scholarly journals In Vitro Tests for Assessing the Neutralizing Ability of Snake Antivenoms: Toward the 3Rs Principles

2021 ◽  
Vol 11 ◽  
Author(s):  
José María Gutiérrez ◽  
Mariángela Vargas ◽  
Álvaro Segura ◽  
María Herrera ◽  
Mauren Villalta ◽  
...  
Keyword(s):  
State Of The Art ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
Enzyme Assays ◽  
Snake Venoms ◽  
Experimental Animals ◽  
Functional Assays ◽  
3Rs Principle

There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between in vivo toxicity tests and in vitro surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A2), (d) in vitro coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity in vitro, (g) use of hens’ eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more ‘humane’ protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new in vitro alternatives and more ‘humane’ experimental designs will emerge in this field.

scholarly journals Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 255 ◽  
Author(s):  
Clara Pérez-Peinado ◽  
Sira Defaus ◽  
David Andreu
Keyword(s):  
Therapeutic Potential ◽  
State Of The Art ◽  
Resistant Bacteria ◽  
Snake Venoms ◽  
Antibiotic Resistant ◽  
Anticancer Peptides ◽  
Therapeutic Development ◽  
Drug Leads

For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

scholarly journals FURTHER STUDIES ON EFFECTS OF TISSUE EXTRACTS ON STAPHYLOCOCCUS AUREUS

1946 ◽  
Vol 84 (3) ◽  
pp. 247-261 ◽  
Author(s):  
Leo G. Nutini ◽  
Sister Eva Maria Lynch
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
The Body ◽  
Brain Extract ◽  
Toxicity Tests ◽  
Control Series ◽  
Experimental Animals ◽  
Tissue Extracts

1. The ability of alcoholic-precipitated extracts of beef tissue—brain, spleen, heart, and kidney—to stimulate the growth of Staphylococcus aureus, in vitro, and to convert the yellow S form to a white R variant with altered biochemical characteristics conforming to those of an avirulent organism, has been confirmed. 2. The avirulence of the white R variant has been established by tests in vivo on mice. 3. Staphylococcus aureus infections induced subcutaneously, intraperitoneally, and intravenously in mice responded favorably to brain extract following subcutaneous or oral administration. The mortality was 2 per cent in 444 experimental animals and 81 per cent in 448 control animals. 4. The extracts appeared equally efficient when used therapeutically (mortality 2 per cent of 162 experimental animals and 90 per cent in the control series) or prophylactically (mortality 2 per cent of 282 experimental animals and 76 per cent in 286 control mice). Extracts of brain and spleen were more effective than those of either heart or kidney. 5. Studies concerning the mechanism of action of the tissue extracts indicate that they prevented the formation of toxin by Staphylococcus aureus, and had but little effect on toxin actions. 6. Toxicity tests revealed that the brain and spleen extracts were relatively non-toxic, dosages equivalent to 2 per cent of the body weight being well tolerated. Kidney and heart extracts were much more toxic, producing mortality in dosages as low as 0.3 per cent of the body weight.

scholarly journals Formulation of Improved Traditional Drugs against virulent species of Salmonella spp in Benin: assessment of the properties from Uvaria chamae, Lantana camara and Phyllantus amarus in Benin, West Africa

2019 ◽  
Author(s):  
Boris LEGBA ◽  
Victorien DOUGNON ◽  
Carène GBAGUIDI ◽  
Alidah ANIAMBOSSOU ◽  
Esther DEGUENON ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Bacterial Load ◽  
Scientific Data ◽  
Lantana Camara ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
Post Inoculation ◽  
Salmonella Spp

Abstract Background Uvaria chamae (Annonaceae), Phyllantus amarus (Phyllantaceae) and Lantana camara (Verbenaceae) are empirically alleged to be used as Beninese medicinal plants in the treatment of salmonellosis. This study aimed to produce scientific data on in vitro and in vivo efficacy of Uvaria chamae, Lantana camara and Phyllantus amarus on multiresistant Salmonella spp isolated in Benin.Results After in vitro tests on aqueous and ethanolic extracts of Uvaria chamae, Lantana camara and Phyllantus amarus , only the aqueous extract of Uvaria chamae (leaves) showed the best anti- Salmonella ’s activity. It has been used for the following experiments. The induction of salmonellosis revealed 9.0 10 8 CFU/ml was optimal concentration for triggering and maintaining the symptoms in chicks. This infective concentration has been used for in vivo assessment. 24 hours post inoculation later, the symptoms of salmonellosis (wet cloaca, diarrhea stool and somnolence) were observed in infected groups. After seven days of treatment, the rate of reduction of bacterial load at 100 mg / L, 200 mg / L, 400 mg / L of this extract was 85%, 52.38% and 98% respectively in the chicks groups infected with Salmonella Typhimurium ATCC 14028. About the groups infected with Salmonella spp (virulent strain), the rate of reduction of bacterial load at 100 mg / L, 200 mg / L, 400 mg / L of this extract was 0%, 98.66% and 99.33%. The toxicity tests did not show any significant effect of the Uvaria chamae ’s extract on the biochemical and hematological parameters of the chicks.Conclusion The aqueous extract of Uvaria chamae is active in vitro and in vivo on multiresistant strains of Salmonella spp . This plant is a good candidate for the development of an improved traditional medicine for the management of salmonellosis.

