BACKGROUND: Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. METHODS: SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. FINDINGS: Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. INTERPRETATION: Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. FUNDING: AstraZeneca.

• MeSH
• antagonisté estrogenového receptoru aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• azetidiny MeSH
• dospělí MeSH
• fulvestrant * aplikace a dávkování   MeSH
• hormonální protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• isochinoliny MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   patologie   mortalita   MeSH
• postmenopauza * MeSH
• receptor erbB-2 * analýza   metabolismus   MeSH
• receptory pro estrogeny * metabolismus   analýza   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antagonisté estrogenového receptoru MeSH
• AZD9833 MeSH Prohlížeč
• azetidiny MeSH
• ERBB2 protein, human MeSH Prohlížeč
• fulvestrant * MeSH
• hormonální protinádorové látky MeSH
• isochinoliny MeSH
• receptor erbB-2 * MeSH
• receptory pro estrogeny * MeSH

The placenta plays a critical role in maternal-fetal nutrient transport and fetal protection against drugs. Creating physiological in vitro models to study these processes is crucial, but technically challenging. This study introduces an efficient cell model that mimics the human placental barrier using co-cultures of primary trophoblasts and primary human umbilical vein endothelial cells (HUVEC) on a Transwell®-based system. Monolayer formation was examined over 7 days by determining transepithelial electrical resistance (TEER), permeability of Lucifer yellow (LY) and inulin, localization of transport proteins at the trophoblast membrane (immunofluorescence), and syncytialization markers (RT-qPCR/ELISA). We analysed diffusion-based (caffeine/antipyrine) and transport-based (leucine/Rhodamine-123) processes to study the transfer of physiologically relevant compounds. The latter relies on the adequate localization and function of the amino-acid transporter LAT1 and the drug transporter P-glycoprotein (P-gp) which were studied by immunofluorescence microscopy and application of respective inhibitors (2-Amino-2-norbornanecarboxylic acid (BCH) for LAT1; cyclosporine-A for P-gp). The formation of functional monolayer(s) was confirmed by increasing TEER values, low LY transfer rates, minimal inulin leakage, and appropriate expression/release of syncytialization markers. These results were supported by microscopic monitoring of monolayer formation. LAT1 was identified on the apical and basal sides of the trophoblast monolayer, while P-gp was apically localized. Transport assays confirmed the inhibition of LAT1 by BCH, reducing both intracellular leucine levels and leucine transport to the basal compartment. Inhibiting P-gp with cyclosporine-A increased intracellular Rhodamine-123 concentrations. Our in vitro model mimics key aspects of the human placental barrier. It represents a powerful tool to study nutrient and drug transport mechanisms across the placenta, assisting in evaluating safer pregnancy therapies.

• Klíčová slova
• LAT1, P‐gp, co‐culture, endothelial cell, placental barrier, polarized monolayer, primary trophoblast, transport,
• MeSH
• biologické modely MeSH
• biologický transport MeSH
• endoteliální buňky pupečníkové žíly (lidské) * metabolismus   MeSH
• inulin metabolismus   MeSH
• isochinoliny MeSH
• kokultivační techniky MeSH
• leucin metabolismus   MeSH
• lidé MeSH
• maternofetální výměna látek * MeSH
• P-glykoprotein metabolismus   MeSH
• placenta * metabolismus   MeSH
• rhodamin 123 metabolismus   MeSH
• těhotenství MeSH
• trofoblasty * metabolismus   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inulin MeSH
• isochinoliny MeSH
• leucin MeSH
• lucifer yellow MeSH Prohlížeč
• P-glykoprotein MeSH
• rhodamin 123 MeSH

BACKGROUND: Resistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes; however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies. METHODS: We compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations. RESULTS: Carfilzomib, via proteasome β5 + β2 inhibition, is more cytotoxic in TNBC than bortezomib, which inhibits β5 + β1 proteasome subunits. The cytotoxicity of carfilzomib was significantly potentiated by nelfinavir or lopinavir. Carfilzomib with lopinavir induced endoplasmic reticulum stress and pro-apoptotic UPR through the accumulation of excess proteasomal substrate protein in TNBC in vitro. Moreover, lopinavir increased the intracellular availability of carfilzomib by inhibiting carfilzomib export from cells that express high levels and activity of ABCB1, but not ABCG2. CONCLUSION: Proteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation.

