Veris, Andrea*
Dotaz
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A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.
- MeSH
- aplikace kožní MeSH
- aplikace lokální MeSH
- farmaceutická chemie metody MeSH
- koncentrace vodíkových iontů MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- kůže metabolismus MeSH
- kyselina mléčná * chemie MeSH
- kyselina polyglykolová * chemie MeSH
- kyselina salicylová * aplikace a dávkování chemie farmakokinetika MeSH
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem MeSH
- rozpustnost MeSH
- salicylany * aplikace a dávkování chemie farmakokinetika MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Yeast lipids and fatty acids (FA) were analyzed in Saccharomyces pastorianus from seven breweries and in the dietary yeast supplement Pangamin. GC-MS identified more than 30 FA, half of which were very-long chain fatty acids (VLCFA) with hydrocarbon chain lengths of ≥22 C atoms. Positional isomers ω-9 and ω-7 were identified in FA with C18-C28 even-numbered alkyl chains. The most abundant ω-7 isomer was cis-vaccenic acid. The structure of monounsaturated FA was proved by dimethyl disulfide adducts (position of double bonds and cis geometric configuration) and by GC-MS of pyridyl carbinol esters. Ultra-high performance liquid chromatography-tandem mass spectrometry with negative electrospray ionization identified the phospholipids phosphatidylethanolamine, phosphatidylinositol and phosphatidylcholine, with more than 150 molecular species. Wild-type unmutated brewer's yeast strains conventionally used for the manufacture of food supplements were found to contain VLCFA.
- MeSH
- fosfolipidy analýza chemie MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- kyseliny mastné mononenasycené MeSH
- mastné kyseliny chemie MeSH
- molekulární struktura MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- Saccharomyces metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- Publikační typ
- časopisecké články MeSH
Pseudomonas fluorescens is a well-known food spoiler, able to cause serious economic losses in the food industry due to its ability to produce many extracellular, and often thermostable, compounds. The most outstanding spoilage events involving P. fluorescens were blue discoloration of several food stuffs, mainly dairy products. The bacteria involved in such high-profile cases have been identified as belonging to a clearly distinct phylogenetic cluster of the P. fluorescens group. Although the blue pigment has recently been investigated in several studies, the biosynthetic pathway leading to the pigment formation, as well as its chemical nature, remain challenging and unsolved points. In the present paper, genomic and transcriptomic data of 4 P. fluorescens strains (2 blue-pigmenting strains and 2 non-pigmenting strains) were analyzed to evaluate the presence and the expression of blue strain-specific genes. In particular, the pangenome analysis showed the presence in the blue-pigmenting strains of two copies of genes involved in the tryptophan biosynthesis pathway (including trpABCDF). The global expression profiling of blue-pigmenting strains versus non-pigmenting strains showed a general up-regulation of genes involved in iron uptake and a down-regulation of genes involved in primary metabolism. Chromogenic reaction of the blue-pigmenting bacterial cells with Kovac's reagent indicated an indole-derivative as the precursor of the blue pigment. Finally, solubility tests and MALDI-TOF mass spectrometry analysis of the isolated pigment suggested that its molecular structure is very probably a hydrophobic indigo analog.
- MeSH
- biologické pigmenty genetika MeSH
- down regulace MeSH
- energetický metabolismus genetika MeSH
- fenotyp MeSH
- fylogeneze MeSH
- genomika MeSH
- mléčné výrobky mikrobiologie MeSH
- oxidoreduktasy genetika MeSH
- potravinářská mikrobiologie * MeSH
- Pseudomonas fluorescens genetika metabolismus MeSH
- spotřeba kyslíku genetika MeSH
- stanovení celkové genové exprese MeSH
- transkriptom genetika MeSH
- tryptofan biosyntéza MeSH
- upregulace MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Adenoid cystic carcinoma is among the most frequent malignancies in the salivary and lacrimal glands and has a grave prognosis characterized by frequent local recurrences, distant metastases, and tumor-related mortality. Conversely, adenoid cystic carcinoma of the breast is a rare type of triple-negative (estrogen and progesterone receptor, HER2) and basal-like carcinoma, which in contrast to other triple-negative and basal-like breast carcinomas has a very favorable prognosis. Irrespective of site, adenoid cystic carcinoma is characterized by gene fusions involving MYB, MYBL1, and NFIB, and the reason for the different clinical outcomes is unknown. In order to identify the molecular mechanisms underlying the discrepancy in clinical outcome, we characterized the phenotypic profiles, pattern of gene rearrangements, and global microRNA expression profiles of 64 salivary gland, 9 lacrimal gland, and 11 breast adenoid cystic carcinomas. All breast and lacrimal gland adenoid cystic carcinomas had triple-negative and basal-like phenotypes, while salivary gland tumors were indeterminate in 13% of cases. Aberrations in MYB and/or NFIB were found in the majority of cases in all three locations, whereas MYBL1 involvement was restricted to tumors in the salivary gland. Global microRNA expression profiling separated salivary and lacrimal gland adenoid cystic carcinoma from their respective normal glands but could not distinguish normal breast adenoid cystic carcinoma from normal breast tissue. Hierarchical clustering separated adenoid cystic carcinomas of salivary gland origin from those of the breast and placed lacrimal gland carcinomas in between these. Functional annotation of the microRNAs differentially expressed between salivary gland and breast adenoid cystic carcinoma showed these as regulating genes involved in metabolism, signal transduction, and genes involved in other cancers. In conclusion, microRNA dysregulation is the first class of molecules separating adenoid cystic carcinoma according to the site of origin. This highlights a novel venue for exploring the biology of adenoid cystic carcinoma.
