A direct enantioselective high-performance liquid chromatography was employed successfully for determination of the enantiomeric purity of levamisole. The elaborated method used S-naphthylethylcarbamoylated beta-cyclodextrin stationary phase in reversed-phase mode. The optimized mobile phase composition was acetonitrile-0.5% triethylammonium acetate buffer, pH 5.0 (2:8, v/v). Linearity, precision, accuracy, and the quantitation limit were determined. The method proved to be capable of determining 0.05% (w/w) of dexamisole (the enantiomeric impurity) contrary to the pharmacopoeial optical rotation measurement, in which only amounts of dexamisole higher than 2.2% (w/w) caused the test to fail. The enantiomeric purity of three different levamisole substances and levamisole tablets was assessed with the use of the method. The content of dexamisole impurity was found to be in the range 0.66-1.60% (w/w).

• MeSH
• antinematodní látky analýza   MeSH
• cyklodextriny MeSH
• kontaminace léku MeSH
• levamisol analýza   MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antinematodní látky MeSH
• cyklodextriny MeSH
• levamisol MeSH

The objective of this study was to compare the concentrations of 17 beta-estradiol, progesterone, cAMP and cGMP in the follicular fluid of the largest cow follicle from the follicular phase of physiological sexual cycle and of follicles after synchronization of fut by cloprostenol (PGF2 alpha) and superovulation treatment with serum gonadotrophin (PMSG), in dependence on steroidal dominance of follicles. 2 x 25 cows, Slovak Pied x Lowland Black-Pied crossbreds with active corpus luteum, were subjected to superovulation treatment on the basis of rectal examination. Rut synchronization was achieved by cloprostenol of Czechoslovak provenience (Oestrophan Spofa), administered at the amount of 500 micrograms per dose. Serum gonadotrophin (Bioveta Concern, Ivanovice na Hané) at the amount of 2500 I. U. was administered forty-eight hours before the second dose of closprostenol. The animals were killed in slaughterhouses 48 hours later, or 72 hours later, since administration of the second dose of cloprostenol. The phase of the sexual cycle of control animals was determined by the method after Ireland et al. (1980) on the basis of morphological appearance of corpus luteum, presence of large preovulation follicle and by means of average concentrations of progesterone in blood serum. Aspirated follicular fluid was centrifuged using a cooling centrifuge at 3000 G. After separation, the supernatant was stored in a freezer at -18 degrees C until further treatment. 17 beta-estradiol and progesterone in the follicular fluid were determined by means of kits under the brand-names RIA-test-ESTRA (SI-125-9), or RIA-test-Prog (SI-125-6). Concentrations of cyclic nucleotides were determined by the RIA kits from the Institute vor Radioisotope Research, Production and Use (Prague), cAMP by 125J RIA kit (RIO12) and cGMP by 125J RIA (RIO42).(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• AMP cyklický analýza   MeSH
• cloprostenol farmakologie   MeSH
• estradiol analýza   MeSH
• folikulární fáze * MeSH
• folikulární tekutina chemie   MeSH
• gonadotropiny koňské farmakologie   MeSH
• guanosinmonofosfát cyklický analýza   MeSH
• ovariální folikul anatomie a histologie   MeSH
• progesteron analýza   MeSH
• skot metabolismus   MeSH
• superovulace účinky léků   MeSH
• synchronizace říje účinky léků   MeSH
• zvířata MeSH
• Check Tag
• skot metabolismus   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• AMP cyklický MeSH
• cloprostenol MeSH
• estradiol MeSH
• gonadotropiny koňské MeSH
• guanosinmonofosfát cyklický MeSH
• progesteron MeSH

