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PubMed1989

Polyamines and neomycin inhibit the purified plasma-membrane Ca2+ pump by interacting with associated polyphosphoinositides.

We investigated the effect of spermine, spermidine, putrescine and neomycin on the activity of the plasma-membrane Ca2+ pump and on its stimulation by negatively charged phospholipids and calmodulin. Millimolar concentrations of spermine and to a lesser extent of spermidine decreased the ATPase activity in the presence of phosphatidylinositol 4,5-bisphosphate (PIP2), without affecting the stimulation by phosphatidylinositol 4-phosphate (PIP). Sub-millimolar concentrations of neomycin inhibited the stimulation of the ATPase by PIP and by PIP2. Neomycin was more effective at the higher concentrations of PIP and PIP2. We discuss that these findings are compatible with the hypothesis that PIP and PIP2 bind to the ATPase and that several of these molecules have to be available to stimulate the ATPase.

Animals↗
PubMed1991

Neomycin does not interfere with the inositol phospholipid metabolism, but blocks binding of alpha-thrombin to intact human platelets.

Neomycin was demonstrated to inhibit the binding of thrombin to intact human platelets. The effects of neomycin on both thrombin binding and thrombin-induced changes in inositol phospholipid metabolism could be reproduced by the thrombin antagonist hirudin. We propose that neomycin inhibits thrombin-induced platelet activation by interference with the cellular receptor.

Blood Platelets↗
PubMed1991

Production of human interferon-beta by Sendai virus and poly(rI).poly(rC): inhibition by neomycin.

Neomycin inhibits the production of interferon-beta (IFN-beta) in human fibroblast cells in response to Sendai virus or to poly(rI).poly(rC) in a concentration-dependent manner, and to the greatest extent effective when added prior to or up to 2 h after induction. This inhibitory effect is negated when the protein kinase C activator, SC-9, is present during IFN-beta production in response to poly(rI).poly(rC), but not in response to Sendai virus. These results suggest that in human cells both virus and poly(rI).poly(rC) utilize an early neomycin-sensitive signal transduction step for the production of IFN-beta; because neomycin binds specific phosphatidylinositol phosphates, both of these inducers very likely require hydrolysis of these phosphates.

Cell Line↗
PubMed1979

Acute and subchronic neuromuscular blocking characteristics of streptomycin: a comparison with neomycin.

The characteristics of the neuromuscular block produced by streptomycin in vivo were studied on the sciatic-tibialis anterior nerve-muscle preparation of eight anaesthetized cats. The lungs of the animals were ventilated mechanically and normocarbia was maintained. During acute exposure to streptomycin (within 2 h), ED50 for blockade of the twitch was 56 (SEM +/- 5) mg kg-1 of the base. The characteristics of block were similar to those of neomycin-induced block in some aspects. There was absence of train-of-four fade and tetanic fade, partial sparing of the responses elicited at 10 Hz and 20 Hz, and total sparing of the 50 Hz tetanus, as well as the post-tetanic twitch. In contrast to neomycin-induced neuromuscular block, however, post-tetanic exhaustion was not observed and prolonged exposure to streptomycin (22-28 h) did not change the characteristics of the block. We conclude that, despite their chemical similarities, streptomycin and neomycin block neuromuscular transmission differently.

Animals↗
PubMedDate not supplied

Hearing loss following the application of topical neomycin.

Profound, irreversible ototoxicity has been reported following oral and topical neomycin therapy. Preexisting renal disease is a known risk factor for this adverse effect. In spite of the potential hazards of this drug, it continues to be used widely both orally and topically. This is a report of a severe, permanent hearing deficit that occurred in a patient with chronic renal failure. The patient, who had developed decubitus ulcers, was treated for three weeks with topical 1% neomycin solution applied in gauze-soaked bandages. Regular hemodialysis failed to prevent this adverse effect. Caution should be exercised in selecting patients to receive prolonged neomycin therapy.

Administration, Topical↗
PubMed1998

Analysis of neomycin, kanamycin, tobramycin and amikacin resistance mechanisms in gentamicin-resistant isolates of Enterobacteriaceae.

Twenty-four gentamicin-resistant isolates of Enterobacteriaceae, obtained from the clinical laboratories of three health centres in Nablus, Palestine, were tested for susceptibility to neomycin, kanamycin, tobramycin and amikacin. Resistance rates were 29.2% for neomycin, 58.3% for kanamycin, 45.8% for tobramycin and 8.3% for amikacin. Fourteen (58.3%) isolates were noted to be multiresistant, i.e., resistant to gentamicin and two or more other aminoglycosides; resistance to gentamicin, kanamycin and tobramycin was the most common pattern of multiple resistance. This pattern implies the involvement of adenyltransferase ANT(")-I activity. Plasmid profiles and curing experiments suggested a plasmid localisation of gentamicin, neomycin, kanamycin and tobramycin resistance genes. However, a chromosomal location is proposed for plasmid-deficient strains. Cross-resistance in two isolates to all aminoglycosides tested suggested membrane impermeability to aminoglycosides as the mechanism of resistance.

