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PubMed1987

Ototoxicity of neomycin and polymyxin B following middle ear application in the chinchilla and baboon.

Previous experimental studies have demonstrated structural damage of the organ of Corti and stria vascularis following application of combination antibiotic otic drops to the middle ear. In this investigation the ototoxic effects of neomycin and polymyxin B (two antibiotics often used together in ototopical preparations) were separately evaluated after administration of each agent to the middle ear cavities of chinchillas and baboons. The antibiotics were administered in saline solution at the same concentrations used in Cortisporin Otic Suspension (3.5 mg/ml neomycin base, 10,000 units/ml polymyxin B). In both the rodent and primate, polymyxin B consistently produced greater cochlear damage than did neomycin. In fact, the extent of hair cell loss and strial injury produced by polymyxin B alone was, in many cases, comparable to that previously observed after application of Cortisporin Otic Suspension itself. Hair cell loss in the baboon was markedly less severe than in the chinchilla. It is believed that differences in position and structure of the round window membrane are important factors in the differing levels of ototoxicity observed in the rodent and primate.

Animals↗

PubMed1988

The effect of (a) neomycin and lactulose treatment on systemic and portal serum GABA levels in rats and (b) pH changes on [3H] GABA binding to isolated rat hepatocytes.

Recently it has been suggested that gamma-aminobutyric acid (GABA), a potent inhibitory neurotransmitter, may be involved in the pathogenesis of hepatic encephalopathy. If so, then therapeutic interventions that are known to improve or exacerbate the encephalopathic state should have significant effects on GABA homeostasis. In the present study, we determined the effect of neomycin and lactulose treatment on systemic and portal venous blood GABA levels in healthy rats and rats having undergone common bile duct ligation. We also studied the effect of alterations in extracellular pH on [3H]GABA binding to isolated rat hepatocytes. The results of the study revealed that systemic serum GABA levels in neomycin (0.38 +/- 0.09 mumoles/L: mean +/- SEM) and lactulose (0.45 +/- 0.11 mumoles/L) treated healthy rats were significantly lower than in healthy controls (0.63 +/- 0.21 mumoles/L, p less than 0.01 and 0.05 respectively). The same was true of portal venous GABA levels (1.02 +/- 0.29, 1.14 +/- 0.69 vs 3.44 +/- 1.6 mumoles/L respectively). In liver diseased rats however, systemic serum GABA levels in neomycin (2.35 +/- 0.22 mumoles/L) and lactulose (1.92 +/- 0.29 mumoles/L) treated rats were similar to those in untreated liver disease controls (2.36 +/- 0.22 mumoles/L) as were portal venous GABA levels (5.76 +/- 0.73, 2.91 +/- 0.46 vs. 3.82 +/- 0.47 mumoles/L respectively). [3H]GABA binding to isolated hepatocytes was significantly decreased (46%) in the presence of an alkaline extracellular environment. The results of this study indicate that, in healthy but not in liver diseased rats, peripheral GABA homeostasis is altered by agents or factors that are known to improve or exacerbate the encephalopathic state in humans.

Animals↗

PubMed1977

[Study of the composition and elaboration of a catalytic method for purifying the gaseous waste from neomycin and monomycin production].

Composition of the waste gases in the production of neomycin and monomycin at the stages of fermentation, coagulation and filtration was studied. It was found that the main components of the waste gases in the production of neomycin and monomycin were carbon dioxide (0.15-6.0 mg/1), moisture (22-34 mg/1) and organic substances (0.5-4.2 mg/1) calculated for carbon dioxide. These substances have a specific unpleasant odour. A procedure for purification of the waste gases in the production of neomycin and monomycin by catalytic oxidation was developed.

Catalysis↗

PubMedDate not supplied

Effect of ascorbic acid in the presence of neomycin on isolated rat stomach strips.

The effects of vitamin C and acetylcholine on the smooth muscle of rat stomach were compared after neomycin-induced blockade of phosphatidylinositol metabolism. The cumulative curves of dose-dependent responses showed a non-competitive antagonism between vitamin C and neomycin. On the other hand, the antagonism between acetylcholine and neomycin was of a mixed, competitive-non-competitive type. The results of the experiments suggest the conclusion that a normal metabolism of phosphatidylinositol controlling calcium transport into the cells is necessary for the stimulating effect of vitamin C on the contractions of the smooth muscles in the digestive tract.

Acetylcholine↗

PubMed1986

[Ammonia and glutamine metabolism of the intestine. The effect of lactulose and neomycin].

