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Biomedical subjects

A Kane

Publications and source records attributed to A Kane.

At least 109 records · Page 6Linked to original sources
PubMed1985

[DNA damage in the spleen, liver and kidneys of mice treated with ochratoxin A].

Ochratoxin A a natural contaminant of feed and food has been shown to induce experimental liver and kidney tumors. Since there is a good correlation between the carcinogenic potency of chemicals and the DNA damages induced in mammalian cells treated either in vivo or in vitro by these compounds, we have measured single-strand breaks induced by ochratoxin A in DNA of liver, spleen and kidney. Our data clearly showed that ochratoxin A induced DNA damages in vitro as well as in vivo. Damages were dose-dependent, reversible and vary upon the time according to the tissue. In spite there is no report up to now on experimental leukemia induced by ochratoxin A, our results indicate that this possibility have to be considered.

Animals↗
PubMed1983

Entamoeba histolytica causes intestinal secretion: role of serotonin.

Lysates of the protozoan parasite Entamoeba histolytica altered active electrolyte transport when present on the serosal surface of rabbit ileum and rat colon. The lysate-induced effects on electrolyte transport were similar to those caused by serotonin, and were blocked by bufotenine, an analog known to inhibit the action of serotonin. The transport effects were partially inhibited by antibody to serotonin. The amebic lysates were shown to contain serotonin by radioimmunoassay, high-performance liquid chromatography, and thin-layer chromatography. These results suggest that the serotonin present in Entamoeba histolytica may be important in the diarrhea seen in amebiasis.

Amebiasis↗
PubMed1983

Comparison of the effects of continuous and intermittent systemic administration on the penetration of gentamicin into infected rabbit eyes.

The effect of the mode of administration on the intraocular penetration of gentamicin in rabbits with bacterial endophthalmitis was examined. Animals were treated over a period of 12 hr either by intramuscular injection every 3 hr or by continuous intravenous infusion; both groups received the same total dose of drug. The mean peak and trough levels in serum with intramuscular injection were 11.4 and 1.6 micrograms/ml, respectively. Mean serum levels during continuous infusion were approximately 7 micrograms/ml. The area under the time-concentration curve for serum was approximately the same in both groups. Mean vitreous humor levels at the end of therapy were 2.8 micrograms/ml in the animals treated by repeated intramuscular injection and 2.6 micrograms/ml in those treated by continuous infusion (P greater than 0.2). In this model, the intraocular penetration of gentamicin was not influenced by the mode of systemic administration.

Animals↗
PubMed1983

Pharmacokinetics of intravitreal carbenicillin, cefazolin, and gentamicin in rhesus monkeys.

Although intravitreal injection of antibiotics is being used more widely in treatment of bacterial endophthalmitis, the pharmacokinetic principles that underlie such therapy have been derived exclusively from experiments in the rabbit. Therefore, we studied several representative antibiotics in normal eyes of rhesus monkeys. Carbenicillin (1,000 micrograms), cefazolin (1,000 micrograms), or gentamicin (100 micrograms) was injected intravitreally. Vitreous and aqueous humors were aspirated at intervals up to 96 hours after injection. The half-life values in the vitreous humor were: carbenicillin 10 hours, cefazolin 7 hours, and gentamicin 33 hours. Concomitant intraperitoneal administration of probenecid prolonged the vitreal half-life of carbenicillin to 20 hours and of cefazolin to 30 hours. The estimated vitreous volumes in these monkeys were approximately 3.0-4.0 ml. These results are consistent with the hypothesis that, in primates as in rabbits, beta-lactam antibiotics are eliminated via the retinal route and the aminoglycoside via the anterior route. This supports the applicability of the rabbit model to the treatment of endophthalmitis in humans.

Animals↗
PubMed1982

Systemic absorption of clindamycin hydrochloride after topical application.

