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Biomedical subjects

J C Murphy

Publications and source records attributed to J C Murphy.

At least 109 records · Page 6Linked to original sources

Toxicological evaluation of poison oak urushiol and its esterified derivative.

Poison oak urushiol was compared with its esterified derivative for toxicity after oral administration to rats and guinea pigs. No hematological or pathological changes were noted and there were no differences seen in clinical chemistry measurements when compared to clinical biochemical and hematological reference values of normal experimental animals. Comparative LD50 studies in mice and tissue reactivity studies in rabbits indicated that acetylated urushiols were substantially less toxic than free urushiols. However, neither poison oak urushiol or poison oak urushiol acetate appeared to produce any tissue toxicity not related to a direct irritant effect. The free urushiol produced a much greater degree of skin irritation than did the urushiol acetate. Whether or not an animal had been sensitized to urushiol apparently had no effect on organ toxicity.

Acetylation↗

Effect of cannabichromene on hepatic microsomal enzyme activity in the mouse.

1. Pretreatment with a Cannabis constituent, cannabichromene (CBC), i.p., had no effect on in vitro hepatic microsomal enzyme activity compared to a known inhibitor of these systems, SKF 525-A. 2. The results indicate that the previously reported CBC potentiation of CNS depressant-induced hypnosis is not mediated by the hepatic microsomal enzyme system.

Aminopyrine N-Demethylase↗

Immunologic studies of poisonous Anacardiaceae: oral desensitization to poison ivy and oak urushiols in guinea pigs.

Poison ivy and oak urushiols or their components were compared with the respective esterified derivatives for efficacy in oral desensitization of Hartley guinea pigs sensitized to urushiols. The esterified derivatives produced a significantly greater degree of hyposensitization than did free urushiol counterparts. Suppression produced by esterified urushiols was of longer duration than that produced by free urushiols. Groups of sensitized guinea pigs were given high (100 mg/kg) or low (10 mg/kg) doses of a mixture of acetylated, saturated urushiol congeners over a 1-, 2-, or 3-week period. High doses produced a greater degree of hyposensitization regardless of the dosage schedule used. Low doses did not produce significant hyposensitization unless given over a shorter (1 week) schedule. Large single booster doses (33 mg/kg/week) of the acetate derivatives produced a rebound in responsiveness when given, 2 weeks following the last dose of the initial series, to animals hyposensitized with 10 mg/kg. No such rebound in sensitivity occurred in animals given a series of high initial doses.

Administration, Oral↗

Evaluation of murine cytomegalovirus antibody detection by serological techniques.

Naturally acquired murine cytomegalovirus (MCMV) infection in laboratory strains of mice induces antibody levels which are generally undetectable by standard techniques; therefore, MCMV has not been included routinely in mouse viral antibody screening programs. The relative sensitivity of three assay systems, the nuclear anticomplement immunofluorescence (NACIF), the enzyme-linked immunosorbent assay (ELISA), and the complement fixation (CF) test, was evaluated for the detection of MCMV antibodies. Sera were harvested from CD1 male mice (33 days old) infected intraperitoneally with salivary gland-passaged MCMV (Smith strain). The sera were assayed separately at weeks 1 through 8, and at week 11, 16, and 25 post-inoculation; a total of 167 mice in 11 groups were tested. The animals tested at 1 week post-inoculation had low levels of antibodies to MCMV as measured by the NACIF test (1:10), whereas only 25% were positive by ELISA, and none was positive by CF until 5 weeks post-inoculation. A higher titer of MCMV antibodies was measured by CF (1:640) than by NACIF (1:40) at 6 months post-inoculation; yet, a titer of 1:3,200 was detected by ELISA from the same serum. The ELISA technique was more sensitive for detecting persistent infection with MCMV, and NACIF was more useful for detecting acute MCMV infection. Since MCMV can have significant long-term effects on the immune system, it is recommended that testing for antibodies to MCMV be included in mouse viral antibody screening protocols.

Animals↗

Biological effects of nonalkaloid-containing fractions of Erythroxylon coca.

Water soluble nonalkaloid fractions of Erythroxylon coca were screened in mice for their effects on oxygen utilization and central nervous system (CNS) activity. The fractions were screened in dogs for cardiovascular, blood glucose, and respiratory changes. No CNS effects were demonstrated in mice; however, there was a reduction in the oxygen utilization rate. Intravenous administration of the extract to dogs produced hyperglycemia, a reduction in heart rate, and a decrease in blood pressure. No substantial change in the respiratory rate and tidal or minute volumes were observed.

Animals↗

Ocular irritancy responses to various pHs of acids and bases with and without irrigation.

