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A total of 450 consecutive patients were patch-tested to both neomycin and framycetin (20% in petrolatum). Thirteen patients were sensitive to both preparations, 10 to neomycin alone and four to framycetin alone. The significance of these results is discussed, with particular reference to the constituents of the preparations and the allergenic groups involved.
The ototoxic effects of RU 25434, a new semi-synthetic aminoglycoside antibiotic, were compared to those of amikacin and neomycin. Experiments were performed in adult and new-born guinea-pigs, ototoxicity being assessed by Preyer's reflex response and the measurement of the cochlear microphonic potentials at the end of treatment. The well known ototoxicity of neomycin was observed and RU 25434 appeared to be relatively less toxic than amikacin. The use of new-born guinea-pigs seem to be particularly suitable for this type of study because of their apparent sensitivity to ototoxicity.
In vitro studies indicate that neomycin C is 50% as active as neomycin B against Staphylococcus epidermidis (ATCC 12228).
Mutant strains resistant to neomycin or to kanamycin sulfate were isolated from Escherichia coli K-12. Nine mutants were analyzed; all were resistant to both antibiotics (about 150 and 100 mug/ml, respectively), and were designated nek. In the mutant strains, the ribosomes are changed from those of the parental strain; for when they were used in assays for polypeptide formation directed by polyadenylic acid or polycytidylic acid, coding fidelity in presence of the drugs was increased and inhibition of synthesis by the drugs was lessened. Mating experiments and transduction tests showed that all of the nine nek mutants are either closely linked or allelic, and the nek locus is closely linked to two genes-str (streptomycin) and spc (spectinomycin)-known to affect the 30S ribosome. The two nek mutants tested were recessive to the sensitive, wild-type allele. When the nek mutants were compared to the parental strain, pleiotropic effects of the nek mutations were observed. Resistance to low levels of streptomycin and spectinomycin was increased, whereas resistance to chloramphenicol was decreased. Also, the mutants were less able to adapt to high concentrations of lincomycin, and could no longer show phenotypic suppression of an arginine requirement by neomycin or kanamycin. Such pleiotropic effects are suggested to be the rule for mutations in genes that participate in the biosynthesis of a cellular organelle.
AIM: To evaluate the clinical efficacy and safety of topical polymyxin B, neomycin, and gramicidin for the treatment of suspected bacterial corneal ulceration at the Leiden University Medical Center. METHODS: Patients with a diagnosis of a suspected bacterial corneal ulcer between April 1995 and February 2002 were retrospectively identified and reviewed; clinical and microbiological features and response to therapy were analysed. All patients were treated with Polyspectran eye drops. RESULTS: In total, 91 patients were included in this analysis. Bacteriological cultures of 46 patients (51%) were positive and revealed 51 microorganisms. Staphylococcus aureus (29.4%) and Pseudomonas aeruginosa (23.5%) were the most frequently encountered bacteria. Eighteen patients switched therapy before complete healing of the corneal ulceration, four patients were lost to follow up. Of the 69 patients who completed Polyspectran treatment, re-epithelialisation occurred in 68 patients (99%) and on average took 12.6 (median 8) days. Among 91 patients, there were four perforations and one evisceration. Seven toxic or allergic reactions were reported. CONCLUSION: This study shows that the combination of polymyxin B, neomycin, and gramicidin is an effective and safe treatment of suspected corneal ulceration.
Neomycin forms insoluble complexes with long-chain fatty acids in vitro. This reduces the diffusion of neomycin but does not directly neutralize its antibiotic activity. Possible effects in vivo are discussed.
The effects of two topical nasal preparations on human nasal ciliary beat frequency in vitro and on nasal mucociliary clearance in vivo were investigated. Betamethasone and betamethasone with neomycin drops were found to be ciliotoxic when ciliated epithelium was exposed to them in vitro, mainly owing to the effects of the preservatives benzalkonium chloride and thiomersal. The nasal mucociliary clearance and in vitro ciliary beat frequency of nasal ciliated epithelium taken from healthy subjects were not adversely affected after topical application; neither did treatment with betamethasone, with or without neomycin, for four weeks affect these indices in two groups of patients with rhinitis. Thus, despite a ciliotoxic effect when ciliated epithelium is exposed to these preparations in vitro, they do not affect nasal clearance or ciliary beat frequency (as measured in vitro) adversely when administered topically to the nose.
