Flow cytometric measurement of bovine milk neutrophil phagocytosis.
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Biomedical subjects
Publications and source records attributed to A M Saad.
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The sieving characteristics of the prototype drugs gentamicin (poorly protein bound) and phenytoin (highly protein bound) were measured in vitro using polysulfone capillary hemofilters similar to those used in clinical continuous arteriovenous hemofiltration. Plasma water, whole plasma, and whole blood were the solvent systems used with variable drug concentrations and solvent flow rates. Our results indicate that the sieving coefficients for both drugs can be accurately defined as the concentration in the ultrafiltrate divided by the concentration in the artery. This correlates with a more rigorously derived expression by Colton and Henderson (r = 0.98, P less than 0.00001 for both drugs) and avoids the necessity of measuring venous concentrations. Drug sieving in the three solvents followed expectations from known protein-binding data and was independent of solvent flow rate. For both drugs, at higher drug concentrations sieving increased in plasma, consistent with the saturation of protein-binding sites. In whole blood, sieving fell for both drugs with increasing drug concentrations, consistent with drug compartmentalization into red blood cells. Although these sieving changes with increasing drug concentrations were statistically significant, their clinical significance is doubtful. Phenytoin sieving in plasma was increased by the addition of free fatty acids, consistent with a protein-drug displacement effect. There appears to be a real, but small, effect of protein concentration polarization, protein-membrane and drug-membrane interactions on drug sieving. Our observations are consistent with the expectation that the major determinant of drug sieving is the extent of drug-protein binding.
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We have discussed the basic principles of pharmacokinetics and convective solute removal in the context of each other. Clinical observations appear to follow the theoretical expectations. For practical purposes plasma and plasma water are not different. In the calculation of drug sieving, venous samples do not contribute enough to warrant their extra costs. We recommend that drug removal in hemofiltration be expressed by the sieving coefficient, UF/A. Drug sieving data in humans undergoing CAVH are tabulated. Recommendations for supplemental dosing are discussed which are applicable to any clinical setting.
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The pathogenic effects of experimental Schistosoma bovis infection in Sudanese sheep and goats were investigated by a variety of clinical, parasitological, physiological and histopathological techniques; uninfected animals of each species were used as controls. Infected animals of both species lost or failed to gain weight and developed a haemorrhagic diarrhoea, inappetence, marked anaemia, hypoalbuminaemia, hyperglobulinaemia, hyperproteinaemia and eosinophilia. These changes first became noticeable around the time of onset of oviposition and their severity was generally related to faecal egg counts. Red cell breakdown and albumin catabolism were much higher in infected than in control animals of the same species, and it was concluded that these changes were due to haemorrhage resulting from the extrusion of large numbers of eggs through the intestinal mucosa. Although all the animals were infected with the same number of cercariae, both the number of worms reaching maturity and the tissue egg counts tended to be higher in sheep than in goats. On the other hand, goats had significantly higher faecal egg counts than sheep and it is suggested that this was the reason for the generally more severe disease in the former species.
Red cell kinetics and albumin metabolism were studied in calves infected with either 100 or 200 Schistosoma bovis cercariae per kg body weight, by the use of 59Fe-labelled transferrin, 51Cr-labelled erythrocytes and 125I-labelled albumin; a third group of worm-free animals acted as controls. The anaemia which developed in the infected calves was shown to be due basically to an accelerated rate of red cell loss from the circulation, and became evident around the seventh week of infection, increased in severity during the following two months, and subsequently subsided. In view of its close similarity to the pattern of faecal egg excretion, it was concluded that haemorrhage into the intestine caused by the exit of eggs was the principal aetiological factor: haemolysis was excluded by the absence of both splenomegaly and hyperferraemia . Erythropoiesis was also accelerated in infected animals, but could not keep pace with the rate of red cell breakdown to which the animals were concurrently subjected. Haemodilution was involved, but not to a significant extent. The hypoalbuminaemia associated with infection was caused by an increased rate of albumin catabolism, and a plasma volume expansion, and was accompanied by marked depletion of all albumin pools, but particularly the extravascular pool. The pattern of albumin catabolism closely followed that of red cell loss, suggesting that passage of plasma as whole blood into the intestine was the basic cause of hypoalbuminaemia. Red cell losses and albumin hypercatabolism were more severe in the more heavily infected group, and although both subsided as egg counts fell, they remained evident even 1 year after infection. This may partly explain the failure of infected animals to regain the weight lost during earlier stages of disease.