Amikacin↗
PubMed1991

Evolved neomycin phosphotransferase from an isolate of Klebsiella pneumoniae.

A new aminoglycoside resistance gene (aphA1-IAB) confers high-level resistance to neomycin. The sequence of aphA1-IAB is closely related to aphA1 found in the transposons Tn4352, Tn903 and Tn602. For example, aphA1-IAB differs from aphA1-903 at five nucleotides that result in four amino acid replacements. The enzyme encoded by aphA1-IAB has a significantly higher turnover number with neomycin, kanamycin and G418 as substrates than does the aphA1-903 enzyme. A parsimonious phylogenetic tree suggests that aphA1-IAB evolved from an ancestral form that is closely related or identical to the aphA1 found in Tn903. The excess of replacement substitutions over silent substitutions in aphA1-IAB, as well as its convergence toward aphA3 from Staphylococcus aureus, is indicative of selective evolution. Our hypothesis to explain these results is that aphA1-IAB evolved under the selective pressure of neomycin use in relatively recent times.

Amino Acid Sequence↗
PubMed1983

Effects on blood group antigens from storage at low ionic strength in the presence of neomycin.

Red blood cells (RBC) stored without plasma in a neomycin, low ionic strength medium at 4 degrees C in excess of 24 h show alterations in antigen reactivity. There is a loss of protease-sensitive RBC antigens and a protease-type increased IgG saline agglutinability of Rh antigens that is associated with increased binding of 125I anti-D. Both the serological findings and the alteration in RBC membrane polypeptides are consistent with protease modification of the membrane due to contamination of the RBC by leukocytes. Neomycin, low ionic strength or leukocytes alone or in dual combination do not produce the observed changes in antigen reactivity. The role of neomycin and low ionic strength in this phenomenon and implication for quality control of reagent RBC used for antibody detection and identification are discussed.

Blood Group Antigens↗
PubMed1982

Effect of neomycin and protein S1 on the binding of streptomycin to the ribosome.

The binding of [3H]dihydrostreptomycin to the 70-S ribosome or to the 30-S subunit has been investigated in the presence of neomycin by the Millipore filtration or the equilibrium dialysis procedure. It was observed that dihydrostreptomycin binds equally well to the 30-S subunit and the 70-S ribosome, and that neomycin stimulates the binding of dihydrostreptomycin to the ribosome by increasing the association constant and not by creating new binding sites. Specific removal of protein S1 from the 30-S subunit neither affected the binding of dihydrostreptomycin to the ribosome nor the stimulation of dihydrostreptomycin binding by neomycin.

Binding Sites↗
PubMed1990

Pharmacokinetics of neomycin in sheep after intravenous, intramuscular, subcutaneous and intratracheal administration.

The pharmacokinetics and bioavailability of neomycin in sheep were investigated following intravenous, intramuscular, subcutaneous and intratracheal administration of 10 mg/kg. A rapid distribution phase (t 1/2 alpha, 3.16 min) was followed by a slower elimination phase (t1/2 beta, 1.98 h). The apparent volume of distribution was 304.69 ml/kg. Absorption half-lives were 18.62, 21.22 and 40.83 min and elimination half-lives 2.68, 2.82 and 2.55 h after IM, SC and IT administration, respectively. Bioavailabilities between 0.74 and 0.85 were obtained for the three routes of administration. Based on the bioavailability and disposition kinetics of neomycin, a twice daily IM dosage regimen should both be practical and adequate to maintain plasma neomycin concentrations within the pharmacologically active but nontoxic range.

Animals↗
PubMedDate not supplied

Failure of neomycin to modify ACTH induced hypertension in sheep.

Studies in rats have shown that neomycin administration attenuates certain types of adrenocortical steroid dependent hypertension, including ACTH hypertension. The effects of oral neomycin on ACTH induced hypertension were examined in conscious sheep. Neomycin has no effect on the blood pressure or metabolic responses to ACTH in sheep.

Adrenocorticotropic Hormone↗
PubMed1995

Neomycin-induced perception deafness following bladder irrigation in patients with end-stage renal disease.

OBJECTIVE: To report a serious side-effect of intravesical instillations of neomycin in patients with end-stage renal disease. PATIENTS AND METHODS: Three patients (two men and a woman, aged 51.71 and 54 respectively) with end-stage renal disease who had undergone bladder irrigation with neomycin sulphate solution suffered complete irreversible deafness, which was assessed by audiogram. RESULTS: All three patients developed complete perception deafness after 3, 4 and 10 months, with characteristic changes in the audiogram. The severe progressive hearing loss was maximal in the high-frequency range. A high-pitched tinnitus was the first sign of impending hearing difficulty and two patients developed a spontaneous nystagmus. CONCLUSION: In view of the doubtful efficacy and, most importantly, the risk of severe disabling side-effects such as ototoxicity, we recommend the avoidance of intravesical instillation with neomycin whenever possible.