Stability and expression of the bacterial neomycin resistance gene (neor) transferred to human continuous marrow cultures by a retroviral vector [pZIP-NeoSV(X)] was evaluated over 4 weeks. Following infection of long-term human marrow cultures with pZIP-NeoSV(X), 10-15% of the stromal cells demonstrated high replating efficiency in a dose of the neomycin analogue G418 that was toxic to stromal cells from uninfected cultures. In contrast, G418 resistance was detected in less than or equal to 1% of GM-CFUc and CFU-GEMM derived from the same virus-infected compared to control cultures. Infection of human CFU-GEMM enriched 100 X by monoclonal antibody selection with pZIP-NeoSV(X) did not increase the percentage of neor progenitors. Marrow cells from cultures infected with pZIP-NeoSV(X) and a replication competent amphotropic virus transferred the vector and G418 resistance to HeLa cells at a frequency of 1/10(5) for nonadherent and 1/10(4) for adherent cells. Two established human hematopoietic (HL60 and K562) and one stromal cell line (KM101) stably expressed the neor gene. Thus, a higher efficiency of infection and expression of a gene transferred by pZIP-NeoSV(X) to permanent human hematopoietic tumor cell lines and fresh marrow stromal cells contrasts with a lower level of expression in fresh CSF-dependent human hematopoietic stem cells.
The mode of action of the hypocholesteremic drug neomycin (2 g/day) was studied in four patients. All showed a significant reduction in plasma cholesterol concentrations (mean 25 percent, range 18-31 percent), and in one of three patients with hyperglyceridemia there was a decrease of plasma triglycerides of 26 percent. Cholesterol absorption was measured in three of four patients: there was a marked decrease. Sterol balance studies in four patients showed an unabating increase in fecal neutral steroid excretion (mean increase 345 mg/day, range 323-361) for 3-5 wk after plasma cholesterol levels had reached a new and lower plateau. Fecal acidic steroid excretion increased temporarily in two patients, with a sustained increase of 93 mg/day in only one. Daily stool weights increased significantly in three of four patients, though none had steatorrhea; there was a significant reduction in excretion of secondary bile acids; neutral sterol degradation rates were not affected by the drug. Slopes of plasma cholesterol-specific activity time curves did not change. These results fail to support the suggestion that neomycin acts as a bile acid precipitant. The finding of increased fecal neutral steroid excretion is consistent with decreased cholesterol absorption, but also with increased cholesterol absorption, but also with increased cholesterol synthesis (secondary to release of negative feedback control), with increased flux of cholesterol from tissues, or with a combination of all three actions.
Many commonly employed otic drops contain aminoglycoside antibiotics that may be toxic to the inner ear. A variety of chemicals such as ionic solutions, certain anesthetics, and epinephrine have been shown to diffuse across the round window membrane into the perilymph. Twelve adult cats were studied in this experiment. The auditory bulla was exposed and solutions containing gentamicin or neomycin concentrations similar to that commonly used in otic drops were applied to the round window niche for 15 minutes and washed with saline solution. The gentamicin and neomycin concentrations in the round window niche wash and the perilymph were then assayed by a radioenzymatic method. Concentrations of both antibiotics were observed in the perilymph. Thus, the round window membrane is a route through which these ototoxins may gain access to the inner ear.
Modified neomycin prepared by the ionic coupling on xanthan with an activity of 380 UI/mg was characterized in regard to its in vitro and in vivo release rate and therapeutic action with artificial tear eluent. The dynamic system in vitro release showed that after 4 h, there appears a "zero-order" kinetic. Ophthalmic inserts were prepared from modified neomycin and they are used in treating bacterial conjunctivitis. Sterilization of the conjunctival sac is obtained 12 h after insert administration.
Several growth factors and their receptors are expressed in inappropriately high abundance in gliomas and are further upregulated during the transition from low- to high-grade malignancy. In glioma cells growth factors induce expression of mitogen-activated protein kinase (MAPK) pathways. Here we report that neomycin restrained glioma cell proliferation in vitro by inhibition of p42/44 MAPK and the cyclic AMP element binding protein (CREB)-directed transcription pathways. Since alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential, neomycin offers great promise for treating cancer and other diseases associated with a sustained MAPK activity.
By means of physiological and morphological techniques the inner ear pathology following exposure to the ototoxic compounds atoxyl and neomycin was analysed in the rat. Primarily a high tone deterioration occurred with a subsequent morphological degeneration pattern among the hair cells in the basal part of the cochlea. The outer hair cells were more frequently affected than the inner hair cells following the administration of both atoxyl and neomycin.
