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Biomedical subjects

A D Watson

Publications and source records attributed to A D Watson.

At least 19 recordsLinked to original sources
PubMed1995

Pathogenesis of atherosclerosis.

The earliest lesion in the development of an atherosclerotic plaque is the fatty streak. This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein (LDL) in the subendothelial space of the artery wall. The trapped LDL is seeded with oxidative species released by the overlying endothelium, and lipid oxidation is initiated within the LDL particle. Some of the lipids that result lead to the activation of NFkB-like transcription factors that cause the expression of genes whose protein products mediate monocyte binding, monocyte chemotaxis into the subendothelial space, and conversion into macrophages. At least 1 major gene modulates the oxidation of LDL lipids and/or the biologic response to these lipids. The inverse relation between high density lipoprotein (HDL) and atherosclerotic events may in part be due to enzymes associated with HDL that destroy the biologically active lipids generated in LDL.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics.

The clinical events resulting from atherosclerosis are directly related to the oxidation of lipids in LDLs that become trapped in the extracellular matrix of the subendothelial space. These oxidized lipids activate an NF kappa B-like transcription factor and induce the expression of genes containing NF kappa B binding sites. The protein products of these genes initiate an inflammatory response that initially leads to the development of the fatty streak. The progression of the lesion is associated with the activation of genes that induce arterial calcification, which changes the mechanical characteristics of the artery wall and predisposes to plaque rupture at sites of monocytic infiltration. Plaque rupture exposes the flowing blood to tissue factor in the lesion, and this induces thrombosis, which is the proximate cause of the clinical event. There appear to be potent genetically determined systems for preventing lipid oxidation, inactivating biologically important oxidized lipids, and/or modulating the inflammatory response to oxidized lipids that may explain the differing susceptibility of individuals and populations to the development of atherosclerosis. Enzymes associated with HDL may play an important role in protecting against lipid oxidation in the artery wall and may account in part for the inverse relation between HDL and risk for atherosclerotic clinical events.

Arteriosclerosis↗
PubMed1995

Effect of ingesta and of tablets of different strengths on the systemic availability of digoxin in normal dogs.

The plasma concentrations of digoxin were measured in eight normal dogs given digoxin on four occasions, using three different feeding regimens and tablets of two strengths. Although ingesta tended to slow the absorption of digoxin, the systemic availability of the drug, based on measurements of Cmax, tmax and AUC did not differ when digoxin tablets were given with canned food, with dry food, or without food. However, some of the pharmacokinetic characteristics and smaller individual variations with the dry food regimen would be considered advantageous for maintenance therapy. Tablets containing 62.5 micrograms or 250 micrograms of digoxin had a similar relative bioavailability. The peak plasma digoxin concentrations were higher in female dogs, and the trends in other data also suggested that the systemic availability of digoxin was better in female dogs.

Animals↗
PubMed1992

Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats.

Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.

Amino Acid Sequence↗
PubMed1992

Erythrocyte protoporphyrin concentrations in clinically normal cats and cats with lead toxicity.

Erythrocyte protoporphyrin (EPP) and blood lead concentrations were determined in 91 clinically healthy cats living in the inner suburban area of Sydney, Australia. The mean EPP concentration was 223.4 +/- 186.1 micrograms litre-1 whole blood and the mean blood lead concentration 0.62 +/- 0.25 mumol litre-1. EPP concentrations were also monitored in three cats with confirmed lead toxicity--at the time of diagnosis and one week and one month after chelation therapy with calcium EDTA. EPP concentrations were elevated in two cats and within the normal range in the third cat at the time of diagnosis. EPP concentration were higher in two cats one week after treatment than at the time of diagnosis. One month after chelation therapy, EPP concentrations were normal in two cats but still substantially elevated in the third cat although its blood lead concentration had returned to normal and all clinical signs of lead toxicity had resolved. It was determined that the predominant form of protoporphyrin present in cats with lead toxicity was zinc protoporphyrin. The EPP assay may have limited value in the diagnosis of acute lead toxicity and in monitoring the success of chelation therapy in cats.

Animals↗
PubMed1992

Blood flow changes in the dental pulp during limited exercise measured by laser Doppler flowmetry.

The effect of limited exercise on pulpal blood flow was assessed by laser Doppler flowmetry (LDF). The primary aim of the investigation was to determine whether clinically significant changes could be induced by mild exercise when LDF was used to monitor pulpal blood flow. Blood flow readings were obtained from the coronal pulps of 17 upper central incisor teeth of 10 human volunteers before, during and after limited exercise. Readings were also obtained from the adjacent attached gingivae. Pulse rate was recorded concurrently. Pulpal blood flow was found to vary during exercise, with a mean percentage change of 38% from the level at rest; the range was from a 100% decrease to a 200% increase. The mean percentage increase in gingival blood flow was 65%, with a range of 6-300%. The main indication that blood flow was being assessed was the pulsatile nature of the output. Results were compared only within individual teeth. The pulse rate increased during exercise (mean percentage increase 54%, range 11-98%). There was no direct relationship between increased pulse rate and pulpal blood flow. It was evident that the mechanisms controlling pulpal and gingival blood flows differed. Laser Doppler flowmetry readings were only reproducible in individual teeth provided that the patient was at rest, and this should be taken into account in clinical or research measurements.