The present work is directed to distinguish between ammonia production by the mucosa and by the intestinal flora, as well as to evaluate the influence of neomycin and lactulose. In vitro studies using rat intestine show that mucosa cells produce ammonia alanine and glutamic acid when incubated with glutamine, whose process can be impaired by neomycin or lactulose. Since the release of the above solutes is virtually the same in germ-free rats, the influence of the bacterial flora might be negligible under the experimental conditions used. Elimination of the aerobic microorganisms results in a minute decrease of ammonia concentration in portal blood in contrast to elimination of the anaerobic flora, which leads to an excessive reduction of ammonia formation. In germ-free rats colonisation with anaerobic microorganisms results in an increment in portal ammonia concentration, whose value, however, is still below levels observed in normal animals. Colonisation with aerobic bacteria has no effect on portal ammonia concentration. Neomycin and lactulose affect ammonia production in the gut by interfering with glutamine uptake in the mucosa cell, thus the influence upon ammonia formation apparently can not be exclusively explained by alterations of the intestinal flora. Possible reasons for the considerable increase in arterial glutamine levels in normal rats are discussed.

Ammonia↗

PubMed1979

[Neomycin resorption from the normal and inflammatorily altered peritoneum].

The clinical problem of the resorption of Neomycin from the normal and inflammatory altered peritoneal cavity was studied experimentally in the guinea pig. In a total of 197 guinea pigs the pharmacokinetics of Neomycin in serum and perilymph after injection subcutaneously or in normal and inflammatorily altered peritoneal cavity of the guinea pig were determined. No statistically significant difference between the pharmacokinetics of Neomycin in serum and perilymph of the different series could be found. The possible clinical relevance of the results is discussed.

Absorption↗

PubMed1977

Systemic absorption of neomycin irrigating solution.

Systemic absorption of neomycin sulfate occurred in ten patients in whom neomycin wound irrigating solutions were used during total hip replacement. The use of neomycin in this manner may be associated with the risk of ototoxicity and nephrotoxicity.

Adult↗

PubMed1982

A prospective randomized study of prophylactic mannitol (10%)-neomycin-cefotaxime therapy in patients undergoing elective colonic and rectal surgery.

A prospective randomized trial was performed to assess the effectiveness of 10% mannitol, oral neomycin, and intravenous cefotaxime in preventing septic complications following elective colonic and rectal surgery in 99 patients. In each of the three regimens, 10% mannitol and oral neomycin were given preoperatively. In regimen 1 (34 patients) intravenous cefotaxime was given perioperatively. In regimen 2 (33 patients) cefotaxime was given perioperatively and for 24 hours postoperatively. Regimen 3 (32 patients) was the same as regimen 2 except that cefazolin sodium was substituted for cefotaxime. Septic complications developed in one patient each on regimens 1 and 3. There were no infections in the patients on regimen 2. This study demonstrates that bowel preparation with 10% mannitol and oral neomycin, coupled with a short perioperative course of cefotaxime or cefazolin sodium, is effective in controlling the septic complications of elective colorectal surgery, and the combinations are simple, safe, and cost effective.

Adult↗

PubMed1983

Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. I. Presynaptic considerations.

The effects of two aminoglycoside antibiotics, streptomycin and neomycin, were studied in voltage-clamped transected twitch fibers of the costocutaneous muscles of garter snakes (species Thamnophis). The concentration-dependent effects of each antibiotic were quantitated by measuring miniature end-plate currents (mepcs) and evoked end-plate currents (epcs) in a single fiber before and in the presence of a wide range of concentrations of each antibiotic. The amplitude and the kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined by the direct method of mean ratios, epc/mepc. A distinct separation was obtained between the concentrations of each antibiotic which demonstrated either pre- or postsynaptic actions. Both streptomycin and neomycin produced a concentration-dependent reduction in epc amplitude at concentrations which did not reduce mepc amplitude. Thus, the primary site of action for these antibiotics was considered of presynaptic origin. Streptomycin was approximately one-tenth as active as neomycin in reducing quantal release of acetylcholine. The marked depression in epc amplitude and quantal content produced by high concentrations of each antibiotic were reversed by elevating the external calcium concentration. Double logarithmic plots of the relationship between external calcium concentration and epc amplitude yielded a slope of approximately 3.8 in control physiological solution. In the presence of blocking concentrations of each antibiotic, increasing the external calcium concentration caused a parallel shift to the right of this relationship. These results suggest that the major mechanism for the neuromuscular depression produced by these aminoglycoside antibiotics is a competitive antagonism with calcium for a common presynaptic site required for evoked transmitter release.