The kinetics of neomycin entry into tissues, including those of the inner ear, was studied in the guinea pig. The animals received daily subcutaneous injections of 100 mg neomycin/kg body weight and were killed after 1, 3, and 6 days and 1, 2, and 3 weeks. In agreement with previous studies, kidney accumulated the drug rapidly and to a high level (450 micrograms neomycin/g tissue at day 7) while levels in heart, liver, lung, and spleen were lower by more than one order of magnitude. The drug was virtually absent from brain at all times. The salient finding was that neomycin content of cochlear tissues was relatively low. For instance, at 2 weeks, concentrations in organ of Corti (0.7 micrograms/mg protein) and lateral wall tissues (0.4 microgram) were similar to those in heart (0.3 microgram), liver (0.5 microgram), lung (0.8 microgram) and spleen (0.6 microgram) while the concentration in kidney was 6.8 micrograms neomycin/mg protein. The results show that mechanisms of drug entry are different for kidney and cochlea. They also show that the frequently discussed 'accumulation' of aminoglycosides in perilymph is apparently not reflected in tissue levels of the drug.
Human serum albumin microspheres containing neomycin sulphate were prepared using emulsion polymerization and polymer dispersion techniques. The many variables which may affect the shape, size, stability, release of the drug from the microspheres such as internal phase to external phase volume ratio, human serum albumin content, stirring rate, polymer content and stabilizing agent concentration, were studied. Unlike the microspheres prepared by the emulsion polymerization technique, polymer dispersion stabilised microspheres were uniform in size and shape with a narrow range of size distribution. In vitro release of neomycin sulphate from albumin microspheres was studied using the dialysis cell method. The drug release from microspheres followed Q versus (t)-1/2 linear relationship. The in vivo distribution studies on prepared microspheres revealed that the localization takes place preferably in lung tissues, liver, spleen and kidney and is found to be dependent on the microsphere size. On administration of microspheres of 3-6 microns size, approximately 55 per cent of administered drug could be localized in the lungs.
The effects of dietary corn bran hemicellulose (CBH) and neomycin (Neo) on hepatic caspase-3 activity and glycoprotein concentration were investigated to explore the possible mechanism of the alleviative action of dietary CBH and Neo on the development of D-galactosamine (GalN)-hepatitis. Rats were fed a diet containing 5% CBH with or without neomycin (Neo) for 7 or 14 d. On the last day of feeding, the rats were treated with GalN (400 mg/kg body weight, i.p.), and their plasma transaminase activities, hepatic glycoprotein concentrations and hepatic caspase-3 activities were determined 6 or 24 h later. Although the elevations of plasma transaminase activities were suppressed by CBH or Neo 24 h after GalN-treatment, the activities were not affected by CBH or Neo at an early stage (6 h) of GalN action. At 6 h, hepatic caspase-3 activity was elevated by CBH diet alone as high as that of the GalN-injected control-diet group, and the activity was not elevated further by GalN. At the same time, both GalN-treatment and CBH feeding reduced the hepatic glycoprotein (Mw. 64,000-74,000) concentration, but Neo did not affect the caspase activity or the glycoprotein concentration. These results suggest that dietary CBH elevates hepatic caspase-3 activity and reduces hepatic glycoprotein concentration, and may imply that CBH would suppress GalN-hepatitis not at the early- or middle-step of apoptosis but at the late-step of apoptosis or necrosis, although the relation between these phenomena and the alleviative effects of CBH and Neo on GalN-induced hepatitis is yet to be clarified.
Chickens were orally inoculated with Salmonella typhimurium and fed rations medicated with either 200 g/ton neomycin sulfate, 200 g/ton oxytetracycline, or a combination of 200 g/ton neomycin sulfate plus 200 g/ton oxytetracycline for 16 days. The incidence of salmonellosis was lower in chickens fed the combined antibiotics, and the numbers of viable S. typhimurium in feces were significantly fewer than in chickens receiving only one antibiotic. Chickens fed the combination also gained significantly more weight on less feed than those fed only one antibiotic.
Transgenic mice were produced to study the expression of amino-3' glycosyl phosphotransferase gene (neomycin resistance gene) in the embryonic fibroblast cells. A 1.9 Kb linear fragment of neomycin resistance gene under the control of pPGK promoter was microinjected into the pronucleus of mouse embryos. Out of 64 potential founders born, 5 were identified to be transgenic by the polymerase chain reaction (PCR) and southern hybridization. Multiple mice from first and second generation from two transgenic founders (N-10 and N-32) were analysed to determine the germline transmission. It was found to be 24.6 and 71.4% in first and second generation respectively. Results were also further confirmed by RT-PCR, sequencing and in vitro bioassays.