BACKGROUND: Ozanimod is a sphingosine 1-phosphate receptor modulator, which selectively binds to sphingosine 1-phosphate receptor subtypes 1 and 5 with high affinity. In the RADIANCE phase 2 study in participants with relapsing multiple sclerosis, ozanimod was associated with better efficacy than placebo on MRI measures and was well tolerated. The RADIANCE phase 3 study aimed to confirm the safety and efficacy of ozanimod versus interferon beta-1a in individuals with relapsing multiple sclerosis. METHODS: We did a 24-month, multicentre, double-blind, double-dummy phase 3 trial in participants with relapsing multiple sclerosis at 147 medical centres and clinical practices in 21 countries. Participants were aged 18-55 years, had multiple sclerosis according to 2010 McDonald criteria, a relapsing clinical course, brain MRI lesions consistent with multiple sclerosis, an expanded disability status scale score of 0·0-5·0, and either at least one relapse within 12 months before screening or at least one relapse within 24 months before screening plus at least one gadolinium-enhancing lesion within the 12 months before randomisation. Participants were randomly assigned (1:1:1) via an interactive voice response system to daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment allocation. The primary endpoint was annualised relapse rate (ARR) over 24 months. The primary analysis was done in the intention-to-treat population of all participants who received study drug and safety was assessed in all randomly assigned participants who received study drug, grouped by highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, NCT02047734, and EudraCT, 2012-002714-40. FINDINGS: Between Dec 27, 2013, and March 31, 2015, we screened 1695 participants, of which 375 did not meet inclusion criteria. 1320 participants were enrolled and randomly assigned to a group, of whom 1313 received study drug (433 assigned to ozanimod 1·0 mg, 439 assigned to ozanimod 0·5 mg, and 441 assigned to interferon beta-1a) and 1138 (86·7%) completed 24 months of treatment. Adjusted ARRs were 0·17 (95% CI 0·14-0·21) with ozanimod 1·0 mg, 0·22 (0·18-0·26) with ozanimod 0·5 mg, and 0·28 (0·23-0·32) with interferon beta-1a, with rate ratios versus interferon beta-1a of 0·62 (95% CI 0·51-0·77; p<0·0001) for ozanimod 1·0 mg and 0·79 (0·65 to 0·96; p=0·0167) for ozanimod 0·5 mg. The incidence of treatment-emergent adverse events was higher in the interferon beta-1a group (365 [83·0%] of 440 participants) than in the ozanimod 1·0 mg group (324 [74·7%] of 434) or the ozanimod 0·5 mg group (326 [74·3%] of 439). More participants in the interferon beta-1a group had treatment-emergent adverse events leading to treatment discontinuation than in the ozanimod groups. Incidences of infections and serious treatment-emergent adverse events were similar across treatment groups. No cases of ozanimod-related symptomatic reduction in heart rate and no second-degree or third-degree cases of atrioventricular block were reported. INTERPRETATION: In this 24-month phase 3 study in participants with relapsing multiple sclerosis, ozanimod was well tolerated and associated with a significantly lower rate of clinical relapses than intramuscular interferon beta-1a. These findings show the potential of ozanimod as an effective oral therapy for individuals with relapsing multiple sclerosis. FUNDING: Celgene International II.

• MeSH
• bradykardie chemicky indukované   MeSH
• dospělí MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• indany aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• infekce etiologie   MeSH
• interferon beta 1a škodlivé účinky   terapeutické užití   MeSH
• lékové postižení jater etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• následné studie MeSH
• neurozobrazování MeSH
• oxadiazoly aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• progrese nemoci MeSH
• receptory sfingosin-1-fosfátu antagonisté a inhibitory   MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   patologie   MeSH
• šedá hmota patologie   MeSH
• stupeň závažnosti nemoci MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví 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
• srovnávací studie MeSH
• Názvy látek
• imunosupresiva MeSH
• indany MeSH
• interferon beta 1a MeSH
• oxadiazoly MeSH
• ozanimod MeSH Prohlížeč
• receptory sfingosin-1-fosfátu MeSH

Simple isocratic HPLC separation of a series of thiazolyl steroids with the 17 beta-2' linkage is described. The chromatographic and spectral characterization utilizes both on-the-fly UV spectral maxima and absorbances changes.