Adolescent↗
PubMed1992

Bioavailability and bioinequivalence of drug formulations in small animals.

Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine. Although comparable bioavailability ('bioequivalence') is though to ensure comparable clinical effectiveness and safety ('therapeutic equivalence'), the relationship between bioinequivalence and therapeutic inequivalence is less clear. Thus the prevalence of clinically important differences in bioavailability is unknown. While similar concerns have arisen about drug products used in small animal practice, there have been few investigations and some earlier reports are incomplete. However, there are indications of bioinequivalence with enteral formulations of ampicillin, aspirin, chloramphenicol, digoxin, mitotane, oxytetracycline, penicillin V and theophylline. Other studies have suggested bioequivalence with enteral formulations of chloramphenicol, digoxin, phenytoin, oxytetracycline and thyroxine. Limited data for injectable preparations showed bioinequivalence with chloramphenicol and possibly oxytetracycline. There is no reason to expect formulation-related bioinequivalence to be less prevalent in veterinary than in human medicine. Indeed, it may be more common in veterinary practice because other potential influences on bioavailability (food, diseases, other drugs, etc.) are frequently ignored, and cheaper generic products are often favoured for economic reasons.

Animals↗
PubMed1991

Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

Adult↗
PubMed1990

Vitamin K-dependent multifactor coagulopathy in Devon Rex cats.

A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.

Animals↗
PubMed1989

Investigations of bone marrow dyscrasia in a poodle with macrocytosis.

A poodle-type dog with bone marrow dyscrasia and macrocytosis was investigated by clinicopathological, cytological and ultrastructural means. Peripheral blood analysis revealed macrocytosis and the presence of nucleated erythroid cells, some with nuclear/cytoplasmic asynchrony. Tendencies towards neutropenia and granulocytic hypersegmentation were observed. Bone marrow examination revealed low normal myeloid to erythroid ratio, the presence of megaloblasts and some giant metamyelocytes. In addition, there were abnormal mitoses, binuclearity and multinuclearity, incomplete nuclear membranes and nuclear clefts, intracytoplasmic parallel-sided membranes and apparent degenerate erythroid cells. Blood biochemical tests indicated normal to high concentrations of serum vitamin B12, serum folate and red cell folate. Transcobalamin I/IIIB12-binding capacity was similar to values for normal dogs, but transcobalamin II-binding capacity appeared high. It was concluded that the condition had similarities to both congenital dyserythropoietic disorders and true megaloblastic conditions, but until further investigations are reported it might be wise to refer to it as "bone marrow dyscrasia" in poodles.

Animals↗
PubMed1989

Pharmacokinetics and metabolism of sulphadimidine in kids at 12 and 18 weeks of age.

The pharmacokinetics and metabolism of sulphadimidine (SDM) following intravenous administration of 100 mg/kg were studied in seven dwarf preruminant kids at 12 weeks of age, and again at the ruminant stage, when the animals were 18 weeks old. The persistence of SDM in 18-week-old kids was prolonged in comparison to the 12-week-old animals: a lower total body clearance and a prolonged elimination of SDM were obtained in the older animals. The renal clearance values of SDM and its metabolites were the same at both ages. The decrease of SDM clearance is related to the significant reduction in SDM hydroxylation at the older age. The reduced oxidative hepatic metabolism may result from the sexual maturation of the kids.

Age Factors↗
PubMed1989

Fat malassimilation in three cats.

Three cats were thin despite eating well. Steatorrhoea was confirmed in each by 72-hour fat assimilation tests. Fat digestibility in all 3 increased twofold when the diet was supplemented with pancreatic enzymes, suggesting the possibility of exocrine pancreatic insufficiency. However, examination of stained faecal smears gave evidence of both maldigestion and malabsorption of fat, without maldigestion of starch, and only one case had indications of protein maldigestion. In the latter cat, fat digestibility normalised with pancreatic enzyme supplementation and exocrine pancreatic insufficiency was considered likely. However, at post-mortem examination enteropathy and pancreatitis, but not exocrine pancreatic insufficiency, were found. The cause of fat malassimilation in these cats was unknown. The evaluation of malassimilation in cats is difficult because investigative tests used in other species are either unsuitable or have not been evaluated in cats.

Animals↗
PubMed1989

Chronic renal disease in bull terriers.

Chronic renal failure was diagnosed in 15 Bull terrier dogs. The dogs ranged in age from one to 8 years. History and clinical findings typically included lethargy, anorexia, polyuria, polydipsia and weight loss. Affected dogs were azotaemic, had elevated serum phosphate and cholesterol, and proteinuria was apparent in all dogs tested (13/13). The concentration of urine was consistently in the nil to minimally concentrated range (specific gravities 1.011-1.017). In those dogs necropsied, both kidneys were approximately two-thirds normal size, tough in consistency, with a pale cortex and a finely nodular capsular surface. Histologically, there was marked nephron loss, diffuse interstitial fibrosis and focal dense radial fibrosis which was especially evident in the renal medulla. Tubular dilation was widespread with focal mineralisation of tubular epithelium and adjacent basement membranes. Glomeruli were often shrunken and segmentally fibrotic. Some Bowman's spaces were extremely dilated. Many less severely affected glomeruli had thickened basement membranes.

Animals↗