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Effects of neomycin on 45Ca binding and distribution in canine arteries.

The effects of neomycin (7.0 mM) on 45Ca movements and distribution were investigated in canine aortae and in canine carotid and terminal mesenteric arteries. Uptake of 45Ca was measured in calcium-free solution; the 45Ca tissue spaces in the carotid and terminal mesenteric arteries were 2--4 times greater than those observed in the aorta. Exposure of the aortae and the terminal mesenteric arteries to 1.5 mM Ca++ during the washout elicited large increases in 45Ca efflux in both preparations (increase in terminal mesenteric greater than aorta). Moreover, in all three arterial preparations, neomycin reduced 45Ca uptake and induced a sustained increase in 45Ca efflux (effects on terminal mesenteric larger than or equal to carotid greater than aorta). The terminal mesenteric and carotid arteries may accumulate and bind 45Ca at superficial membrane sites (readily exchangeable 45Ca) to a greater degree than does the aorta. If Ca++ located at these membrane sites contributes directly to the maintenance of mechanical responsiveness, then agents which alter membrane binding of Ca++ (e.g. neomycin) may exert a stronger action on these highly reactive vessels. Thus, contractile responsiveness in peripheral arteries may depend upon depots of superficially bound Ca++ to a greater degree than in the more centrally located aorta.

Animals↗

A double-blind comparison of a new combination (halcinonide-neomycin-amphotericin) and active controls in cutaneous candidiasis and steroid-responsive dermatoses.

One hundred patients participated in the studies of cutaneous candidiasis and steroid-responsive dermatoses. Seventy patients with the former diagnosis were treated with either halcinonide-neomycin-amphotericin or hydrocortisone-iodochlorhydroxyquin ointment combinations on a double-blind parallel comparison basis. Similar results were obtained after both therapies. Thirty patients with symmetrical bilateral lesions of steroid-responsive dermatoses were treated with halcinonide-neomycin-amphotericin cream on the lesions on one side of the body and hydrocortisone-iodochlorhydroxyquin cream on the opposite side. A double-blind design was used in directly comparing the response to each of the two drugs. Considering the results of all dermatoses together the test combination was statistically superior to the control cream (p less than 0-05). However, while numerical superiority of good responses to the halcinonide combination was recorded in psoriasis, no statistical significance could be derived due to the limited number of cases. No side-effects occurred with any drug combination use. In the opinion of the authors halcinonide-neomycin-amphotericin cream and ointment are safe and effective in the treatment of cutaneous candiasis and steroid-responsive dermatoses.

Administration, Topical↗

Antiproliferative effect of neomycin in glioma cells.

The angiogenic growth factor (AGF) family of signaling molecules has been implicated in normal development and in physiological process as well as in human malignancy. Since blockage of nuclear translocation of AGF in endothelial cells with neomycin resulted in inhibition of the growth factor capacity to induce angiogenesis, we treated glioma cells with neomycin and assessed its effects on cell proliferation. Administration of 10mM neomycin during two days resulted in a 56% inhibition of glioma cells proliferation. This result may provide the basis for the development of a novel adjuvant therapeutic strategy forgliomas.

Animals↗

Inhibition of rat glioma growth by neomycin. Preliminary report.

Tumor development is known to largely depend on angiogenesis, and nuclear translocation of angiogenic factors is one of the crucial steps in tumor angiogenesis. This preliminary study was designed to investigate the suppression of tumor growth by neomycin, an inhibitor of nuclear translocation of several angiogenic factors overexpressed in gliomas. We found that intratumoral osmotic pump delivery of 10 mM neomycin caused significant inhibition of C6 glioma tumor development (85%) in rats. The data establish neomycin as a potential inhibitor of angiogenesis-dependent tumor growth and raise the possibility for its use as therapy in pathologies in which neovascularization is involved, including neoplasia.

Animals↗

Ototoxicity after use of neomycin eardrops is unrelated to A1555G point mutation in mitochondrial DNA.

Ear drops containing neomycin only rarely cause ototoxicity. The authors report on three patients with a tympanic membrane perforation who developed severe ototoxicity after use of eardrops containing 0.35 per cent neomycin. Mitochondrial DNA analysis revealed that there was no A1555G point mutation in these patients. This finding indicates that application of low concentration neomycin to the middle ear can cause severe inner ear damage even in humans who are not hyper-susceptible to aminoglycosides.

Anti-Bacterial Agents↗

Morphological changes in the normal and neomycin-perfused guinea pig cochlea following chronic prosthetic implantation.

