Disease relevance of Ambilhar

• We investigated the immunosuppressive effects of the standard antihelminthic regimen of niridazole (25 mg/kg/day for seven days) in five patients with schistosomiasis [1].
• Suppression of delayed hypersensitivity in schistosome-infected patients by niridazole [1].
• Although 15-minute skin reactions to schistosomal antigens remained unchanged, niridazole reduced or ablated positive 48-hour skin reactions to tuberculin (PPD), mumps and schistosome antigens in all patients tested six and 15 days after therapy began [1].
• We report here further studies on the mechanism of this drug-induced suppression of cellular hypersensitivity; the data show that niridazole active serum does not block the production of migration inhibitory factor once it has been initiated [2].
• The mutagenicity of niridazole for Salmonella typhimurium depends upon the enzymic reduction of the nitro function [3].

High impact information on Ambilhar

• Letter: Schistosomiasis, immunosuppression and niridazole [4].
• It is concluded that therapeutic doses of niridazole suppress delayed hypersensitivity and antigen-induced lymphocyte transformation in man [1].
• Detection of mutagenic activity of metronidazole and niridazole in body fluids of humans and mice [5].
• The carcinogenicity of 1-(5-nitro-2-thiazolyl)-2-imidazolidinone (niridazole), a widely used schistosomicide, was examined in Swiss mice and Syrian golden hamsters [6].
• Two stages in lymphocyte mediator production by differential susceptibility to blockade using niridazole [2].

Chemical compound and disease context of Ambilhar

• In vitro susceptibilities of 40 Campylobacter fetus subsp. jejuni strains to niridazole and metronidazole [7].
• We have used the hamster model of antibiotic-induced Clostridium difficile intestinal disease to evaluate nitazoxanide (NTZ), a nitrothiazole benzamide antimicrobial agent [8].
• For definition of the characteristics and causes of post-treatment eosinophilic responses, 47 patients with Bancroft's filariasis, who were treated with diethylcarbamazine, and eight patients with schistosomiasis mansoni, who were treated with niridazole, were studied [9].
• Against anaerobic bacteria the nitrothiazole derivatives are unique, since the extremely low MIC's are not approached by any other of the nitro-compounds nor by any other of the common antibiotics tested, such as clindamycin, ampicillin and tetracycline [10].
• Influence of immunomodulators, niridazole and levamisole, on autoimmune murine thyroiditis [11].

Biological context of Ambilhar

• In both isogeneic (Sarcoma 1 in A/JAX mice) and allogeneic (Sarcoma 180 in C57BL/6 mice) mouse tumor systems, treatment of the tumor-bearing mice with niridazole, an antiprarasitic drug, known to be a potent suppressor of cell mediated but not humoral immunity caused enhancement of metastases to regional popliteal nodes [12].
• Effect of genotype on mutagenicity of niridazole in nitroreductase-deficient bacteria [3].
• The results are taken to indicate that the residual activity (4.4%) seen in the strain with a base substitution mutation reflects the activity of an enzyme with an amino acid substitution, while the basal level (0.19%) of activity indicates the action of a different nitroreductase with a low specificity for niridazole [3].
• Relative importance of bacterial and mammalian nitroreductases for niridazole mutagenesis [13].
• The response of niridazole nitroreductase-deficient bacteria to niridazole is reduced to 4.4 and 0.19% that exhibited by the enzyme-proficient parent strain when the deficiency is the result of a base substitution and frame-shift mutation, respectively [3].

Anatomical context of Ambilhar

• Sera from guinea pigs given niridazole, an anti-schistosomal compound, have been shown to reversibly block the production of antigen-induced migration inhibitory factor by sensitized guinea pig lymph node cells [2].
• Administration of niridazole to Lewis rats beginning 2 days before sensitization with guinea pig spinal cord in combination with immunologic adjuvants exerted a dose related suppressive influence on development of experimental allergic encephalomyelitis (EAE) [14].
• In the present study the effect of niridazole on the magnitude and kinetics of the primary and secondary antibody responses of mice to sheep erythrocytes, human serum albumin, and keyhold limpet hemocyanin was investigated [15].
• On the other hand, sera taken from nonsensitized guinea pigs after they had received 100 mg/kg of niridazole markedly diminished antigen-induced inhibition of migration of sensitized peritoneal exudate cells in vitro [16].
• Aerobic metabolism of niridazole by rat liver microsomes [17].

Associations of Ambilhar with other chemical compounds

• Niridazole given in a single oral dose of 100 mg/kg to guinea pigs sensitized to ortho-chlorobenzoyl chloride-bovine gamma-globulin (OCB-BGG) regularly abolished delayed cutaneous reactivity [16].
• Drug combinations incorporating niridazole at a lower dosage or for a shorter period were less effective, and azathioprine and prednisolone on their own or used together prolonged graft survival only marginally in this model [18].
• Oxamniquine and niridazole significantly increased the AHH activity in vivo and in vitro, while the antimonial drugs enhanced the enzyme activity only in vivo [19].
• MtzS strains displayed the greatest sensitivity towards niridazole and satranidazole, the latter having the highest redox potential of the 5-nitroimidazoles [20].
• Of the two antischistosomal agents tested, hycanthone yielded an increase of 20-fold in the number of micronuclei over control at 40 mg/kg administered i.p. for five days, while with niridazole no increase in micronuclei at several concentrations tested both by single and multiple injection was found [21].

Gene context of Ambilhar

• These studies suggest that metabolites of niridazole, but not the parent compound itslef, suppress delayed hypersensitivity in guinea pigs and prevent MIF production by lymphocytes without affecting the macrophage response to MIF [16].
• Identically purified fractions prepared from urine of rats and the patient before they received niridazole showed no immunosuppressive activity either in the MIF or in the granuloma assay systems [22].
• Inhibition of human mixed lymphocyte reactions by sera and urine dialysates from niridazole-treated rats [23].
• A therapeutic effect as determined by a reduction of bacterial counts per spleen of mice infected with Salm. typhimurium could only be achieved with those agents which displayed a similar side chain as niridazole, i.e. an imidazolidinone ring [24].
• Administration of oxamniquine and niridazole increased, whereas praziquantel and hycanthone lowered the cytochrome P-450 content [19].

Analytical, diagnostic and therapeutic context of Ambilhar

• Niridazole, an anti-parasitic drug, suppresses manifestations of delayed hypersensitivity and retards allograft rejection in laboratory animals [1].
• Successful renal transplantation followed by niridazole treatment of the schistosomiasis induced a transient relapse of renal dysfunction with proteinuria and a fall in serum complement [25].
• Inhibition of the mixed lymphocyte reaction by fractionated niridazole urine dialysate [26].
• To define further the role of circulating immune complexes in acute schistosomiasis, serial determinations of [125I]Clq binding activity (ClqBA) in 15 patients with this disease were made before and after treatment with niridazole [27].
• The minimum inhibitory concentrations for niridazole ranged from 0.0037 to 1.0 microgram/ml and, for metronidazole, from 0.25 to 128 micrograms/ml [28].

References