scholarly journals In Vitro Effects of Paralytic Shellfish Toxins and Lytic Extracellular Compounds Produced by Alexandrium Strains on Hemocyte Integrity and Function in Mytilus edulis

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 544
Author(s):  
Virginia Angélica Bianchi ◽  
Ulf Bickmeyer ◽  
Urban Tillmann ◽  
Bernd Krock ◽  
Annegret Müller ◽  
...  
Keyword(s):  
Mytilus Edulis ◽  
Phagocytic Activity ◽  
In Vitro Assays ◽  
Shellfish Toxins ◽  
Paralytic Shellfish Toxins ◽  
Paralytic Shellfish ◽  
In Vitro Effects ◽  
Dose Dependent

Harmful effects caused by the exposure to paralytic shellfish toxins (PSTs) and bioactive extracellular compounds (BECs) on bivalves are frequently difficult to attribute to one or the other compound group. We evaluate and compare the distinct effects of PSTs extracted from Alexandrium catenella (Alex5) cells and extracellular lytic compounds (LCs) produced by A. tamarense (NX-57-08) on Mytilus edulis hemocytes. We used a 4 h dose–response in vitro approach and analyzed how these effects correlate with those observed in a previous in vivo feeding assay. Both bioactive compounds caused moderated cell death (10–15%), being dose-dependent for PST-exposed hemocytes. PSTs stimulated phagocytic activity at low doses, with a moderate incidence in lysosomal damage (30–50%) at all tested doses. LCs caused a dose-dependent impairment of phagocytic activity (up to 80%) and damage to lysosomal membranes (up to 90%). PSTs and LCs suppressed cellular ROS production and scavenged H2O2 in in vitro assays. Neither PSTs nor LCs affected the mitochondrial membrane potential in hemocytes. In vitro effects of PST extracts on M. edulis hemocytes were consistent with our previous study on in vivo exposure to PST-producing algae, while for LCs, in vivo and in vitro results were not as consistent.

Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice

1995 ◽  
Vol 14 (8) ◽  
pp. 623-629 ◽  
Author(s):  
DH Kim ◽  
EJ Kim ◽  
SS Han ◽  
JK Roh ◽  
TC Jeong ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Liver Microsomes ◽  
Receptor Antagonists ◽  
Sleeping Time ◽  
Icr Mice ◽  
In Vitro Effects ◽  
Hexobarbital Metabolism ◽  
Dose Dependent

1 The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2 Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O- deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethy lase(ERDM) activities, respectively. It was found that hist amine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3 Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibito ry effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY- 80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4 It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5 The present results indicate that mifentidine and its derivatives not only antagonise the H 2-receptor but also inhibit P450 enzymes.

scholarly journals Sls1p Stimulates Sec63p-Mediated Activation of Kar2p in a Conformation-Dependent Manner in the Yeast Endoplasmic Reticulum

2000 ◽  
Vol 20 (18) ◽  
pp. 6923-6934 ◽  
Author(s):  
Mehdi Kabani ◽  
Jean-Marie Beckerich ◽  
Claude Gaillardin
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Translocation ◽  
Synthetic Lethality ◽  
In Vitro Assays ◽  
Endoplasmic Reticulum Membrane ◽  
Dependent Manner ◽  
Dose Dependent

ABSTRACT We previously characterized the SLS1 gene in the yeastYarrowia lipolytica and showed that it interacts physically with YlKar2p to promote translocation across the endoplasmic-reticulum membrane (A. Boisramé, M. Kabani, J. M. Beckerich, E. Hartmann, and C. Gaillardin, J. Biol. Chem. 273:30903–30908, 1998). A Y. lipolytica Kar2p mutant was isolated that restored interaction with an Sls1p mutant, suggesting that the interaction with Sls1p could be nucleotide and/or conformation dependent. This result was used as a working hypothesis for more accurate investigations in Saccharomyces cerevisiae. We show by two-hybrid an in vitro assays that the S. cerevisiae homologue of Sls1p interacts with ScKar2p. Using dominant lethal mutants of ScKar2p, we were able to show that ScSls1p preferentially interacts with the ADP-bound conformation of the molecular chaperone. Synthetic lethality was observed between ΔScsls1 and translocation-deficientkar2 or sec63-1 mutants, providing in vivo evidence for a role of ScSls1p in protein translocation. Synthetic lethality was also observed with ER-associated degradation and folding-deficient kar2 mutants, strongly suggesting that Sls1p functions are not restricted to the translocation process. We show that Sls1p stimulates in a dose-dependent manner the binding ofScKar2p on the lumenal J domain of Sec63p fused to glutathione S-transferase. Moreover, Sls1p is shown to promote the Sec63p-mediated activation of Kar2p's ATPase activity. Our data strongly suggest that Sls1p could be the first GrpE-like protein described in the endoplasmic reticulum.

scholarly journals 757 M9657, a novel tumor-targeted conditional anti-CD137 agonist displays MSLN-dependent anti-tumor immunity

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A792-A792
Author(s):  
Chunxiao Xu ◽  
Brain Rabinovich ◽  
Amit Deshpande ◽  
Xueyuan Zhou ◽  
Frederic Christian Pipp ◽  
...  
Keyword(s):  
Bispecific Antibody ◽  
Animal Experiments ◽  
Immune Memory ◽  
In Vitro Assays ◽  
Therapeutic Window ◽  
Cytotoxic T Cell ◽  
Functional Assay ◽  
Dose Dependent

