A wound healing study of chlorhexidine digluconate in guinea pigs.

Formulations with and without chlorhexidine digluconate, a broad-spectrum antimicrobial, were tested for their effects on the healing of incisions and abrasions surgically induced in male guinea pigs. Formulations containing chlorhexidine were a skin cleanser formulation (4% w/v), a tinted tincture (0.5% w/v), and both 0.5 and 4% w/v aqueous solutions. Control materials were saline, and both the skin cleanser and the tincture formulations without chlorhexidine. Presurgical preparation was limited to closely clipping the hair and wiping each wound area with saline to remove loose hair, dander, and dirt. Each incision and abrasion was irrigated with its assigned material at surgery and daily thereafter until necropsy. Guinea pigs were killed on Days 3, 6, 9, 14, and 21, and wound sites were removed and fixed for histologic evaluation of healing. Daily progress of the wound healing appeared comparable for all treatment groups and there was no gross evidence of treatment effects at necropsy. For the animals with incisions, there were no remarkable histological differences among the treatment groups at Day 3. At Days 6 and 9, the two formulations containing 4% chlorhexidine produced a slight delay in healing when compared with the other treatment groups. These differences decreased with time, and by Day 21, there were no remarkable histological differences among animals of the various treatment groups. For the animals with abrasions, all treatment groups with and without chlorhexidine had slightly delayed healing compared to the saline control animals on Day 3 and 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a direct blood pressure measurement technique for canine toxicity studies.

Repeated direct puncture of the central ear (intermediate auricular) artery to obtain mean arterial blood pressure in control and hypertensive dogs was evaluated. Unilateral nephrectomy and partial constriction of the contralateral renal artery were performed on four dogs to create hypertension. Ear artery blood pressure measurements and electrocardiograms were recorded twice pretest and after surgery at Weeks 1, 2, 4, 6, 8, 9, 10, and 11 on control (n = 6) and hypertensive (n = 4) dogs. Mean ear arterial blood pressures from the hypertensive dogs were significantly increased from Weeks 2 to 11. Indwelling omocervical artery catheters were implanted in both control and hypertensive dogs at Week 8. Mean omocervical artery blood pressures from hypertensive dogs were significantly increased at Weeks 8 through 11. Mean omocervical artery pressures were only significantly increased over mean ear artery pressures at Week 8 for control dogs and at Week 10 for hypertensive dogs. Nonspecific electrocardiographic changes in the ST-T segment and U waves occurred with greater frequency in hypertensive dogs than in control dogs. Hypertensive dogs developed subendothelial proliferation in the renal artery and aorta, and a proliferative vasculopathy in the heart and lungs. This ear artery technique was used successfully in two canine toxicity studies of different ICI pharmaceutical compounds. The ear artery method for measuring mean arterial blood pressure is suitable for canine toxicity studies and is a reasonably accurate measurement of systemic pressure.

A computerized data management system for behavioral teratology studies.

A computerized system was designed for behavioral teratology studies to (1) generate preprinted data recording/submission forms, (2) calculate testing dates, (3) generate a daily activity schedule for testing, and (4) update established data sets for access by data entry personnel. The computer-generated forms are used to record data from the following behavioral/developmental tests for rats: pup weights, pinna detachment, surface righting, cliff avoidance, incisor eruption, eye opening, negative geotaxis, olfactory discrimination, swimming development, open field, swimming maze and operant visual discrimination learning. Three behavioral teratology studies have been conducted in our laboratory using this computerized system. The human error rates in these studies were 0.26, 0.34 and 0.46 percent, respectively. The advantages of this system include: (1) computer-calculated test dates; (2) elimination of manual data transcription; (3) more consistent data recording and scoring conditions; (4) better scheduling control; and (5) faster data entry and statistical analysis.

Toxicological, pathological, and teratological studies in animals with cephradine.

Cephradine, a semisynthetic cephalosporin antibiotic, has a low order of oral and parenteral toxicity in animals. The oral LD(50) in mice and rats ranged from 5 to >8 g/kg, and the intraperitoneal LD(50) values in mice and rats were 0.7 to 1.5 g/kg and 4.0 g/kg, respectively. The intravenous LD(50) in mice ranged from 3.0 to 3.8 g/kg. In anesthetized dogs, intravenous doses of cephradine (40 and 120 mg/kg, given 45 min apart) had no effect on either the renal or cardiovascular systems. Single intramuscular injections (0.25 ml or 0.5 ml of a solution containing 125 to 235 mg of cephradine/ml) elicited no signs of either pain or local irritation in dogs, and only transient signs of slight-to-moderate irritation were observed in rabbits. In subacute toxicity studies, cephradine was administered for 4 weeks to rats (daily intraperitoneal doses of 160, 480, or 1,600 mg/kg) and dogs (daily intravenous doses of 80, 240, or 800 mg/kg); in addition, over a 2-week period, monkeys were given daily intravenous doses of 60, 180, or 600 mg/kg. No clinical, biochemical, gross, or micropathological changes due to cephradine were observed in these animals; especially notable was the absence of any signs of nephrotoxicity. In chronic toxicity studies, daily doses of cephradine were administered orally to rats (100 to 1,000 mg/kg), dogs (50 to 500 mg/kg), and monkeys (50 to 500 mg/kg) for 26, 26, and 13 weeks, respectively. Significant responses were observed only in rats, in which grossly enlarged, but histologically normal, ceca developed, a common finding in rodents dosed with antibiotics; in addition, there were increases in the relative and absolute weights of the adrenal glands. None of these effects was observed in rats that were necropsied 3 weeks after termination of dosage. In reproduction studies in mice and rats given either daily oral doses (100 or 300 mg/kg) or daily intraperitoneal doses (rats only; 80 or 320 mg/kg) of cephradine, no drug-related teratogenic changes in the offspring were observed.