Clindamycin has become a highly popular drug for the topical therapy of acne; however, the extent to which it is systemically absorbed from the skin has has not been established. We measured the serum level and urinary excretion of clindamycin on the third day and the twenty-seventh day of therapy in thirteen patients who were applying 1% clindamycin hydrochloride topically for acne. There was no detectable antibiotic in the serum of any subject (less than 0.4 microgram/ml); in contrast, clindamycin was found in the urine of ten of the thirteen patients. There was marked intersubject variation in the urinary excretion of the drug, ranging from less than 10 to 500 micrograms/day. However, there was a highly significant correlation (p less than 0.0001) for a given subject between excretion values on days 3 and 27. There was no correlation between urinary excretion of clindamycin and either racial pigmentation or severity of acne in this relatively small group of patients. After topical application of 1% clindamycin hydrochloride, an average of 4% to 5% of clindamycin appears to be absorbed systemically, but greater amounts are absorbed in some individuals.

Acne Vulgaris↗
PubMed1982

Ocular penetration of subconjunctival oxacillin, methicillin, and cefazolin in rabbits with staphylococcal endophthalmitis.

The concentrations of oxacillin, methicillin, and cefazolin were examined in the infected eyes of pigmented rabbits with Staphylococcus aureus endophthalmitis after a subconjunctival dose of 100 mg. The three drugs had fairly similar ocular pharmacokinetics. The tissue concentration usually peaked within 30 min. Levels in the aqueous humor rose more slowly; the respective maximal concentrations of methicillin, oxacillin, and cefazolin were 72, 1,180, and 111 micrograms/ml. Oxacillin also produced the highest levels in the cornea. Penetration of the vitreous humor was poor with all three drugs, apparently owing to a diffusional barrier in the choroid-retina tissue complex. The respective median vitreous levels of methicillin, oxacillin, and cefazolin were 0.7, 0.6, and less than 0.8 micrograms/ml. These values are close to the concentrations usually required to inhibit S. aureus in vitro. Our results suggest that subconjunctival oxacillin achieves higher concentrations in anterior ocular tissues than do the other two drugs, but more aggressive approaches are necessary in treating endophthalmitis.

Animals↗
PubMed1982

The effects of infection and probenecid on the transport of carbenicillin from the rabbit vitreous humor.

We examined the effects of inflammation (S. aureus endophthalmitis) and of probenecid on the kinetics of intravitreally injected carbenicillin in rabbits. The half-life of antibiotic in the vitreous of animals with normal eyes was only 5 hr and levels in anterior ocular sites (cornea, aqueous, iris) were low. There findings are consistent with an active retinal transport pump for organic anions. Concomitant intraperitoneal administration of probenecid caused a marked prolongation of the ocular half-life of carbenicillin to 13 hr and augmentation of the levels in anterior sites, as might be anticipated from inhibition of the retinal transport pump. Inflammation produced an intermediate effect that is most readily explained by postulating two opposing consequences: partial inhibition of the transport pump and simultaneous "leakiness" of the normal retinal barrier. There findings suggest that the intraocular kinetics of antibiotics in inflamed eyes are markedly different from those in normal ones and that systemic probenecid significantly augments the intraocular levels of carbenicillin.

Animals↗
PubMed1981

Penetration of ocular tissues and fluids by moxalactam in rabbits with staphylococcal endophthalmitis.

Moxalactam was administered subconjunctivally in 100-mg doses to rabbits with infected eyes (Staphylococcus aureus endophthalmitis). High concentrations of drug were detected in the sclera, cornea, and choroid; much lower levels were found in the retina, whereas peak concentrations in the vitreous were about 6 microgram/ml. Repeated intramuscular injections of 50 mg/kg every 4 h produced peak serum levels of about 100 microgram/ml. A gradient between the choroid and the retina was again evident, and peak vitreous levels were about 6 microgram/ml after six injections. These data are consistent with the concept of a blood-retina barrier analogous to the blood-brain barrier. Moxalactam appears to penetrate the eye somewhat better than do other beta-lactams; however, the peak levels produced in the vitreous humor in this animal model were below the level required to inhibit most strains of Pseudomonas aeruginosa.

