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Rinsho Byori. the Japanese Journal of... Oct 2015Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the... (Review)
Review
Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease and is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. DMD is characterized by a deficiency of the muscle dystrophin as a result of mutations in the dystrophin gene. Currently, no effective treatment for DMD is available. Promising molecular therapies which are mutation-specific have been developed. Transformation of an out-of-frame mRNA into an in-frame dystrophin message by inducing exon skipping is considered one of the approaches most likely to lead to success. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence results in exon skipping and production of the dystrophin protein in DMD case for the first time. After extensive studies, anti-sense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients. Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations, which are detected in 19% of DMD cases. The clinical effectiveness of gentamicin and PTC124 has been reported. We have demonstrated that arbekacin-mediated read-through can markedly ameliorate muscular dystrophy in vitro. We have already begun a clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.
Topics: Animals; Codon, Nonsense; Dibekacin; Dystrophin; Exons; Gentamicins; Humans; Mice; Molecular Targeted Therapy; Muscular Dystrophy, Duchenne; Oligonucleotides, Antisense; Pathology, Molecular; Prostaglandin D2
PubMed: 26897856
DOI: No ID Found -
Carbohydrate Research Jul 19763',4',-Dideoxykanamycin B, the kanamycin B derivative that is active against resistant bacteria, was prepared from kanamycin B via N-tosylation, 3',4'-O-sulphonylation,...
3',4',-Dideoxykanamycin B, the kanamycin B derivative that is active against resistant bacteria, was prepared from kanamycin B via N-tosylation, 3',4'-O-sulphonylation, 3',4'-unsaturation, and hydrogenation. The unsaturated intermediate was obtained from the 3',4'-di-O-sulphonyl derivatives by the action of sodium iodide in N,N-dimethylformamide; if zinc dust was added in this reaction, aziridine derivatives were formed. Removal of the tosyl group was successfully performed by using sodium in ammonia-ethylamine.
Topics: Dibekacin; Kanamycin; Magnetic Resonance Spectroscopy; Methods; Optical Rotation
PubMed: 963688
DOI: 10.1016/s0008-6215(00)83132-8 -
Emerging Infectious Diseases Apr 2007To investigate the exact isolation frequency of 16S rRNA methylase-producing, gram-negative pathogenic bacteria, we tested 87,626 clinical isolates from 169 hospitals....
To investigate the exact isolation frequency of 16S rRNA methylase-producing, gram-negative pathogenic bacteria, we tested 87,626 clinical isolates from 169 hospitals. Twenty-six strains from 16 hospitals harbored 16S rRNA methylase genes, which suggests sparse but diffuse spread of pan-aminoglycoside-resistant microbes in Japan.
Topics: Aminoglycosides; Anti-Bacterial Agents; Dibekacin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Japan; Methyltransferases; Microbial Sensitivity Tests; RNA, Ribosomal, 16S
PubMed: 17553289
DOI: 10.3201/eid1304.060501 -
The Japanese Journal of Antibiotics May 1979
Topics: Aged; Dibekacin; Female; Humans; Infusions, Parenteral; Kanamycin; Lung Abscess; Male
PubMed: 459090
DOI: No ID Found -
International Journal of Clinical... Nov 1995Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface...
Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion. The antibiotic was assayed in plasma and urine by means of a high performance liquid chromatography (HPLC) method. A two compartment kinetic model was used to describe the bi-phasic decline of plasma concentration and to calculate the different pharmacokinetic parameters. Slow disposition and elimination rate constants beta and k10 respectively, and total body clearance were markedly diminished in anephric patients (p << 0.001): t1/2 beta = 2.12 h, k10 = 0.642 h-1 and Cl = 0.882 ml/min per kg, in normal subjects and t1/2 beta = 4.73 h, k10 = 0.278 h-1 and Cl = 0.693 ml/min per kg in anephric patients. The apparent volumes of distribution increased while the creatinine clearance of the patients decreased. Thus Vd(area) of volunteers with normal renal function was statistically significantly lower than that of anephric patients (p < 0.001), from a value of 0.162 to 0.281 l/kg respectively. A good correlation (r = 0.982) between patient's slow disposition constant beta and creatine clearance was found. Urinary recovery at 24 h was 85.6% of the dose given to normal volunteers. This value decreased while impairment increased. The mean extraction coefficient, during hemodialysis was about 0.35.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Anti-Bacterial Agents; Dibekacin; Female; Humans; Male; Middle Aged; Renal Dialysis
PubMed: 8688988
DOI: No ID Found -
The Journal of Antimicrobial... Jan 1980
Topics: Biological Assay; Dibekacin; Half-Life; Humans; Injections, Intramuscular; Kanamycin; Kidney Failure, Chronic; Kinetics; Renal Dialysis
PubMed: 7358604
DOI: 10.1093/jac/6.1.113 -
The Journal of Antibiotics Jun 1981The degrees of binding of [3H]dibekacin to LiCl-treated cores of E. coli ribosomes were reduced by increasing LiCl concentrations. The 1.15 M LiCl core lost 70...
