scholarly journals In VitroActivities of Hexaazatrinaphthylenes against Leishmania spp.

2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Content Type ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Leishmania Spp ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Potential Use

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

scholarly journals Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box

2021 ◽  
Vol 14 (12) ◽  
pp. 1219
Author(s):  
Atteneri López-Arencibia ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
Carlos J. Bethencourt-Estrella ◽  
Desirée San San Nicolás-Hernández ◽  
...  
Keyword(s):  
Cell Death ◽  
Protozoan Parasite ◽  
Leishmania Amazonensis ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Parasite Leishmania ◽  
Novel Therapeutic

The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. amazonensis promastigotes and intracellular amastigotes. Moreover, studies on the mechanism of cell death showed that compounds 3 and 5 induced an apoptotic process while the compounds 7, 9 and 10 seem to induce an autophagic mechanism. The present findings underline the potential of these five molecules as novel therapeutic leishmanicidal agents.

Inhibition by dipyridamole of cerebral vasospasm induced in vitro by whole blood

1983 ◽  
Vol 58 (3) ◽  
pp. 352-355 ◽  
Author(s):  
Martin Linder
Keyword(s):  
Cerebral Artery ◽  
Whole Blood ◽  
Prostaglandin Synthesis ◽  
Cerebral Vessel ◽  
Content Type ◽  
Arterial Blood ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

✓ This study evaluates the effect of dipyridamole, an inhibitor of platelet aggregation, on cerebral artery contraction induced in vitro by the addition of whole blood. Whole fresh arterial blood added to isolated rabbit basilar artery bathed in a physiological buffer produces a sustained contraction in vessels observed for 60 minutes. Significant dose-dependent inhibition of contraction was observed when dipyridamole was added to the vessel bath. This effect was not influenced by preincubating cerebral vessels with aspirin, an inhibitor of prostaglandin synthesis. It is suggested that inhibition of whole blood-induced cerebral artery contraction by dipyridamole does not result from potentiation of cerebral vessel prostaglandin pathways, but possibly from a direct effect on platelets.

Differences between antigenic determinants of pig and cat zona pellucida proteins

Reproduction ◽  
2000 ◽  
pp. 15-23 ◽  
Author(s):  
K Jewgenow ◽  
M Rohleder ◽  
I Wegner
Keyword(s):  
In Vitro Fertilization ◽  
Zona Pellucida ◽  
Antigenic Determinants ◽  
Vitro Fertilization ◽  
Contraceptive Vaccine ◽  
Sperm Binding ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.

scholarly journals In vitro interactions of PGE and cAMP with murine and human erythroid precursors

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 74-79 ◽  
Author(s):  
GB Rossi ◽  
AR Migliaccio ◽  
G Migliaccio ◽  
F Lettieri ◽  
M Di Rosa ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Colony Growth ◽  
Inhibitory Influence ◽  
Adherent Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulating Factor ◽  
In Vitro Interactions

Abstract Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.

scholarly journals On the Molecular Pharmacology of Resveratrol on Oxidative Burst Inhibition in Professional Phagocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Radomír Nosáľ ◽  
Katarína Drábiková ◽  
Viera Jančinová ◽  
Tomáš Perečko ◽  
Gabriela Ambrožová ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Antioxidant Activities ◽  
Raw 264.7 Cells ◽  
Human Neutrophils ◽  
Nitrite Production ◽  
Inos Protein Expression ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Resveratrol—3,5,4′-trihydroxystilbene—possesses antioxidant activitiesin vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol. Results from isolated human neutrophils revealed that resveratrol was active extracellularly as well as intracellularly in inhibiting the generation of reactive oxygen species. Liberation of ATP and analysis of apoptosis showed that in the concentration of 100 μM, resveratrol did not change the viability and integrity of isolated neutrophils. Western blot analysis documented that resveratrol in concentrations of 10 and 100 μM significantly decreased PMA-induced phosphorylation of PKCα/βII. Dose-dependent inhibition of nitrite production and iNOS protein expression in RAW 264.7 cells indicated possible interference of resveratrol with reactive nitrogen radical generation in professional phagocytes. The results suggest that resveratrol represents an effective naturally occurring substance with potent pharmacological effect on oxidative burst of human neutrophils and nitric oxide production by macrophages. It should be further investigated for its pharmacological activity against oxidative stress in ischaemia reperfusion, inflammation, and other pathological conditions, particularly neoplasia.

scholarly journals Influence of Human Sera on the In Vitro Activity of the Echinocandin Caspofungin (MK-0991) against Aspergillus fumigatus

2000 ◽  
Vol 44 (12) ◽  
pp. 3302-3305 ◽  
Author(s):  
Tom Chiller ◽  
Kouros Farrokhshad ◽  
Elmer Brummer ◽  
David A. Stevens
Keyword(s):  
Aspergillus Fumigatus ◽  
Human Serum ◽  
Hyphal Growth ◽  
Significant Inhibition ◽  
Dependent Inhibition ◽  
Human Sera ◽  
Dose Dependent Inhibition ◽  
Synthase Inhibitor ◽  
Dose Dependent