Animals↗
PubMed1981

Intravitreal injection of gentamicin in rabbits. Effect of inflammation and pigmentation on half-life and ocular distribution.

Most regimens for intravitreal injection of antibiotics are based on studies in normal albino rabbits. We examined the effect of two variables, infection and pigmentation, on the ocular distribution of an intravitreal injection of 50 micrograms of gentamicin in rabbit eyes. The half-life of gentamicin in the vitreous of normal pigmented rabbits after intravitreal administration was 24 hr. Antibiotic levels in cornea and aqueous reached a peak 18 hr after injection; terminal half-lives in these sites were similar to those in vitreous. With inflammation, the half-life in the vitreous was decreased to 10 hr, and there was no accumulation of drug in anterior sites. To the extent that these data are applicable to humans, they suggest that the treatment of bacterial endophthalmitis by the intravitreal route may require more frequent injections than had been recommended on the basis of studies in normal eyes. Normal pigmented and albino rabbits showed similar levels of gentamicin in the cornea, aqueous, and vitreous; however, the drug was barely detectable in iris, choroid-retina, and sclera of pigmented animals, presumably on account of an interaction with melanin-containing tissues. This effect of pigment may explain the differences in the reported thresholds for toxicity of gentamicin with intravitreal injection.

Animals↗
PubMed1981

The difficulty of determining the route of intraocular penetration of gentamicin after subconjunctival injection in the rabbit.

In small animals such as the rabbit the ratio of eye size to body size is much larger than it is in humans. Accordingly, periocular injection of antibodies in this animal model results in significantly higher serum concentrations than does a comparable does in a human. To assess the effect of the systemic drug component on ocular penetration, we compared the levels of gentamicin in ocular tissues and fluids of the rabbit following injection of 20 mg by subconjunctival or intramuscular routes. Blood levels of gentamicin were similar with the two routes of administration. In normal rabbit eyes, no antibiotic was detectable in the vitreous humor for the first 3 hr after either subconjunctival or intramuscular injection. By 6 hr, low vitreous levels of drug were detectable after subconjunctival, but not after intramuscular, injection. Because these concentrations were so close to the threshold of sensitivity of the assay, it was not clear that the difference between the routes was significant in normal eyes. In infected eyes, the concentrations of gentamicin in the vitreous were similar after subconjunctival and intramuscular injection. These data indicate that the penetration of gentamicin in to the infected vitreous humor of rabbits after subconjunctival injection could be attributed as well to hematogenous carriage as to direct penetration. The problem in distinguishing systemic from direct transport with periocular injections may be inherent in any small animal model in which the ratio of eye size to body size is high.

Adult↗
PubMed1980

Oxacillin for bacterial endophthalmitis: subconjunctival, intravenous, both, or neither?

We compared the intraocular concentrations of oxacillin given by continuous intravenous infusion, subconjunctival injection, or combined therapy in a rabbit model of Staphylococcus aureus endophthalmitis. At equilibrium during intravenous infusion, concentrations in the aqueous humor, cornea, and choroid-retina were 25% to 30% of the serum level; in contrast, vitreous levels were only 2% of the serum concentration. Subconjunctival injection produced extremely high levels in the cornea and aqueous and moderate concentrations in the choroid-retina; vitreous penetration remained poor (<1 microgram/ml). Combined therapy offered little advantage in terms of concentrations in the aqueous or cornea and had a modest effect on levels in the choroid-retina. Vitreous concentrations showed a striking relation to serum levels with all regimens, including subconjunctival ones; although this could have been fortuitous, it suggests an important role for the hematogenous route in this model. Only those modes of delivery producing serum concentrations greater than 50 micrograms/ml consistently resulted in vitreous levels greater than 0.4 microgram/ml. The optimal therapy of bacterial endophthalmitis may require direct intravitreal injection of antibiotic.

Animals↗
PubMed1979

Radioactive and bioassay of intraocular antibiotics: double-assay technique to compare penicillin G, cefamandole, and gentamicin in ocular tissues in vivo.

