunt instrument.

• Klíčová slova
• Autopsy, Axe, Brain contusion, Forensic medicine, Homicide, Slash wounds,
• MeSH
• bodné rány patologie   MeSH
• fraktury lebky patologie   MeSH
• kontuze mozku patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• penetrující poranění hlavy patologie   MeSH
• tříštivé fraktury patologie   MeSH
• vražda * MeSH
• zbraně * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Upconversion nanoparticles (UCNPs) are an emerging class of optical materials with high potential in bioimaging due to practically no background signal and high penetration depth. Their excellent optical properties and easy surface functionalization make them perfect for conjugation with targeting ligands. In this work, capillary electrophoretic (CE) method with laser-induced fluorescence detection was used to investigate the behavior of carboxyl-silica-coated UCNPs. Folic acid, targeting folate receptor overexpressed by wide variety of cancer cells, was used for illustrative purposes and assessed by CE under optimized conditions. Peptide-mediated bioconjugation of antibodies to UCNPs was also investigated. Despite the numerous advantages of CE, this is the first time that CE was employed for characterization of UCNPs and their bioconjugates. The separation conditions were optimized including the background electrolyte concentration and pH. The optimized electrolyte was 20 mM borate buffer with pH 8.

• Klíčová slova
• Laser diode, Near-infrared excitation, Photon upconversion, Separation method,
• MeSH
• elektroforéza kapilární metody   MeSH
• fluorescenční barviva chemie   MeSH
• fluorescenční spektrometrie metody   MeSH
• kyselina listová chemie   MeSH
• limita detekce MeSH
• lineární modely MeSH
• nanokonjugáty chemie   MeSH
• protilátky chemie   MeSH
• reprodukovatelnost výsledků MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluorescenční barviva MeSH
• kyselina listová MeSH
• nanokonjugáty MeSH
• protilátky MeSH

As proven in clinical trials, superficial fungal infections can be effectively treated by single topical application of terbinafine hydrochloride (Ter-HCl) in a film forming system (FFS). Poly(lactic-co-glycolic acid) (PLGA) derivatives, originally synthesized with intention to get carriers with optimized properties for drug delivery, and multifunctional plasticizers - ethyl pyruvate, methyl salicylate, or triacetin - were used for formulation of Ter-HCl loaded FFSs. After spraying, a biodegradable, transparent, adhesive, and occlusive thin layer is formed on the skin, representing drug depot. In situ formed films were characterized by thermal, structural, viscoelastic, and antifungal properties as well as drug release and skin penetration. DSC and SEM showed fully amorphous films with Ter-HCl dissolved in PLGA in high concentration (up to 15%). FFSs are viscoelastic fluids with viscosity which can be easily adjusted by the type of plasticizer used and its concentration. The formulations showed excellent bioadhesion properties, thus ensuring persistence on the skin. In situ film based on branched PLGA/A plasticized with 10% of ethyl pyruvate allowed prolonged release of Ter-HCl by linear kinetics for the first 6 days with a total time of almost 14 days. During ex vivo human skin penetration experiment, Ter-HCl was found to be located only in its target layer, the epidermis. According to our results, plasticized branched PLGA derivatives loaded by Ter-HCl are suitable for the development of FFSs for superficial fungal infections treatment.

• Klíčová slova
• Bioadhesion, Drug release, FFS, PLGA, Skin penetration, Terbinafine hydrochloride,
• MeSH
• antifungální látky MeSH
• lidé MeSH
• mykózy * MeSH
• nosiče léků * MeSH
• terbinafin MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antifungální látky MeSH
• nosiče léků * MeSH
• terbinafin MeSH

BACKGROUND: Pregnenolone sulfate (PregS) is known as a steroid conjugate positively modulating N-methyl-D-aspartate receptors on neuronal membranes. These receptors are responsible for permeability of calcium channels and activation of neuronal function. Neuroactivating effect of PregS is also exerted via non-competitive negative modulation of GABA(A) receptors regulating the chloride influx. Recently, a penetrability of blood-brain barrier for PregS was found in rat, but some experiments in agreement with this finding were reported even earlier. It is known that circulating levels of PregS in human are relatively high depending primarily on age and adrenal activity. METHODS: Concerning the neuromodulating effect of PregS, we recently evaluated age relationships of PregS in both sexes using polynomial regression models known to bring about the problems of multicollinearity, i.e., strong correlations among independent variables. Several criteria for the selection of suitable bias are demonstrated. Biased estimators based on the generalized principal component regression (GPCR) method avoiding multicollinearity problems are described. RESULTS: Significant differences were found between men and women in the course of the age dependence of PregS. In women, a significant maximum was found around the 30th year followed by a rapid decline, while the maximum in men was achieved almost 10 years earlier and changes were minor up to the 60th year. The investigation of gender differences and age dependencies in PregS could be of interest given its well-known neurostimulating effect, relatively high serum concentration, and the probable partial permeability of the blood-brain barrier for the steroid conjugate. CONCLUSIONS: GPCR in combination with the MEP (mean quadric error of prediction) criterion is extremely useful and appealing for constructing biased models. It can also be used for achieving such estimates with regard to keeping the model course corresponding to the data trend, especially in polynomial type regression models.

• MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• mladiství MeSH
• pohlavní dimorfismus * MeSH
• předškolní dítě MeSH
• pregnenolon krev   MeSH
• senioři MeSH
• stárnutí krev   MeSH
• zdraví * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• pregnenolon MeSH
• pregnenolone sulfate MeSH Prohlížeč

The biophysical simulation tool PARTRAC has been primarily developed to model radiation physics, chemistry and biology on nanometre to micrometre scales. However, the tool can be applied in simulating radiation effects in an event-by-event manner over macroscopic volumes as well. Benchmark simulations are reported showing that PARTRAC does reproduce the macroscopic Bragg peaks of proton beams, although the penetration depths are underestimated by a few per cent for high-energy beams. PARTRAC also quantifies the increase in DNA damage and its complexity along the beam penetration depth. Enhanced biological effectiveness is predicted in particular within distal Bragg peak parts of therapeutic proton beams.

• MeSH
• algoritmy MeSH
• DNA účinky záření   MeSH
• dvouřetězcové zlomy DNA účinky záření   MeSH
• lineární přenos energie MeSH
• metoda Monte Carlo MeSH
• počítačová simulace * MeSH
• poškození DNA MeSH
• protonová terapie MeSH
• protony MeSH
• relativní biologická účinnost MeSH
• software MeSH
• voda MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• protony MeSH
• voda MeSH