Acids and alkalies were instilled into the eyes of 2 groups of rabbits; the eyes of one group were washed with tap water 30 s after exposure. Damage seen in washed and unwashed eyes was not always related to pH. Some strong acids with greater acidity than pH 2.5 produced opacities while 0.3% hydrochloric acid with a pH of 1.28 produced no ocular damage. Phenol (5%) and acetic acid (5%) with pHs greater than 2.5 produced damage equivalent to or greater than that produced by equal concentrations (w/v) of the mineral acids. All alkalies with pHs ranging from 11.5 to 13.5 produced opacities and other ocular damage of different degrees depending upon the alkali and its concentration. For example, low concentrations of some alkalies in the pH range from 11.3 to 12.8 produced no ocular changes. The duration of the corneal opacities produced by phenol, 1% sodium hydroxide, acetic acid and anhydrous sodium carbonate and the onset of corneal opacity produced by 5% sulfuric acid, the weak acids and 1% sodium hydroxide were reduced as a result of washing the test eyes 30 s after instillation of the test material. These data suggest that acidity and alkalinity of the test material are not the only factors to be considered in relation to a substances' capacity to produce severe ocular injury. The concentration of the test chemical and its period of contact with the eye prior to washing are also important.

Acids↗

A comparison of two tuberculins in nonsensitized macaques.

Two tuberculins (mammalian and Old Tuberculin) were compared in three species of macaques after one of the tuberculins elicited nonspecific reactions up to 72 hours after intradermal inoculation in nontuberculous monkeys. A significant difference in initial intradermal eyelid reactivity between the tuberculins was found in some subjects. The heterogeneity of tuberculins and the necessity of accurate interpretation of intradermal testing are important components in addressing tuberculosis screening in nonhuman primate colonies.

Animals↗

Proliferative colitis in ferrets.

During a 4-month period, 31 of 156 ferrets (Mustela putorius) in a biomedical research program developed protracted diarrhea. Clinical signs were green mucohemorrhagic fecal material, partially prolapsed rectum, anorexia, body weight loss, and dehydration. Nine of the affected animals were necropsied. On gross examination, the descending colon was grossly thick and histologically characterized by marked proliferation of the mucosa, relatively few goblet cells, mixed inflammatory cell infiltrate, and penetration of the mucosal glands through the muscularis mucosa into the submucosa and tunica muscularis. Campylobacter fetus subsp jejuni was isolated from 6 of 9 ferrets with proliferative colitis. Warthin-Starry stained sections of hyperplastic colon revealed large numbers of organisms in the apical portion of epithelial cells, and organisms similar to Campylobacter spp were observed by electron microscopy in hyperplastic colonic epithelium. The proliferative colitis in the ferret is compared with the pathologic and bacterial features of similar intestinal proliferative diseases in swine and hamsters.

Animals↗

Immunological studies of poisonous anacardiaceae: production of tolerance in guinea pigs using 3-n-pentadecylcatechol-"modified" autologous blood cells.

The development of contact sensitivity to poison ivy urushiol in guinea pigs was prevented by intravenous injection of 3-n-pentadecylcatechol (I) coupled to autologous blood cells. Hartley, line-bred, guinea pigs were treated with pentadecylcatechol-"modified" blood cells or sham-treated blood cells 2 weeks prior to attempted topical sensitization with I. Skin testing of all guinea pigs with 3-, 1-, and 0.3-microgram doses of I applied in 5 microliter of acetone to abdominal skin sites was begun 2 weeks after attempted sensitization and repeated at 2- or 4-week intervals thereafter for 6 months or until study termination. Profound tolerance to I was observed at all skin testing intervals in the group receiving haptenated red cells and did not weaken with time. Contact sensitivity to I in control animals, however, waned with time; the study was terminated at 6 months because of the low sensitivity level of the control animals at that period. Complete or partial tolerance was induced in approximately 80% of the treated animals. The immune tolerance obtained by the single injection of pentadecylcatechol-associated red blood cells was of long duration and urushiol specific. This treatment also conferred tolerance to three unsaturated congeners of I. The allergenic potencies of the pentadecylcatechols declined with increasing saturation of the alkyl side chain. Binding studies using tritiated pentadecylcatechol showed that 81% of the activity incorporated into the red cell was membrane associated and that 19% was cell sap associated.

Animals↗

Immunological studies of poisonous anacardiaceae: effect of vehicle on absorption of 3-n-pentadecylcatechol and its diacetate ester derivative after oral feeding in rats.

Tritium-labeled 3-n-pentadecylcatechol and its diacetate ester were fed to Sprague-Dawley rats. Both compounds were dissolved in ethanol and in corn oil vehicles and administered by gavage. The rats were placed in metabolic cages, and the urine and feces was determined by liquid scintillation counting, and the percentage of the administered dose was utilized as a measure of absorption. While there was no difference between the absorption of either compound, absorption was affected by the vehicle. Approximately 30% of the administered radioactivity appeared in the urine when ethanol was the vehicle, but about half that amount (14%) was excreted in the urine when the compounds were dissolved in corn oil. A subsequent bile cannulation study showed that the balance of the radioactivity found in the feces was not a result of biliary excretion. The majority of the activity recovered from urine and feces was eliminated within 48 hr after dosing. These data indicate that oil is a poor vehicle for GI absorption of urushiol components.

