Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neomycin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2003

Structure-activity relationship of neomycin, paromomycin, and neamine-arginine conjugates, targeting HIV-1 gp120-CXCR4 binding step.

We have recently designed and synthesized aminoglycoside-arginine conjugates (AACs) as potential anti-HIV-1 agents. AACs exert a number of activities related to Tat antagonism. We here present a new set of AACs, conjugates of neomycin B, paromomycin, and neamine with different number of arginines (1-6), their (a) uptake by human T-cell lines, (b) antiviral activities, (c) competition with monoclonal antibody (mAb) 12G5 binding to CXCR4, (d) competition with stromal cell-derived factor-1 (SDF-1alpha) binding to CXCR4, and (e) competition with HIV-1 coat protein gp120 cell penetration. The appearance of mutations in HIV-1 gp120 gene in AACs resistant HIV-1 isolates, supports that AACs inhibit HIV-1 infectivity via interference of gp120-CXCR4 interaction. Our results point that the most potent AACs is the hexa-arginine-neomycin conjugate, the other multi-arginine-aminoglycoside conjugates are less active, and the mono-arginine conjugates display the lowest activity. Our studies demonstrate that, in addition to the core, the number of arginines attached to a specific aminoglycoside, are also important in the design of potent anti-HIV agents. The AACs play an important role, not only as HIV-1 RNA binders but also as inhibitors of viral entry into human cells.

Anti-HIV Agents↗
PubMedDate not supplied

Response of the endolymphatic sac in the guinea pig to neomycin ototoxicity.

The guinea pig provides an excellent model for studying the effects of ototoxic antibiotics on the epithelium of the endolymphatic sac (ELS). Intracochlear injection of neomycin produces consistent destruction of cochlear and vestibular sensory cells, and the response to this traumatic insult can be documented by light and electron microscopy of the ELS. The histologic findings suggest that ELS epithelial cells are relatively resistant to ototoxic levels of neomycin. The study confirms the ability of the ELS to increase its activity during periods of labyrinthine stress.

Aminoglycosides↗
PubMed1998

The effect of explantation and neomycin on hair cells and supporting cells in organotypic cultures of the adult guinea-pig utricle.

Recent reports suggest that immature hair bundles are observed following aminoglycoside-induced hair-cell loss in the mammalian utricle in vitro as well as in vivo. It is therefore important to document the initial morphological changes associated with both culturing and aminoglycoside application so that degeneration can be clearly distinguished from regeneration. In this study, utricles from adult guinea pigs were maintained in culture for either 3 or 8 days, half being exposed to neomycin for days 2 and 3. They were then processed for microscopical examination and compared with control utricles from animals of the same age. The numbers of hair-cell and supporting-cell nuclei were counted and hair-cell morphology assessed. Bundles were classified as having either stepped (SHB) or unstepped (UHB) stereocilia, and their density determined. The numbers of hair-cell, but not supporting-cell, nuclei declined significantly compared with controls in both untreated and treated explants, the greatest reduction occurring 5 days after neomycin administration. The density of SHBs also declined but there was no significant change in UHB density, resulting in a residual population of hair bundles of more immature appearance in both untreated and treated utricles in vitro than in vivo. Although degenerative events such as hair-cell ejection from, or retraction into, the sensory epithelium were observed, no evidence of regeneration was found.

Animals↗
PubMed1999

Determination of hair cell degeneration and hair cell death in neomycin treated cultures of the neonatal rat cochlea.

The spatial-temporal course of hair cell degeneration and hair cell death was examined in the mammalian cochlea following aminoglycoside treatment. Organotypic cultures were established from postnatal rats (P3) and treated with 1 mM neomycin sulfate for 12-48 h and analyzed using a live/dead assay under epifluorescence microscopy. Live hair cells were labeled with calcein, a probe whose fluorescence and cellular retention depends upon intracellular esterase activity and cell-membrane integrity, respectively. Hair cell death was determined by ethidium homodimer-1, a probe that can enter cells with compromised cell membranes only. Inside the cell it binds to DNA. Hair cell morphology was also examined using phalloidin labeling, scanning electron microscopy and semi-thin section analysis. Results showed that hair cell degeneration and hair cell death occurred in a time dependent gradient from base to apex. After 48 h of neomycin treatment, most apical hair cells survived while most basal hair cells died. Calcein labeling provides a sensitive functional assay for measuring hair cell survival.