• MeSH
• androstenoly chemie   izolace a purifikace   MeSH
• molekulární struktura MeSH
• spektrofotometrie ultrafialová MeSH
• thiazoly chemie   izolace a purifikace   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• androstenoly MeSH
• thiazoly MeSH

BACKGROUND: Ozanimod, a sphingosine 1-phosphate receptor modulator, selectively binds to receptor subtypes 1 and 5 with high affinity. The RADIANCE phase 2 study showed that ozanimod had better efficacy than placebo on MRI measures, with a favourable safety profile, in participants with relapsing multiple sclerosis. The SUNBEAM study aimed to assess the safety and efficacy of ozanimod versus intramuscular interferon beta-1a in participants with relapsing multiple sclerosis. METHODS: SUNBEAM was a randomised, double-blind, double-dummy, active-controlled phase 3 trial done at 152 academic medical centres and clinical practices in 20 countries. We enrolled participants aged 18-55 years with relapsing multiple sclerosis, baseline expanded disability status scale (EDSS) score of 0·0-5·0, and either at least one relapse within the 12 months before screening or at least one relapse within 24 months plus at least one gadolinium-enhancing lesion within 12 months before screening. Participants were randomly assigned 1:1:1 by a blocked algorithm stratified by country and baseline EDSS score to at least 12 months treatment of either once-daily oral ozanimod 1·0 mg or 0·5 mg or weekly intramuscular interferon beta-1a 30 μg. Participants, investigators, and study staff were masked to treatment assignment. The primary endpoint was annualised relapse rate (ARR) during the treatment period and was assessed in the intention-to-treat population. Safety was assessed in all participants according to the highest dose of ozanimod received. This trial is registered at ClinicalTrials.gov, number NCT02294058 and EudraCT, number 2014-002320-27. FINDINGS: Between Dec 18, 2014, and Nov 12, 2015, 1346 participants were enrolled and randomly assigned to ozanimod 1·0 mg (n=447), ozanimod 0·5 mg (n=451), or interferon beta-1a (n=448). 91 (6·8%) participants discontinued the study drug (29 in the ozanimod 1·0 mg group; 26 in the ozanimod 0·5 mg group; and 36 in the interferon beta-1a group). Adjusted ARRs were 0·35 (0·28-0·44) for interferon beta-1a, 0·18 (95% CI 0·14-0·24) for ozanimod 1·0 mg (rate ratio [RR] of 0·52 [0·41-0·66] vs interferon beta-1a; p<0·0001), and 0·24 (0·19-0·31) for ozanimod 0·5 mg (RR 0·69 [0·55-0·86] vs interferon beta-1a; p=0·0013). Few ozanimod-treated participants discontinued treatment because of adverse events (13 [2·9%] who received ozanimod 1·0 mg; seven [1·5%] who received ozanimod 0·5 mg; and 16 [3·6%] who received interferon beta-1a). No first-dose, clinically significant bradycardia or second-degree or third-degree atrioventricular block was reported. The incidence of serious adverse events was low and similar across treatment groups (13 [2·9%] participants who received ozanimod 1·0 mg; 16 [3·5%] who received ozanimod 0·5 mg; and 11 [2·5%] who received interferon beta-1a). No serious opportunistic infections occurred in ozanimod-treated participants. INTERPRETATION: In participants with relapsing multiple sclerosis treated for at least 12 months, ozanimod was well tolerated and demonstrated a significantly lower relapse rate than interferon beta-1a. These findings provide support for ozanimod as an oral therapy for individuals with relapsing multiple sclerosis. FUNDING: Celgene International II.

• MeSH
• atrioventrikulární blokáda chemicky indukované   MeSH
• bradykardie chemicky indukované   MeSH
• dospělí MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• indany škodlivé účinky   terapeutické užití   MeSH
• interferon beta 1a škodlivé účinky   terapeutické užití   MeSH
• kognitivní poruchy etiologie   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• neurozobrazování MeSH
• oxadiazoly škodlivé účinky   terapeutické užití   MeSH
• progrese nemoci MeSH
• receptory sfingosin-1-fosfátu antagonisté a inhibitory   MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   patologie   psychologie   MeSH
• šedá hmota patologie   MeSH
• stupeň závažnosti nemoci MeSH
• velikost orgánu MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví 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
• srovnávací studie MeSH
• Názvy látek
• imunosupresiva MeSH
• indany MeSH
• interferon beta 1a MeSH
• oxadiazoly MeSH
• ozanimod MeSH Prohlížeč
• receptory sfingosin-1-fosfátu MeSH

