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PubMedDate not supplied

Technology of eye drops containing aloe (Aloe arborescens Mill.--Liliaceae) and eye drops containing both aloe and neomycin sulphate.

Eye drops made of aloe are a sterile, aqueous extract of fresh leaves of Aloe arborescens Mill., containing necessary additives and neomycin sulphate. The aim of the studies was to establish the technology of eye drops containing biologically active aloe substances and those containing both chemical constituents of aloe and neomycin sulphate. Within the studies, the formulary content and the way of preparing eye drops were determined, criteria were defined and methods of qualitative assessment of drops were proposed. On the basis of the proposed analytical methods, the physicochemical and microbiological stability of the eye drops stored at a temperature of 20-25 degrees C was studied. As the criteria of qualitative assessment of the eye drops, the following analyses were considered: sterility, appearance of the eye drops (clarity), pH, osmotic pressure, density, viscosity, TLC analysis, content of aloenin and aloin, studies of anti-microbial activity of neomycin in the drops, and preservative efficiency of thiomersal in the eye drops. The studies showed that the additives such as: sodium chloride, benzalkonium chloride, chlorhexidine diacetate and digluconate, phenylmercuric borate and Nipagins M and P could not be used to prepare the eye drops because they were involved in pharmaceutical interactions with chemical constituents of aloe in the eye drops. The eye drops containing: aqueous extract of fresh leaves of aloe, boric acid, thiomersal, sodium pyrosulphite, disodium EDTA, beta-phenylethyl alcohol and neomycin sulphate, both freshly prepared and after two years of storage, met the requirements of the Polish Pharmacopoeia (PPh V) mentioned in the monograph Guttae ophthalmicae. They were sterile, clear, their osmotic pressure approximated the osmotic pressure of lacrimal fluid and they were characterized by appropriate pH. Aloenin in the drops was much more stable than aloin. Neomycin after two years of storage retained almost 98% of its starting antimicrobial activity which allows the conclusion that the biologically active aloe substances did not decrease the stability of neomycin in the drops. The preservation assay showed that thiomersal, both in the freshly prepared drops and after two years of storage, maintained antimicrobial activity, which was in accordance with PPh V.

Aloe↗
PubMed1977

Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial.

A randomized double blind clinical comparison of neomycin and lactulose was performed in 33 cirrhotic patients with chronic portal-systemic encephalopathy (PSE) at seven cooperating hospitals. In order to maintain double blindness, sorbitol syrup was used as a control solution along with neomycin and was compared with lactulose syrup and placebo tablets in a double drug protocol. Twenty-nine patients were studied in a crossover investigation in which each received both therapeutic regimens preceded and followed by control periods. Four additional patients received one or the other agent, but did not receive both. Serial, semiquantitative assessments were made in all patients of mental status, asterixis, and the trailmaking test (TMT) and electroencephalograms (EEG) and arterial ammonia levels. Both neomycin-sorbitol and lactulose were effective in the majority of patients (83 and 90%, respectively). Each of these parameters (mental state, asterixis, TMT, EEG, and NH3) was improved significantly by neomycin-sorbitol and lactulose. The post-treatment levels for each of these measures were similar in the neomycin and lactulose-treated groups. Mean stool pH was reduced by neomycinsorbitol to 6.1 and by lactulose to 5.5. This difference was highly significant statistically. Bowel activity was similar in the two groups. Both drugs were free of toxicity. These investigations demonstrate that both lactulose and neomycin-sorbitol are effective in the treatment of chronic portal-systemic encephalopathy.

Aged↗
PubMed1991

[Experimental cochlear damage by neomycin ear drops].