Animals↗

PubMed1978

Determination of neomycin residues in eggs and stability of residues after cooking.

The procedure for neomycin residues used a surfactant to improve extraction, a centrifuge step to eliminate solids that interfere with the diffusion of the antibiotic, and a heat treatment to destroy interfering lysozyme activity. The use of Bcillus stearothermophilus and a 65 degree C incubation yielded a rapid assay with a sensitivity of 0.2 microgram neomycin activity/g egg. Frying eggs caused little or no loss of activity, poaching resulted in 25% loss, and soft boiling and hard boiling caused little or no loss of applied activity. Neomycin residues in eggs were quite stable to normal egg preparation procedures.

Cooking↗

PubMed1981

Lactose enemas plus placebo tablets vs. neomycin tablets plus starch enemas in acute portal systemic encephalopathy. A double-blind randomized controlled study.

A randomized, double-blind comparison of lactose enemas plus placebo tablets vs. starch enemas plus neomycin tablets was performed on 18 patients with acute portal systemic encephalopathy. Ten patients received starch enemas (10%; 1000 ml t.i.d.) plus neomycin tablets and 8 patients received lactose enemas (20%; 1000 ml t.i.d.) plus placebo tablets. A significant mental state improvement was demonstrated in the group of patients treated with starch enemas-neomycin tablets (p less than 0.05) and in the group of patients treated with lactose enemas-placebo tablets (p less than 0.025). Both treatments significantly improved the frequency of asterixis, ammonia blood levels, and electroencephalograms. In addition, patients treated with lactose enemas showed significant improvement in number-connection test times (p less than 0.02), and their stools showed a more acid pH (p less than 0.05). No side effects were evident with either treatment. Lactose enemas are a safe and effective treatment for acute portal systemic encephalopathy.

Acute Disease↗

PubMedDate not supplied

[Microstructure of pea nodules infected with a neomycin-resistant mutant of nodule bacteria].

The neomycin-resistance mutation of pea nodule bacteria does not interfere with the formation of infection threads when the bacterium inoculates the host plant, or with the axial differentiation of the nodular tissue. At the same time, intracellular neomycin-resistant nodule bacteria do not acquire the bacteroid structure. Once the bacterium is incorporated into the cytoplasm of the host cell, it loses the peribacteroid membrane and undergoes lysis. Therefore, the neomycin-resistant pea nodule bacterium realizes the initial infection stage (including the formation of infection threads), but is defective in the subsequent stages. Hence, the described stages of plant infection are determined by independent properties of the bacterium.

Drug Resistance, Microbial↗

PubMed1980

[Therapeutic effectiveness of neomycin in staphylococcal and Pseudomonas aeruginosa corneal lesions].

Ophthalmic films (OPHF) with neomycin were used in treatment of 15 patients with staphylococcal infections of the cornea. OPHF were effective in treatment of 5 patients with affection of the cornea surface layers. These patients were discharged from the hospital on days 4-5 of the treatment. In the other 10 patients deeper layers of the cornea were affected by the infiltrates and their treatment with OPHF required longer periods (10-15 days). Another 5 patients developed severe keratitis caused by Ps. aeruginosa after removal of foreign bodies from the eyes. These patients were treated with neomycin injections, electrophoresis and OPHF. When the patients received such treatment within the first days of the disease (3 patients), the development of the cornea purulent infection ceased and a favourable therapeutic effect was attained. When neomycin was administered at later periods (2 patients), i.e. 3-4 days after the infection, the treatment was not efffective. It is recommended that broad spectrum antibiotics be used for prevention of the cornea staphylococcal infections after removal of foreign bodies from the cornea surface.

Corneal Diseases↗

PubMedDate not supplied

Rapid determination of neomycin by a microbiological agar diffusion assay using triphenyltetrazolium chloride.

The standard, quantitative determination of neomycin activity by the agar diffusion method requires an 18 to 24 h incubation time. To reduce incubation time, an alternative method using triphenyltetrazolium chloride has been developed. The inhibition zone appears much earlier; hence, an effort was made to standardize it. This indicator develops a physical response, related to the biological one, after a determined period. A Staphylococcus epidermidis suspension inoculated into solid medium at a concentration low enough that growth is not visible can reduce the dye to formazan. There is enough contrast to read the inhibition zone optically after a 7 h incubation. There is no significant difference between standard curves for 7 and 24 h incubations. Comparative assays for some pharmaceutical drugs containing neomycin in different forms show that it is possible to reduce incubation time. This modification is valid because no dispersion of results was detected by statistical analysis, which indicates that they belong to the same population. Thus, a rapid microbiological assay of neomycin has been validated and standardized.