Endocrine Disruptors: A Critical Review of In Vitro and In Vivo Testing Strategies for Assessing Their Toxic Hazard to Humans

2000 ◽  
Vol 28 (1) ◽  
pp. 81-118 ◽  
Author(s):  
Robert D. Combes
Keyword(s):  
Endocrine Disruptors ◽  
Human Exposure ◽  
Mechanisms Of Action ◽  
Environmental Chemicals ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
Wide Range ◽  
The Us

Currently, there is much concern that a wide range of both synthetic and naturally occurring environmental chemicals can act as endocrine disruptors (EDs), and can adversely affect humans and wildlife. Many in vivo and in vitro tests have been proposed for screening EDs, and several regulatory agencies, including the US Environmental Protection Agency (EPA), have recommended tier-testing schemes. Unfortunately, most of the proposed toxicity tests have substantial problems, including non-specificity and lack of reproducibility. There is also uncertainty concerning their relevance for generating useful hazard data for risk assessment purposes, in view of the diversity of the possible ED mechanisms of action (for example, receptor binding, steroidogenesis and modulation of the homeostatic processes which regulate endogenous responses to hormones). Moreover, most of the suggested test methods have yet to be validated according to internationally accepted criteria, although the OECD and the US EPA have defined tests for validation, and an interlaboratory “prevalidation” exercise has been initiated by the OECD. All this is compounded by the lack of information regarding human exposure levels to EDs, and a lack of direct evidence for a causal link between exposure and the development of adverse human health effects. In addition, the regulatory testing of EDs has important negative implications for animal welfare, as some of the proposed in vivo tests require large group sizes of animals and stressful procedures. From a detailed analysis of the available published literature, it is concluded that it is impossible to assess the relative values of currently available in vitro and in vivo toxicity tests for EDs, or to recommend any test or test battery. Any plans for the widespread testing of EDs are therefore premature and might be unnecessary, at least for detecting possible human effects. Several recommendations are made for rectifying this unsatisfactory situation, including the postponement of screening programmes pending: a) more information on human exposure; b) further details of the mechanisms of action of EDs; and c) the development of improved tests, followed by their proper scientific validation.

scholarly journals Formulation of Improved Traditional Drugs against virulent species of Salmonella spp in Benin: assessment of the properties from Uvaria chamae, Lantana camara and Phyllantus amarus in Benin, West Africa

2019 ◽  
Author(s):  
Boris LEGBA ◽  
Victorien DOUGNON ◽  
Carène GBAGUIDI ◽  
Alidah ANIAMBOSSOU ◽  
Esther DEGUENON ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Bacterial Load ◽  
Scientific Data ◽  
Lantana Camara ◽  
Toxicity Tests ◽  
In Vitro Tests ◽  
Post Inoculation ◽  
Salmonella Spp

Abstract Background Uvaria chamae (Annonaceae), Phyllantus amarus (Phyllantaceae) and Lantana camara (Verbenaceae) are empirically alleged to be used as Beninese medicinal plants in the treatment of salmonellosis. This study aimed to produce scientific data on in vitro and in vivo efficacy of Uvaria chamae, Lantana camara and Phyllantus amarus on multiresistant Salmonella spp isolated in Benin.Results After in vitro tests on aqueous and ethanolic extracts of Uvaria chamae, Lantana camara and Phyllantus amarus , only the aqueous extract of Uvaria chamae (leaves) showed the best anti- Salmonella ’s activity. It has been used for the following experiments. The induction of salmonellosis revealed 9.0 10 8 CFU/ml was optimal concentration for triggering and maintaining the symptoms in chicks. This infective concentration has been used for in vivo assessment. 24 hours post inoculation later, the symptoms of salmonellosis (wet cloaca, diarrhea stool and somnolence) were observed in infected groups. After seven days of treatment, the rate of reduction of bacterial load at 100 mg / L, 200 mg / L, 400 mg / L of this extract was 85%, 52.38% and 98% respectively in the chicks groups infected with Salmonella Typhimurium ATCC 14028. About the groups infected with Salmonella spp (virulent strain), the rate of reduction of bacterial load at 100 mg / L, 200 mg / L, 400 mg / L of this extract was 0%, 98.66% and 99.33%. The toxicity tests did not show any significant effect of the Uvaria chamae ’s extract on the biochemical and hematological parameters of the chicks.Conclusion The aqueous extract of Uvaria chamae is active in vitro and in vivo on multiresistant strains of Salmonella spp . This plant is a good candidate for the development of an improved traditional medicine for the management of salmonellosis.

