Ivermectin
A mixture of mostly avermectin H2B1a (RN 71827-03-7) with some avermectin H2B1b (RN 70209-81-3), which are macrolides from STREPTOMYCES avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other CHLORIDE CHANNELS. It is a broad spectrum antiparasitic that is active against microfilariae of ONCHOCERCA VOLVULUS but not the adult form.
Heterocyclic Compounds
Molecular Structure
Toxoplasma
Drug Repositioning
Life Cycle Stages
Apicomplexa
Anthelmintics
Onchocerciasis
Elephantiasis, Filarial
Antinematodal Agents
Heliotropium
Inventions
6-Cyano-7-nitroquinoxaline-2,3-dione
Streptomyces
Chromatography
Techniques used to separate mixtures of substances based on differences in the relative affinities of the substances for mobile and stationary phases. A mobile phase (fluid or gas) passes through a column containing a stationary phase of porous solid or liquid coated on a solid support. Usage is both analytical for small amounts and preparative for bulk amounts.
Cell Fractionation
Fermentation
Fraud
Medicare Assignment
Insurance, Health, Reimbursement
Competitive Bidding
Comparison of serological and parasitological assessments of Onchocerca volvulus transmission after 7 years of mass ivermectin treatment in Mexico. (1/370)
OBJECTIVE AND METHOD: To compare the utility of an ELISA using 3 recombinant antigens with that of the skin biopsy to estimate incidence of infections in a sentinel cohort of individuals living in an endemic community in southern Mexico during a set of 11 subsequent ivermectin treatments. RESULTS: The apparent community prevalence of infection and microfilarial skin infection before and after 11 treatments with ivermectin plus nodulectomy were 78% and 13%, and 0.68 mf/mg and 0.04 mf/mg, respectively, as measured by skin biopsy. Of a group of 286 individuals participating in all surveys, a sentinel cohort of 42 mf and serologically negative individuals had been followed since 1994. The annual percentage of individuals becoming positive in this cohort was 24% (10/42), 28% (9/33), 0%, and 4.3% (1/23) in 1995, 1996, 1997 and 1998, respectively. Likewise, the incidence in children 5 years and under (n = 13) within this sentinel cohort was 15% (2/13), 18% (2/11), 0% and 11% (1/9), respectively. All individuals became positive to both tests simultaneously, indicating that seroconversion assessed infection incidence as accurately as skin biopsy in the sentinel group. CONCLUSION: Incidence monitoring of a sentinel cohort provides an estimation of the parasite transmission in the community; it is less costly than massive sampling, and a finger prick blood test might be more acceptable in some communities. (+info)Selective effect of 2',6'-dihydroxy-4'-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis. (2/370)
2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 micrograms/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 micrograms/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 micrograms of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs. (+info)Improvement of in vitro and in vivo antileishmanial activities of 2', 6'-dihydroxy-4'-methoxychalcone by entrapment in poly(D,L-lactide) nanoparticles. (3/370)
The inhibition of intracellular Leishmania amazonensis growth by 2', 6'-dihydroxy-4'-methoxychalcone (DMC) isolated from Piper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions. (+info)Eotaxin expression in Onchocerca volvulus-induced dermatitis after topical application of diethylcarbamazine. (4/370)
In persons with onchocerciasis, topical application of the anthelminthic diethylcarbamazine (DEC) induces clinical and histologic responses similar to acute papular onchodermatitis, including recruitment of eosinophils to the skin. To determine whether the eosinophil chemokine eotaxin is likely to be associated with eosinophil recruitment in onchodermatitis, DEC was applied to a 5-cm2 area on the skin of infected persons, and biopsies were taken from lesions 24 h later. Histologic analysis showed elevated dermal and epidermal eosinophils compared with tissue from an adjacent (untreated) site. Reverse transcription-polymerase chain reaction showed that eotaxin gene expression in DEC-treated skin was elevated 2- to 17-fold compared with control tissue. Eotaxin immunoreactivity was noted in mononuclear cells and eosinophils in the perivascular region of the dermis and in lymphatic and vascular endothelial cells. Together, these observations are consistent with a role for eotaxin in recruitment of eosinophils to the dermis in early stage onchocercal skin disease. (+info)Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. (5/370)