Agar↗

PubMed1976

[Deafness due to topical neomycin (author's transl)].

Today neomycin is almost exclusively given as an ointment in combination with other antibiotics, because of its known oto- and nephrotoxicity. Topical application in high dosage can cause ototoxicity as proved by one patient from this clinic. After laryngectomy and neck dissection for an extensive carcinoma of the epiglottis a 2 X 2 cm dehiscent pyocyaneus infected wound was treated daily with neomycin sulphate solution. A total of 30 gm was given over 3 months during which time the patient became deaf neomycin caused the deafness.

Carcinoma↗

PubMed1983

Expression of a neomycin phosphotransferase gene from Streptomyces fradiae in Escherichia coli after interplasmidic recombination.

Plasmid pIJ2 carrying the neomycin phosphotransferase gene of Streptomyces fradiae was fused to E. coli plasmid pBR325 and the hybrid molecules were introduced into E. coli K12 by transformation. The neomycin phosphotransferase gene of the hybrid plasmid was not expressed in E. coli, except after interplasmidic recombination. Physical analysis of such an in vivo recombinant plasmid revealed that the recombination brought one neomycin phosphotransferase gene to a position downstream from the tet-promoter of pBR325. Subcloning experiments indicated that this is the gene copy expressed, and that transcription is initiated at the tet-promoter of pBR325.

Escherichia coli↗

PubMed2003

Effect of neomycin B on rotavirus plus- and minus-strand RNA synthesis.

Rotavirus multiplication was inhibited by neomycin B by affecting the synthesis of the viral genome. Genome replication involves a two-step mechanism, one is plus-strand synthesis or transcription, and the other is minus-strand synthesis or replication. The results indicate that both activities are inhibited by aminoglycoside. The effect on the minus-strand was determined by an in vitro assay using a template-dependant open core preparation. The effect on transcription was explored using transcriptionally active virus particles. In the case of transcription, the inhibitory effect of neomycin B was studied in both initiation and the elongation of the mRNA. Initiation was defined by the synthesis of short transcripts of less than 25 nucleotides in length and elongation as an extension of those molecules into full-length transcripts. The inhibitory effect of neomycin was also mimicked by other aminoglycosides such as lividomycin, paromomycin, and tobramycin. The results may be explained based on the ability of the drug to interact with the stem and loop regions, which, in the case of rotavirus, have been identified at the end of the templates required for both transcription and minus-strand synthesis.

Animals↗

PubMed2003

Biochemical analysis of neomycin-resistance in the methanoarchaeon Methanothermobacter thermautotrophicus and some implications for energetic processes in this strain.

Methanogenesis-driven ATP synthesis in a neomycin-resistant mutant of Methanothermobacter thermautotrophicus (formerly Methanobacterium thermoautotrophicum strain DeltaH) was strongly inhibited at both pH 6.8 and pH 8.5 by the uncoupler 3,3',4',5 -tetrachlorosalicylanilide (TCS) in the presence of either 1 or 10 mM NaCl. The generation of a membrane potential in the mutant cells at pH 6.8 was also strongly inhibited by TCS in the presence of 1 or 10 mM NaCl. On the other hand, at pH 8.5 in the presence of 10mM NaCl, a protonophore-resistant membrane potential of approximately 150 mV was found. These results indicate that in the mutant cells the process of energy transduction between methanogenesis and membrane potential generation is not impaired. In contrast to the wild-type strain, ATP synthesis in the mutant cells was driven by an electrochemical gradient of H(+) under alkaline conditions. Unlike wild-type cells, the mutant lacks the capacity to transduce an uncoupler-resistant membrane potential energy at pH 8.5 into ATP synthesis. Na(+)/H(+) exchange was comparable in the wild type and the mutant cells. Western blots of sub-cellular fractions with polyclonal antiserum reactive to the B-subunit of the halobacterial A-type H(+)-translocating ATPase confirmed the presence of A-type ATP synthase in the mutant cells. Furthermore, in the mutant cells a protein band of molecular mass about 45 kDa is absent but there was an abundant protein band at about 67 kDa. Based on the observed bioenergetic features of the mutant cells, neither the A(1)A(o) ATP synthase alone nor together with the Na(+)/H(+) antiporter seems to be responsible for ATP synthesis driven by sodium motive force. Rather, some other links between neomycin-resistance and failure of sodium motive force-dependent ATP synthesis in the neomycin resistant mutant are discussed.

Journal Article↗