Damage caused by neomycin sulphate solution, identical in concentration to that in ear drops, was tested on the cochleas of 28 guinea pigs. Neomycin sulphate with dexamethasone sodium, and physiologic salt solutions were also tested. Only neomycin solutions damaged the cochlea, and even after only a single exposure. The damage after a single exposure was to the supporting cells and not to the hair cells. However, because of the importance of the supporting cells for normal hearing and because destruction of supporting cells leads to shedding of hair cells, the resulting functional impairment is similar. As a result of further exposure to neomycin the hair cells themselves are damaged, and there is also loss of cell hair. Damage to either the cells or to the hair causes hearing loss. From our work it is clear that in guinea pigs neomycin is absorbed from the middle ear into the inner ear and damages the cochlea. Increased exposure to neomycin increases the damage.

Animals↗
PubMed1986

Morphological effects of high dose neomycin sulphate on the small and large intestine.

The morphology of the intestinal wall and the activity of certain mucosal enzyme systems in the course of neomycin treatment were evaluated. Conventional and, to study the role of the bacterial flora, germ-free rats received 500 mg neomycin daily by stomach tube. Rats were sacrificed after seven days and small intestine (proximal and distal part) together with segments of the colon were removed and prepared for histochemistry. The colon and proximal small intestine of untreated conventional and germ-free animals did not show appreciable differences in staining activity after treatment with neomycin. Neomycin diminished both in normal and germ-free rats the activity of NAD tetrazolium reductase, succinate dehydrogenase, esterase, alkaline phosphatase and acid phosphatase in the distal small intestine. The findings of this study indicate that explanations for the beneficial effects of neomycin on hyperammonemia in liver disease should not only include the bactericidal action of neomycin but also its influence on absorption and metabolic functions of the mucosal cells.

Acid Phosphatase↗
PubMed1983

Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. II. Postsynaptic considerations.

The postsynaptic effects of two aminoglycoside antibiotics, streptomycin and neomycin, were studied on miniature end-plate currents (mepcs) and acetylcholine-induced end-plate current fluctuations in voltage-clamped costocutaneous muscles of the garter snake (species Thamnophis). Neomycin decreased the amplitude of mepcs and accelerated the time constants of mepc decay in a concentration-dependent manner without altering the single exponential nature of mepc decay. Neomycin also produced a voltage- and concentration-dependent nonlinearity in the current/voltage relationship. The relationship between the time constants of mepc decay and membrane potential was progressively reduced with increasing concentrations of neomycin. A concentration-dependent reduction in single channel conductance and channel lifetime was also obtained with neomycin. In contrast, streptomycin, in concentrations up to 5 X 10(-5) M, did not significantly alter either mepc amplitude, the time constant of mepc decay, the relationship between the mepc decay time constant and membrane potential or the lifetime and conductance of single end-plate channels. In very high concentrations (greater than 1 mM) streptomycin decreased mepc amplitude and prolonged mepc decay at hyperpolarized membrane potentials. The results suggest that neomycin interacts with the ionic channels of the acetylcholine receptor in their open configuration, whereas streptomycin acts primarily by blocking the receptor. The significant differences in the molecular actions of these two antibiotics may provide an explanation for the observed differences in the character and reversal of the neuromuscular block produced by these antibiotics.

Animals↗
PubMed1984

Effect of neomycin on azoxymethane-induced colon carcinogenesis in F344 rats.

The effect of oral administration of neomycin (100 and 200 micrograms/ml in drinking water) on colon tumors induced by azoxymethane [(AOM); CAS: 25843-45-2] was studied in female F344 rats. Five-week-old rats were fed NIH-07 diet and given daily in drinking water 0, 100, and 200 micrograms neomycin/ml (0, 100, and 200 ppm). At 7 weeks of age, all animals except vehicle-treated groups received weekly sc injections of 8 mg AOM/kg body weight for 8 weeks. The AOM- or vehicle-treated groups were necropsied 30 weeks after the last injection of AOM. The combined incidence of adenomas and adenocarcinomas of the colon did not differ significantly among the 3 groups. The animals in the groups given 100 and 200 micrograms neomycin had a higher incidence of colon adenocarcinomas than did those in the control group. Colonic and cecal bacterial beta-glucuronidase activity was significantly lower in the group given 200 micrograms neomycin than it was in the control group. The excretion of fecal cholesterol, total bile acids, and deoxycholic acid was increased significantly in animals given 100 and 200 micrograms neomycin as compared to animals given no neomycin. These results suggest that long-term oral administration of neomycin increases the incidence of colon adenocarcinomas.

