Disease relevance of Dock2

• We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits [1].
• We studied a representative invasive human isolate of Borrelia burgdorferi for which the MBC of ceftriaxone was 0.050 microg/ml [2].
• In 30 mice given MBC and sodium nitrite, 10 lymphosarcomas were found [3].
• Malignant lymphomas were induced in Swiss mice treated intragastrically with methyl-2-benzimidazole carbamate (MBC, BCM, Carbendazim) and given sodium nitrite in their drinking water [3].
• We evaluated the in vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia using a susceptible strain and one with low-level resistance (MIC/MBC of levofloxacin: 0.06/0.06 and 4/4 mg/L, respectively) [4].

High impact information on Dock2

• Here, we analyze the roles of DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, and phosphoinositide-3-kinase (PI3K) during lymphocyte recirculation [5].
• Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC [6].
• Swiss mice at different stages of pregnancy were treated intragastrically with the pesticide Carbendazim (MBC, BCM, methyl-2-benzimidazole carbamate) together with sodium nitrite [7].
• A sepsis BALB/c mice model was used to investigate the relationship between mortality and the bacteraemic profile produced by a serotype 6B Streptococcus pneumoniae clinical isolate (MIC/MBC of amoxicillin 4/4 mg/L and of cefotaxime 2/4 mg/L) [8].
• We observed a hierarchy of in-vivo efficacy as follows: azithromycin > spiramycin = clarithromycin > roxithromycin = erythromycin which did not correlate with in-vitro MIC or MBC [9].

Chemical compound and disease context of Dock2

• When a compound produced infertility through direct effects of testicular function (Carbendazim (MBC) and dibutyl phthalate (DBP)), then testis weight, testicular histology, and testicular sperm head counts provided sensitive indicators of toxicity [10].

Biological context of Dock2

• Mutagenicity and carcinogenicity profiles are developed to provide a complete overview and to determine whether an association can be made between benomyl- and MBC-induced mouse liver tumors and aneuploidy [11].
• In general, the effects were small, but it was observed that benomyl and MBC significantly induced micronuclei as well as aneugenic effects, hyperdiploidy (no metaphases with more than one or two extra chromosomes, 2n + 1 or 2n + 2, were observed) and polyploidy (4n) [12].
• Evidence is presented that MBC acts through inhibition of mitosis and that for this action the carbamoyl group is a necessary but not a sufficient condition [13].
• MBC and MEB are poorly soluble in water and therefore have a low bioavailability in vivo [14].
• These data demonstrate that spermatogenesis is sensitive to high-dose MBC exposure resulting in an altered ratio of testicular cell types present, abnormal sperm head morphology, and an altered sperm chromatin structure [15].

Anatomical context of Dock2

• Other benzimidazole derivatives, with the exception of the parent compound of MBC, benomyl, and the very closely related substance 2-benzimidazolylurea, did not produce micro-nuclei in mouse bone marrow [13].
• Effects of the fungicide methyl-benzimidazol-2-yl carbamate (MBC) on mouse germ cells as determined by flow cytometry [15].
• MBC had no effect on body weights, but testis weights and sperm parameters were altered, with few exceptions, only at the highest exposure level [15].
• Dual-parameter (DNA, RNA) flow cytometry (FCM) measurements were made on testicular and epididymal sperm cells isolated from mice exposed by oral gavage to 0, 250, 500, or 1000 mg/kg X 5 d of the fungicide methylbenzimidazol-2-yl carbamate (MBC), which is known to bind with tubulin subunits and inhibit polymerization and microtubule formation [15].

Associations of Dock2 with chemical compounds

• In contrast, methyl 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-beta-D-glucoside (MTIG) and methyl 3,4,6-tri-O-acetyl-2-deoxy-2-bromo-beta-D-glucoside (MTBG) showed promising brain uptake (160% MBC for MTBG) with a good brain-to-blood concentration ratio of 0 [16].
• Meropenem killed intracellular S. aureus at concentrations equal to eight times the MBC while imipenem did not [17].
• The in-vivo results can be explained by in-vitro and pharmacokinetic data: the MIC and MBC of 14-hydroxy clarithromycin are half those of clarithromycin and erythromycin, while the combination of clarithromycin and its metabolite was synergistic in terms of bacteriostatic and bactericidal activities [18].
• The known aneuploidogens, benomyl and its metabolite, carbendazim (methyl 2-benzimidazole carbamate (MBC)), were selected for the third in a series of ongoing projects with selected pesticides [11].
• Methyl thiophanate significantly induced micronuclei, but it was less effective than benomyl and MBC [12].

Analytical, diagnostic and therapeutic context of Dock2

• It was noted that the minimum inhibitory concentration (MIC, 33.0 +/- 2.9 ppm) and minimum bactericidal concentration (MBC, 50.0 +/- 0.0 ppm) values of reuterin for P. aeruginosa were significantly lower than their glutaraldehyde counterparts (MIC, 130.0 +/- 8.2 ppm and MBC, 180.0 +/- 18.3 ppm) [19].

References