V článku autor referuje o novinkách u fibromyalgie jak z hlediska patofyziologie a diagnostiky, tak z hlediska hodnocení klinické manifestace i léčby. Za největší změnu lze pokládat současnou interpretaci patofyziologických mechanismů v mozku (nociplastická bolest), které jsou příčinou klinické manifestace příznaků, zejména rozsáhlých bolestí svalů a vazů. V klinické diagnostice bylo největší změnou opuštění vyšetřování tzv. citlivých bodů a použití novějších diagnostických kritérií. V medikamentózní léčbě se věnujeme zejména použití pregabalinu, duloxetinu a milnacipranu, jejich optimálnímu dávkování a nežádoucím účinkům. Mnoho významných odborníků se domnívá, že fibromylagie patří do rukou neurologů, a to nejen mechanismem vzniku, ale i používanými léky.
The article discusses new developments in fibromyalgia disease in terms of diagnosis, evaluation of clinical manifestation and treatment. The most important change is the elucidation of the pathophysiological mechanisms in the brain (nociplastic pain) that underlie the clinical manifestation of the symptoms, especially the widespread muscle and ligament pain. In clinical diagnosis, the biggest change has been the abandonment of the investigation of the so-called tender points and the use of newer diagnostic criteria. In drug therapy, we are particularly concerned with the use of pregabalin, duloxetine and milnacipran, their optimal dosage and side effects. Many eminent experts believe that the disease belongs in the hands of neurologists, not only in terms of the mechanism of origin, but also in terms of the treatment used, neurologists are best qualified to do so.
Predkladaný článok popisuje využitie rezervného karbapenemového antibiotika imipeném v kombinácii s novým inhibítorom b-laktamázy relebaktámom v liečbe ventilátorovej pneumónie vznikajúcej v teréne infekcie SARS-CoV-2 u mladej gravidnej pacientky. V úvode stručne popisuje mechanizmus a spektrum účinku antibiotika, vrátane jeho dávkovania.
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- Klíčová slova
- relebaktam,
- MeSH
- antibakteriální látky aplikace a dávkování MeSH
- císařský řez MeSH
- COVID-19 komplikace terapie MeSH
- farmakoterapie COVID-19 MeSH
- fixní kombinace léků MeSH
- inhibitory beta-laktamasy aplikace a dávkování farmakologie MeSH
- kombinace léků imipenem a cilastatin * aplikace a dávkování farmakologie MeSH
- komplikace těhotenství farmakoterapie terapie MeSH
- lidé MeSH
- mladý dospělý MeSH
- pneumonie etiologie farmakoterapie terapie MeSH
- těhotenství MeSH
- ventilátorová pneumonie * etiologie farmakoterapie terapie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.
- MeSH
- antivirové látky aplikace a dávkování škodlivé účinky MeSH
- benzimidazoly aplikace a dávkování škodlivé účinky MeSH
- chinoxaliny aplikace a dávkování škodlivé účinky MeSH
- chronická hepatitida C krev komplikace farmakoterapie virologie MeSH
- cyklopropany aplikace a dávkování škodlivé účinky MeSH
- fixní kombinace léků MeSH
- genotyp * MeSH
- Hepacivirus enzymologie genetika MeSH
- jaterní cirhóza komplikace farmakoterapie MeSH
- kyseliny aminoisomáselné aplikace a dávkování škodlivé účinky MeSH
- leucin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrocyklické laktamy aplikace a dávkování škodlivé účinky MeSH
- polymorfismus genetický MeSH
- prolin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- pyrrolidiny aplikace a dávkování škodlivé účinky MeSH
- RNA virová krev genetika MeSH
- senioři MeSH
- setrvalá virologická odpověď MeSH
- sulfonamidy aplikace a dávkování škodlivé účinky MeSH
- virové nestrukturální proteiny genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- MeSH
- anestezie a analgezie * dějiny MeSH
- chloroform dějiny MeSH
- cyklopropany dějiny MeSH
- ether dějiny MeSH
- kokain dějiny MeSH
- oxid dusný MeSH
- spinální anestezie dějiny MeSH
- Publikační typ
- zprávy MeSH