Animals↗
PubMed1982

Effects of lactulose and neomycin on urea metabolism in cirrhotic subjects.

In our previous studies of cirrhotic subjects lactulose caused a 25% decrease in the urea production rate associated with a decrease in urinary urea excretion and an increase in stool nitrogen. The decrease in the rate of urea production was an indirect measure of reduction in gut ammonia production. The present study was designed to determined if the poorly adsorbed antibiotic neomycin had an additive effect in reducing ammonia production when administered in combination with lactulose. Six stable cirrhotic subjects received isonitrogenous diets during separate lactulose and lactulose + neomycin treatment periods. The addition of neomycin to a lactulose regimen caused a 17% reduction in the urea production rate that was quantitatively accounted for by a 70% reduction in the urea degradation rate. The intestinal urea clearance rate demonstrated a parallel reduction, indicating an inhibition of bacterial ureolysis. There was no evidence that neomycin altered the effects of lactulose since urinary urea excretion did not rise, fecal nitrogen remained high, and stools remained acidic. These results demonstrate that neomycin inhibited bacterial ureolysis when administered with lactulose while lactulose itself was metabolized and its individual effect on nitrogen metabolism persisted. Lactulose and neomycin, when administered together, had an additive effect in reducing gut ammonia production in cirrhotic subjects.

Aged↗
PubMed1980

[Antibiotic concentration in postoperative wound secretions and in serum of patients after implantation of hip endoprostheses having used neomycin-bacitracin loaded bone cement (author's transl)].

Antibiotic concentrations in postoperative wound secretions and in serum give some indication of the local and general effects of an antibiotic additive to bone cement. Ten patients received hip endoprostheses using a prepacked mixture of the bone cement Sulfix 6 with neomycin + bacitracin (Sulfix 6 A). After operation secretions from Redon drains were collected over the next 48 hours as well as venous blood over 14 days in order to measure neomycin and bacitracin levels. Neomycin was found in sera of some patients up to the eighth postoperative day, whereby concentrations did not exceed 0.75 mcg/ml. Bacitracin was not detected in any serum samples. In secretions from Redon drains neomycin as well as bacitracin reached effective levels during the first 48 hours. The results indicate that the addition of neomycin and bacitracin to the bone cement Sulfix 6 for local antibiotic prophylaxis is justified since effective antibiotic concentrations are thereby obtained in the wound without the danger of general toxicity arising when neomycin and bacitracin are administered by the usual method of topical application.

Aged↗
PubMed1994

[Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial].

OBJECTIVES: The effectiveness of the association of lactulose with neomycin in the treatment of acute hepatic encephalopathy has never been assessed. The aim of this study was to compare the effects of lactulose-neomycin combination versus placebo in acute hepatic encephalopathy. METHODS: Eighty patients with cirrhosis were randomly treated for 5 days with placebo (n = 40) or with lactulose-neomycin (n = 40). Both groups were similar for all variables. RESULTS: The course of encephalopathy was similar in both groups. In the lactulose-neomycin group: 26 PATIENTS recovered, 3 remained unchanged, 3 worsened, 6 died, 2 were lost to follow-up. In the placebo group: 28 recovered, 2 remained unchanged, 2 worsened, 6 died, one was lost the follow-up, one dropped out of the study. Lactulose-neomycin treatment was not well tolerated in a significant number of patients. CONCLUSION: Lactulose-neomycin combination should not be used in the treatment of acute hepatic encephalopathy.

Acute Disease↗
PubMed1994

Reversal of behavioral changes in rats subjected to portacaval shunt with oral neomycin therapy.

