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Biomedical subjects

L B Murgatroyd

Publications and source records attributed to L B Murgatroyd.

15 recordsLinked to original sources

1H-NMR spectroscopy as a means of monitoring nephrotoxicity as exemplified by studies with cephaloridine.

1. Male albino rats were dosed intravenously with either 0.9% saline or cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2. Urine analysis on day 3, after two doses of cephaloridine showed dose-related increases in glucose, total protein, N-acetyl beta-D-glucosaminidase, gamma-glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR spectroscopy showed corresponding disturbed profiles of products of intermediary metabolism indicative of a disruption of renal function. 3. By day 6, after five doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed that all indices had returned to normal. 1H-NMR was demonstrated to provide useful complementary information to conventional techniques on the time course of the onset of the nephrotoxicity and the recovery phase, and was at least as sensitive as conventional urine analysis.

Animals

Safety evaluation of meropenem in animals: studies on the kidney.

The effect of meropenem on animal kidneys has been assessed in rats (5 of each sex/group), rabbits (3 of each sex/group) and monkeys (3 of each sex/group) in comparative iv studies with ceftazidime, cefotaxime, cephaloridine and imipenem (without cilastatin). Diarrhoea occurred in rabbits and monkeys dosed with imipenem or meropenem. Emesis occurred only after the administration of imipenem to monkeys. After 14 days administration to rats evidence of nephrotoxicity was seen only in males dosed with cephaloridine (850 mg/kg); no changes were seen with ceftazidime, cefotaxime or meropenem (all at 1000 mg/kg). Four days after a single dose to rabbits renal tubular necrosis was seen in all animals receiving imipenem (150 mg/kg) and cephaloridine (250 mg/kg). Minimal histopathological changes to the kidneys were seen with cefotaxime, ceftazidime and meropenem (all at 400 mg/kg). After seven days' administration to cynomolgus monkeys imipenem (180 mg/kg) caused moderate to severe tubular necrosis. No tubular damage was seen with meropenem at 180 mg/kg or with cefotaxime or ceftazidime (both at 500 mg/kg). At 500 mg/kg meropenem caused mild tubular regeneration and/or fat accumulation in 3/6 animals, with mild tubular necrosis in one of these. The data from these three species indicate that meropenem has a low nephrotoxic potential in these animal models.

Animals

The use of a basic dye (azure A or toluidine blue) plus a cationic surfactant for selective staining of RNA: a technical and mechanistic study.

Selective purple staining of RNA-rich structures such as basophilic cytoplasms of exocrine pancreas and plasma cells, Nissl substance, and nucleoli was achieved by treating tissue sections as follows. Stain dewaxed sections for 1/2 hour in a dyebath containing 0.1% w/v axure A or toluidine blue and 1% cationic surfactant (Hyamine 2389, a 50% w/v aqueous solution of diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride; or benzyldimethylammonium chloride, or cetylpyridinium bromide, or cetyltrimethylammonium bromide) buffered to pH 7 with phosphate. Rinse in water, blot, air dry and mount in synthetic resin. Intense purple staining of RNA-rich regions occurred after fixation in neutral formalin or in Carnoy's or Gendre's fluids, though satisfactory results were also found after fixation in acetone or alcohol. Chromatin generally stained a very pale azure after all fixations, though occasionally nuclei were unstained (Gendre's or Zenker's fluids). Subjecting tissue sections to acid hydrolysis or to digestion by RNAase eliminated or reduced the purple staining, but left the azure staining of nuclei unaffected. Satisfactory staining of RNA-rich structures was not critically dependent on the precise concentrations of dye, surfactant or inorganic salts in the dyebath, nor on pH, staining time or chemical nature of the surfactant. The staining patterns can be rationalized with a tissue model that considers both surface charge and permeability factors, since present in the dyebath are small dye cations and large cationic surfactant micelles. As micelles and dye will both quickly penetrate basophilic structures considered to be porous, such as chromatin, competition will then greatly reduce staining of such substrates. But the large micelles will only slowly penetrate regions considered to be more impermeable, such as basophilic cytoplasms, so consequently small fast moving dye ions may enter and stain without competition.

Animals

Psoriasis--changes in surface microtopography.

Easily prepared adhesive slides have been used to obtain surface-layer biopsy specimens from psoriasis and other scaly dermatoses that occur on the limbs. Psoriasis obliterates the normal skin pattern, but the change is not specific. However, as psoriasis undergoes spontaneous or treatment-induced resolution, the skin surface pattern reappears and develops through a series of pattern changes that closely correlate with the clinical appearance of the lesion. This method may be used to monitor changes in the stratum corneum.

Adult