ABSTRACT There have been several reports that the activity of echinocandin antifungal agents is not affected or decreased in the presence of human sera. It is known that these drugs are bound >80% in animal and human sera. The activity of the echinocandin caspofungin (MK-0991), a 1,3-β-d-glucan synthase inhibitor, againstAspergillus fumigatus with and without human sera was studied. Conidia of A. fumigatus in microtest plate wells formed germlings after overnight culture in RPMI 1640. Caspofungin was then added with or without serum, and the germlings were incubated at 37°C for 24 h. Human serum (5%) in RPMI 1640 alone did not significantly inhibit the growth of A. fumigatus in vitro. Caspofungin in RPMI 1640 exhibited dose-dependent inhibition, with concentrations of 0.1 and 0.05 μg/ml inhibiting 24.9% +/− 10.4% and 11.7% +/− 3.6%, respectively (n = 10;P < 0.01). The addition of 5% human serum to caspofungin at 0.1 or 0.05 μg/ml increased the inhibition to 78.6% +/− 5.8% or 58.3% +/− 19.2%, respectively (n = 10; P < 0.01 versus controls and versus the drug without serum). Lower concentrations of serum also potentiated drug activity. The effect of human sera was further seen when using caspofungin that had lost activity (e.g., by storage) against A. fumigatus at 0.1 μg/ml. Inactive caspofungin alone demonstrated no significant inhibition of hyphal growth, whereas the addition of 5% human serum to the inactive drug showed 83% +/− 16.5% inhibition (n = 5; P < 0.01). The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. In contrast to prior reports, this study suggests that human serum acts synergistically with caspofungin to enhance its inhibitory activity in vitro against A. fumigatus.

scholarly journals In vitro interactions of PGE and cAMP with murine and human erythroid precursors

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 74-79 ◽  
Author(s):  
GB Rossi ◽  
AR Migliaccio ◽  
G Migliaccio ◽  
F Lettieri ◽  
M Di Rosa ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Colony Growth ◽  
Inhibitory Influence ◽  
Adherent Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulating Factor ◽  
In Vitro Interactions

Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.

Effect of PGE2 and alpha-adrenergic agonists on AVP-dependent cAMP levels in rabbit and rat CCT

1988 ◽  
Vol 255 (1) ◽  
pp. F43-F48 ◽  
Author(s):  
D. Chabardes ◽  
C. Brick-Ghannam ◽  
M. Montegut ◽  
S. Siaume-Perez
Keyword(s):  
Adrenergic Agonists ◽  
Camp Production ◽  
Synthesis Inhibitor ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Prostaglandin Synthesis Inhibitor ◽  
Collecting Tubules ◽  
Camp Levels ◽  
Dose Dependent

The effect of prostaglandins and alpha-adrenergic agonists on arginine vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) production was investigated in microdissected rat and rabbit cortical collecting tubules (CCT) incubated in vitro. In rabbit CCT, addition to all media of a prostaglandin synthesis inhibitor increased this production; exogenous prostaglandin E2 (PGE2) induced a reproducible dose-dependent inhibition of cAMP accumulation. Maximal inhibition (mean: 57.5%) was observed with 0.3 microM PGE2, and threshold inhibition was observed with concentrations ranging from 3 to 10 nM PGE2. Inhibition of cAMP levels in rabbit CCT was also obtained with 0.3 microM PGF2 alpha (mean inhibition: 44.3%) but not with alpha-adrenergic agonists studied under the same conditions. The opposite was observed in rat CCT studied in parallel: the alpha-agonists inhibited cAMP production by up to 80%, but PGE2 had no effect.

Aluminum inhibits bone nodule formation and calcification in vitro

1993 ◽  
Vol 264 (5) ◽  
pp. F882-F890 ◽  
Author(s):  
S. M. Sprague ◽  
N. S. Krieger ◽  
D. A. Bushinsky
Keyword(s):  
Calcium Uptake ◽  
Calcium Content ◽  
Neonatal Mouse ◽  
Nodule Formation ◽  
Collagen Production ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Bone Nodule Formation

Cells isolated from neonatal mouse calvariae can be induced to form mineralized nodules after exposure to ascorbic acid and beta-glycerophosphate. To determine whether aluminum inhibits nodule formation and subsequent mineralization, cells isolated from neonatal mouse calvariae were induced to form nodules and incubated with increasing concentrations of aluminum (10(-7) to 10(-5) M). Compared with control and 10(-7) M aluminum-supplemented cultures, the number of nodules formed and the number of nodules calcified were reduced in cells incubated with 10(-6) and 10(-5) M aluminum. The cumulative net calcium uptake into the nodules and their final calcium content were also decreased with 10(-6) and 10(-5) M aluminum. After 10 and 18 days of incubation, aluminum did not affect DNA synthesis or release of alkaline phosphatase but significantly inhibited collagen production. Thus aluminum induced a dose-dependent inhibition of nodule formation and calcification that may be related to its inhibition of collagen production.

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