The portacaval shunt rat is often used as a model of human portal-systemic encephalopathy, but its relevance to human portal-systemic encephalopathy remains uncertain. Specifically, it has not been demonstrated that the behavioral changes seen in this model respond to measures known to improve portal-systemic encephalopathy in human subjects. Accordingly, the aim of this study was to establish whether neomycin (an effective treatment for portal-systemic encephalopathy in human beings) added to the drinking water of rats subjected to portacaval shunt reversed or ameliorated the reduction in spontaneous motor activity, which represents a measure of encephalopathy in this animal model. A randomized, placebo-controlled crossover design was used, with each animal serving as its own control. After establishment of baseline activities, 12 rats with portacaval shunt and 12 sham-operated rats were divided into two equal groups: Group A animals received neomycin for 1 wk; this was followed by 1 wk off neomycin; in group B rats, the sequence was reversed. Spontaneous intake of neomycin for 7 days at doses comparable to human usage (0.1 to 0.2 gm/kg/day) was associated with a significant increase in spontaneous motor activity in rats subjected to portacaval shunt (26.4% in group A, 66.3% in group B; p < 0.01 for each protocol) with no significant effect in sham-operated animals. Withdrawal of neomycin resulted in reversal of this effect in group A rats subjected to portacaval shunt. Similar significant improvements for exploratory activity as measured on the basis of nose-hole pokes was also seen in rats subjected to portacaval shunt and given neomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗
PubMed2000

Structural rearrangements of HIV-1 Tat-responsive RNA upon binding of neomycin B.

Binding of human immunodeficiency virus type 1 (HIV-1) transactivator (Tat) protein to Tat-responsive RNA (TAR) is essential for viral replication and is considered a promising starting point for the design of anti-HIV drugs. NMR spectroscopy indicated that the aminoglycosides neomycin B and ribostamycin bind to TAR and that neomycin is able to inhibit Tat binding to TAR. The solution structure of the neomycin-bound TAR has been determined by NMR spectroscopy. Chemical shift mapping and intermolecular nuclear Overhauser effects define the binding region of the aminoglycosides on TAR and give strong evidence for minor groove binding. Based on 15 nuclear Overhauser effect-derived intermolecular distance restraints, a model structure of the TAR-neomycin complex was calculated. Neomycin is bound in a binding pocket formed by the minor groove of the lower stem and the uridine-rich bulge of TAR, which adopts a conformation different from those known. The neamine core of the aminoglycoside (rings I and II) is covered with the bulge, explaining the inhibition of Tat by an allosteric mechanism. Neomycin reduces the volume of the major groove in which Tat is bound and thus impedes essential protein-RNA contacts.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1979

Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population.

A study population of 1,158 paid adult volunteers was obtained. Prior to patch testing, a history of previous exposure to four allergens also was obtained. Prevalence of positive reactions to patch tests was nickel, 5.8%; neomycin, 1.1%; ethylenediamine, 0.43%; and benzocaine, 0.17%. Nine percent of women reacted to nickel compared with 0.9% of men. There was a strong correlation of nickel sensitivity with a history of pierced ears, earlobe rash, and jewelry rash. Ten of 12 neomycin-positive subjects used neomycin for one week or longer on an inflammatory dermatosis, compared with six of 36 age-, race-, and sex-matched controls. By history, 85% were exposed to benzocaine, 48% to neomycin, and 15% to Mycolog (ethylenediamine). Of 127 patients referred to clinics for evaluation of contact dermatitis, 11% yielded positive tests to nickel, 6.3% to neomycin, 3.1% to ethylenediamine, and 1.6% to benzocaine. Data obtained from testing contact dermatitis patients are not applicable to the general population.

Adult↗
PubMed2007

Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin.

The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl:L-glutamate aminotransferase, respectively. The joint activity of Neo-11 and Neo-18 is responsible for the conversion of paromamine to neamine in the biosynthetic pathway of neomycin through a mechanism of FAD-dependent dehydrogenation followed by a pyridoxal-5'-phosphate-mediated transamination. Neo-18 is also shown to catalyze deamination at C-6''' of neomycin, thus suggesting bifunctional roles of the two enzymes in the formation of both neosamine rings of neomycin. The product of the btrB gene, a homologue of neo-18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans, exhibits the same activity as Neo-18; this indicates that there is a similar reaction sequence in both butirosin and neomycin biosynthesis.