Administration, Intravesical↗
PubMed1987

Absorption of neomycin from the equine uterus: effect of stage of oestrous cycle and volume of vehicle.

Plasma concentrations of neomycin were measured following intrauterine infusion of 3.3 mg/kg bodyweight neomycin sulphate. Mares in oestrus absorbed approximately 6 per cent of neomycin infused whereas mares in a luteal phase absorbed 56 per cent. The volume of infusate also affected absorption as increased volume resulted in decreased absorption. The decreased absorption both during oestrus and when large volumes were used was probably due to reflux of antibiotic through the cervix.

Absorption↗
PubMed1976

Influence of subtherapeutic levels of a combination of neomycin and oxytetracycline on Salmonella typhimurium in swine, calves, and chickens.

Subtherapeutic levels of oxytetracycline plus neomycin in animal feeds did not bring about increases in the quantity, prevalence, or shedding of Salmonella typhimurium in swine, calves, or chickens. In fact, the medication generally reduced the proportion of animals carrying S. typhimurium. The medicated groups were fed rations containing oxytetracycline plus neomycin commencing 5 days prior to oral inoculation with S. typhimurium and continuing through a 28-day postinoculation period. Colonization of S. typhimurium occurred in all three animal species, as evidenced by clinical signs of infection and/or colony counts in feces. Only from swine and on only one occasion was a single resistant colony isolated. It is concluded that no evidence has been obtained which would implicate the continuous low-level feeding of oxytetracycline and neomycin for a 4-week period to a potential increased incidence of disease in animals or as a hazard to humans.

Animals↗
PubMed1975

Efficacy of combined furazolidone and neomycin in the control of contamination in Leptospira cultures.

The in vitro effectiveness of furazolidone combined with neomycin for the control of contaminants in Leptospira cultures was investigated. Enhanced additive or synergistic bactericidal activity was apparent with the combination when it was compared with each agent used separately or when compared with 5-fluorouracil. Combined furazolidone and neomycin, at 5-mug/ml concentrations each in Fletcher medium or in implanted sensitivity disks of 50 mug and 10 mug, respectively, was effective in inhibiting contaminants and did not interfere with the growth of leptospira belonging to 66 leptospiral collection serotypes. A simple technique for decontaminating swine kidneys from an abattoir for cultural isolation of leptospiras is described. The method involves exposing renal tissue diluted in saline containing furazolidone and neomycin in combination (each in a concentration of 25 mug/ml) for 1 h prior to inoculating culture media. The method is suitable for routine use in the isolation of leptospiras from contaminated clinical or pathological specimens.

Drug Combinations↗
PubMed1969

Large-plate method for the assay of neomycin in serum.

A large-plate method employing radial diffusion from small paper discs for assaying serum levels of neomycin is described. More than 120 discs placed on a loading plate and loaded with 20 muliters of sample could all be brought into contact with the agar plate at one time. The requirement for elaborate statistical design to compensate for time-dependent bias was thus eliminated. The dose-response curve was linear for a range of at least 0.5 to 2.5 mug/ml. The experimental limits for the actual zone width (distance from the edge of the paper disc to the outer edge of the inhibition zone) for 120 repetitions of the assay of neomycin in one and the same serum, carried out simultaneously on one large plate, were about +/- 6% (95% confidence interval). The 95% confidence interval for the distribution of difference between duplicate zones obtained for the assay of neomycin in 34 different sera, also carried out on one plate, was about +/- 10%. The dose-response lines for a standard and for three unknown sera, when carried out together on one plate, were parallel within the variability (+/- SD one) of the zone width. The large-plate method is considered to be more efficient than the use of the smaller petri dishes. The method is suitable for the assay of penicillin in serum and can most probably be used for the assay of a wide variety of substances for which radial diffusion from paper discs into agar is feasible.

Agar↗
PubMed1971

Factors which influence synergism by neomycin and oxytetracycline.

Six strains of enteropathogenic gram-negative bacteria were tested for susceptibility to neomycin or oxytetracycline alone and combined in fixed ratios. The minimal inhibitory concentration for the combination was less than one-half of that expected if the antibiotic activities were simply additive. Neomycin alone was more effective against bacteria multiplying in the presence of abundant oxygen, whereas oxytetracycline alone was more effective against bacteria multiplying in relatively anaerobic environments; when combined, the antibiotics complemented each other by their opposing optima for activity. Oxygen concentration, pH, and neomycin activity are related, and the depression of acid production by oxytetracycline is believed to be partially responsible for the synergistic activity of this pair of antibiotics.

Agar↗