Comparative efficacy of standard antihookworm drugs against various test nematodes

1981 ◽  
Vol 55 (4) ◽  
pp. 273-278 ◽  
Author(s):  
Anuradha Misra ◽  
P. K. S. Visen ◽  
J. C. Katiyar
Keyword(s):  
Broad Spectrum ◽  
Lethal Effect ◽  
Economic Importance ◽  
Nippostrongylus Brasiliensis ◽  
Comparative Efficacy ◽  
Ancylostoma Ceylanicum ◽  
Primary Screening ◽  
Host Parasite ◽  
Hookworm Infections

ABSTRACTThe chemotherapeutic responses of three test nematodes, Nippostrongylus brasilietxsis, Nematospiroidesdubius and Ancylostoma ceylanicum to standard antihookworm drugs were assessed in order to select asuitable host-parasite system for the primary screening of potential antihookworm compounds. N. dubiusbehaved inconsistently and, with some infections, required more drug to achieve 100% clearance. Nippostrongylus brasiliensis was found to be sensitive to thiabendazole, tetramisole and levamisole but the broad spectrum anthclmintic mebendazole was ineffective. A. ceylanicum was very sensitive to mebendazole, sensitive to tetramisole and levamisole and refractory to thiabendazole. In vitro, none of the compounds had any lethal effect against any of the nematodes, except mebendazole against A. ceylanicum.A. ceylanicum does occur in man and its chemotherapeutic reactions are similar to those of target hookworm infections of economic importance. As such, although not equally sensitive to standard anthelmintics, it is recommended for routine primary screening.

The relevance of in vitro anthelmintic screening tests employing the free-living stages of trichostrongylid nematodes

1984 ◽  
Vol 58 (2) ◽  
pp. 107-112 ◽  
Author(s):  
O.F. Ibarra ◽  
D.C. Jenkings
Keyword(s):  
Broad Spectrum ◽  
Haemonchus Contortus ◽  
Screening Tests ◽  
Nippostrongylus Brasiliensis ◽  
Good Activity ◽  
Free Living ◽  
Ostertagia Ostertagi ◽  
Nematospiroides Dubius ◽  
Antiparasitic Agents

AbstractThe response of the free-living stages of Nippostrongylus brasiliensis, Nematospiroides dubius, Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia ostertagi to a wide variety of antiparasitic agents in vitro was investigated.All the major broad spectrum veterinary anthelmintics showed good activity against each of these worms with EC30 values varying from about 00002mg/1 for certain benzimidazoles and ivermectin to about 6–5 mg/1 for febantel. Of 22 known narrow spectrum anthelmintics useful only against H. contortus and/or helminths other than trichostrongyles, only 10% showed good activity at concentrations equal to or less than 100mg/1. Further, only one of 15 antiprotozoal agents showed good activity in these tests at the 100mg/1 level.

Acetyicholinesterase secretion–a parameter for the interpretation of in vitro anthelmintic screens

Parasitology ◽  
1986 ◽  
Vol 92 (2) ◽  
pp. 425-430 ◽  
Author(s):  
E. B. Rapson ◽  
A. S. Chilwan ◽  
D. C. Jenkins
Keyword(s):  
Anthelmintic Activity ◽  
Biochemical Parameter ◽  
Nippostrongylus Brasiliensis ◽  
Microscopical Examination ◽  
Drug Induced ◽  
Primary Screening ◽  
Time Required ◽  
Parameter Dependent ◽  
Nematode Development

SUMMARYInterpretation of anthelmintic activity using in vitro screens has, until now, relied on the detection of drug-induced effects on nematode development, viability and motility. A novel biochemical parameter dependent upon the spectrophotometric assay of acetyicholinesterase (AChE), an enzyme secreted in large quantities by certain trichostrongylid nematodes, has been developed to replace these often subjective indices of activity. Using Nippostrongylus brasiliensis, a worm frequently employed for primary screening, the secretion of this enzyme in the presence or absence of a large number of drugs in vitro was determined. During a 4-day incubation period in a complex undefined medium without serum, AChE was secreted by normal 4th larval and immature adult stages of the worm in a linear fashion. All modern broad-spectrum veterinary anthelmintics, regardless of their mode of action, dramatically reduced the amount of enzyme secreted. Correlation between the biochemical and observa tional parameters was excellent and the selectivity of the assay when based solely on enzyme secretion was not lost. Other advantages were that the time required for the activity of certain slow-acting compounds to be detected was reduced from 7 to 4 days and that close microscopical examination of the worms was not necessary.