The fruit fly Drosophila melanogaster was used to examine the mode of action of the novel insecticide and acaricide nodulisporic acid. Flies resistant to nodulisporic acid were selected by stepwise increasing the dose of drug in the culture media. The resistant strain, glc(1), is at least 20-fold resistant to nodulisporic acid and 3-fold cross-resistant to the parasiticide ivermectin, and exhibited decreased brood size, decreased locomotion, and bang sensitivity. Binding assays using glc(1) head membranes showed a marked decrease in the affinity for nodulisporic acid and ivermectin. A combination of genetics and sequencing identified a proline to serine mutation (P299S) in the gene coding for the glutamate-gated chloride channel subunit DmGluClalpha. To examine the effect of this mutation on the biophysical properties of DmGluClalpha channels, it was introduced into a recombinant DmGluClalpha, and RNA encoding wild-type and mutant subunits was injected into Xenopus oocytes. Nodulisporic acid directly activated wild-type and mutant DmGluClalpha channels. However, mutant channels were approximately 10-fold less sensitive to activation by nodulisporic acid, as well as ivermectin and the endogenous ligand glutamate, providing direct evidence that nodulisporic acid and ivermectin act on DmGluClalpha channels. (+info)Fipronil modulation of gamma-aminobutyric acid(A) receptors in rat dorsal root ganglion neurons. (6/370)
The gamma-aminobutyric acid (GABA) receptor is an important site of action of a variety of chemicals, including barbiturates, benzodiazepines, picrotoxin, bicuculline, general anesthetics, alcohols, and certain insecticides. Fipronil is the first phenylpyrazole insecticide introduced for pest control. It is effective against some insects that have become resistant to the existing insecticides. To elucidate the mechanism of fipronil interaction with the mammalian GABA system, whole-cell patch-clamp experiments were performed using rat dorsal root ganglion neurons in primary culture. Fipronil suppressed the GABA-induced whole-cell currents reversibly in both closed and activated states. The IC(50) values and Hill coefficients for fipronil block of the GABA(A) receptor were estimated to be 1.66 +/- 0.18 microM and 1.23 +/- 0.14 for the closed receptor, respectively, and 1.61 +/- 0.14 microM and 0.96 +/- 0.06 for the activated receptor, respectively. The association rate and dissociation rate constants of fipronil effect were estimated to be 673 +/- 220 M(-1) s(-1) and 0.018 +/- 0.0035 s(-1) for the closed GABA(A) receptor, respectively, and 6600 +/- 380 M(-1) s(-1) and 0.11 +/- 0.0054 s(-1) for the activated GABA(A) receptor, respectively. Thus, both the association and dissociation rate constants of fipronil for the activated GABA(A) receptor are approximately 10 times as large as those for the closed receptor. Experiments with coapplication of fipronil and picrotoxinin indicated that they did not compete for the same binding site to block the receptor. It is concluded that although fipronil binds to the GABA(A) receptor without activation, channel opening facilitates fipronil binding to and unbinding from the receptor. (+info)GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans. (7/370)
1. We report the cloning and expression of a novel Caenorhabditis elegans polypeptide, GLC-3, with high sequence identity to previously cloned L-glutamate-gated chloride channel subunits from nematodes and insects. 2. Expression of glc-3 cRNA in XENOPUS oocytes resulted in the formation of homo-oligomeric L-glutamate-gated chloride channels with robust and rapidly desensitizing currents, an EC(50) of 1.9+/-0.03 mM and a Hill coefficient of 1.5+/-0.1. GABA, glycine, histamine and NMDA all failed to activate the GLC-3 homo-oligomer at concentrations of 1 mM. The anthelminthic, ivermectin, directly and irreversibly activated the L-glutamate-gated channel with an EC(50) of 0.4+/-0.02 microM. 3. The GLC-3 channels were selective for chloride ions, as shown by the shift in the reversal potential for L-glutamate-gated currents after the reduction of external Cl(-) from 107.6 to 62.5 mM. 4. Picrotoxinin failed to inhibit L-glutamate agonist responses at concentrations up to 1 mM. The polycyclic dinitrile, 3,3-bis-trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile (BIDN), completely blocked L-glutamate-induced chloride currents recorded from oocytes expressing GLC-3 with an IC(50) of 0.2+/-0.07 microM. The phenylpyrazole insecticide, fipronil, reversibly inhibited L-glutamate-gated currents recorded from the GLC-3 receptor with an IC(50) of 11.5+/-0.11 microM. 5. In this study, we detail the unusual antagonist pharmacology of a new GluCl subunit from C. elegans. Unlike all other native and recombinant nematode GluCl reported to date, the GLC-3 receptor is insensitive to picrotoxinin, but is sensitive to two other channel blockers, BIDN and fipronil. Further study of this receptor may provide insights into the molecular basis of non-competitive antagonism by these compounds. (+info)Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. (8/370)