Triacylglycerols (TAGs) containing cyclofatty acids (cycloFAs) from two oilseeds of Sterculia foetida and Hydnocarpus wightiana were analysed using both reversed-phase (RP18) and chiral phase columns. TAGs were identified using high-resolution electrospray ionization mass spectrometry in the positive ion mode. Fifty-five molecular species of TAGs have been identified in sterculic oil, 27 of which contained at least one cyclopropenyl-FA (e.g., malvalic or sterculic acids). The structures of regioisomers and enantiomers were determined for five major TAGs with cyclopropenyl-FAs. One hundred thirty-six TAGs were identified in chaulmoogra oil, 71 of which contained at least one cyclopentenyl-FA (e.g., gorlic, chaulmoogric, and hydnocarpic acids, etc.). Furthermore, in three molecular species, regioisomers and enantiomers were identified using HPLC on a chiral phase column. Eight molecular species of TAGs were prepared through organic synthesis to facilitate the identification of enantiomers. Retention times of fatty acid-containing triacylglycerols with one ring and one double bond are very similar to triacylglycerols with a dienoic fatty acid, but elution times are shorter. For example, dimalvaloylpalmitate elutes earlier than dilinoleylpalmitate. The order of elution of TAGs on the chiral column differs. In TAGs with 2 degrees of unsaturation (ring and double bond, e.g. PStP-StPP-PPSt), the order of elution is symmetric-asymmetric-asymmetric TAGs. TAGs with 4 degrees of unsaturation (one ring and three double bonds or two rings and two double bonds) present a different pattern. When TAGs contain two rings and two double bonds, the order of elution TAGs is asymmetric-symmetric-asymmetric (StStP-StPSt-PStSt); when TAGs contain a ring and 3 double bonds, the elution order is symmetric-asymmetric-asymmetric TAGs (OStO-StOO-OOSt). In species with a higher degree of unsaturation (e.g., 5), the elution order of the TAGs is asymmetric-asymmetric-symmetric (e.g. CCO-OCC-COC).
- MeSH
- chromatografie s reverzní fází MeSH
- cyklopropany analýza MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- kyseliny mastné mononenasycené analýza MeSH
- mastné kyseliny analýza chemie izolace a purifikace MeSH
- oleje rostlin chemie MeSH
- Sterculia chemie MeSH
- stereoizomerie MeSH
- triglyceridy chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
In 2018, more than 50 cases of horse death by equine atypical myopathy (AM) were reported in the Czech Republic. This disease is often associated with the toxin hypoglycine A (HGA), which is found in several maple plant materials. To monitor this toxin in products of these trees that grow in or around horse pastures, a rapid and inexpensive analytical method that can provide the required accuracy is needed. Until now, maple samples have been prepared for gas chromatography using time-consuming methods, with preparation processes taking longer than 1 h. In this work, a shorter method (25 min) with an accuracy of 90-94 %, reproducibility of 2-5%, precision of 3-9%, and linearity, with an R2 of 0.999, is presented. This sample preparation consists of a procedure without an SPE extraction step and consumes a lower volume of solvent during the extraction. The limit of quantitation for HGA in plant material was improved from 0.5 μg/g of plant material in previous studies to 0.2 μg/g. The method was validated according to the guideline CD 2002/657/EC and ISO 17025, and was found to have good performance characteristics. This simple and rapid method was tested for the monitoring of hypoglycine A level in maple sycamore plant material (seeds, seedlings, and leaves) during the entire growth of the trees.
Damage of alveolar-capillary barrier, inflammation, oxidative injury, and lung cell apoptosis represent the key features of acute lung injury (ALI). This study evaluated if selective phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the mentioned changes in lavage-induced model of ALI. Rabbits with ALI were divided into 2 groups: ALI without therapy (A group) and ALI treated with roflumilast i.v. (1 mg/kg; A+R group). One group of healthy animals without ALI served as ventilated controls (C group). All animals were oxygen-ventilated for further 4 h. At the end of experiment, total and differential counts of cells in bronchoalveolar lavage fluid (BALF) and total and differential counts of white blood cells were estimated. Lung edema formation was assessed from determination of protein content in BALF. Pro-inflammatory cytokines (TNFalpha, IL-6 and IL-8) and markers of oxidation (3-nitrotyrosine, thiobarbituric-acid reactive substances) were detected in the lung tissue and plasma. Apoptosis of lung cells was investigated immunohistochemically. Treatment with roflumilast reduced leak of cells, particularly of neutrophils, into the lung, decreased concentrations of cytokines and oxidative products in the lung and plasma, and reduced lung cell apoptosis and edema formation. Concluding, PDE4 inhibitor roflumilast showed potent anti-inflammatory actions in this model of ALI.