Animals↗
PubMed1980

The dose at which neomycin and polymyxin B can be applied for selective decontamination of the digestive tract in mice.

Oral treatment of mice with various doses of neomycin or polymyxin B was performed in order to determine which dose caused substantial suppression of aerobic gram-negative rods. In addition the effect of the various doses on Streptococcus faecalis and on other factors of the colonization resistance (CR) of the digestive tract were studied. It was found that polymyxin B was effective in suppressing sensitive gram-negative bacteria following daily doses of 3.2 mg/mouse, and that even extremely high daily doses of 9.7 mg/mouse did not affect the CR. Neomycin was effective in suppressing Enterobacteriaceae species following oral daily doses of 5.4 mg/mouse. With this dose, however, the CR was somewhat decreased which was also evidenced by the increased concentration of beta-aspartylglycine in the faeces and the increased size (weight) of the caecum in these animals. Suppression of Str. faecalis was seen from doses of 24 mg/mouse on.

Animals↗
PubMed2006

Recognition of B-DNA by neomycin--Hoechst 33258 conjugates.

Recent developments have indicated that aminoglycoside binding is limited not to RNA but to nucleic acids that, like RNA, adopt conformations similar to the A-form. We have further sought to expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Described herein are novel neomycin-Hoechst 33258 conjugates developed for exploring B-DNA groove recognition. We have varied the two reported conjugates in linker length and composition in an effort to improve our understanding of the spatial differences that define B-DNA binding. Spectroscopic studies such as ultraviolet (UV) melting, isothermal fluorescence titrations, differential scanning calorimetry (DSC), and circular dichroism (CD) together illustrate the mode of binding by such conjugates. Both conjugates exhibit enhanced thermal stabilization of A.T rich duplexes when compared to Hoechst 33258.

AT Rich Sequence↗
PubMed1997

Enhanced selection for homologous-recombinant embryonic stem cell clones with a neomycin phosphotransferase gene in antisense orientation.

Gene targeting in embryonic stem cells via homologous recombination can occur at a very low frequency. In order to enrich the selection for homologous recombinants, replacement targeting vectors are now commonly used that contain the thymidine kinase gene placed outside of the targeted homology. The additional negative selection requires the presence of antiviral drugs in the culture medium which are known to reduce the ability of embryonic stem cells to colonize the germ line. We have therefore tested alternative negative selection procedures with replacement targeting vectors that allow the expression of either a ribozyme directed against the neomycin-resistance gene (neo(r)) or of an antisense neo(r) RNA at random integration sites. The hammerhead ribozyme was found to be catalytically inactive in embryonic stem cell cultures maintained in the presence of the selecting drug neomycin. Thus, the replacement targeting vector that contains ribozyme sequences did not enhance the frequency of homologous recombination. However, placing a promotor sequence that can enable the transcription of antisense neo(r) RNA outside of the targeted homology led to a significant enrichment of the selection for homologous recombination. This enrichment is similar to previously reported enrichments obtained with the thymidine kinase gene. The advantage, however, is that no antiviral drugs are needed for the selection.

Animals↗
PubMed2005

Prevention of neomycin-induced nephrotoxic event in pig proximal tubular epithelial cell line by apolipoprotein E3.

Nephrotoxicity is one of critical problems of aminoglycoside antibiotics. We examined the protective effect of apolipoprotein E3 (apoE3), one of ligands for megalin, on neomycin-induced extracellular release of lactate dehydrogenase, a marker of cell necrosis using pig proximal tubular LLC-PK1 cells. Neomycin significantly induced the extracellular release of lactate dehydrogenase, but apoE3 successfully suppressed it. This result indicated that apoE3 protects the proximal tubular cells from the eventual cell death induced by nephrotoxic aminoglycosides.