- MeSH
- adenoidně cystický karcinom genetika patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA analýza MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory oka genetika patologie MeSH
- nádory slinných žláz genetika patologie MeSH
- nemoci slzného ústrojí genetika patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- triple-negativní karcinom prsu genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
X-linked Adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene resulting in the accumulation of very long chain fatty acids (VLCFA). X-ALD is the most common peroxisomal disorder with adult patients (male and female) presenting with progressive spastic paraparesis with bladder disturbance, sensory ataxia with impaired vibration sense, and leg pain. 80% of male X-ALD patients have an adrenal failure, while adrenal dysfunction is rare in women with X-ALD. The objective of this study was to define optimal serum VLCFA cutoff values in patients with X-ALD-like phenotypes for the differentiation of genetically confirmed X-ALD and Non-X-ALD individuals. Three groups were included into this study: a) X-ALD cases with confirmed ABCD1 mutations (n = 34) and two Non-X-ALD cohorts: b) Patients with abnormal serum VCLFA levels despite negative testing for ABCD1 mutations (n = 15) resulting from a total of 1,953 VLCFA tests c) Phenotypically matching patients as Non-X-ALD controls (n = 104). Receiver operating curve analysis was used to optimize VLCFA cutoff values, which differentiate patients with genetically confirmed X-ALD and Non-X-ALD individuals. The serum concentration of C26:0 was superior to C24:0 for the detection of X-ALD. The best differentiation of Non-X-ALD and X-ALD individuals was obtained with a cutoff value of < 1.0 for the C24:0/C22:0 ratio resulting in a sensitivity of 97%, a specificity of 94.1% and a positive predictive value (PPV) of 83.8% for true X-ALD. Our findings further suggested a cutoff of < 0.02 for the ratio C26:0/C22:0 leading to a sensitivity of 90.9%, a specificity of 95.0%, and a PPV of 80.6%. Pearson correlation indicated a significant positive association between total blood cholesterol and VLCFA values. Usage of serum VLCFA are economical and established biomarkers suitable for the guidance of genetic testing matching the X-ALD phenotype. We suggest using our new optimized cutoff values, especially the two ratios (C24:0/C22:0 and C26:0/C22:0), in combination with standard lipid profiles.
- MeSH
- ABC transportéry genetika MeSH
- adrenoleukodystrofie krev diagnóza MeSH
- astrocyty patologie MeSH
- biologické markery krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mastné kyseliny krev MeSH
- mutace genetika MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. METHODS: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. RESULTS: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (P<0.01 for LOD versus each of the other strategies). CONCLUSIONS: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.
- MeSH
- akutní koronární syndrom krev diagnóza mortalita MeSH
- algoritmy MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dospělí MeSH
- elektrokardiografie MeSH
- hodnocení rizik MeSH
- infarkt myokardu krev diagnóza mortalita MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování * MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- troponin I krev MeSH
- upregulace MeSH
- věkové faktory MeSH
- zdravotní stav MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
- Geografické názvy
- Evropa MeSH
Ultrasonografie je velmi jednoduchou a přesnou metodou pro zobrazení periferních nervů prakticky v celém jejich rozsahu. Určení místa léze, zobrazení strukturálních změn nervu a detekce případných vedlejších nálezů v okolních měkkých tkáních může být velmi užitečné pro určení dalšího terapeutického postupu u pacientů. Vedle zobrazení skýtá ultrazvuk i možnost navigace diagnostických či terapeutických intervenčních metod v reálném čase. V naší kazuistice chceme prezentovat poranění nervus radialis u mladého muže, které vzniklo jaké následek sádrové fixace po úrazu paže. Morfologie a přesná lokalizace léze nervu byla zobrazitelná pouze pomocí ultrazvukového vyšetření. Dále uvádíme ukázku intervenčního postupu, který jsme u tohoto pacienta provedli s dobrým terapeutickým efektem.
Ultrasonography is a very simple and precise method for imaging of the whole range of peripheral nerves. Determining the site of the lesion, depiction of structural changes of the nerve and detection of possible additional findings in the surrounding soft tissues might be beneficial for further management of the patient. Besides imaging ultrasounds can help in navigation of diagnostic and therapeutic interventional methods in real time. In our case study we want to present a lesion of radial nerve in young male which occurred as a result of cast for upper extremity injury. The morphology and exact localization of the nerve lesion was only visible by ultrasound. We also present an example of interventional procedure that we performed in this patient and which had good therapeutic effect.
Secretory carcinoma, originally described as mammary analog secretory carcinoma (MASC), is a low-grade salivary gland tumor characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 gene fusion. Most MASCs are localized to the parotid gland and intraoral minor salivary glands. Moreover, ETV6-rearranged carcinomas with secretory features have been reported recently in the thyroid (with and without a history of radiation exposure), skin, and in very rare instances in the sinonasal tract. Here, we describe 2 cases of primary MASC in the sinonasal tract and provide a detailed clinical and histopathologic characterization of their morphology, immunohistochemical profile, and genetic background and highlight features allowing for its separation from its recently described molecular mimicker, ETV6-rearranged low-grade sinonasal adenocarcinoma.
- MeSH
- adenokarcinom chemie genetika patologie MeSH
- biopsie MeSH
- diferenciální diagnóza MeSH
- fúzní onkogenní proteiny genetika MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza genetika MeSH
- nádory nosu chemie genetika patologie chirurgie MeSH
- nosní dutina chemie patologie chirurgie MeSH
- počítačová rentgenová tomografie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prediktivní hodnota testů MeSH
- registrace MeSH
- sekreční karcinom mamárního typu chemie genetika patologie chirurgie MeSH
- senioři MeSH
- stupeň nádoru MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.