A Sudanese isolate of Schistosoma bovis from experimentally infected sheep was found to be highly pathogenic to albino mice. Eggs were first found in the livers 42 days after exposure. The distribution of eggs in the liver and small and large intestines changed little during the course of infection. Results are compared with others using an Iranian isolate of S. bovis, which causes only a mild infection, and S. mattheei.
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Epizootiological observations on Schistosoma bovis in cattle at Kosti, Sudan, showed a significant fall in age-specific prevalence and intensity with age, based on fecal egg count. To test the possibility that this is due to acquired resistance, Kosti cattle and a control group of cattle of similiar breed and age from a nonenzootic area were experimentally challenged with 70,000 S. bovis cercariae. Clinical observations showed very clearly that the Kosti cattle were able to withstand almost completely the effects of the challenge, whereas the controls developed lethal infections. Resistance was further demonstrated by clear differences between the two groups in terms of their body weights, hematological measurements, histopathological and pathophysiological responses, and worm and egg counts. The data suggested that the main basis of the resistance was a suppression of egg production by the worms from the challenge, rather than absolute prevention of their maturation. There was also evidence of a suppression of the fecundity of worms in the naturally infected Kosti cattle.
Previous work has shown that cattle can acquire a strong resistance to Schistosoma bovis infection following repeated natural exposure. Partial resistance to a laboratory challenge with S. bovis has also been demonstrated in calves after immunization with an irradiated schistosomular or cercarial vaccine. The aim of the present study was to see whether this type of vaccine could protect calves under the very different conditions of natural exposure to S. bovis in the field. Thirty 6- to 9-month-old calves were each immunized with 10,000 irradiated S. bovis schistosomula by intramuscular injection and 8 weeks later were released into an enzootic area along with 30 unvaccinated animals. The calves were followed up for 10 months, during which period protection was evidenced by a lower mortality rate, a slower rate of acquisition of infection, and lower fecal egg counts in the vaccinated calves. Necropsy of the survivors showed 60--70% reductions in worm and tissue egg counts of the vaccinated calves as compared to those not vaccinated.
The clinico-pathological effects of Schistosoma bovis were monitored in zebu calves for a year after exposure to 100 or 200 cercariae/kg body weight and were related to the number and reproductive activities of the parasites present. The disease was characterised by diarrhoea, weight loss or poor weight gain, anaemia, serum protein changes and eosinophilia. These changes were broadly related to the level of infection and were most prominent during the two months following patency when faecal egg counts were highest. Subsequently, the condition of most animals improved. This was associated with a marked reduction in faecal egg excretion which in turn was related to worm deaths, reduced worm fecundity and egg retention in the tissues.
A simple method is described for the rapid quantitative analysis of acetaminophen in plasma. The acetaminophen and its conjugates present in the plasma following drug administration are hydrolyzed with 4 N HCl to p-aminophenol. This compound is coupled with 5% vanillin reagent to form a stable yellow color whose concentration is determined spectrophotometrically at 395 nm. Application of this method to a study of three dogs treated with 650 mg of acetaminophen is described.
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A rapid GLC assay for acetaminophen, dichloralantipyrine, and isometheptene mucate in capsules was developed. These substances are chromatographed directly, using phenyl methyl silicone gum as the stationary phase. The standard calibration curves are linear up to 14 mg/ml, with a lower limit of sensitivity of 2 mg/ml. This method is simple and rapid and does not require derivative formation.
A rapid method for the routine determination of acetaminophen and dichloralantipyrine in capsules is reported. The determination of acetaminophen is based on the ability of its hydrolytic product, p-aminophenol, to produce an intensive yellow color with vanillin. The determination of dichloralantipyrine is based on the fact that it, as well as its major metabolite chloral hydrate, produces a blue color with quinaldine ethiodide. No interferences were encountered, and good recovery and precision data were obtained.
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