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Evaluation of the effect of ototopical neomycin on spiral ganglion cell density in the guinea pig.

The development of a reproducible unilateral deafness animal model was the primary objective of this study. Because of its importance in the function of cochlear prostheses, the status of the VIIIth nerve was used as the measure of deafness. The effect of a concentrated neomycin solution applied locally to the middle ear of the guinea pig was evaluated. Spiral ganglion cell survival was quantitated at 1, 2, 4, 6 and 10 weeks after exposure. Although the intermediate time periods showed moderate inter-animal variability, by ten weeks, consistent spiral ganglion cell loss was seen with maximum cell loss at the extreme apex (18.8% of control) and base (30.3% of control) and maximum cell survival in the lower middle turns of the cochlear spiral (53% of control).

Animals↗

Flow microcalorimetric assay of antibiotics--III. Zinc bacitracin and its combinations with polymyxin B sulphate and neomycin sulphate on interaction with Micrococcus luteus.

A flow microcalorimetric assay for zinc bacitracin has been developed which has better reproducibility (relative standard deviation less than 2%) and sensitivity (0.02 micrograms ml-1) than conventional microbiological assays, and requires an assay time of between 7.5-9 h. The assay is not suitable for zinc bacitracin determinations in the presence of equimolar concentrations of polymyxin B sulphate or neomycin sulphate, or of these antibiotics in the proportions in which they occur in the commercial preparation Trisep (ICI, Macclesfield, UK).

Bacitracin↗

Transcriptional mapping of the promoter of the aminoglycoside acetyltransferase gene (aacC9) of neomycin-producing Micromonospora chalcea.

We have studied the promoter of the gene encoding aminoglycoside acetyltransferase (aacC9) in neomycin-producing Micromonospora chalcea. S1 nuclease mapping showed that the transcription initiation point of this gene is at the translation start point, with no evidence of a conventional ribosome-binding site. The aac of paromycin-producing Streptomyces rimosus forma paromomycinus shows the same characteristic; there is no homology in the promoter regions of the two genes, whereas the coding sequences are very similar.

Acetyltransferases↗

Neomycin improves cationic lipid-mediated transfection of DNA in human cells.

Delivery of oligonucleotides has been a major impediment in the development of nucleic acid based drugs. In this report, we show that neomycin, an aminoglycoside antibiotic, when combined with a cationic lipid preparation such as DOTAP, enhances transfection efficiency of both reporter plasmids and oligonucleotides and results in a significant increase in transgene expression. The results described here open a new lead in ongoing efforts for oligonucleotide delivery.

Carbohydrate Sequence↗

Combined treatment of Acanthamoeba keratitis with propamidine, neomycin, and polyhexamethylene biguanide.

We developed an intensive treatment regimen of topical neomycin, propamidine, and polyhexamethylene biguanide that was tapered to a maintenance level over a 14- to 28-day period as toxicity developed. Since July 1991, we used this treatment on six eyes of five patients in whom Acanthamoeba keratitis was diagnosed clinically. All patients had positive cultures for microorganisms from their corneas or contact lens cases or had pathognomonic findings of pseudodendritic subepithelial infiltrates and radial keratone-uritis. After therapy, all patients improved within two to four weeks, with regression or resolution of neuritis and infiltrates, healing of epithelial defects, and lessening of pain. By three to four months, visual acuity had returned to 20/20 in all eyes. We believe the addition of polyhexamethylene biguanide to our treatment regimen in Acanthamoeba keratitis dramatically aided and hastened the clinical improvement in five consecutive patients and may, with early diagnosis, increase the number of medical cures.

Acanthamoeba Keratitis↗

Kinetic characterization of TAR RNA-Tat peptide and neomycin interactions by acoustic wave biosensor.