Animals↗
PubMed1977

Effects of oral neomycin and kanamycin in chronic uremic patients: II. Nitrogen balance.

Nitrogen balance was studied for five to seven days before and during oral administration of neomycin or kanamycin to 14 patients with severe chronic renal failure who were receiving long-term nutritional therapy consisting of protein restriction and supplements of essential amino acids or their nitrogen-free analogues. There was a significant improvement in nitrogen balance during the antibiotic period when compared to the control period, averaging +0.80 g of N per day (P less than 0.005). There was no significant change in average dietary nitrogen, fecal nitrogen, the excretion of non-urea urinary nitrogen, or urea appearance (defined as the sum of urinary urea and the change in the urea pool) during the antibiotic period. However, total nitrogen intake increased by 0.47 g per day owing to nitrogen contained in the drugs. The lack of a change in fecal nitrogen implies that fecal nitrogen not attributable to the drug must have fallen substantially. We conclude that oral neomycin and kanamycin may improve nitrogen balance in patients with severe chronic renal failure by diminishing endogenous fecal nitrogen.

Administration, Oral↗
PubMed2003

Binding affinity and inhibitory potency of neomycin and streptomycin on the Tat peptide interaction with HIV-1 TAR RNA detected by on-line acoustic wave sensor.

The binding of two aminoglycoside antibiotics, neomycin and streptomycin, to a segment of the transactivation responsive region (TAR) RNA of the human immunodeficiency virus, and their inhibitory potency to disrupt the interaction of the RNA with a regulatory Tat protein-derived peptide, have been studied using a flow-through acoustic wave detector system. Binding affinity is directly correlated with the inhibitory potency of these molecules and the acoustic wave detection system shows that neomycin exhibits at least a ten-fold greater affinity for TAR RNA and that it is also a more potent inhibitor than streptomycin. These results are in agreement with previous studies. However, unlike the time-consuming batch-based assays, use of the flow-through format offers considerable potential for the rapid screening of the chemistry of relatively small-molecule-nucleic acid binding events.

Acoustics↗
PubMed1987

Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis.

Provision of GTP (or other nucleotides capable of acting as ligands for activation of G-proteins) together with Ca2+ (at micromolar concentrations) is both necessary and sufficient to stimulate exocytotic secretion from mast cells permeabilized with streptolysin-O. GTP and its analogues, through their interactions with Gp, also activate polyphosphoinositide-phosphodiesterase (PPI-pde generating inositol 1,4,5-trisphosphate and diglyceride [DG]). We have used mast cells labeled with [3H]inositol to test whether the requirement for GTP in exocytosis is an expression of Gp activity through the generation of DG and consequent activation of protein kinase C, or whether GTP is required at a later stage in the stimulus secretion sequence. Neomycin (0.3 mM) inhibits activation of PPI-pde, but maximal secretion due to optimal concentrations of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) can still be evoked in its presence. When ATP is also provided the concentration requirement for GTP-gamma-S in support of exocytosis is reduced. This sparing effect of ATP is nullified when the PPI-pde reaction is inhibited by neomycin. We argue that the sparing effect of ATP occurs as a result of enhancement of DG production and through its action as a phosphoryl donor in the reactions catalyzed by protein kinase C.

Animals↗
PubMed1983

Trimethoprim-polymyxin B ophthalmic solution in the treatment of presumptive bacterial conjunctivitis--a multicentre trial of its efficacy versus neomycin-polymyxin B-gramicidin and chloramphenicol ophthalmic solutions.

Two-hundred and thirty patients with a diagnosis of presumptive bacterial conjunctivitis were assessed in a randomized double-blind multicentre trial. In two of the centres the patients had been treated with either trimethoprim-polymyxin B or neomycin-polymyxin B-gramicidin ophthalmic solution. In the other two centres the patients had been treated with either trimethoprim-polymyxin B or chloramphenicol ophthalmic solution. All of the preparations used were shown to be effective and very few adverse reactions were encountered. No significant difference in clinical efficacy could be demonstrated between trimethoprim-polymyxin B and neomycin-polymyxin B -gramicidin but trimethoprim-polymyxin B was found to be significantly better (P = 0.03) than chloramphenicol in reducing signs and symptoms.