PURPOSE: We investigated whether the reproducibility of standard visual reporting (STD method) in flutemetamol (FMM) PET can be improved using a newly introduced method that uses grey matter edges derived from the perfusion phase (GM-EDGE method). METHODS: Two-phase FMM PET was performed in 121 patients with mild cognitive impairment. Five nuclear medicine physicians blindly and independently evaluated all late-phase scans, initially employing the STD method and later the GM-EDGE method. A five-point scale was used to express the degree of amyloid positivity, and a binary classification (positive/negative) was used in combination with subjective confidence (five-point scale). Multirater Fleiss' kappa, intraclass correlation coefficient (ICC) and inter-rater reliability (Cohen's kappa) were determined for the STD and GM-EDGE methods. RESULTS: The weighted Cohen's kappa values for the five-point measure of amyloid positivity ranged from 0.63 to 0.73 (median 0.70) for the STD method and from 0.76 to 0.89 (median 0.80) for the GM-EDGE method (ICC 0.84, 95% CI 0.79-0.88, for the STD method; 0.91, 95% CI 0.89-0.94, for the GM-EDGE method). The nonweighted Cohen's kappa value for the binary classification ranged from 0.73 to 0.93 (median 0.82) for the STD method and 0.90 to 0.97 (median 0.93) for the GM-EDGE method (Fleiss' kappa 0.82, 95% CI 0.77-0.88, for the STD method; 0.93, 95% CI 0.87-0.99, for the GM-EDGE method). The GM-EDGE method resulted in significantly greater subjective confidence in the readings of four physicians (p < 0.010). The binary classification was concordant among all five physicians in 80.8% of the scans using the STD method and in 91.6% of the scans using the GM-EDGE method (p = 0.016). CONCLUSION: The newly introduced GM-EDGE method was associated with significantly higher inter-rater agreement among physicians and higher subjective confidence in the reading. The method is easy to implement in clinical practice, especially when the perfusion phase is utilized clinically.

• Klíčová slova
• Amyloid, Brain, Dementia, Flutemetamol, Positron emission tomography, Reproducibility,
• MeSH
• amyloidní beta-protein metabolismus   MeSH
• dospělí MeSH
• kognitivní dysfunkce diagnostické zobrazování   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• PET/CT * MeSH
• počítačové zpracování obrazu * MeSH
• šedá hmota diagnostické zobrazování   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidní beta-protein MeSH

A sensitive system for D,L-amino acid analysis has been developed, using fluorescence derivatization with o-phthaldialdehyde in the presence of sodium salt of 1-thio-beta-D-glucose. The reagents rapidly form fluorescent diastereoisomeric derivatives with primary amino acids. These derivatives are efficiently separated on a conventional reversed-phase column with an analysis time of 60 min. Simultaneous determination of enantiomers of various amino acids was achieved by a simple binary gradient elution with methanol in 0.05 M aqueous sodium acetate.

• MeSH
• aminokyseliny analýza   krev   MeSH
• glukosa analogy a deriváty   MeSH
• indikátory a reagencie MeSH
• myši MeSH
• o-ftalaldehyd MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1-thioglucose MeSH Prohlížeč
• aminokyseliny MeSH
• glukosa MeSH
• indikátory a reagencie MeSH
• o-ftalaldehyd MeSH