The basic treatment of leishmaniasis consists in the administration of pentavalent antimonials. The mechanisms that contribute to pentavalent antimonial toxicity against the intracellular stage of the parasite (i.e., amastigote) are still unknown. In this study, the combined use of several techniques including DNA fragmentation assay and in situ and cytofluorometry terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling methods and YOPRO-1 staining allowed us to demonstrate that potassium antimonyl tartrate, an Sb(III)-containing drug, was able to induce cell death associated with DNA fragmentation in axenic amastigotes of Leishmania infantum at low concentrations (10 microg/ml). This observation was in close correlation with the toxicity of Sb(III) species against axenic amastigotes (50% inhibitory concentration of 4.75 microg/ml). Despite some similarities to apoptosis, nuclease activation was not a consequence of caspase-1, caspase-3, calpain, cysteine protease, or proteasome activation. Altogether, our results demonstrate that the antileishmanial toxicity of Sb(III) antimonials is associated with parasite oligonucleosomal DNA fragmentation, indicative of the occurrence of late events in the overall process of apoptosis. The elucidation of the biochemical pathways leading to cell death could allow the isolation of new therapeutic targets. (+info)
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IvermectinBroad spectrum antiparasitic agentsCompoundsDrugsPotential antiparasiticAntifungalDerivativesAntimicrobialsAnticancer AgentsAntibioticAntimicrobial Agents and CChemotherapyMechanism of actParasiteInfectionsAntibacterial agentsNitazoxanideOrganismsTherapeutic2017CausativeEfficacyParasitesTherapiesQuinineHumansActivityChagasVitaminsOralInfestationsCryptosporidiumEffectiveCompound
Ivermectin9
- As a potential antileukemic agent, ivermectin induced cell death at low micromolar concentrations in acute myeloid leukemia cell lines and primary patient samples preferentially over normal hematopoietic cells. (ashpublications.org)
- As an antiparasitic, ivermectin binds and activates chloride ion channels in nematodes, so we tested the effects of ivermectin on chloride flux in leukemia cells. (ashpublications.org)
- Ivermectin is a broad-spectrum antiparasitic agent. (drugs.com)
- The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. (biomedsearch.com)
- Ivermectin is the first in a series of antiparasitic agents derived from the avermectin family of compounds. (drugs.com)
- Ivermectin MDA is a different delivery method and has a different mode of action from current malaria control agents. (ajtmh.org)
- The widely used antiparasitic agent ivermectin is non-polar and has a high tendency to sorb to surfaces. (springer.com)
- Ivermectin is one of the most important veterinary and human anti-parasitic agents ever," Mackenzie said. (redorbit.com)
- Co-treatment with other drugs that are P-glycoprotein substrates/inhibitors (for example, ivermectin and other antiparasitic macrocyclic lactones, erythromycin, prednisolone and cyclosporine) could give rise to pharmacokinetic drug interactions. (vetuk.co.uk)
Broad spectrum antiparasitic agents3
- The compounds are broad spectrum antiparasitic agents having utility as anthelmintics, ectoparasiticides, insecticides and acaricides. (google.com)
- The avermectins are a group of broad spectrum antiparasitic agents referred to previously as the C-076 compounds. (google.com)
- and when R.sup.4 is H, R is H, R.sup.1 is OH, and R.sup.2 is not 2-buten-2-yl, 2-penten-2-yl or 4-methyl-2-penten-2-yl.The compounds are broad spectrum antiparasitic agents having utility as anthelmintics, ectoparasiticides, insecticides and acaricides. (patentgenius.com)
Compounds6
- This invention relates to antiparasitic agents and in particular to compounds related to the avermectins and milbemycins but having a novel substituent group at the 25-position and to a process for their preparation. (google.com)
- The present invention relates to compounds of the formula (I) and pharmaceutically acceptable salts thereof, compositions containing such compounds and the uses of such compounds as antiparasitic agents. (patentsencyclopedia.com)
- Disclosed compounds with modifications of the pentose ring aimed to mimic ATP, are only expected to have an antiparasitic activity. (archives-ouvertes.fr)
- The compounds are thus potent antiparasitic agents and compositions and methods for such uses are also disclosed. (google.com)
- To identify known drugs with previously unrecognized anticancer activity, we compiled and screened a library of such compounds to identify agents cytotoxic to leukemia cells. (ashpublications.org)