Administration, Oral↗

Immunologic studies of poisonous Anacardiaceae: I. Production of tolerance and desensitization to poison Ivy and oak urushiols using esterified urushiol derivatives in guinea pigs.

The development of contact sensitivity to poison ivy urushiol in Hartley guinea pigs was inhibited by i.v. injection of the diacetate esters of poison ivy and oak urushiols into guinea pigs 2 weeks prior to attempted sensitization with homologous antigen. Immune tolerance to urushiols of poison ivy and oak developed in 80% or more of the treated animals and persisted for the duration of the study, 8 weeks. The tolerance was immunologically specific for urushiols since the tolerant animals were sensitizable to the unrelated sensitizer 2, 4-dinitrochlorobenzene. Guinea pigs already sensitive to urushiol were also desensitized or hyposensitizied by i.v. injection of urushiol acetates in successively increasing doses. After receiving the equivalent of 16 mg of poison ivy and oak urushiols in the acetate form over a period of 12 weeks, 54% of a group of guinea pigs were desensitized to poison ivy. all of the remaining 46% of the guinea pigs still sensitive to poison ivy were substantially hyposensitized (no longer responded to 1.5 or 0.80 microgram test doses of PDC). A control group of guinea pigs was not hyposensitized by injection of vehicle, and remained highly sensitive throughout the 15 week study. The majority of treated animals (less than 80%) were also hyposensitized to poison sumac and cashew nut shell liquid allergens.

Animals↗

Concentration of tetracycline in human gingival fluid after single doses.

The concentration of tetracycline in gingival fluid was measured following the oral administration of single doses of 250 or 500 mg. Six volunteers received a single dose of either 250 mg or 500 mg of tetracycline and gingival fluid was sampled at 15-min intervals during the first 2 h, 30-min intervals for the following 2 h and at hours 5, 6 and 7. Four volunteers were given a single dose of either 250 mg or 500 mg and were sampled every hour for 24 h. Gingival fluid was sampled using an intracrevicular technique from four gingival sites and blood was obtained by finger puncture. The concentration of tetracycline in gingival fluid peaked at 3 1/2-7 h achieving average levels typically in the range of 5-12 micrograms/ml. Blood levels peaked at 3-4 h and reached values between 1.0 to 2.6 micrograms/ml. Tetracycline was detectable in gingival fluid at least 19 h after a single dose but rarely was detectable at 24 h. The results demonstrated that tetracycline in the gingival fluid was typically 2-10 times blood levels after a single dose.

Gingival Crevicular Fluid↗

Gingival crevicular fluid levels of clindamycin compared with its minimal inhibitory concentrations for periodontal bacteria.

Clindamycin concentrations in gingival crevicular fluid and in blood were determined over a 7-h period and were related to the minimal inhibitory concentrations of this agent for 340 bacterial strains isolated from diseased periodontal sites. The clindamycin levels after administration of single 300-mg oral doses were measured in gingival crevicular fluids by using an agar diffusion bioassay. Minimal inhibitory concentrations were determined by agar dilution techniques for 30 species of periodontal bacteria. With the exception of Eikenella corrodens and Actinobacillus actinomycetemcomitans, most of the bacteria were inhibited by a concentration of 1.0 microgram of clindamycin per ml or less. The peak concentrations in crevicular fluid (2.0 +/- 0.3 microgram/ml) and in blood (1.9 +/- 0.3 micrograms/ml) were approximately the same. However, crevicular fluid levels of 1.0 micrograms/ml and above were present for up to 6 h, whereas blood concentrations dropped below 1.0 micrograms/ml within 2 h after administration. Based on its minimal inhibitory concentrations, clindamycin at crevicular fluid levels of 1.0 micrograms/ml or above should inhibit most bacteria associated with diseased periodontal sites.

Bacteria↗

Tetracycline: levels achievable in gingival crevice fluid and in vitro effect on subgingival organisms. Part I. Concentrations in crevicular fluid after repeated doses.

The concentration of tetracycline in gingival crevice fluid and blood was determined using a sensitive bioassay after oral administration of repeated doses of tetracycline. Crevicular fluid was sampled by an intracrevicular technique from four gingival sites in each individual and blood was obtained by finger puncture. Four volunteers received doses of 250 mg of tetracycline-HCl either every 6 hours or every 12 hours and were sampled at hours 0 to 15, 21 to 36, 48 to 60 and 96 to 102. Volunteers given 250 mg every 6 hours had average crevicular fluid concentrations between 4 to 8 micrograms/ml and blood concentrations between 2 to 2.5 micrograms/ml after 48 hours. The levels in crevicular fluid and blood of volunteers who received 250 mg every 12 hours were 2 to 4 micrograms/ml and 0.3 to 1.4 micrograms/ml respectively after 48 hours. The results demonstrated that after repeated doses of tetracycline the crevicular fluid levels were typically 2 to 4 times the blood levels.

Administration, Oral↗