Spectral evidence for two forms of acid ferrihemoglobin

There is evidence that suggests that two forms of ferrihemoglobin may exist under various experimental conditions. We have studied the spectral changes brought about by the use of glycerol-water mixtures as a solvent for ferrihemoglobin. Our results indicate that in the presence of substantial amounts of glycerol a form of acid ferrihemoglobin spectrally resembling that of the imidazole complex of ferrihemoglobin is stabilized. A quantitative analysis of the spectral changes suggests that the effect of glycerol on ferrihemoglobin can in large part be ascribed to its effect on the activity of the solvent water.     

Continuous intravenous infusion in athymic (nude) rats: an animal model for evaluating the efficacy of anti-cancer agents

The athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets. Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion. The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse.     

Intravenous tolerability of an acid vehicle in Sprague Dawley rats and beagle dogs after daily slow bolus injection and infusion for one hour during 14 days

To assess the tolerability of an acid vehicle to be used in toxicology studies, a low pH aqueous solution containing 16.4 mg/ml of citric acid, 4.2 mg/ml of disodium phosphate, 25 mg/ml of mannitol, adjusted with phosphoric acid/NaOH 1 M to pH 3 was daily administered intravenously to rats and dogs for 14 consecutive days. The dosing regimen consisted of a slow intravenous bolus injection given over 30 s (0.75 and 0.625 ml/kg, for rats and dogs, respectively) followed by intravenous infusion for one hour (3.75 and 2.75 ml/kg/h, for rats and dogs, respectively). In rats, the dose was administered via the lateral tail vein. In dogs, the intravenous bolus dose was administered via the vena cephalica, vena saphena or vena jugularis, whilst the infusion dose was given into the vena cephalica or vena saphena. In rats, administration of the vehicle was associated with clinical signs (occasional mild vocalization and agitation) which were considered to be due to local irritation during the dosing procedure. Nevertheless, only mild histopathological changes at the injection site were found, while no relevant clinical chemistry changes were found in this species. However, the vehicle caused significant vascular damage with thrombus formation in the dog. It is therefore concluded that this vehicle is suitable for 2-week rat toxicity studies, if carefully applied. The vehicle with its present regimen should not be used in dogs, in view of the prohibitive findings.     

Molecular mechanisms involved in the prevention and reversal of ketamine-induced schizophrenia-like behavior by rutin: the role of glutamic acid decarboxylase isoform-67, cholinergic,Nox-2-oxidative stress pathways in mice

Molecular Biology Reports - Mounting evidences have shown that nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox-2) pathway modifies glutamic-acid decarboxylase-67 (GAD67) (GABAergic...