BACKGROUND: In patients with septic shock, the presence of an elevated heart rate (HR) after fluid resuscitation marks a subgroup of patients with a particularly poor prognosis. Several studies have shown that HR control in this population is safe and can potentially improve outcomes. However, all were conducted in a single-center setting. The aim of this multicenter study is to demonstrate that administration of the highly beta1-selective and ultrashort-acting beta blocker landiolol in patients with septic shock and persistent tachycardia (HR ≥ 95 beats per minute [bpm]) is effective in reducing and maintaining HR without increasing vasopressor requirements. METHODS: A phase IV, multicenter, prospective, randomized, open-label, controlled study is being conducted. The study will enroll a total of 200 patients with septic shock as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization period of 24-36 h. Patients are randomized (1:1) to receive either standard treatment (according to the Surviving Sepsis Campaign Guidelines 2016) and continuous landiolol infusion to reach a target HR of 80-94 bpm or standard treatment alone. The primary endpoint is HR response (HR 80-94 bpm), the maintenance thereof, and the absence of increased vasopressor requirements during the first 24 h after initiating treatment. DISCUSSION: Despite recent studies, the role of beta blockers in the treatment of patients with septic shock remains unclear. This study will investigate whether HR control using landiolol is safe, feasible, and effective, and further enhance the understanding of beta blockade in patients with septic shock. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2017-002138-22 . Registered on 8 August 2017.

• Klíčová slova
• Beta-blocker, Landiolol, Randomized controlled trial, Sepsis, Septic shock, Tachycardia,
• MeSH
• antiarytmika škodlivé účinky   terapeutické užití   MeSH
• beta blokátory škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• jednotky intenzivní péče * MeSH
• klinické zkoušky, fáze IV jako téma MeSH
• krevní tlak účinky léků   MeSH
• lidé MeSH
• močovina škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• morfoliny škodlivé účinky   terapeutické užití   MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• septický šok diagnóza   farmakoterapie   patofyziologie   MeSH
• srdeční frekvence účinky léků   MeSH
• vazokonstriktory terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antiarytmika MeSH
• beta blokátory MeSH
• landiolol MeSH Prohlížeč
• močovina MeSH
• morfoliny MeSH
• vazokonstriktory MeSH

Three chiral stationary phases were prepared by dynamic coating of sulfobutylether-β-cyclodextrin (SBE-β-CD) with different degrees of substitution, onto strong anion-exchange stationary phases. The enantioselective potential and stability of newly prepared chiral stationary phases were examined using a set of structurally different chiral analytes. Measurements were performed in RP-HPLC. Mobile phases consisted of methanol/formic acid, pH 2.10, and methanol/10 mM ammonium acetate buffer, pH 4.00, in various volume ratios. SBE-β-CDs with degrees of substitution (DS) 4, 6.3, and 10 proved suitable for the enantioseparation of 14, 11, and 8 analytes, respectively. The SBE-β-CD DS 4 based chiral stationary phase enabled the enantioseparation of the nearly all basic and neutral compounds. Chiral stationary phases with higher sulfobutylether-β-cyclodextrin substitution (especially DS 10) yielded higher enantioresolution values for acidic compounds.

• Klíčová slova
• Chromatography, Degree of substitution, Dynamic coating, Enantioseparation, Sulfobutylether-β-cyclodextrin,
• MeSH
• beta-cyklodextriny chemie   MeSH
• chemické modely MeSH
• chromatografie s reverzní fází MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• SBE4-beta-cyclodextrin MeSH Prohlížeč

The metoclopramide test for latent hyperprolactinaemia was done on 174 randomly chosen infertile women in the midfollicular phase of the cycle. 54 women had latent hyperprolactinaemia which was defined as a PRL level of at least 150 ng/ml after metoclopramide. Just before the metoclopramide was given, blood was taken to measure the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), 17-beta estradiol (E2) and total testosterone (T). Women with latent hyperprolactinaemia had significantly lower levels of LH (p < 0.01) and E2 (p < 0.001) and higher levels of T (p < 0.05) in the midfollicular phase when compared with women without this condition. FSH levels showed no statistically significant difference.

• MeSH
• antagonisté dopaminu MeSH
• dospělí MeSH
• estradiol krev   MeSH
• folikulární fáze fyziologie   MeSH
• folikuly stimulující hormon krev   MeSH
• hyperprolaktinemie krev   diagnóza   MeSH
• lidé MeSH
• luteinizační hormon krev   MeSH
• metoklopramid MeSH
• mladiství MeSH
• testosteron krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté dopaminu MeSH
• estradiol MeSH
• folikuly stimulující hormon MeSH
• luteinizační hormon MeSH
• metoklopramid MeSH
• testosteron MeSH