The effects of chronic prosthetic implantation and interval electrical stimulation were studied in the normal and neomycin-perfused cochlea of the guinea pig. One group of guinea pigs was implanted with a multiple-electrode prosthesis in the scala tympani. During a 4-week period, the device was stimulated for 3 hours weekly with a continuous, 1 kHz sinusoidal current of constant intensity. A second group of guinea pigs underwent identical implantation and stimulation except that cochlear perfusion with .1 M neomycin was performed at the time of implantation. Current intensities ranged from .1 to .6 mA RMS. Two complementary control groups were implanted but not stimulated. The animals were sacrificed, the cochleae were perfused with a fixative, and the temporal bones were prepared for examination under a light, transmission, or scanning electron microscope. In the electrically stimulated cochleae, degenerative changes occurred in both the inner and outer hair cells and supporting elements. A decrease was apparent in spiral ganglion cell and nerve fiber populations in areas of inner hair cell depletion and did not seem to correspond to the survival of supporting cells. The electrically active electrodes were uniformly surrounded by a connective tissue matrix and areas of immature bone. These changes occurred at all the intensities tested, and did not monotonically relate in severity to current intensity. None of the changes was apparent in the normal control ears. Morphological changes induced by the ototoxic drug neomycin were so severe is both stimulated and unstimulated cochleae that comparison was not possible; this form of pretreatment is apparently unsuitable for use in studies of electrically induced damage. It appears that in the normal animal, chronic implantation with interval electrical stimulation results in a cumulative form of sensory and neural damage histologically similar to that proceeding from chronic noise exposure as well as other ototoxic agents. Such effects should be minimized if surviving sensorineural and supporting elements in the functionally compromised cochlea are to be preserved.

Animals↗

Effect of neomycin, carbadox and length of adaptation to calorimeter on performance, fasting metabolism and gastrointestinal tract of young pigs.

Five sets of littermate gilts (8.2 +/- .19 kg average initial weight) were randomly assigned within litter to a 16% protein corn-soybean meal basal diet (B), B + .308% neomycin, or B + 55 ppm carbadox. Each set was equally-fed individually once daily for 16 d in metabolism cages and 5 d in calorimeters. The average daily feed intake for 21 d was 276 g. Oxygen consumption and CO2 production were measured during an 8- to 24-h postprandial period on d 16, 19, 20 and 21, and during a 32- to 48-h postprandial period after the d 21 feeding. Pigs were killed 50 h postprandially for gastrointestinal tract measurements. Dietary supplementation of antimicrobial agents (neomycin and carbadox) resulted in improvements (P less than .01) in daily gain and efficiency of feed utilization and lower (P less than .05) small intestinal mass in pigs. There was no difference (P greater than .05) in daily gain, feed efficiency or small intestinal mass between pigs fed neomycin- or carbadox-supplemented diets. Whole-animal fasting O2 consumption and CO2 production measured during the 8- to 24-h or 32- to 48-h postprandial period were not affected (P greater than .05) by the supplementation or the source of dietary antimicrobial agents. There were no differences (P greater than .05) in 8- to 24-h fasting O2 and CO2 measurements determined on d 16, 19, 20 and 21, indicating that adaptation to calorimeters was not needed by the pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of perilymphatic perfusion with neomycin on the cochlear microphonic potential in the guinea pig.

The effects of three concentrations of neomycin, administered by a method of acute perilymphatic perfusion of the guinea pig cochlea, on the cochlear microphonic potential (CM) at 4 kHz and 500 Hz are described. A concentration-dependent reduction in CM occured during the 60 minute perfusion period. Neomycin at 10-4 M did not change the CM magnitude, while at 10-3 and 102 M it caused 4 kHz (and 500 Hz) CM reductions which began within 24 (for both frequencies) minutes and 10 (and 12) minutes of drug application respectively. CM reduction proceeded at a higher rate for greater neomycin concentration. The perfusion technique, the implication of the frequency indifference, and the potential of the perfusion technique for inner ear biochemical analysis are discussed.

Action Potentials↗

Routine postpartum treatment of dairy cattle with intrauterine neomycin sulfate boluses.

Within location, 119 dairy cattle from two experiment station herds, which had no problems associated with parturition, were randomly either treated by insertion of two intrauterine boluses containing a total of 1000 mg neomycin sulfate 24 h postpartum or maintained as a control. Uteri and ovaries of all cows were palpated 17 to 24 days postpartum and at 14 day intervals thereafter until inovulation of the uterus was judged complete and an estrus had been observed. All cows were inseminated at the first estrus after 60 days postpartum and at each estrus thereafter until conception. Cows treated with neomycin sulfate required more services per conception (1.7 to 1.4) and were open more days before conception (100.5 to 88.5) than the controls. The probable cause of the lowered reproductive efficiency is discussed. Treatment did not later significantly days to ovulation, estrus, involution, or first service. Three treated and five control animals needed additional uterine treatment. Routine intrauterine treatment of all cows with neomycin sulfate boluses should not be recommended.