Chloramphenicol↗
PubMed1993

The 35-kilodalton protein gene (p35) of Autographa californica nuclear polyhedrosis virus and the neomycin resistance gene provide dominant selection of recombinant baculoviruses.

Autographa californica nuclear polyhedrosis virus (AcMNPV) recombinants were constructed to test the effectiveness of the AcMNPV 35-kilodalton protein gene (35K gene) and the bacterial neomycin resistance gene (neo) as dominant selectable markers for baculoviruses. Insertion of the AcMNPV apoptosis suppressor gene (p35) into the genome of p35-deletion mutants inhibited premature host cell death and increased virus yields up to 1200-fold at low multiplicities in Spodoptera frugiperda (SF21) cell cultures. When placed under control of an early virus promoter, the bacterial neomycin resistance gene (neo) restored multiplication of AcMNPV in the same cells treated with concentrations of the antibiotic G418 that inhibited wild-type virus growth greater than 1000-fold. The selectivity of these dominant markers was compared by serial passage of recombinant virus mixtures. After four passages, the proportion of p35-containing virus increased as much as 2,000,000-fold relative to deletion mutants, whereas the proportion of neo-containing viruses increased 500-fold relative to wild-type virus under G418 selection. The strength and utility of p35 as a selectable marker was further demonstrated by the construction of AcMNPV expression vectors using polyhedrin-based transfer plasmids that contain p35. Recombinant viruses with foreign gene insertions at the polyhedrin locus accounted for 15 to 30% of the transfection progeny. The proportion of desired viruses was increased to greater than 90% by linearizing the parental virus DNA at the intended site of recombination prior to transfection. These results indicate that p35 and neo facilitate the selection of baculovirus recombinants and that p35, in particular, is an effective marker for the generation of AcMNPV expression vectors.

Animals↗
PubMed1979

Interaction of neuromuscular blocking effects of neomycin and polymyxin B.

Neomycin and polymyxin B produce neuromuscular blocks with distinct features by different mechanisms of action. In eight anesthetized cats the authors studied their interaction by examining the neuromuscular block produced by an equipotent mixture. Values of onset, potency, dose-response relations, duration and reversibility of block, the train-of-four and tetanic responses during block, the frequency-block relationships, and the posttetanic twitch behavior were well approximated by averaging the corresponding values previously reported for each antibiotic. Edrophonium, 0.2 mg/kg, reversed the block by 8 to 35 per cent. 4-Aminopyridine, 0.6 mg/kg, completely reversed the block and caused a long-lasting overshoot of the twitch response. The authors conclude that neomycin and polymyxin B are additive in neuromuscular effects, not only in terms of potency and duration, but also in terms of the characteristics of the blocks produced.

Aminopyridines↗
PubMed2004

Declining susceptibility to neomycin and polymyxin B of pathogens recovered in otitis externa clinical trials.

BACKGROUND: Otitis externa is usually treated empirically with topical neomycin/polymyxin B/hydrocortisone. The predominant pathogens associated with this infection are Pseudomonas aeruginosa and Staphylococcus aureus. METHODS: Two multicenter clinical trials (one in adults and adolescents, and one in children), conducted between 1995 and 1996, compared neomycin/polymyxin B/hydrocortisone with ofloxacin for the treatment of otitis externa; two similar trials were conducted between 1999 and 2000. Assessments included the minimum inhibitory concentrations (MICs) of each antimicrobial drug for the major pathogens, bacterial eradication, and clinical efficacy. RESULTS: The MICs of all bacterial isolates (including P. aeruginosa) for neomycin and polymyxin B increased markedly in the 1999 to 2000 studies compared with the 1995 to 1996 studies. In the later studies, mean MICs for all major pathogens tested had increased above the breakpoint for polymyxin B (> or = 4 microg/ml). In contrast, MICs of all isolates for ofloxacin remained similar between the two study periods and were within the susceptible range for this drug. CONCLUSIONS: Although the bacterial eradication rates for both treatments in each study were equivalent, the clinical cure rate for neomycin/polymyxin B/hydrocortisone was lower (87%) than for ofloxacin (93%). Therefore, the organisms most often causing otitis externa appear to be developing resistance to neomycin and polymyxin B but not to ofloxacin.