We examined the correlation between radioactive assay and trephine-discbioassay of penicillin G sodium, cefamandole nafate, and gentamicin sulfate in ocular tissues of pigmented rabbits after subconjuctival administration of antibiotic. We devised a technique whereby a single sample of tissue could be assayed by both methods. This was achieved by performing the bioassay first, then measuring the resudual radioactivity in the agar and specimens. The results of both methods were generally within 13%. An exception was gentamicin in iris and choroidretina, for which the bioassay result was strikingly less than the radioassay value. No such discrepancy was evident when similar studies were carried out with gentamicin in albino rabbits. This suggests that the phenomenon is due to tight binding of gentamicin by melanin-containing tissues. The trephine-disc bioassay provides an accurate measure of diffusible bioactive antibiotic in ocular tissues.

Animals↗
PubMed1979

Marked differences between pigmented and albino rabbits in the concentration of clindamycin in iris and choroid-retina.

The concentrations of clindamycin were significantly higher in iris and choroid-retina or pigmented rabbits than in those of albino rabbits after subconjunctival injection. Equilibrium dialysis experiments showed no affinity of clindamycin for synthetic melanin or for collagenase digests of pigmented tissues. In contrast, strips of iris and choroid-retina took up clindamycin rapidly from solution, achieving concentrations substantially higher than those in the medium. Uptake by tissue strips was not influenced by temperature (4 C vs. 37 C), cyanide, or ouabain. However, N-ethylmaleimide, which reacts with sulfhydryl groups, decreased the tissue-to-medium ratios by about 50% for both albino and pigmented choroid-retina. Even in the presence of this inhibitor, the ratio for pigmented tissues remained higher than that for albino specimens. These findings suggest the existence of one, or possibly two, mechanisms of energy-independent accumulation of clindamycin by pigmented ocular tissues: one may relate to protein sulfhydryl bonds that are present in both breeds; the other may involve the pigmentation apparatus.

Animals↗
PubMed1979

Intraocular levels of cefamandole compared with cefazolin after subconjunctival injection in rabbits.

We compared the intraocular pharmacokinetics of cefazolin with those of cefamandole, a recently marketed cephalosporin with enhanced activity against gram-negative bacilli. Following subconjunctival injection of 12.5 mg into infected eyes (S. aureus endophthalmitis) of pigmented rabbits, both drugs reached peak concentrations greater than 100 microgram/gm in cornea, sclera, and choroid-retina. The half-life was markedly shorter in sclera and choroid-retina than in cornea. Levels in the aqueous humor rose and fell more slowly than those in ocular tissues, reaching a maximum of only 5 to 10 microgram/ml. The pharmacokinetics of the two drugs were virtually identical in most intraocular sites. When cefazolin, which was less irritating than cefamandole by the subconjunctival route, was given in a dosage of 100 mg, levels in ocular tissues were increased by twofold to fourfold and in aqueous humor by 15-fold, compared to the concentrations produced by the 12.5 mg dosage. Levels in the vitreous humor were exceedingly low with both drugs; mean peak concentrations were 0.24 microgram/ml after the 12.5 mg dosage of cefamandole and less than 1.6 microgram/ml after the 100 mg dose of cefazolin.

Animals↗
PubMed1978

Efficacy of penicillin G, cefazolin, and gentamicin in M-K medium at 4 degrees C.

Corneal-scleral shells are routinely stored in McCarey-Kaufman (M-K) medium at 4 degrees C. Antibiotics are added to the medium to suppress bacterial growth. We examined the antibacterial activity of penicillin G potassium, 100 microgram/ml, cefazolin sodium, 100 microgram/ml, and gentamicin sulfate, 20 microgram/ml against test organisms in M-K medium at 4 degrees, 23 degrees, and 37 degrees C for periods up to 18 hours. Within the limits of the experimental conditions, none of the antibiotics used could be relied on to sterilize an inoculum of sensitive bacteria in M-K medium at 4 degrees C, the recommended storage temperature.

Anti-Bacterial Agents↗