- In addition, several compounds of natural origin have also shown in vitro antiparasitic activity: the polyphenols mangiferin and (-)-epigallocatechin-3-gallate (EGCG), curcumin, resveratrol and the synthetic polyphenol propyl gallate. (wikipedia.org)
Drugs12
- These enzymes have therefore emerged as promising targets for antiparasitic drugs. (nih.gov)
- These data, in conjunction with comparative inhibition kinetics, provide insight into the molecular mechanisms that drive cysteine protease inhibition by vinyl sulfones, the binding specificity of these important proteases and the potential of vinyl sulfones as antiparasitic drugs. (nih.gov)
- Other major antiprotozoal drugs are also reviewed, including those used for malaria, infections with gastrointestinal protozoa, leishmaniasis, and trypanosomiasis, but an exhaustive list of all antiparasitic drugs is not included. (monash.edu)
- Throughout this chapter, we indicate which antiparasitic drugs are currently approved by the U.S. Food and Drug Administration (FDA). (monash.edu)
- The antiparasitic drugs can be divided into antiprotozoal and antihelminthic drugs. (china-sinoway.com)
- Porto I. Antiparasitic drugs and lactation: focus on anthelmintics, scabicides, and pediculicides. (nih.gov)
- Chemically, nitazoxanide is the prototype member of the thiazolides, a class of drugs which are synthetic nitrothiazolyl-salicylamide derivatives with antiparasitic and antiviral activity. (wikipedia.org)
- In particular the interaction of novel antiparasitic agents with DNA (the subject of a European Community Cost Action) with the aim of developing new drugs for the treatment of parasitic diseases ref. (pharmweb.net)
- Treatments for Chagas disease have been administered since the first attempts by Mayer & Rocha Lima (1912, 1914) and up to the drugs currently in use (nifurtimox and benznidazole), along with potential drugs such as allopurinol and first, second and third-generation antifungal agents (imidazoles and triazoles), in separate form. (bioline.org.br)
- Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis. (pubmedcentralcanada.ca)
- Antiparasitic agents: new drugs on the horizon. (semanticscholar.org)
- Increased resistance of the parasite and the side-effects of the reference drugs employed in the treatment of giardiasis make necessary to seek new therapeutic agents. (scielo.br)
Potential antiparasitic1
- The last group of patents consists of carboxamidines and inhibitors of nucleoside transporters with potential antiparasitic effect. (archives-ouvertes.fr)
Antifungal2
- Additionally, antibacterial and antifungal agents that can also be used for treatment of protozoal infections, such as the 5-nitroimidazoles, trimethoprim-sulfamethoxazole, azithromycin, and amphotericin, are not discussed in detail here, but their general indications for parasitic infections are shown in Tables 1 and 2. (monash.edu)
- These studies demonstrate that atovaquone has pronounced in vitro and in vivo antifungal activity against filamentous fungi by disrupting both metal homeostasis and mitochondrial function, and therefore has potential as a novel antifungal agent. (arvojournals.org)
Derivatives1
- Among the patents disclosed recently, only iminoribitol derivatives have documented antiparasitic activities, especially against nucleoside N-hydrolases (NH), purine nucleoside phosphorylase (PNP) and also against 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP), an enzyme at the border of polyamine biosynthesis and purine salvage. (archives-ouvertes.fr)
Antimicrobials2
- Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials. (strath.ac.uk)
- The aim of this study was to evaluate the toxicity of parasiticides agent, antimicrobials agent and insecticides on A. franciscana to establish Predicted No-Effect Concentration (PNEC) on marine organisms and obtain guidance levels for the protection of aquatic life. (edu.pe)
Anticancer Agents1
- In this paper, we aim to present an updated overview of in vitro and in vivo studies that show the significant therapeutic properties of the crude extracts and phytochemicals derived from H. sabdariffa as antimicrobial, antiparasitic, and anticancer agents. (prolekare.cz)
Antibiotic2
- We have characterized the antibiotic megalomicin (MGM) as an antiparasitic drug against several taxonomically distant parasites. (asm.org)
- In case of identification of the causative pathogen, an antibiotic or an anti-parasitic agent may be used. (news-medical.net)
Antimicrobial Agents and C2
- Antimicrobial Agents and Chemotherapy 29:620-624 (1986). (patentgenius.com)
- Antimicrobial Agents and Chemotherapy 31:744-747 (1987). (patentgenius.com)
Chemotherapy1