Administration, Topical↗

Neomycin biosynthesis: the incorporation of D-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring. Postulated involvement of 2-deoxyinosose synthase in the biosynthesis.

D-[6-3H3]6-Deoxy-5-ketoglucose (10) and D-[5,6-3H2]6-deoxyglucose (11) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. D-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor D-glucose, and was found to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the previous proposals that in the formation of 2-deoxystreptamine the C-6 hydroxyl group of D-glucose is removed prior to the cyclisation reaction. Studies using the incorporation of D-[3-3H]glucose, D-[3,4-3H2]glucose and D-[5-3H]glucose into neomycin followed by the degradation of the latter established that in the biosynthesis of the 2-deoxystreptamine ring the C-4 and C-5 hydrogen atoms of glucose are removed. The loss of the C-4 hydrogen atom of the glucose is attributed to the formation of a 4-keto derivative which facilitates the removal of the C-5 hydrogen atom thus setting the stage for the expulsion of the C-6 hydroxyl group. The 5,6-olefinic intermediate formed in the process then undergoes cyclisation eventually releasing 2-deoxyinosose. The enzyme systems which participate in the conversion of D-glucose equivalent into 2-deoxyinosose may be described as 2-deoxyinosose synthase that in broad mechanistic terms resembles dehydroquinate synthase.

Deoxyglucose↗

[Aminoglycoside antibiotics neomycin and kanamycin inhibit the increase of of pyroglutamyl aminopeptidase activity by depolarizing synaptosomes of the frontal cortex of the rate].

INTRODUCTION: Thyrotrophin releasing hormone (TRH) has emerging in the last few years as a neuropeptide with important functions, not only as neurohormone into the hypothalamus-pituitary axis, but as neurotransmitter in several areas of the nervous system. Although little is known about its extra-endocrine functions, TRH has been related with several types of psychiatric disorders. Pyroglutamyl aminopeptidase (pGluAP) is the enzyme involved in the degradation of TRH. OBJECTIVES: The present research studies the levels of pGluAP activity under basal (resting) and KCl-stimulated (depolarized) conditions. The role of intracellular free calcium homeostasis, by means of the aminoglycoside antibiotics neomycin and kanamycin as voltage-dependent calcium channels blockers, is also studied. MATERIAL AND METHODS: Both pGluAP activity and intracellular free calcium concentration were analyzed in synaptosomes obtained from the frontal cortex of rats. Synaptosomes were incubated in artificial cerebrospinal fluid, under basal (resting) or KCl-stimulated (depolarized) conditions, with of without neomycin or kanamycin at different concentrations. RESULTS: Depolarization increases significantly pGluAP activity, which is completely abolished by neomycin and kanamycin at the lower concentrations used. On the contrary, aminoglycoside antibiotics do not block completely the increase on intracellular free calcium concentration induced by depolarization. Under basal conditions, no changes were found on pGluAP activity nor intracellular free calcium. CONCLUSIONS: pGluAP activity could regulate the neurotransmitter/neuromodulatory functions of TRH trough intracellular free calcium movements through aminoglycoside-sensitive voltage-dependent calcium channels. A role for inositol 4,5-bisphosphate breakdown products is also suggested.

Animals↗

[Haloprogin. Its effects in the presence of glucocorticoids and neomycin].

The problem was studied whether the activity of haloprogin is decreased in the presence of glucocorticoids (6-methyl-prednisolone hemisuccinate sodium; hydrocortisone) or in the presence of a bacteriostatic antibiotic (neomycin). Antifungal activity was determined by measuring changes in oxygen consumption of Saccharomyces cerevisiae in the resting phase. The results revealed that neither glucocorticoids in concentrations which activate yeast metabolism, nor neomycin impair the antifungal activity of haloprogin. Therefore, haloprogin may safely be used together with glucocorticoids and neomycin in topical therapy.

Administration, Topical↗

[Determination of neomycin in the film-forming aerosol preparation "Neotizol'"].

A colorimetric method for guantitative determination of neomycin in the aerozol preparation "Neotizol" was developed. The determination was performed after neomycin isolation from the film-forming composition with the carboxylic ion exchange resins IRC-50 and KB-2 containing 2.5-3 per cent of divinylbenzol. The results of the colorimetric determination were compared with the data of the microbiological assay. The results of neomycin determination in the aerozol preparation "Neotizol" were treated statistically.

Aerosols↗

Effectiveness of neomycin and polymyxin ointments: prevention of Staphylococcus Aureus keratitis in rabbits.