EFFECT OF DEFICIENT DIETS ON CORTICOSTEROID SYNTHESIS BY RAT ADRENALS IN VITRO AND ITS RELATIONSHIP TO INFECTIONS WITH NIPPOSTRONGYLUS BRASILIENSIS

1969 ◽  
Vol 43 (3) ◽  
pp. 333-345 ◽  
Author(s):  
KAREN R. CLARKE
Keyword(s):  
Body Weight ◽  
Acquired Resistance ◽  
Female Rats ◽  
Male Rats ◽  
Adrenal Weight ◽  
Initial Contact ◽  
Nippostrongylus Brasiliensis ◽  
Male And Female Rats ◽  
Host Parasite

SUMMARY Rats were fed on a low protein (LP) and a glucose—filter paper (GFP) diet; they were then infected with 1000 larvae of the nematode worm Nippostrongylus brasiliensis (Travassos, 1914) and killed 5 or 10 days later. The adrenals of male and female rats on the GFP diet for 21 days showed atrophy and so did those of female rats on the LP diet for 42 or 56 days. The adrenals of male rats on the LP diet for 21 days were hypertrophic. Referred to body weight, the adrenal weights of male rats on both diets were higher than those of the controls, the weights of the adrenals of female rats on the deficient diets were lower. Adrenal weight and adrenal weight as a percentage of body weight were shown to bear no relationship to corticosteroid production in vitro, since the capacity for corticosteroid synthesis in vitro was increased in rats on the GFP diet only. Significantly more parasites were found in the intestine after 5, but not after 10 days on both deficient diets suggesting that the deficient diets increased the susceptibility of the rats on initial contact with the parasite and before the development of acquired resistance. Later more parasites were lost by the rats on the deficient diets than from controls. These findings were not related to changes in the rate of corticosteroid synthesis. The effects of stress, and the administration of cortisone or corticotrophin on host—parasite relationships is discussed in relation to the results of the present experiments. It is concluded that though these factors can increase susceptibility and lower acquired resistance, the effect on susceptibility can also be produced independently by severe dietary deficiency.

Timing of sub-lethal insecticide exposure determines parasite establishment success in an insect-helminth model

Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 120-125
Author(s):  
Suraj Dhakal ◽  
Nicolai Vitt Meyling ◽  
Kathrine Eggers Pedersen ◽  
Nina Cedergreen ◽  
Brian Lund Fredensborg
Keyword(s):  
Lethal Effect ◽  
Parasite Infection ◽  
Hymenolepis Diminuta ◽  
Environmental Toxicants ◽  
Establishment Success ◽  
Insecticide Exposure ◽  
Before And After ◽  
Parasite Viability ◽  
Host Parasite

AbstractEnvironmental toxicants are pervasive in nature, but sub-lethal effects on non-target organisms and their parasites are often overlooked. Particularly, studies on terrestrial hosts and their parasites exposed to agricultural toxicants are lacking. Here, we studied the effect of sequence and timing of sub-lethal exposures of the pyrethroid insecticide alpha-cypermethrin on parasite establishment using the tapeworm Hymenolepis diminuta and its intermediate insect host Tenebrio molitor as a model system. We exposed T. molitor to alpha-cypermethrin (LD20) before and after experimental H. diminuta infection and measured the establishment success of larval tapeworms. Also, we conducted in vitro studies quantifying the direct effect of the insecticide on parasite viability. Our results showed that there was no direct lethal effect of alpha-cypermethrin on H. diminuta cysticercoids at relevant concentrations (LD10 to LD90 of the intermediate host). However, we observed a significantly increased establishment of H. diminuta in beetles exposed to alpha-cypermethrin (LD20) after parasite infection. In contrast, parasite establishment was significantly lower in beetles exposed to the insecticide before parasite infection. Thus, our results indicate that environmental toxicants potentially impact host-parasite interactions in terrestrial systems, but that the outcome is context-dependent by enhancing or reducing parasite establishment depending on timing and sequence of exposure.

Preliminary in Vitro Investigations on The Inhibitory Activity of The Original Dietary Supplement Oxidal® on Pathogenic Bacterial Strains

2020 ◽  
Vol 11 ◽  
pp. 37-43
Author(s):  
Prof. Teodora P. Popova ◽  
Toshka Petrova ◽  
Ignat Ignatov ◽  
Stoil Karadzhov
Keyword(s):  
Dietary Supplement ◽  
Broad Spectrum ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Clinical Effectiveness ◽  
Inhibitory Effect ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Microbial Strains

The antimicrobial action of the dietary supplement Oxidal® was tested using the classic Bauer and Kirby agar-gel diffusion method. Clinical and reference strains of Staphylococcus aureus and Escherichia coli were used in the studies. The tested dietary supplement showed a well-pronounced inhibitory effect against the microbial strains commensurable with that of the broad-spectrum chemotherapeutic agent Enrofloxacin and showed even higher activity than the broad spectrum antibiotic Thiamphenicol. The proven inhibitory effect of the tested dietary supplement against the examined pathogenic bacteria is in accordance with the established clinical effectiveness standards for antimicrobial agents.

Repurposing of auranofin against bacterial infections: An In silico and In vitro study

2020 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Sharma ◽  
Arti Singh ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Antibacterial Agent ◽  
Bacterial Infections ◽  
In Vitro Assays ◽  
Infection Model ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

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