scholarly journals Characterization of Fibrous Wollastonite NYAD G in View of Its Use as Negative Standard for In Vitro Toxicity Tests

Minerals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1378
Author(s):  
Dario Di Giuseppe ◽  
Valentina Scognamiglio ◽  
Daniele Malferrari ◽  
Luca Nodari ◽  
Luca Pasquali ◽  
...  
Keyword(s):  
Biological Response ◽  
Toxicity Tests ◽  
In Vitro Toxicity ◽  
In Vitro Tests ◽  
In Vivo Models ◽  
Mineral Fibre ◽  
In Vivo Testing ◽  
Positive Controls

Today, despite considerable efforts undertaken by the scientific community, the mechanisms of carcinogenesis of mineral fibres remain poorly understood. A crucial role in disclosing the mechanisms of action of mineral fibres is played by in vitro and in vivo models. Such models require experimental design based on negative and positive controls. Commonly used positive controls are amosite and crocidolite UICC standards, while negative controls have not been identified so far. The extensive characterisation and assessment of toxicity/pathogenicity potential carried out in this work indicate that the commercial fibrous wollastonite NYAD G may be considered as a negative standard control for biological and biomedical tests involving mineral fibres. Preliminary in vitro tests suggest that wollastonite NYAD G is not genotoxic. This material is nearly pure and is characterized by very long (46.6 µm), thick (3.74 µm) and non-biodurable fibres with a low content of metals. According to the fibre potential toxicity index (FPTI) model, wollastonite NYAD G is an inert mineral fibre that is expected to exert a low biological response during in vitro/in vivo testing.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Metallic Elements (Cu, Zn, Ni and Mn) Toxicity Effects Determination on a Fresh Water Fish Cyprinus Carpio (Common Carp) Laboratory Acclimatized

2017 ◽  
Vol 68 (8) ◽  
pp. 1711-1715
Author(s):  
Stefania Gheorghe ◽  
Gabriela Geanina Vasile ◽  
Cristina Gligor ◽  
Irina Eugenia Lucaciu ◽  
Mihai Nita Lazar
Keyword(s):  
Cyprinus Carpio ◽  
Aquatic Organisms ◽  
Control Fish ◽  
Toxicity Tests ◽  
Fresh Water Fish ◽  
Metallic Elements ◽  
Mn Toxicity ◽  
Vitro Effect

Metallic elements copper (Cu), zinc (Zn), nickel (Ni) and manganese (Mn) are some of the most commonly found in water and sediment samples collected from the Danube - Danube Delta. These elements are important as essential micronutrients, being normally present at low concentrations in biological organisms, but in high concentrations they become toxic with immediate and delayed effects. The role of this metals is still controversial, that�s why bioconcentration potential is so important. In this non-clinical study, we tested in vitro effect of heavy metals on carp, Cyprinus carpio, reproducing in vivo presence of Cu, Zn, Ni and Mn in the Romanian�s surface water. The toxicity tests were performed according to OECD 203 by detecting the average (50%) lethal concentration - LC50 on aquatic organisms (freshwater fish) at 96h. The results pointed out that, copper value for LC 50 at 96h was estimated as 3.4 mg/L (concentrations tested in the range of 0.1 - 4.75 mg/L). Zinc value for LC 50 at 96h was estimated as 20.8 mg/L (concentrations tested in the range of 0.028 � 29.6 mg/L). Nickel value for LC 50 at 96h was estimated as 40.1 mg/L (concentrations tested in the range of 0.008 - 84.5 mg/L). For manganese the mortality effects has recorded at LC 50 at 96h at estimated value higher than 53 mg/L (concentrations tested in the range of 0.04 - 53.9 mg/L). The accuracy of the testing metals concentration was insured by the screening of the dilution water, as well as food and control fish, acclimated in laboratory conditions.

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