• MeSH
• ABC transportér z rodiny G, člen 2 * metabolismus   antagonisté a inhibitory   MeSH
• apoptóza účinky léků   MeSH
• bortezomib * farmakologie   MeSH
• inhibitory HIV-proteasy * farmakologie   MeSH
• inhibitory proteasomu farmakologie   MeSH
• lidé MeSH
• Lopinavir * farmakologie   MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny antagonisté a inhibitory   metabolismus   MeSH
• nelfinavir * farmakologie   MeSH
• oligopeptidy * farmakologie   MeSH
• P-glykoproteiny metabolismus   MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   MeSH
• signální dráha UPR * účinky léků   MeSH
• stres endoplazmatického retikula účinky léků   MeSH
• synergismus léků * MeSH
• triple-negativní karcinom prsu * farmakoterapie   patologie   MeSH
• XBP1 metabolismus   genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportér z rodiny G, člen 2 * MeSH
• ABCB1 protein, human MeSH Prohlížeč
• ABCG2 protein, human MeSH Prohlížeč
• bortezomib * MeSH
• carfilzomib MeSH Prohlížeč
• inhibitory HIV-proteasy * MeSH
• inhibitory proteasomu MeSH
• Lopinavir * MeSH
• nádorové proteiny MeSH
• nelfinavir * MeSH
• oligopeptidy * MeSH
• P-glykoproteiny MeSH
• XBP1 protein, human MeSH Prohlížeč
• XBP1 MeSH

Venetoclax (VEN), a B-cell lymphoma 2 (BCL2) inhibitor, has a promising single-agent activity in mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), and large BCLs, but remissions were generally short, which call for rational drug combinations. Using a panel of 21 lymphoma and leukemia cell lines and 28 primary samples, we demonstrated strong synergy between VEN and A1155463, a BCL-XL inhibitor. Immunoprecipitation experiments and studies on clones with knockout of expression or transgenic expression of BCL-XL confirmed its key role in mediating inherent and acquired VEN resistance. Of note, the VEN and A1155463 combination was synthetically lethal even in the cell lines with lack of expression of the proapoptotic BCL2L11/BIM and in the derived clones with genetic knockout of BCL2L11/BIM. This is clinically important because BCL2L11/BIM deletion, downregulation, or sequestration results in VEN resistance. Immunoprecipitation experiments further suggested that the proapoptotic effector BAX belongs to principal mediators of the VEN and A1155463 mode of action in the BIM-deficient cells. Lastly, the efficacy of the new proapoptotic combination was confirmed in vivo on a panel of 9 patient-derived lymphoma xenografts models including MCL (n = 3), B-ALL (n = 2), T-ALL (n = 1), and diffuse large BCL (n = 3). Because continuous inhibition of BCL-XL causes thrombocytopenia, we proposed and tested an interrupted 4 days on/3 days off treatment regimen, which retained the desired antitumor synergy with manageable platelet toxicity. The proposed VEN and A1155463 combination represents an innovative chemotherapy-free regimen with significant preclinical activity across diverse BCL2+ hematologic malignancies irrespective of the BCL2L11/BIM status.