The kinetics of binding of short Tat peptides and an aminoglycoside molecule to the human immunodeficiency virus-type 1(HIV-1) TAR RNA and to a bulge mutant analogue (MTAR) is studied in a biosensor format by monitoring the time course of the response in a series resonance frequency, using an acoustic wave biosensor. Association and dissociation rate constants are evaluated by fitting the experimental data to a simple 1:1 (Langmuir) model. Kinetic rate and equilibrium dissociation constants show that MTAR-peptide complexes are subject to a higher dissociation rate and are less stable compared to the corresponding TAR-peptide complexes. In addition, longer peptides display enhanced discrimination ability than a shorter peptide according to the equilibrium dissociation constants evaluated using this technique. K(D) values for TAR-Tat vs. MTAR-Tat complexes are 2.6 vs. 3.8 microM for Tat-12, 0.87 vs. 4.3 microM for Tat-18 and 0.93 vs. 1.6 microM for Tat-20. The equilibrium dissociation constant for TAR-neomycin complex is 12.4 microM and it is comparable to the values obtained from non-biosensor type assays. These findings are in parallel with those cited in the literature and the results from this study underline the potential of the acoustic wave sensor for detailed biophysical analysis of nucleic acid-ligand binding.

Acoustics↗

Neomycin blocks substance P-induced calcium entry in cultured rat spinal cord neurons.

Substance P (SP) plays an important role in sensitization of spinal cord neurons. In this study, we investigated SP-induced calcium activities in cultured rat spinal cord neurons with confocal laser scanning microscopy. Our results showed that SP increased [Ca(2+)](i) by calcium entry rather than release from intracellular calcium stores. Neomycin (100 microM), an antagonist of phosphatidylinositol 4,5-bisphosphate (PIP(2)), blocked SP-induced calcium entry. Ca(2+)-free medium induced capacitative entry, which was significantly potentiated by SP. As activation of SP receptor (NK-1) leads to production of inositol 1,4,5-trisphosphate (IP(3)) by PIP(2) turnover, the results indicates that SP-induced calcium entry and SP-potentiated capacitative calcium entry might be mediated or regulated by IP(3)/diacylglycerol (DG) pathway.

Animals↗

Neomycin and gadolinium applied to an L5 spinal nerve lesion prevent mechanical allodynia-like behaviour in rats.

In male Wistar rats, the left ventral ramus of the L5 spinal nerve (RvL5) was cut, and animals were tested for allodynia-like behaviour in response to mechanical stimuli which were applied with von Frey hairs (4.3-205 mN) to the plantar skin of the hindpaw supplied by the intact L4 spinal nerve. After surgery, allodynia-like behaviour was evoked prominently on the operated (left) side and weakly on the contralateral (right) side. Eleven sham-operated rats displayed low levels of allodynia-like behaviour on the operated side comparable to that seen contralateral to the lesion in nerve-transected animals. In 14 rats, allodynic behaviour to mechanical stimuli on either side was dose dependently and permanently reduced, after 4-32 mg of the antibiotic Nebacetin had been applied locally at the transection site immediately after cutting the nerve. The same effect was observed when one of the active compounds of Nebacetin, neomycin, but not the other, bacitracin, was applied by continuous local infusion. Allodynia-like behaviour to stimuli between 4.3 mN and 124 mN was also prevented when 1-8 mg gadolinium acetate was applied at the transection site, whereas allodynic behaviour to stimuli of 205 mN was not affected at least for the first 7 days after the lesion. Both gadolinium and Nebacetin failed to prevent allodynic behaviour when applied later than 7 h after the nerve lesion. Neither substance interfered with the development of tactile allodynia when applied to the nerve rostral to the lesion site. The results suggest that Nebacetin and gadolinium interfere with the mechanisms at the RvL5 transection site crucial for the initiation of sensitisation of dorsal horn neurones and the development of mechanical allodynia.

Administration, Topical↗

The effects of lithium, indomethacin, and neomycin on vasopressin-induced contractions in rat urinary bladder.

