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Biomedical subjects

D L Murray

Publications and source records attributed to D L Murray.

At least 55 records · Page 3Linked to original sources

Glutathione synthesis and glutathione redox pathways in naphthalene cataract of the rat.

This investigation examined many parameters during the course of early development of naphthalene-induced cataract in a time span of 0 to 79 days of treatment. Feeding naphthalene daily to Black-Hooded rats resulted in gradual progressive development of cataract. The first faint opacities were detectable after 7 days. Free soluble total glutathione (oxidized and reduced) of these lenses was shown to gradually decrease to a maximum loss of about 20%, a value reached by day 30 of treatment. No activity loss of either enzyme required for glutathione synthesis (gamma-glutamylcysteine synthetase or glutathione synthetase) was observed in homogenates of naphthalene versus control lenses. There was also neither impairment of [35S]-L-cystine uptake nor of [35S]-glutathione synthetic capacity in lenses cultured from rats after 12, 24 or 36 days of naphthalene feeding when compared to control lenses. Hence, glutathione loss cannot be explained by a damaged glutathione synthesis system. Progressive activity loss of glutathione peroxidase and glutathione reductase was observed. The loss of glutathione peroxidase activity was especially remarkable. Thus, the defense system against oxidative damage is impaired and may be a significant factor in naphthalene-induced cataract of the rat.

Animals↗

Conditions for maximizing and inhibiting synthesis of glutathione in cultured rat lenses: an application of HPLC with radioisotope detection.

This investigation was concerned with factors which would maximize and inhibit L-cyst(e)ine uptake and glutathione synthesis of rat lenses cultured for 24 hours in a medium containing [35S]-L-cystine. The lenticular protein-free extract was separated and quantified by use of HPLC equipment which included an in-line radioisotope detector coupled with extensive post-run computer analysis. Six thiols were assessed for their ability to increase the uptake of L-cyst(e)ine and its utilization for glutathione synthesis. The most successful was 2-mercaptoethanol, which increased the L-cyst(e)ine uptake 3.6-fold and glutathione synthesis 2.9-fold. This work demonstrated that the rate of glutathione synthesis was directly proportional to the rate of uptake of L-cyst(e)ine. An inhibitor of glutathione synthesis, buthionine sulfoximine, in a concentration range of 0.11-3 mM, decreased uptake of the [35S]-label by one-third. The 3.0 mM concentration inhibited glutathione synthesis 98.7% and decreased glutathione 51% in 24 hours. The data indicate that half the glutathione disappeared in 23 hours in these cultured rat lenses. Because determination of this value did not depend upon the variable rate of cysteine transport, the value may approximate the in vivo value.

Animals↗

Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study.

Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag.

Administration, Oral↗

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections.

In two prospective, randomized multicenter double-blind studies with a dosage of either 250 mg given four times a day (study A) or 500 mg given two times a day (study B), the comparative efficacy and safety of cephalexin hydrochloride (LY061188; Keftab) and cephalexin monohydrate (Keflex) for treatment of skin and soft tissue infections were determined. In study A, 97 patients received cephalexin hydrochloride and 101 patients received cephalexin monohydrate. In study B, 75 patients received cephalexin hydrochloride and 70 patients received cephalexin monohydrate. Diagnoses included abscesses, cellulitis, wound infections, and infected dermatitis, and were comparable in the different treatment groups. Pathogens were isolated from 82% of patients enrolled; the majority of isolates were of Staphylococcus aureus, Streptococcus pyogenes, other staphylococcal species, and a few gram-negative bacteria. In study A, 68 of 71 (95.7%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 73 of 81 (90%) patients who received cephalexin monohydrate also responded satisfactorily. In study B, 56 of 58 (96.5%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 47 of 50 (94%) patients who received cephalexin monohydrate also responded satisfactorily. An adverse clinical event leading to discontinuation of the treatment drug developed in 17 of 343 (4.95%) patients in both studies. No differences were noted between the two drugs. Skin eruptions, pruritus, and mild gastrointestinal symptoms were the common adverse effects. These data suggest that cephalexin hydrochloride, a new formulation of cephalexin, is a safe and effective antimicrobial agent for treatment of a variety of skin and subcutaneous infections in a dosage of either 250 mg four times a day or 500 mg twice a day.

Adult↗

Determination of immune status to measles, rubella, and varicella-zoster viruses among medical students: assessment of historical information.

