BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.
- MeSH
- antidepresiva škodlivé účinky MeSH
- indany * MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu * škodlivé účinky MeSH
- lidé MeSH
- oxadiazoly * MeSH
- roztroušená skleróza * chemicky indukované MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- serotonin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.
- MeSH
- chitosan * chemie MeSH
- doxorubicin chemie MeSH
- jodacetamid MeSH
- lidé MeSH
- monoklonální protilátky chemie MeSH
- nádory prsu * farmakoterapie MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- systémy cílené aplikace léků MeSH
- trastuzumab MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. PATIENTS AND METHODS: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. RESULTS: MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. CONCLUSION: MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
- MeSH
- bendamustin hydrochlorid MeSH
- cyklofosfamid MeSH
- doxorubicin MeSH
- folikulární lymfom * MeSH
- galium * terapeutické užití MeSH
- lidé MeSH
- prednison MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- reziduální nádor farmakoterapie MeSH
- rituximab MeSH
- vinkristin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVES: To evaluate the efficacy and tolerability of a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg twice a day for 7 days, compared with a recommended single dose of ceftriaxone plus single dose of oral azithromycin, for treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhoea. METHODS: A noninferiority, open-label, multicentre randomized controlled trial was conducted in Prague, Czech Republic. Some 161 patients, 18-65 years of age diagnosed with uncomplicated urogenital, rectal, or pharyngeal gonorrhoea by nucleic acid amplification test (NAAT) were randomized to treatment with single dose of cefixime 800 mg plus doxycycline 100 mg twice a day for 1 week or a single dose of ceftriaxone 1 g intramuscularly plus single dose of azithromycin 2 g. The primary outcome was the number of participants with negative culture and NAAT at 1 week and 3 weeks, respectively, after treatment initiation. RESULTS: In all, 161 patients were randomized and 152 were included in per-protocol analyses. All 76 (100%; 95% CI, 0.95-1.00) patients treated with ceftriaxone plus azithromycin achieved negative cultures and NAAT after treatment. In the cefixime plus doxycycline arm at week 1, culture was negative in all 76 (100%) patients; at week 3, culture was negative in 70 of the 76 patients (92%; 95% CI, 0.84-0.97) and NAAT negative in 66 of the 76 patients (87%; 95% CI, 0.77-0.94). At week 3, culture and NAAT were negative in 65 of the 76 patients (86%; 95% CI, 0.76-0.93). Per-protocol risk difference was 14.5%; 95% CI, 6.56-22.38. All treatment failures observed in the cefixime arm were pharyngeal gonorrhoea cases. DISCUSSION: The combination of cefixime and doxycycline did not achieve noninferiority to ceftriaxone and azithromycin for treatment of gonorrhoea when including pharyngeal gonorrhoea. It did, however, show high efficacy for urogenital and rectal gonorrhoea.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- azithromycin terapeutické užití MeSH
- cefixim terapeutické užití MeSH
- ceftriaxon * MeSH
- dospělí MeSH
- doxycyklin terapeutické užití MeSH
- gonorea * farmakoterapie mikrobiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Neisseria gonorrhoeae MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Thermophilic bacteria of four genera in contrast to the commonly used production strains such as Bacillus subtilis, produce homologs other than menaquinone (MK) with seven isoprene units. The number of isoprene units and the configuration of double bonds are essential factors for their biological activity. The goal was to obtain a strain of bacteria that produces a wide range of MK homologs and only all-trans geometrical isomers, which was the strain G. kaustophilus. Using off-line two-dimensional LC-tandem MS in columns with the RP18 phase and the COSMOSIL cholester phase (separation according to the geometric configuration of double bonds) it was shown that thermophilic bacteria grown at different temperatures produce only all-trans isomers of menaquinones from MK-5 (menaquinone with five isoprenyl units) to MK-15 (fifteen isoprenyl units). Therefore, G. kaustophilus appears to be a biotechnologically important strain produces only trans isomers and additionally homologs from 5 to 15 isoprene units.
- MeSH
- Bacteria * MeSH
- butadieny * MeSH
- hmotnostní spektrometrie MeSH
- vitamin K 2 chemie MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
- MeSH
- albuminy * metabolismus MeSH
- cévní endotel účinky léků metabolismus MeSH
- Evansova modř MeSH
- glykokalyx * metabolismus účinky léků MeSH
- hyaluronoglukosaminidasa farmakologie MeSH
- kapilární permeabilita * účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Environmental compartments polluted with animal charcoal from the skin and hide cottage industries are rich in toxic heavy metals and diverse hydrocarbon classes, some of which are carcinogenic, mutagenic, and genotoxic, and thus require a bio-based eco-benign decommission strategies. A shotgun metagenomic approach was used to decipher the microbiome, hydrocarbon degradation genes, and heavy metal resistome of a microbial consortium (FN8) from an animal-charcoal polluted site enriched with fluorene. Structurally, the FN8 microbial consortium consists of 26 phyla, 53 classes, 119 orders, 245 families, 620 genera, and 1021 species. The dominant phylum, class, order, family, genus, and species in the consortium are Proteobacteria (51.37%), Gammaproteobacteria (39.01%), Bacillales (18.09%), Microbulbiferaceae (11.65%), Microbulbifer (12.21%), and Microbulbifer sp. A4B17 (19.65%), respectively. The microbial consortium degraded 57.56% (28.78 mg/L) and 87.14% (43.57 mg/L) of the initial fluorene concentration in 14 and 21 days. Functional annotation of the protein sequences (ORFs) of the FN8 metagenome using the KEGG GhostKOALA, KofamKOALA, NCBI's conserved domain database, and BacMet revealed the detection of hydrocarbon degradation genes for benzoate, aminobenzoate, polycyclic aromatic hydrocarbons (PAHs), chlorocyclohexane/chlorobenzene, chloroalkane/chloroalkene, toluene, xylene, styrene, naphthalene, nitrotoluene, and several others. The annotation also revealed putative genes for the transport, uptake, efflux, and regulation of heavy metals such as arsenic, cadmium, chromium, mercury, nickel, copper, zinc, and several others. Findings from this study have established that members of the FN8 consortium are well-adapted and imbued with requisite gene sets and could be a potential bioresource for on-site depuration of animal charcoal polluted sites.