• MeSH
• apoptóza účinky léků   MeSH
• benzothiazoly MeSH
• bicyklické sloučeniny heterocyklické * farmakologie   terapeutické užití   MeSH
• chemorezistence * MeSH
• isochinoliny MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protein bcl-X * metabolismus   antagonisté a inhibitory   MeSH
• protein BCL2L11 * metabolismus   genetika   MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• protoonkogenní proteiny c-bcl-2 metabolismus   antagonisté a inhibitory   MeSH
• sulfonamidy * farmakologie   terapeutické užití   MeSH
• synergismus léků MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• A-1155463 MeSH Prohlížeč
• BCL2L1 protein, human MeSH Prohlížeč
• benzothiazoly MeSH
• bicyklické sloučeniny heterocyklické * MeSH
• isochinoliny MeSH
• protein bcl-X * MeSH
• protein BCL2L11 * MeSH
• protinádorové látky MeSH
• protoonkogenní proteiny c-bcl-2 MeSH
• sulfonamidy * MeSH
• venetoclax MeSH Prohlížeč

The isoquinoline alkaloids found in Amaryllidaceae are attracting attention due to attributes that can be harnessed for the development of new drugs. The possible molecular mechanisms by which montanine exerts its inhibitory effects against cancer cells have not been documented. In the present study, montanine, manthine and a series of 15 semisynthetic montanine analogues originating from the parent alkaloid montanine were screened at a single test dose of 10 μM to explore their cytotoxic activities against a panel of eight cancer cell lines and one non-cancer cell line. Among montanine and its analogues, montanine and its derivatives 12 and 14 showed the highest cytostatic activity in the initial single-dose screening. However, the native montanine exhibited the greatest antiproliferative activity against cancer cells, with a lower mean IC50 value of 1.39 µM, compared to the displayed mean IC50 values of 2.08 µM for 12 and 3.57 µM for 14. Montanine exhibited the most potent antiproliferative activity with IC50 values of 1.04 µM and 1.09 µM against Jurkat and A549 cell lines, respectively. We also evaluated montanine's cytotoxicity and cell death mechanisms. Our results revealed that montanine triggered apoptosis of MOLT-4 cells via caspase activation, mitochondrial depolarisation and Annexin V/PI double staining. The Western blot results of MOLT-4 cells showed that the protein levels of phosphorylated Chk1 Ser345 were upregulated with increased montanine concentrations. Our findings provide new insights into the mechanisms underlying the cytostatic, cytotoxic and pro-apoptotic activities of montanine alkaloids in lung adenocarcinoma A549 and leukemic MOLT-4 cancer cell types.

• Klíčová slova
• Apoptosis, Cell cycle arrest, Cytotoxicity, DNA damage, Manthine, Montanine, Semisynthetic derivatives,
• MeSH
• alkaloidy amarylkovitých * farmakologie   MeSH
• alkaloidy * MeSH
• Amaryllidaceae * MeSH
• apoptóza MeSH
• cytostatické látky * MeSH
• isochinoliny farmakologie   MeSH
• lidé MeSH
• nádory plic * MeSH
• protinádorové látky * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy amarylkovitých * MeSH
• alkaloidy * MeSH
• cytostatické látky * MeSH
• isochinoliny MeSH
• montanine MeSH Prohlížeč
• protinádorové látky * MeSH

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

• Klíčová slova
• lower urinary tract symptoms, overactive, peroneal nerve, solifenacin succinate, transcutaneous electric nerve stimulation, urinary bladder,
• MeSH
• antagonisté muskarinových receptorů MeSH
• hyperaktivní močový měchýř * farmakoterapie   MeSH
• kvalita života MeSH
• lidé MeSH
• prospektivní studie MeSH
• solifenacin sukcinát * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté muskarinových receptorů MeSH
• solifenacin sukcinát * MeSH