1. [Arg8]Vasopressin (AVP) induced a contraction response in rat urinary bladder smooth muscle in a dose-dependent manner. 2. Indomethacin in a 10-microM concentration cannot change the effects of AVP on urinary bladder smooth muscle, which seem to be mediated by a direct action on the muscle rather than indirectly through prostanoid release. 3. Lithium (0.5, 1, and 10 mM) made the muscle more sensitive to AVP action. 4. Neomycin (1.25, 2.5, and 5 mM) had an inhibitory effect on AVP-induced contraction. 5. It seems that in rat urinary bladder vasopressin-induced contraction is mediated through phosphoinositide metabolism.

Animals↗

Developmental differences in susceptibility to neomycin-induced hair cell death in the lateral line neuromasts of zebrafish (Danio rerio).

Mechanosensory hair cells of the inner ear are susceptible to death when exposed to a variety of drugs including aminoglycoside antibiotics. During avian and mammalian development, there is a period of relative insensitivity to aminoglycoside-induced hair cell death. This study was designed to test the hypothesis that zebrafish (Danio rerio) have developmental differences in sensitivity to aminoglycoside-induced hair cell death in the lateral line neuromasts. Larval zebrafish of various ages were exposed to several concentrations of neomycin, and their hair cells were examined using the potentiometric vital dye, DASPEI. Results indicate that zebrafish larvae aged 4 days post-fertilization are relatively insensitive to aminoglycoside-induced hair cell death compared to older fish. Thus zebrafish hair cells show developmental differences in sensitivity to aminoglycoside-induced death similar to those reported for inner ear hair cells of birds and mammals.

Analysis of Variance↗

Simultaneous identification and quantitative determination of neomycin sulfate, polymixin B sulfate, zinc bacytracin and methyl and propyl hydroxybenzoates in ophthalmic ointment by TLC.

A thin layer chromatographic-densitometric method for identification and quantitation of neomycin sulfate, polymixin B sulfate, zinc bacytracin and auxiliary substances (methyl and propyl hydroxybenzoates) in ophthalmic ointment was developed. To separate these constituents the silica gel coated TLC plates and two mobile phases were used. The suitable mobile phases were: methanol-n-butanol-ammonia 25%-chloroform (14:4:9:12, v/v/v/v) for determination of antibiotics and n-pentane-glacial acetic acid (66:9, v/v) for methyl and propyl hydroxybenzoates. The antibiotic chromatograms were detected by using ninhydrin ethanol solution, while densitometric measurements were made at lambda = 550 nm. Hydroxybenzoates were identified by UV measurements at lambda = 260 nm. The constituents under consideration were well separated at sufficient detection level. The recovery for all constituents ranged from 98.08% to 104.95%.

Anti-Bacterial Agents↗

Fecal excretion pattern of bile acids in rats fed high fat diets and neomycin in induced colon tumorigenesis.

Neomycin augments colon tumorigenesis in 1,2 - dimethylhydrazine treated rats fed polyunsaturated fat diet and decreases fecal cholic acid excretion, while it inhibits tumorigenesis with increased cholic acid and decreased deoxycholic acid excretions in rats fed high cholesterol diet. Participation of other fecal bile acids seems to be insignificant in relation to colon carcinogenesis.

1,2-Dimethylhydrazine↗

Long-term ototoxic effects of neomycin applied topically in the middle ear: a morphological study in the guinea pig.

Neomycin was instilled daily, uni- or bilaterally, into the middle ear of guinea pigs for three months. The cochleae were examined, by light and electron microscopy, six months after the end of treatment. The organs of Corti of the treated ears were completely destroyed, and in the most advanced lesions, were substituted by a single layer of very thin flat cells. In the spiral ganglion only some glial cells and a few neurons could be observed. All surviving neurons were myelinated, and their ultrastructure was greatly altered, with disorganization of the rough endoplasmic reticulum and ribosomes. The basilar membrane almost disappeared, losing it amorphous and filamentous components. The spiral limbus and the stria vascularis were atrophic and were also covered, in the final stages, by flat elongated cells. In view of its morphological characteristics, this epithelium may arise from the displacement of the interdental cells and perhaps from the cochlear surface of Reissner's membrane.

