Sale and supply of veterinary medicines.
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Biomedical subjects
Publications and source records attributed to B R Edwards.
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Both dietary unsaturated fat and raw soybean products are known to enhance pancreatic carcinogenesis when fed during the postinitiation phase. A comparison of these two dietary components was made to evaluate the relative potency of each ingredient for enhancing pancreatic carcinogenesis and to determine if this enhancement was correlated with an increase in plasma cholecystokinin (CCK) levels. Male Wistar rats were initiated with a single dose of azaserine (30 mg/kg body weight) at 14 days of age. The rats were weaned to test diets formulated from purified ingredients. Dietary protein at 20% by weight was either casein or soy protein isolate (heat treated or raw). Corn oil was the unsaturated fat of major interest and it was fed at either 5 or 20% by weight. Pancreases were quantitatively evaluated for carcinogen-induced lesions at 2- and 4-month postinitiation. In a second experiment designed to closely mimic the above experiment, rats were implanted with cannulae which allowed plasma to be repetitively sampled over a 2.5-week period during which the test diets were fed. Plasma was collected both prior to introduction of the test diets and afterwards. Plasma CCK was measured by a specific radioimmunoassay. Both the 20% corn oil diet and the raw soy protein isolate diet enhanced pancreatic carcinogenesis. The effects of the raw soy protein isolate on the growth of the carcinogen-induced lesions were significantly greater than the effects of the 20% corn oil diet. Plasma CCK values were not elevated in the rats fed the 20% corn oil diet, but they were significantly elevated in the rats fed the raw soy protein isolate. Heat-treated soy protein isolate neither enhanced carcinogenesis nor elevated the plasma CCK level. This study demonstrates that certain plant proteins enhance the growth of carcinogen-induced pancreatic foci and that this effect is considerably greater than the enhancement by high levels of dietary unsaturated fat. Furthermore, the enhancement by the raw soy protein isolate may be mediated by CCK; but this does not appear to be the mechanism by which the unsaturated fat, corn oil, enhances pancreatic carcinogenesis.
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The effects of the new regulations on veterinary practice are minimal. Veterinarians are mainly concerned with drugs in schedules 2 and 3 to the regulations and the requirements relating to these drugs are virtually unchanged. Pentazocine (Fortral) has been added to schedule 3 and from April 1, 1986, veterinarians must comply with the following additional requirements with respect to this drug or any other in schedule 3: use of written requisition for purchase of supplies and the prescription requirements for controlled drugs. Further details of the legislation applying to the labelling and dispensing of medicinal products and the requirements relating to schedule 2 controlled drugs, can be found in 'Legislation Affecting The Veterinary Profession in the United Kingdom', 4th edn (1984) Royal College of Veterinary Surgeons. For details of the legislation relating to schedule 3 drugs, see VR, December 22/29, 1984, p649.
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Chronic exposure of rats to a simulated altitude of 18,000 ft (5,500 m) results in severe polycythemia and consequent reduction of the plasma fraction. However, glomerular filtration rate is usually well maintained. This study was conducted to determine whether an increase in effective renal blood flow (ERBF) plays a role in maintaining a normal glomerular filtration rate in the chronically hypoxic rats. Various measurements of renal function were made in conscious trained and chronically catheterized animals. After exposure to high altitude for 30 days, hematocrit ranged from 64 to 77%. Despite this severe reduction in the plasma fraction, however, renal plasma flow decreased by only 25%, primarily owing to an increase in ERBF. The glomerular filtration rate was within the normal range. Since blood pressure remained unchanged, the increase in ERBF must have resulted from renal vasodilation. Acute removal of the hypoxic stimulus did not reverse the increased ERBF, suggesting that the vasodilation may have been of structural origin.
Because of their hypothalamic diabetes insipidus (DI), Brattleboro homozygous rats exhibit profound polyuria and polydipsia with elevated plasma osmolalities. This combination of symptoms has led to the tacit assumption that these animals are chronically volume contracted. However, the few direct measurements that have been published indicate otherwise. In the present study, total body water (TBW), total body lipid content, and plasma volume were measured in conscious DI rats and compared with corresponding values in weight-matched conscious Long-Evans (LE) rats. Fat content of DI rats (5.0 +/- 0.4 g/100 g body wt) was significantly lower than that of LE rats (7.6 +/- 0.6, P less than 0.005). TBW was not significantly different between the two strains whether expressed as milliliters per 100 g wet wt (DI 69.2 +/- 0.4 vs. LE 67.7 +/- 0.7) or as milliliters per 100 g fat-free wet wt (DI 73.4 +/- 0.5 vs. LE 73.3 +/- 0.4). Plasma volume of DI rats (4.4 +/- 0.1 ml/100 g body wt) was significantly higher than that of LE rats (3.9 +/- 0.2, P less than 0.025). Extracellular fluid volume was similar in the two strains although, for this measurement, the animals were neither weight- nor age-matched. Accordingly, the data indicate that under the conditions of this study the DI rat is not chronically volume contracted. It would appear that, given an adequate water supply, water balance can be achieved via the thirst mechanism, perhaps abetted by vasopressin-independent mechanisms of urine concentration.
Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water for 24 h. Glomerular filtration rate (GFR) falls concurrently and might contribute to the increased concentrating ability. The present studies concerned the time course of the changes in concentrating ability and GFR during the early hours of dehydration. Experiments were performed in 10 chronically catheterized conscious DI rats in the normally hydrated control state and during 3 h of fluid deprivation. Urine osmolality (Uosmol) increased from 97 +/- 6 (SE) to 325 +/- 11 mosmol/kg H2O at 3 h. Averaged over the 3 h, neither GFR nor effective renal blood flow changed significantly (103 +/- 2 and 106 +/- 4% of control, respectively). Fractional excretion of sodium (FENa) rose markedly from 0.3 +/- 0.1 to 1.3 +/- 0.1% at its peak. Clearly, a fall in GFR cannot explain the rise in Uosmol during the first 3 h. Plasma oxytocin (OT) increased from 5.6 +/- 0.8 to 36.4 +/- 4.5 pg/ml after 3 h of dehydration. In additional experiments, d(CH2)5-D-Phe-VAVP, an antidiuretic antagonist (anti-ADH), was administered to eight DI rats after 3-h dehydration. Control, 3-h dehydration, and post-anti-ADH values were, respectively: for Uosmol, 102 +/- 7, 347 +/- 14, 145 +/- 11 mosmol/kg H2O; for GFR, 1,003 +/- 43, 1,042 +/- 59, 866 +/- 54 microliter X min-1 X 100 g body wt-1; for FENa, 0.4 +/- 0.1, 1.4 +/- 0.1, 0.5 +/- 0.1%. The decreases following anti-ADH were all statistically significant. We conclude that OT is released during the early hours of dehydration in the DI rat and has at least three renal effects. It causes a natriuresis, it maintains renal hemodynamics and GFR during the volume contraction, and it elicits a weak antidiuretic response.
Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water. Ultimately this rise in urine osmolality must follow from increased osmolality of the corticopapillary gradient and/or increased osmotic equilibration across the collecting ducts. In this study we examined the concentrations and contents of total solute, urea, and nonurea solute in tissue from cortex to papillary tip of DI rats before and after dehydration for 12, 24, and 48 h. The greatest increase in osmolality occurred during the first 12 h; both urea and nonurea solute concentrations increased, but urea preferentially. From 12 to 48 h there were only small further increases in these concentrations, largely as a result of decreased tissue water content. Osmotic equilibration (reflected by urine/papillary tip osmolality) increased dramatically during dehydration, presumably because of decreased flow rate, attaining full equilibration by 48 h. The rise in urine osmolality during the first 12 h of dehydration was due to increased osmotic equilibration and to the enhanced corticopapillary gradient; urine became more concentrated from 12 to 48 h largely as a result of increased osmotic equilibration.
Despite the absence of vasopressin, Brattleboro homozygous (DI) rats can concentrate their urine to hypertonic levels when deprived of drinking water. When DI rats are infused with vasopressin, freeze-fracture electron microscopy has revealed increases in intramembranous particle clusters (IPC) in papillary collecting duct luminal membrane that parallel the rise in urine osmolality. In the present study, we examined whether the increase in concentrating ability of DI rats dehydrated for 24 h was associated with a change in IPC. For comparison, oral water loading and 24-hour dehydration were used to suppress and stimulate endogenous vasopressin secretion in Long-Evans (LE) rats, and the effects on urine osmolality and IPC were examined. In LE rats, the induced changes in water balance resulted in alterations in IPC frequency that paralleled urine osmolality, whereas, in DI rats, frequency of IPC remained low under all conditions, even when urine osmolality rose to almost 1,000 mosm/kg H2O as a result of 24-hour dehydration. These results suggest that the increased concentrating ability of dehydrated DI does not depend upon increased water permeability of the papillary collecting ducts.
The total restoration of urinary concentrating ability of the DI rat given daily injections of vasopressin takes several weeks, although complete osmotic equilibrium across the collecting duct is manifest within hours. This suggests that there may be other deficiencies of the renal concentrating mechanism that, if corrected by vasopressin treatment, are corrected more slowly. I have focussed on just three possibilities. First, the morphology of the medullary interstitium is different from normal rats. Perhaps associated with this finding are alterations in the levels of medullary glycosaminoglycans which may have a role to play in water balance. Functional and morphological changes in the juxtamedullary nephrons are also evident. Second, the possibility exists that the countercurrent multiplier of the DI rat operates less efficiently than in the normal animal. Finally, reduced synthesis of PGs in the renal medulla of DI rats may also influence the concentrating mechanism, although in a favorable direction. While most (if not all) of these differences are secondary to the lack of vasopressin, in some instances it appears that it is the high water turnover (possibly the altered chemical composition of the medullary interstitium) that is the primary culprit. While the DI rat remains an excellent model for the study of water balance and the action of vasopressin, the presence of multiple defects within the system should be borne in mind. This is particularly true when comparing data obtained following acute treatment with vasopressin versus that following chronic treatment.
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