The aim of the study was to point out the contribution of new invasive therapeutic procedures in the treatment of advanced stages of Parkinson's disease (PD) in comparison with classical oral pharmacotherapy. Data originated from a group of 43 patients with PD, 39% (17) with classic treatment, 23% (10) with intestinal gel of methyl ester levodopa (Duodopa), 19% (8) of patients were using subcutaneous delivery of apomorphine (APO) and the same quantity of patients had undergone deep brain stimulation (DBS). Majority of patients had advanced stages of PD, stage 4, by standards of Hoehn and Yahr scale (Hoehn and Yahr, 1967). Research observed improvement in majority of patients with novel treatments. A positive effect was also noted in the reduced need for oral therapy, where there was a significant decrease in all new therapies. Benefits were observed in the amount of antiparkinsonic drugs taken per os, where we observed reduction in all new therapies. A positive effect of the new therapeutic approaches in reducing "off" periods in patients has also been noted. In the case of Duodopa and DBS, the "off" period was shortened up to 50% and in the apomorphine pump up to 40%. Patients also reported reduction of some symptoms like rigidity, tremor and bradykinesis while dyskinesis still remains suba challenge. On the basis of the obtained results, it can be concluded that new therapeutic procedures for PCh will make it possible to manage symptoms typical of advanced stages of the disease, which without these procedures would lead to disability, which is the main reason for their indication. However, in early stages, well responding patients or in slow progressing disease oral antiparkinsonics are remaining as golden standard of treatment. This is not just due to good response but also because these classic drug formulations are significantly less expensive. In Slovakia, novel treatments are accessible through healthcare insurance only after secondary revision by insurance company doctors.

• Klíčová slova
• Duodopa, Parkinson’s disease, apomorphine pump, deep brain stimulation, pharmacotherapy,
• MeSH
• aplikace orální MeSH
• apomorfin MeSH
• estery MeSH
• lidé MeSH
• Parkinsonova nemoc * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• apomorfin MeSH
• estery MeSH

Current diagnostic options for Parkinson's disease are very limited and primarily based on characteristic clinical symptoms. Thus, there are urgent needs for reliable biomarkers that enable us to diagnose the disease in the early stages, differentiate it from other atypical Parkinsonian syndromes, monitor its progression, increase knowledge of its pathogenesis, and improve the development of potent therapies. A promising group of potential biomarkers are endogenous tetrahydroisoquinoline metabolites, which are thought to contribute to the multifactorial etiology of Parkinson's disease. The aim of this critical review is to highlight trends and limitations of available traditional and modern analytical techniques for sample pretreatment (extraction and derivatization procedures) and quantitative determination of tetrahydroisoquinoline derivatives in various types of mammalian fluids and tissues (urine, plasma, cerebrospinal fluid, brain tissue, liver tissue). Particular attention is paid to the most sensitive and specific analytical techniques, involving immunochemistry and gas or liquid chromatography coupled with mass spectrometric, fluorescence, or electrochemical detection. The review also includes a discussion of other relevant agents proposed and tested in Parkinson's disease.

• Klíčová slova
• Tetrahydroisoquinolines, biomarker, fluids, mammals, quantitative analysis, tissues,
• MeSH
• biologické markery MeSH
• lidé MeSH
• Parkinsonova nemoc * diagnóza   MeSH
• tetrahydroisochinoliny * analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• tetrahydroisochinoliny * MeSH