Anti-Bacterial Agents↗
PubMed1975

Influence of monovalent and divalent electrolytes on sorption of neomycin sulfate to attapulgite and montmorillonite clays.

Langmuir isotherms for the adsorption of neomycin sulfate to clays such as attapulgite, bentonite, and magnesium aluminum silicate were constructed. Monovalent and divalent cations were investigated for their influence on the formation of neomycin-clay adsorbates and the resulting equilibrium concentration in a neomycin solution. Divalent magnesium ions were more effective in displacing the antibiotic from each clay than were monovalent sodium ions. Ions present in the GI fluid might increase the bioavailability of neomycin from such neomycin-clay adsorbates.

Adsorption↗
PubMed1983

Ototoxicity of oral neomycin and vancomycin.

In contrast to parenteral neomycin, which may result in severe and progressive ototoxicity, oral neomycin has been widely used for 25 years, and its index of safety has been regarded as high. Ototoxicity is viewed as an uncommon complication of oral neomycin most likely to occur in patients with renal failure or gastrointestinal inflammation. Two cases of ototoxicity resulting from oral neomycin are presented. Serial audiometric and neomycin blood level testing are suggested as a means of auditory monitoring in patients receiving the drug. A review of experience with oral vancomycin indicates that this drug has not been shown to cause ototoxicity.

Administration, Oral↗
PubMed1994

Neomycin inhibition of hormone-stimulated smooth muscle contractions in myometrial tissue.

These studies sought to determine the effects of neomycin, a phospholipase C inhibitor, on hormone-stimulated myometrial contractions. For these studies, computer digitalized in vitro isometric contraction data were analyzed for changes in contractile activity in response to oxytocin and aluminum fluoride with and without neomycin. Neomycin (1-5 mM) produced dose-related inhibition of oxytocin and aluminum fluoride-stimulated myometrial contractions. This neomycin effect was apparent within 2-3 minutes of addition and was completely reversible, with resolution of its inhibitory effects within 6-8 minutes of washout. This study is the first to demonstrate the functional effect of neomycin inhibition of the phosphatidylinositol signaling pathway in myometrial smooth muscle tissue.

Aluminum Compounds↗
PubMed1995

The effect of neomycin on PDGF-induced mitogenic response and actin organization in cultured human fibroblasts.

Actin organization and DNA synthesis were studied in cultured, serum-starved, subconfluent human fibroblasts in response to human recombinant platelet-derived growth factor (PDGF)-BB and neomycin, an inhibitor of phosphoinositide (PI) turnover. The labeling of F-actin with TRITC-phalloidin showed that PDGF (10 ng/ml) and neomycin (3.5 mM) induced, within minutes, similar changes in the actin cytoskeleton and when used together potentiated each other's effects. PDGF stimulated a twofold increase in DNA synthesis, as shown by [3H]thymidine incorporation, 48 h after the beginning of incubation. Neomycin did not induce DNA synthesis but reduced the mitogenic response to PDGF to control levels. Stimulation of DNA synthesis was correlated with an intense increase in lamellipodia formation and ruffling, whereas inhibition of the DNA synthesis was correlated with the development of elongated cell shape with few ruffles and lamellipodia, similarly to untreated control cells. Our findings support the conclusion that early changes in the actin cytoskeleton and induction of DNA synthesis are separable biological processes that are mediated by different pathways. The inhibitory effect of neomycin on PDGF-induced DNA synthesis was dose-dependent during the first 24 h of PDGF incubation, after which the cells were irreversibly and maximally stimulated to synthesize DNA. Results of experimental treatments with neomycin at various times during the incubation with PDGF indicate that the critical period during which PDGF acts to stimulate DNA synthesis is after the 1st h but before the 12th h of incubation.

Actins↗
PubMed1994

Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients.

Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