We examined the serological susceptibility of entering medical students to measles, rubella, and varicella-zoster (VZV) viruses over a four-year period. Serological results were then compared to historical information to ascertain whether undocumented histories of disease or vaccination could be used to identify students who may not need serological testing. For measles, historical information was of no benefit in predicting immunity. For VZV and, to a greater extent, rubella, a higher seropositive rate was seen in students claiming a positive history.

Antibodies, Viral↗

Effect of adrenocorticotropin and dietary ascorbic acid on the graft-versus-host reaction capacity of chickens.

Two trials using the splenomegaly assay were conducted to assess the effects of adrenocorticotropin (ACTH) and dietary ascorbic acid (AA) on the ability of chickens to mount a graft-vs.-host reaction (GVHR). Broiler chicks served as blood donors. Birds received AA at levels of 0, 150, or 300 mg/kg of feed (ppm). At 6 wk of age, donor birds from each AA group received either three intramuscular injections of ACTH in gelatin at 12-h intervals, comparable injections of the gelatin, or no injections. Thirteen-day-old Single Comb White Leghorn embryos served as recipients. Two recipient embryos per donor were injected in a chorioallantoic vein with either whole blood (Trial 1) or saline-washed and reconstituted blood cells (Trial 1). Eggs were further incubated for 6 days, at which time the embryos were killed and each spleen excised. Relative spleen weights were expressed as milligrams of spleen/100 g embryonic body weight. Significant differences in relative spleen weight or donor plasma corticosterone (CS) levels did not occur in Trial 1. In Trial 2, regardless of AA treatment, relative spleen weights of embryos that received blood cells from donors treated with ACTH were significantly lower than controls. Donor CS was significantly lower in birds that received ACTH. These results indicate that, when washed and reconstituted blood cells are injected into recipients and donor plasma CS is decreased, GVHR capacity is suppressed in ACTH-treated donors.

Adrenocorticotropic Hormone↗

Effect of cortisol on cutaneous basophil hypersensitivity to phytohemagglutinin in chickens.

Three independent trials were conducted to determine if cutaneous basophil hypersensitivity (CBH) to the mitogen phytohemagglutinin (PHA-P) was affected by the injection of cortisol in broiler cockerels. Trials 1 and 2 were similar, and Trial 3 imposed a period of heat stress in combination with cortisol. At 6 wk of age, chicks were injected intramuscularly with 2 mg of cortisol in a corn oil vehicle/500 g body weight at 48, 36, 24, and 12 h prior to challenge with PHA-P. Controls received an equal amount of corn oil on the same schedule. Each chick received .05 mL of PHA-P (100 micrograms) in the right wattle and an equal volume of saline in the left wattle. The CBH was assessed by measuring the thickness of wattles at various times from 0 to 48 h after challenge with PHA-P. Wattle indices were calculated. Birds were necropsied at 48 h post-PHA-P, and bursa of Fabricius, spleen, and both adrenals excised and weighed. Cortisol produced a significantly greater CBH response in Trials 1 and 2 as indicated by higher wattle indices at 48 h and at 6 h in Trial 3. Regression analysis indicated significantly greater intercepts for the cortisol responses in Trials 1 and 3 and a significantly greater linear component for the cortisol response in Trial 2. Body weights and relative bursa and spleen weights were reduced significantly by cortisol, whereas relative adrenal weights were increased significantly in Trials 2 and 3. These data indicated that cortisol enhanced CBH to the mitogen PHA-P in broiler cockerels. This is in contrast to reported immunosuppressive effects of other glucocorticoids.

Animals↗

Preretinal oxygen changes in the rabbit under conditions of light and dark.

Preretinal oxygen measurements were made in pigmented rabbits under conditions of light and dark. The avascular rabbit retina was chosen to eliminate the effects of autoregulation by the retinal vasculature, thus more clearly defining the role of the photoreceptors on preretinal measurements of oxygen delivery from the choroid. Measurements were made 50-100 micron away from the retina using oxygen microelectrodes. An average preretinal oxygen value of 9.8 +/- 1.3 SE mm Hg (n = 12) was measured in room light under normoxic conditions. A change from light to dark conditions always resulted in a measured decrease in preretinal oxygen levels. During the first 30 min of dark adaptation, a 25.8% (+/- 5.5% SD) decrease was obtained. This oxygen decrease is reversible during sequential light adaptation, reaching plateau in approximately 15-20 min. These results indicate that the photoreceptors have a significant effect on choroidal oxygen transmission across the retina.