- However, the lack of financial incentives to develop new agents is a major limitation to the future of antiparasitic chemotherapy. (monash.edu)
Mechanism of act1
- Its antiparasitic mechanism of action is through binding selectively to certain ion channels present in invertebrate nerve and muscle cells but not present in mammals. (fiercebiotech.com)
Parasite2
- Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses. (medscape.com)
- Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages of Toxoplasma and the related apicomplexan parasite Plasmodium falciparum (a malaria agent). (asm.org)
Infections5
- Antiparasitic agents are important both for therapy of infected individual patients and for control of parasitic infections at the community level. (monash.edu)
- Emerging resistance among parasites, lack of effective antiparasitic vaccines, and the enormous burden of disease worldwide also pose challenges to the effective management of parasitic infections. (monash.edu)
- Nitazoxanide is a broad-spectrum antiparasitic and broad-spectrum antiviral drug that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. (wikipedia.org)
- Numerous studies have described the potential use of HSE and its phytochemicals as significant antimicrobial and antiparasitic agents in the treatment of various infections. (prolekare.cz)
- Corticosteriods, antihistamines, or other antiinflammatory agents (i.e., aspirin) may be prescribed concurrently in serious infections to reduce the likelihood of a Mazzotti reaction. (pdr.net)
Antibacterial agents1
- In particular, antibacterial agents are incredibly important worldwide, with the emergence of multi-drug resistant bacteria. (rsc.org)
Nitazoxanide3
- Another agent, nitazoxanide, has both anthelmintic and antiprotozoal activity and is also discussed. (monash.edu)
- Nitazoxanide is the only broad-spectrum antiparasitic drug that has been approved in the United States for treatment of cryptosporidiosis. (cdc.gov)
- Tizoxanide, an active metabolite of nitazoxanide in humans, is also an antiparasitic drug of the thiazolide class. (wikipedia.org)
Organisms1
- Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA. (labome.org)
Therapeutic2
- 21. The pharmaceutical composition according to claim 20 further comprising a second therapeutic agent. (patentsencyclopedia.com)
- The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-infective drug discovery. (benthamscience.com)
20171
- The Antiparasitic Agents market report addresses forecast and growth patterns by company, regions and type or application from 2017 to 2021. (medgadget.com)
Causative2
- Eurytrema coelomaticum is a digenean flatworm of ruminants that is the causative agent of eurytrematosis, a disease of veterinary health concern. (usda.gov)
- The species was also identified as the causative agent of outbreaks of scuticociliatosis that occurred between summer 1999 and spring 2000 in turbot (Scophthalmus maximus) cultivated in the Atlantic Ocean (Galicia, Northwest Spain). (wikipedia.org)
Efficacy1
- Its convenience, broad spectrum efficacy and wide safety margin make it an excellent antiparasitic product for horses. (drugs.com)
Parasites1
- If the cause of the diarrhea is detected, and it is due to bacteria or parasites, agents useful against these pathogens may be used. (news-medical.net)
Therapies1
- This chapter focuses on the mechanisms of action, pharmacology, clinical utility, and adverse effects of common first-line antiparasitic therapies and newer drug alternatives. (monash.edu)
Quinine1
- Tonic water contains approximately 80 mg/L quinine sulphate as a flavouring agent. (inchem.org)
Humans1
- Malaria remains one of the most important diseases of humans in terms of both mortality and morbidity, with Plasmodium falciparum being the most important infecting agent ( 24 ). (asm.org)
Activity1
- Due to the effects of MGM on the Golgi and on the replication of enveloped viruses, we decided to test whether it has any antiparasitic activity. (asm.org)
Chagas1
- The flagellated protozoan Trypanosoma cruzi is the etiologic agent of American trypanosomiasis (Chagas' disease), a major public health problem in many Latin American countries, with an estimated 15 million people infected. (asm.org)
Vitamins1
- Antiparasitic Agents, Vitamins, Amino Aci. (weiku.com)
Oral1
- Trifexis® is an oral agent. (petplace.com)
Infestations1
- Antiparasitic agents are used in parasitic infestations. (news-medical.net)
Cryptosporidium1
- What is the only agent for cryptosporidium? (brainscape.com)
Effective1
- Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain. (asm.org)
Compound1
- In addition, an immunosuppressive agent is a role played by a compound which is exhibited by a capability to diminish the extent and/or voracity of an immune response. (ebi.ac.uk)