Combinations of neomycin sulfate and polymyxin B sulfate are commonly used in ophthalmic ointments for the treatment or the prevention of bacterial keratoconjunctivitis. In this study we evaluated the effectiveness of various ointments containing these two antibiotics, alone and in combination, in preventing Staphylococcus aureus keratitis in rabbits. Rabbit eyes were infected by intracorneal inoculation, treated topically with ointment and graded by gross observation 24 hours after inoculation. Treatment with ointments containing neomycin alone offered significant protection against these corneal infections. The polymyxin B ointments, as well as the vehicle controls, were ineffective in preventing S aureus infections in the rabbit eyes. However, by far, the most effective ointment formulations tested were the combination ointments and specifically those containing 1.75-3.50 mg neomycin and 3,000-6,000 units polymycin B per gram of ointment.

Administration, Topical↗

Rifaximin versus neomycin on hyperammoniemia in chronic portal systemic encephalopathy of cirrhotics. A double-blind, randomized trial.

Preliminary data suggest that rifaximin a new non-absorbable rifamycin-derivate, has beneficial effects on chronic portal systemic encephalopathy (PSE). To compare the efficacy and safety of rifaximin vs neomycin in the treatment of the hyperammoniemic state of PSE, 30 cirrhotic patients with grade I to III of PSE were randomly allocated to one of two groups: group A (15 patients) receiving rifaximin (400 mg/8h) and group B (15 patients) neomycin (1gr/8h). The duration of treatment was 21 consecutive days. Age, sex, hepatic and renal function, level of PSE, EEG and number connection test were similar in both groups. A significant decrease in blood ammonia levels was observed at the end of the treatment period in both groups; moreover rifaximin produced an earlier reduction of blood ammonia levels. The neuropsychic syndrome related to the PSE improved in both groups without significant difference. No side effects attributable to therapy were observed in the rifaximin group. These results indicate that, rifaximin is at least as effective as neomycin in the achievement and maintenance of low blood ammonia levels in cirrhotics with chronic PSE.

Aged↗

Erythroderma from systemic contact dermatitis: a complication of systemic gentamicin in a patient with contact allergy to neomycin.

A patient who was sensitive to potassium dichromate and neomycin showed a universal exfoliative erythroderma following intravenous gentamicin therapy. When his ear canals were later treated with a neomycin-containing topical medication, he reacted so severely that the skin of his ears was temporarily depigmented. Withdrawal of aminoglycoside antibiotics along with use of a topical steroid preparation under occlusion brought the eruption under control. Since approximately half of the persons with contact allergy to neomycin will also react to gentamicin, it seems unwise to treat such patients with other intravenous aminoglycosides that are closely related chemically. In our patient, multiple patch tests to other aminoglycosides caused positive reactions to all reagents containing a deoxystreptamine ring, but there was no reaction to streptomycin, which lacks that structure.

Aged↗

[Location of determinants of stability to neomycin and kanamycin as well as DNA segments, responsible for amplification in Streptomyces plasmids pSU3 and pSU10].

The S. rimosus amplifying sequence AUD-Sr1 encodes kanamycin and neomycin resistance, defined in the case of neomycin by aminoglycoside phosphotransferase. Its cloning on plasmid SLP1.2 makes possible the co-amplification of the obtained hybrid plasmids in S. lividans. In our study the regions responsible for resistance to aminoglycoside antibiotics and the capacity for amplification the two hybrid plasmids pSU10 and pSU3 were determined. Experiments on subcloning of the AUD-Sr1 sequence fragments on vector pIJ702 revealed localization of kanamycin and neomycin resistance determinants between PvuII(6) and BglII(7) on the AUD-Sr1 sequence fragments of 2.0 kb length. Two regions responsible for amplification of the hybrid plasmids were detected with deletion and insertion mapping. The first region is localized in the region of the plasmid SLP1.2 BamHI site and the second region is localized on the PstI(4)-PvuII(6) of the AUD-Sr1 sequence fragment of 1.1 kb length.

Deoxyribonuclease HindIII↗

[Antibiotic sensitivity of Campylobacter jejuni and Campylobacter coli strains with special reference to sensitivity to erythromycin and neomycin].

166 strains of C. jejuni and 46 strains of C. coli were typed against 14 antibiotics using the agar diffusion test. All strains were resistant against Penicillin G, Oxacillin and Rifampicin. Susceptibility were found against Chloramphenicol, Erythromycin, Neomycin, Oxytetracyclin, Streptomycin and Gentamycin. The minimal inhibition concentration was performed for Erythromycin and Neomycin. All strains tested were inhibited by less than or equal to 2 micrograms/ml Neomycin, one strain was resistant against 4 micrograms/ml Erythromycin.

Campylobacter↗