Animals↗

Inhibitory effect of Azone (1-dodecylazacycloheptan-2-one) on herpes simplex viruses. In vivo and in vitro studies.

Enhanced activity of antiviral agents, when mixed with a penetration enhancer like Azone (1-dodecylazacycloheptan-2-one) in topical preparations, is well-recognized. These studies were undertaken to investigate whether Azone, per se, has any activity against herpes simplex (HSV) type 1 and type 2 viruses. When HSV-1 and HSV-2 were mixed with 5, 10 and 20% Azone, there was a 1-4.5 log10 decrease in virus titers. The efficacy of 5 and 10% Azone applied topically was evaluated during the treatment of HSV-1 cutaneous infections in guinea pigs. HSV-1 infection was produced by intradermally inoculating guinea pigs with 10(7.7) HSV-1/ml. The mean number of lesions per site was reduced by more than 50% in Azone-treated sites as compared to no treatment (control) sites (p less than 0.01). Similarly, the surface area of each lesion in the Azone-treated sites was only 40% of that seen in control sites (p less than 0.001). More than 80% of the lesions on Azone-treated sites healed by day 4 as compared to only 3% on control sites (p less than 0.001). These data indicate that Azone, a lipophilic chemical, may have antiviral properties when used topically.

Animals↗

Effect of adrenocorticotropin and dietary ascorbic acid on cutaneous basophil hypersensitivity to phytohemagglutinin in chickens.

Two trials were conducted to assess the effects of adrenocorticotropin (ACTH) and dietary ascorbic acid (AA) on cutaneous basophil hypersensitivity (CBH) to phytohemagglutinin (PHA-P) in chickens. Broiler chicks received AA at levels of 0, 150, or 300 mg/kg of feed (ppm) continuous from hatching. At 6 to 7 wk of age, birds from each AA group received either 2 IU ACTH/100 g of body weight, 4% gelatin, or no ACTH or gelatin injections. Injections were given 12 h prior to, at the time of, and at 12 and 24 h after an intradermal wattle injection with PHA-P. Responses to PHA-P were determined as wattle indices. Injections of ACTH reduced body weight gain in both trials and decreased relative bursa weight in Trial 1. Injections of ACTH and dietary AA increased plasma cholesterol in both trials. Peak CBH wattle response occurred at 24 h post PHA-P injection. Injections of ACTH decreased mean wattle index at 18 and 36 h post PHA-P injection in Trial 1 and 18 and 24 h post PHA-P injection in Trial 2. The addition of AA ameliorated the ACTH-mediated suppression of CBH in a dose-related manner.

Adrenocorticotropic Hormone↗

Effects of adrenocorticotropin and dietary ascorbic acid on delayed type hypersensitivity to human gamma globulin in chickens.

Three trials were conducted to assess the effects of adrenocorticotropin (ACTH) and dietary ascorbic acid (AA) on delayed type hypersensitivity (DTH) to human gamma globulin (HGG) in chickens. Broiler chicks received AA at 0, 150, or 300 mg/Kg of feed (ppm) continuously from hatching, were sensitized at 5 wk of age to HGG emulsified in complete Freund's adjuvant, and 2 wk postsensitization, were challenged with an intradermal injection of HGG into a wattle. Birds from each AA group received ACTH at either HGG sensitization, challenge, or both. There were uninjected controls and a vehicle control group, which received gelatin at both sensitization and challenge. The ACTH and gelatin injections were given at 12-h intervals beginning 12 h prior to HGG. Responses to DTH were determined as wattle indices. In all three trials, birds that received ACTH at challenge exhibited a DTH response at 18 and 24 h postchallenge that suppressed, compared with that of controls. Birds that received ACTH at sensitization had a greater wattle response than that of birds that received ACTH at challenge, and this effect was enhanced by dieting AA. In Trial 2, birds that received ACTH at sensitization had a greater wattle response at 18 h post HGG challenge than that of controls. Total leucocyte numbers were unaffected; however, heterophil:lymphocyte ratios were lower in birds that received ACTH at sensitization than in birds that received ACTH at challenge and birds that received ACTH at challenge had fewer lymphocytes. Whether given at challenge or at sensitization, ACTH decreased plasma AA when measured at those times. The 300 ppm level of AA increased plasma AA concentration. Adrenal gland and wattle AA levels were unaffected; however, spleen AA concentration was lower in birds given ACTH at challenge.

Adrenocorticotropic Hormone↗