- MeSH
- biodegradace MeSH
- dřevěné a živočišné uhlí MeSH
- fluoreny MeSH
- Gammaproteobacteria * MeSH
- látky znečišťující půdu * analýza MeSH
- lidé MeSH
- mikrobiota * genetika MeSH
- polycyklické aromatické uhlovodíky * metabolismus MeSH
- půda MeSH
- půdní mikrobiologie MeSH
- těžké kovy * MeSH
- uhlovodíky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chuť i míra hladu, ale i rychlost metabolizmu jsou geneticky determinovány a regulace probíhá na třech úrovních v mozku a také ve střevě, a to pomocí střevních hormonů a neuromodulátorů. Hubnutí není fyziologický proces, tělo je nastaveno tak, že bychom měli neustále přibírat až na hmotnost, která je nám zřejmě geneticky předurčena. Poslední roky se objevují nové moderní a velmi bezpečné léky na hubnutí a na léčbu obezity jako nemoci. Začíná převládat názor, že obezitu je třeba léčit doživotně, za pomoci nejen změny životního stylu, ale také za použití léků nebo postupů bariatrické chirurgie.
Appetite and hunger, as well as metabolic rate, are genetically determined and regulated at three levels in the brain and also in the bowel by bowel hormones and neuromodulators. Weight loss is not a physiological process, the body is set up to enable continuous weigh gaining up to the weight that is probably genetically predetermined for us. In recent years, new modern and very safe drugs are emerging for weight loss and for treating obesity as a disease. The opinion that obesity should be treated for life, not only with lifestyle changes but also with drugs or bariatric surgery procedures, is becoming predominant.
- MeSH
- bupropion terapeutické užití MeSH
- fentermin terapeutické užití MeSH
- glukagonu podobný peptid 1 terapeutické užití MeSH
- látky proti obezitě aplikace a dávkování terapeutické užití MeSH
- liraglutid terapeutické užití MeSH
- nadváha etiologie farmakoterapie genetika psychologie terapie MeSH
- naltrexon terapeutické užití MeSH
- obezita etiologie farmakoterapie genetika psychologie terapie MeSH
- orlistat terapeutické užití MeSH
- MeSH
- Borrelia burgdorferi komplex klasifikace patogenita MeSH
- ceftriaxon farmakologie terapeutické užití MeSH
- dítě MeSH
- doxycyklin farmakologie terapeutické užití MeSH
- erythema chronicum migrans diagnóza etiologie klasifikace MeSH
- lidé MeSH
- lymeská nemoc * diagnóza farmakoterapie komplikace prevence a kontrola MeSH
- lymská neuroborelióza diagnóza komplikace mikrobiologie MeSH
- protilátky bakteriální analýza klasifikace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
This study investigates the potential relationship between exposure to polycyclic aromatic hydrocarbons (PAHs), specifically monohydroxylated metabolites (OH-PAHs), in urine, and the prevalence of respiratory diseases in 2-year-old children residing in two locations within the Czech Republic - České Budějovice (control location) and the historically contaminated mining district of Most. Despite current air quality and lifestyle similarities between the two cities, our research aims to uncover potential long-term health effects, building upon previous data indicating distinctive patterns in the Most population. A total of 248 urine samples were analysed for the presence of 11 OH-PAHs. Employing liquid-liquid extraction with ethyl acetate and clean-up through dispersive solid-phase extraction, instrumental analysis was conducted using ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The incidence of respiratory diseases was assessed through questionnaires administered by paediatricians. The concentrations of OH-PAHs were elevated in urine samples from 2-year-olds in Most compared to those from České Budějovice. The incidence of respiratory diseases showed statistically significant higher levels of OH-PAHs in children from Most, together with a higher incidence of influenza. This association underlines the impact of environmental PAH exposure on children's respiratory health. It suggests that elevated urinary OH-PAH levels indicate an increased risk of developing respiratory diseases in the affected population. Further studies are needed to clarify the possible long-term health effects and to contribute to sound public health strategies.
- MeSH
- lidé MeSH
- nemoci dýchací soustavy epidemiologie moč MeSH
- pilotní projekty MeSH
- polycyklické aromatické uhlovodíky * moč MeSH
- předškolní dítě MeSH
- vystavení vlivu životního prostředí škodlivé účinky analýza MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