The degrees of binding of [3H]dibekacin to LiCl-treated cores of E. coli ribosomes were reduced by increasing LiCl concentrations. The 1.15 M LiCl core lost 70 approximately 80% of the original binding capacity. The antibiotic attachment to the 1.15 M LiCl core was restored by reconstitution with the split proteins (SP), which were obtained by the treatment of 70S ribosomes with LiCl at concentrations of 0.8 approximately 1.15 M. The basic proteins, split off during the transition from 0.4 M LiCl core to 0.8 approximately 1.15 M LiCl core, seemed to be involved in the drug binding. SP0.4 approximately 1.15, which was obtained by the treatment of the 0.4 M LiCl core with 1.15 M LiCl, was fractionated by CM-Sephadex C-25 column chromatography, and each fraction was assayed for protein composition and the capability of restoring the ability of the 1.15 M LiCl core to bind the drug. Of ribosomal proteins eliminated with 1.15 M LiCl, the addition of either S9 or L6 alone to the 1.15 M LiCl core was observed to restore approximately 50% of the binding as compared to the 70S ribosome alone, and both proteins restored about 70% of the binding. The results suggested that ribosomal proteins S9 and L6 were involved in the attachment of [3H]dibekacin to the ribosome. The antibiotic binding to the 70S ribosome and 1.15 M LiCl core reconstituted with S9 and L6 was considerably inhibited by unlabelled dibekacin or kanamycin, and partially inhibited by gentamicin or neomycin, but was not significantly affected by streptomycin or viomycin.
Topics: Aminoglycosides; Anti-Bacterial Agents; Chlorides; Dibekacin; Escherichia coli; Kanamycin; Lithium; Lithium Chloride; Protein Binding; Ribosomal Protein S9; Ribosomal Proteins; Ribosomes
PubMed: 6268595
DOI: 10.7164/antibiotics.34.763 -
Chemical & Pharmaceutical Bulletin May 1987
Topics: Chemical Phenomena; Chemistry; Dibekacin; Glucosamine; Glucose; Kanamycin
PubMed: 3664822
DOI: No ID Found -
International Journal of Clinical... 1985Dosages and pharmacokinetics of dibekacin were studied in a group of 15 children with cystic fibrosis (CF) and a control group of 9 children. The mean dosage regimens of...
Dosages and pharmacokinetics of dibekacin were studied in a group of 15 children with cystic fibrosis (CF) and a control group of 9 children. The mean dosage regimens of dibekacin were respectively equal to 2.19 mg/kg and 2.16 mg/kg in the CF and non-CF patients. The mean peak serum values for the CF and non-CF groups were respectively equal to 5.3 micrograms/ml. Comparison of pharmacokinetic parameters (i.e. half-life, distribution volume, total body clearance and area under the curve) showed no significant difference between the two groups (p greater than 0.05).
Topics: Aspartate Aminotransferases; Child; Creatinine; Cystic Fibrosis; Dibekacin; Humans; Kanamycin; Kinetics; Time Factors
PubMed: 4018945
DOI: No ID Found -
Arzneimittel-Forschung 1984O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1----6)-O-[2,6-diamino-2,3,4,6 -tetradeoxy-alpha-D-erythro-hexopyrano-hexopyranosyl-(1----4 ) ]-2-deoxy-L- streptamine...
O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1----6)-O-[2,6-diamino-2,3,4,6 -tetradeoxy-alpha-D-erythro-hexopyrano-hexopyranosyl-(1----4 ) ]-2-deoxy-L- streptamine (dibekacin), like other known aminoglycoside antibiotics, possesses a dose-dependent neuromuscular blocking activity in vivo. d-Tubocurarine, at a dose which per se does not influence the contraction of gastrocnemius muscle elicited by sciatic nerve stimulation, significantly potentiates the neuromuscular blockade produced by dibekacin. Neostigmine methylsulfate is unable to reverse the neuromuscular blocking activity of dibekacin, whereas calcium chloride antagonizes the neuromuscular blockade produced by this antibiotic.
Topics: Animals; Calcium; Dibekacin; In Vitro Techniques; Kanamycin; Male; Neostigmine; Neuromuscular Junction; Rats; Rats, Inbred Strains; Sciatic Nerve; Tubocurarine
PubMed: 6543128
DOI: No ID Found