- MeSH
- akutní poškození plic farmakoterapie metabolismus MeSH
- aminopyridiny farmakologie terapeutické užití MeSH
- apoptóza účinky léků fyziologie MeSH
- benzamidy farmakologie terapeutické užití MeSH
- bronchoalveolární lavážní tekutina MeSH
- cyklopropany farmakologie terapeutické užití MeSH
- inhibitory fosfodiesterasy 4 farmakologie terapeutické užití MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- oxidační stres účinky léků fyziologie MeSH
- pneumonie farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ceftazidim aplikace a dávkování farmakologie terapeutické užití MeSH
- cilastatin farmakologie terapeutické užití MeSH
- injekce intravenózní MeSH
- klinické laboratorní techniky MeSH
- krev mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meningitida vyvolaná Escherichia coli * diagnóza etiologie mikrobiologie MeSH
- počítačová rentgenová tomografie využití MeSH
- vankomycin aplikace a dávkování farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Whereas a selective phosphodiesterase-4 (PDE4) inhibitor roflumilast has exerted potent anti-inflammatory properties, this study evaluated if its intravenous delivery can influence inflammation, edema formation, and respiratory parameters in rabbits with a lavage-induced model of ALI. ALI was induced by repetitive saline lung lavage (30 ml/kg). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with roflumilast i.v. (1 mg/kg; ALI+Rofl), and healthy ventilated controls (Control), and were ventilated for following 4 h. Respiratory parameters (blood gases, ventilatory pressures, lung compliance, oxygenation indexes etc.) were measured and calculated regularly. At the end of experiment, animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated microscopically. Lung edema was expressed as wet/dry lung weight ratio. Treatment with roflumilast reduced leak of cells (P<0.01), particularly of neutrophils (P<0.001), into the lung, decreased lung edema formation (P<0.01), and improved respiratory parameters. Concluding, the results indicate a future potential of PDE4 inhibitors also in the therapy of ALI.
- MeSH
- akutní poškození plic farmakoterapie etiologie patofyziologie MeSH
- aminopyridiny aplikace a dávkování MeSH
- benzamidy aplikace a dávkování MeSH
- bronchoalveolární laváž škodlivé účinky MeSH
- bronchoalveolární lavážní tekutina MeSH
- chlorid sodný toxicita MeSH
- cyklopropany aplikace a dávkování MeSH
- inhibitory fosfodiesterasy 4 aplikace a dávkování MeSH
- intravenózní podání MeSH
- králíci MeSH
- modely nemocí na zvířatech * MeSH
- plíce účinky léků fyziologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The retention behavior of primary aliphatic amines (homologous series of aliphatic alkyl amines and cycloalkyl amines) and positional isomers of alkylamines in the hydrophilic interaction chromatography mode was studied. The study was carried out on a TSKgel Amide-80 column followed by postcolumn derivatization with fluorescence detection to describe the retention mechanism of tested compounds. The effect of chromatographic conditions including column temperature, acetonitrile content in the mobile phase, mobile phase pH (ranging from 3.5 to 6.8), and salt concentration in the mobile phase was investigated. The final mobile phase consisted of acetonitrile and solution of 20 mM potassium formate pH 3.5 in ratio 80:20 v/v. The analyses were carried out at mobile phase flow rate of 1.0 mL/min and the column temperature of 20°C. The developed method was fully validated in terms of linearity, sensitivity (limit of detection and limit of quantification), accuracy, and precision according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. The proposed new methods were proved to be highly sensitive, simple, and rapid, and were successfully applied to the determinations of isopropylamine, cyclohexylamine, and cyclopropylamine in relevant active pharmaceutical ingredients.
- MeSH
- aminy izolace a purifikace MeSH
- cyklohexylaminy izolace a purifikace MeSH
- cyklopropany izolace a purifikace MeSH
- hydrofobní a hydrofilní interakce MeSH
- léčivé přípravky chemie MeSH
- merkaptoethanol * MeSH
- o-ftalaldehyd * MeSH
- propylaminy izolace a purifikace MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