Administration, Topical↗
PubMed1987

Comparative pharmacokinetics of gentamicin, neomycin and oxytetracycline in newborn calves.

The pharmacokinetics of three antibiotics--gentamicin, neomycin and oxytetracycline were determined in newborn calves. The kinetic determinations, using two-compartment open models, were made at increasing ages from 1 day to 42 days and compared with those made from older calves (250+ days). Although all three antibiotics are eliminated unchanged primarily by glomerular filtration, there were marked differences in the development of elimination processes for individual drugs. The pharmacokinetics of neomycin were not influenced by age. Although the elimination half-life of gentamicin appeared to decrease with age, the changes were not significant and were due to an increased elimination rate in only one calf. There was no change with age in the remaining three calves. Oxytetracycline elimination was significantly reduced in newborn calves. This was exemplified by a decrease in the half-life of elimination t1/2 (beta) from 672.5 +/- 99.4 in the newborn to 385.6 +/- 76.8 at 6 weeks of age, and 377.3 +/- 40.8 min in the 250-day-old calf. These changes were consistent in all four calves. The rate of elimination remained low for the first 4 weeks of life. The volume of distribution Vd, area was not changed after the first week of life. Based on pharmacokinetic changes, an adjustment of dosage is indicated for oxytetracycline in the newborn calf as compared to the older calf or adult.

Age Factors↗
PubMed1989

Neuromuscular blockade induced by flunarizine alone and in combination with pancuronium, suxamethonium or neomycin: studies in isolated rat phrenic-hemidiaphragm preparations.

The in vitro effects of flunarizine on indirectly- and directly-elicited contractions in rat phrenic-hemidiaphragm preparations were studied. The interactions of flunarizine with non-depolarizing and depolarizing neuromuscular blocking drugs (pancuronium and suxamethonium) and with an aminoglycoside antibiotic (neomycin) were also evaluated. Flunarizine induced a slowly developing concentration-dependent reduction of indirectly-elicited diaphragm twitch height, but only slightly reduced directly-elicited contractions. Flunarizine 1 and 5 mumol.l-1 produced a concentration-dependent enhancement of pancuronium-induced neuromuscular blockade, whereas suxamethonium blockade was significantly increased by flunarizine 5 mumols.l.-1 only. Moreover, both flunarizine 1 and 5 mumols.l-1 also increased the neuromuscular blockade induced by neomycin. In conclusion, flunarizine induced neuromuscular blockade and enhanced the effects of several neuromuscular blocking agents to varying degrees in vitro.

Animals↗
PubMed1994

Effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in two rat strains.

1. Standard renal clearance techniques were used to compare the acute effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in Sprague-Dawley and Fischer 344 rats. 2. Significant hypercalciuric and hypermagnesiuric responses to all three drugs (P < 0.01) were apparent within 30 min of the onset of drug infusion. 3. The magnitude of the acute hypercalciuric and hypermagnesiuric response to the three aminoglycosides was comparable. This contrasts with their nephrotoxic action where neomycin >> gentamicin > tobramycin. The magnitude of the acute physiological responses to these drugs do not therefore reflect their nephrotoxic potential. 4. Sprague-Dawley rats were at least as responsive as Fischer rats in their acute renal responses to gentamicin. If Fischer rats are more sensitive to aminoglycoside nephrotoxicity than Sprague-Dawley rats, this is not reflected in their acute responses to gentamicin.

Animals↗