Antibiotic resistance in diarrhea-causing bacteria and its disruption of gut microbiota composition are health problems worldwide. The development of combinatory agents that increase the selective inhibitory effect (synergism) against diarrheagenic pathogens and, simultaneously, have a lowered impact (antagonism) or no negative action on the gut microbiota is therefore proposed as a new strategy efficient for chemotherapy against diarrheal conditions. In this study, the in vitro selective combinatory effect of ciprofloxacin with nitroxoline, sanguinarine, and zinc pyrithione, representing various classes of alkaloid-related compounds (nitroquinolines, benzylisoquinolines and metal-pyridine derivative complexes) against selected standard diarrhea-causing (Bacillus cereus, Enterococcus faecalis, Listeria monocytogenes, Shigella flexneri, and Vibrio parahaemolyticus) and gut-beneficial (Bifidobacterium adolescentis, Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, Lactobacillus casei, and Lactobacillus rhamnosus) bacteria, was evaluated according to the sum of fractional inhibitory concentration indices (FICIs) obtained by the checkerboard method. The results showed that the individual combination of ciprofloxacin with nitroxoline, sanguinarine, and zinc pyrithione produced a synergistic effect against the pathogenic bacteria, with FICI values ranging from 0.071 to 0.5, whereas their antagonistic interaction toward the Bifidobacterium strains (with FICI values ranging from 4.012 to 8.023) was observed. Ciprofloxacin-zinc pyrithione produced significant synergistic action against S. flexneri, whereas a strong antagonistic interaction was observed toward B. breve for the ciprofloxacin-nitroxoline combination. These findings suggest that certain combinations of agents tested in this study can be used for the development of antidiarrheal therapeutic agents with reduced harmful action on the gastrointestinal microbiome. However, further studies focused on their pharmacological efficacy and safety are needed before they are considered for clinical trials. IMPORTANCE Diarrheal infections, which are commonly treated by antibiotics, are still responsible for over 4 to 5 million cases of human deaths annually. Moreover, the rising incidence of antibiotic resistance and its negative effect on beneficial bacteria (e.g., Bifidobacteria) of the gut microbial community are another problem. Thus, the development of selective agents able to inhibit diarrheal bacteria and, simultaneously, that have no negative impact on the gut microbiota, is important. Our results showed that individual combinations of ciprofloxacin with nitroxoline, sanguinarine, and zinc pyrithione produced synergism against the pathogenic bacteria, whereas their antagonistic interaction toward the beneficial strains was observed. The antagonism can be considered a positive effect contributing to the safety of the therapeutic agents, whereas their synergism against diarrheal bacteria significantly potentiates total antimicrobial efficacy. The certain combinations tested in this study can be used for the development of antidiarrheal agents with reduced harmful action on the gastrointestinal microbiome.

• Klíčová slova
• antagonism, antimicrobial agents, diarrhea, gut microbiota, selectivity, synergism,
• MeSH
• antibakteriální látky farmakologie   MeSH
• Bacteria MeSH
• benzylisochinoliny * MeSH
• Bifidobacterium MeSH
• ciprofloxacin farmakologie   MeSH
• lidé MeSH
• nitrochinoliny * MeSH
• obstipancia MeSH
• průjem farmakoterapie   MeSH
• pyridiny farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• benzylisochinoliny * MeSH
• ciprofloxacin MeSH
• nitrochinoliny * MeSH
• nitroxoline MeSH Prohlížeč
• obstipancia MeSH
• pyridiny MeSH
• pyrithione zinc MeSH Prohlížeč
• sanguinarine MeSH Prohlížeč

This study aimed to assess the toxicity of praziquantel (anthelmintic drug) in different developmental stages of common carp (Cyprinus carpio) based on mortality, early ontogeny, growth, oxidative stress, antioxidant enzymes, histology and behaviour. Praziquantel at all tested concentrations ranging from 1 to 4 mg/L showed no significant adverse effects on mortality, the early ontogeny and behaviour locomotory (activity, moved distance and velocity) of carp after 35-day exposure. Concentrations of 3 and 4 mg/L caused significantly (P < 0.01) lower growth, total superoxide dismutase and catalase activities compared with controls. Praziquantel is safe for the early life of carp in concentrations ≤ 2 mg/L.

• MeSH
• antioxidancia farmakologie   MeSH
• chemické látky znečišťující vodu * toxicita   MeSH
• embryo nesavčí MeSH
• kapři * MeSH
• katalasa farmakologie   MeSH
• larva MeSH
• praziquantel farmakologie   MeSH
• superoxiddismutasa farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• chemické látky znečišťující vodu * MeSH
• katalasa MeSH
• praziquantel MeSH
• superoxiddismutasa MeSH