BackgroundThe costimulatory receptor CD137 (also known as 4-1BB and TNFRSF9) plays an important role in sustaining effective cytotoxic T cell immune responses and its agonism has been investigated as a cancer immunotherapy. In clinical trials, the systemic administration of the 1st generation CD137 agonist monotherapies, utomilumab and urelumab, were suspended due to either low anti-tumor efficacy or hepatotoxicity mediated by recognized epitope on CD137 and FcγR ligand-dependent clustering.MethodsM9657, a bispecific antibody was engineered a tetravalent bispecific antibody (mAb2) format with the Fab portion binding to the tumor antigen Mesothelin (MSLN) and a modified CH2-CH3 domain as Fc antigen binding (Fcab) portion binding to CD137. M9657 has a human IgG1 backbone with LALA mutations to abrogate the binding to Fcγ receptor. The biological characteristics and activities of M9657 were investigated in a series of in vitro assays and the in vivo efficacy was investigated in syngeneic tumor models with FS122m, a murine-reactive surrogate with the same protein structure of M9657.ResultsM9657 binds efficiently to both human and Cynomolgus CD137 as well as MSLN. In the cellular functional assay, M9657 displayed MSLN- and TCR/CD3 interaction (signal 1)-dependent cytokine release and tumor cell cytotoxicity associated with Bcl-XL activation and immune memory formation. FS122m demonstrated potent MSLN- and dose- dependent in vivo anti-tumor efficacy (figure 1). Comparing with 3H3, a Urelumab surrogate Ab, FS122m displayed an improved therapeutic window with significantly lower for on-target /off-tumor toxicity.ConclusionsTaken together, M9657 exhibits a promising developability profile as a tumor-targeted immune agonist with potent anti-cancer activity, but without systemic immune activation.Ethics ApprovalAll animal experiments were performed in accordance with EMD Serono Research & Development Institute (protocol 17-008, 20-005) and Wuxi AppTec Animal Care and Use Committee (IACUC) guidelines.Abstract 757 Figure 1FS122m displayed dose-dependent anti-tumor efficacy

scholarly journals In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Qi Xin ◽  
Miaomiao Yuan ◽  
Huanping Li ◽  
Xiaoxia Song ◽  
Jun Lu ◽  
...  
Keyword(s):  
Energy Production ◽  
Alveolar Echinococcosis ◽  
Weekly Treatment ◽  
Significant Toxicity ◽  
Liver And Kidney ◽  
In Vitro Effects ◽  
In Vivo Effects ◽  
Dose Dependent

AbstractWhile searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).

scholarly journals Effects of zearalenone, α-zearalenol, and genistein on boar sperm motility in vitro

2017 ◽  
Vol 62 (No. 10) ◽  
pp. 435-445 ◽  
Author(s):  
A. Krejcárková ◽  
P. Folková ◽  
O. Šimoník ◽  
M. Šašková ◽  
R. Krejčířová ◽  
...  
Keyword(s):  
Sperm Motility ◽  
Computer Assisted ◽  
Sperm Analysis ◽  
Toxicological Research ◽  
Computer Assisted Sperm Analysis ◽  
In Vitro Effects ◽  
Dose Dependent Increase ◽  
Dose Dependent

Genistein (GEN) and zearalenone (ZEA), environmental oestrogens commonly present in feedstuff for pigs, are known for their effects on reproductive functions. The aim was to verify the in vitro effects of 0.5–20 µM concentrations of GEN, ZEA and its metabolite α-zearalenol (α-ZOL) on pig sperm motility. A dose-dependent increase of the immotile sperm amount against fast and medium-fast sperm clusters was observed with all three oestrogens from the lowest concentrations tested. Individual CASA (computer-assisted sperm analysis) parameters of motile sperms seemed to be less sensitive indicators. This should be considered especially in toxicological research on a sperm model. Background of inconsistencies in to date-published papers is discussed. The results shift the effective concentrations of ZEA, α-ZOL, and GEN to values achievable in vivo and raises the questions of risk assessment of these compounds in pig reproduction.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects

A in Vivo Assay for Standardizing Heparin Preparations

1979 ◽  
Vol 41 (03) ◽  
pp. 576-582
Author(s):  
A R Pomeroy
Keyword(s):  
In Vitro Assays ◽  
British Pharmacopoeia ◽  
In Vitro Method ◽  
Standard Preparation ◽  
Reliable Estimation ◽  
Assay Procedure ◽  
Accuracy And Precision ◽  
Heparin Preparation

SummaryThe limitations of currently used in vitro assays of heparin have demonstrated the need for an in vivo method suitable for routine use.The in vivo method which is described in this paper uses, for each heparin preparation, four groups of five mice which are injected intravenously with heparin according to a “2 and 2 dose assay” procedure. The method is relatively rapid, requiring 3 to 4 hours to test five heparin preparations against a standard preparation of heparin. Levels of accuracy and precision acceptable for the requirements of the British Pharmacopoeia are obtained by combining the results of 3 to 4 assays of a heparin preparation.The similarity of results obtained the in vivo method and the in vitro method of the British Pharmacopoeia for heparin preparations of lung and mucosal origin validates this in vivo method and, conversely, demonstrates that the in vitro method of the British Pharmacopoeia gives a reliable estimation of the in vivo activity of heparin.

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