Administration, Topical↗

A double-blind comparative study of ofloxacin otic drops versus neomycin-polymyxin B-hydrocortisone otic drops in the medical treatment of chronic suppurative otitis media.

Active chronic suppurative otitis media poses a management problem when patients are being considered for surgical treatment. Topical antibiotics have demonstrated varying degrees of success in the management of discharging ears. The introduction of quinolones has revived interest in these topical agents. This double-blind study compares two antibiotics, namely ofloxacin and neomycin-polymyxin B, with similar in vitro sensitivities to Gram positive and Gram negative organisms. Fifty-two patients were selected randomly and the results show that ofloxacin eardrops have marginal benefits in symptomatic improvement (89 per cent versus 79 per cent, p = 0.27) and bacterial eradication (81 per cent versus 75 per cent, p = 0.81) in active chronic suppurative otitis media. Significantly fewer patients (seven per cent versus 29 per cent, p = 0.04) in the ofloxacin group had active disease at the end of the two-week treatment. We recommend the use of ofloxacin eardrops in managing active chronic suppurative otitis media since it has high clinical efficacy, contains no steroid component and has no demonstrated risk of ototoxicity.

Anti-Infective Agents↗

Aminoglycoside (neomycin) preference is for A-form nucleic acids, not just RNA: results from a competition dialysis study.

Aminoglycosides have been at the forefront of antimicrobial therapy for the past 50 years. Their specificity is believed to lie in binding duplex RNAs (rRNA). Competition dialysis studies of various nucleic acid forms with 9-aminoacridine, quinacrine, and a neomycin-acridine conjugate were carried out. Our results suggest a strong preference for aminoglycoside binding to nucleic acids that can adopt an A-type conformation. These results challenge the common belief that aminoglycoside specificity is simply for duplex RNAs.

Acridines↗

Reaching into the major groove of B-DNA: synthesis and nucleic acid binding of a neomycin-hoechst 33258 conjugate.

Synthesis of a neomycin-Hoechst 33258 conjugate is reported. The conjugate combines the ligands known to selectively bind in the duplex and the triplex groove. The conjugate stabilizes DNA duplex over DNA triplex. The conjugate selectively stabilizes the DNA duplex (in the presence of salt), with as little as 2 muM of the ligand leading to a DeltaTm of 25 degrees C.

Bisbenzimidazole↗

Tuning the regioselectivity of the Staudinger reaction for the facile synthesis of kanamycin and neomycin class antibiotics with N-1 modification.

[reaction: see text] A novel method for achieving the desired regioselective reduction of the N-1 azido group on a tetraazidoneamine has been developed that leads to the synthesis of both kanamycin and neomycin class antibiotics bearing N-1 modification. Both classes of aminoglycosides are active against aminoglycoside-resistant bacteria carrying APH(3')-I and AAC(6')/APH(2'').

Amikacin↗

A comparative trial between diclofenac-gentamicin and betamethasone-neomycin drops in patients undergoing cataract extraction.

Eighty patients were randomised in a single-masked parallel-group study to receive topically either the test drug, a diclofenac and gentamicin combination, or a betamethasone and neomycin combination after routine cataract extraction and intraocular lens implantation. Each group was assessed over a 6 week period for post-operative inflammation. The two drug combinations were equally effective in suppressing inflammation in the early post-operative stages and the diclofenac-gentamicin combination was slightly more effective in the later stages. The test drug was well tolerated and showed no adverse effects. We feel it is an effective and relatively safe drug which has a role as an anti-inflammatory agent after cataract extraction and has potential advantages in certain circumstances.

Aged↗