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S Heffernan

Publications and source records attributed to S Heffernan.

10 recordsLinked to original sources
PubMed1996

Changes of extracellular matrix in a baboon (Papio hamadryas) model of insulin dependent diabetes: studies using electron microscopy and X-ray diffraction techniques.

Extracellular matrix plays an important role in many physiological functions and its abnormalities are thought to play a key role in the pathogenesis of diabetic complications. In this paper we used the techniques of electron microscopy, immunostaining and X-ray diffraction to document some of the early events in the changes of extracellular matrix in a model of insulin dependent diabetes in baboons. Our results show that thickening of basement membrane and enlargement of mesangium are demonstrable in the glomeruli of prepubertal diabetic baboons within 2 years from the onset of diabetes. Concomitant with this was the accumulation of type IV collagen and laminin in the mesangium. By contrast, even the very sensitive technique of X-ray diffraction failed to demonstrate changes in the equatorial direction of collagen molecules of the skin and tendon. We conclude that changes of glomerular extracellular matrix are demonstrable early in insulin dependent diabetes even in prepubertal baboons. These can be used as endpoints in evaluating the efficacy of pharmacological agents such as aminoguanidine in preventing diabetic complications.

Animals↗
PubMed1995

A baboon (Papio hamadryas) model of insulin-dependent diabetes.

Over a period of four years, streptozocin has been used to induce diabetes in 10 baboons, all of whom are insulin dependent. We describe our experience with their husbandry, induction of diabetes, insulin therapy, metabolic control and growth rate. Streptozocin dosage of 60 mg/kg readily induces hyperglycemia with minimal hepatic or renal toxicity. Using a once daily injection of mixed short and intermediate acting insulins at a dosage of 2-4 U/kg, it is possible to maintain a degree of metabolic control similar to that attained in patients.

Aging↗
PubMed1993

Fine needle aspiration cytology of thyroid nodules: review of 36 months experience.

Studies suggest that fine needle aspiration of thyroid nodules is a sensitive and specific tool for the detection of thyroid cancers thus preventing unnecessary operations. This technique was introduced in our institution in 1987 and performed where indicated under strictly defined criteria. We reviewed the aspirates performed over a 36 month period to critically evaluate the role of this procedure. Review was limited to F.N.A.s of nodules considered to be potentially malignant by conventional criteria and hence all the following criteria needed to be fulfilled: (1) solitary or dominant nodules in a multinodular goitre, (2) cold on isotope scanning, (3) solid or complex cystic nodule on ultrasonography. During the period May 1987 to May 1990 88 aspiration procedures were performed on 77 patients. 93% of the 77 patients had adequate aspirates and of these approximately 30% were considered suspicious or malignant. The overall resection rate was 23.4% which is approximately one third of the rate expected should suspicion have been based solely on conventional imaging criteria. The yield of neoplasia (adenoma and carcinoma) at resection was 89%. We found FNA to be a very useful adjunct in the management of nodular thyroid disease when used in conjunction with clinical laboratory and radiological evaluation. It is safe, inexpensive and provides useful additional information towards making appropriate decisions in an area beset with uncertainty.

Biopsy, Needle↗
PubMed1991

Changes in hepatic glutathione metabolism in diabetes.

Glutathione is important in the regulation of the redox state, and a decline in its tissue level has often been considered to be indicative of increased oxidative stress in diabetes. In this study of diabetic rats, the level of hepatic glutathione was normal unless food intake was restricted. Thus, the previous report of a reduction in hepatic glutathione in diabetes is likely to be the result of food deprivation rather than diabetes alone. In contrast to changes characteristic of oxidative stress, the efflux of glutathione in bile from diabetic animals was significantly decreased, whereas hepatic mixed disulfides were unchanged, and the hepatic gamma-glutamyltransferase activity was considerably increased. These changes were not reproduced by food deprivation. The decrease in biliary excretion of glutathione in diabetes may reflect an attempt to conserve glutathione by activation of the hepatic gamma-glutamyl cycle. We conclude that the disturbances of glutathione metabolism in diabetes are not typical of those seen in oxidative stress or food restriction.

Animals↗
PubMed1991

Interaction of ascorbic acid and glucose on production of collagen and proteoglycan by fibroblasts.

Collagen and proteoglycans are two major constituents of the extracellular matrix, and their abnormalities have been incriminated in the pathogenesis of diabetic complications. A decrease of plasma ascorbic acid has been reported in diabetes and thus may play a role in the collagen and proteoglycan abnormalities in diabetes. Ascorbic acid and glucose share structural similarity, and their metabolism may interact at the level of membrane transport and cellular action. In this study, we used a fibroblast culture system to explore this possibility. Ascorbic acid increased collagen and proteoglycan both in the culture medium and the cell layer. This stimulatory action of ascorbic acid was inhibited by the presence of glucose at a concentration of 25 mM. The effect of high glucose concentration was not mediated by inhibition of ascorbic acid uptake by fibroblasts. Insulin is able to abolish this inhibitory action of glucose on collagen production, but the precise mechanism is unclear. These results show that the high glucose concentration in diabetes can impair the action of ascorbic acid at the cellular level. This may further accentuate the problem of decreased availability of this vitamin as a result of its low plasma concentration.

Amino Acids↗
PubMed1990

Abnormalities of ascorbic acid metabolism and diabetic control: differences between diabetic patients and diabetic rats.

Ascorbic acid is required in the synthesis of collagen and is also an important anti-oxidant. In a previous study, plasma ascorbic acid concentration was found to be decreased in diabetic patients but there was no relationship with blood glucose level. In the current study of diabetic patients, both plasma ascorbic acid and its urinary excretion correlated inversely with glycosylated hemoglobin level. Plasma ascorbic acid was also lower in diabetic rats but urinary ascorbic acid was elevated. The divergent trend in urinary ascorbic acid excretion observed in diabetic patients and diabetic rats may be due to difference in the ability of these two species to synthesize ascorbic acid. Difference in renal reabsorption of ascorbic acid may also be a relevant factor. The lower plasma and urinary ascorbic acid levels in diabetic patients with more severe hyperglycaemia indicates that this group of patients is particularly at risk of developing deficiency of this vitamin. As ascorbic acid has many important functions in the body, it may be necessary to supplement this vitamin in patients with chronically poorly controlled diabetes.

Adult↗
PubMed1989

Ascorbic acid metabolism and polyol pathway in diabetes.

It has been reported previously that the plasma concentration of ascorbic acid (AA) is reduced in streptozocin-induced diabetic rats and can be normalized by treatment with the aldose reductase inhibitor tolrestat. This study was designed to investigate further the relationship between the polyol pathway and AA metabolism in diabetic rats. Disturbance of AA metabolism was demonstrable after 1 wk of diabetes. Dietary myo-inositol supplementation was effective in normalizing plasma AA levels, as was treatment with tolrestat. In untreated diabetes, despite low plasma AA concentration, there was increased urinary excretion of AA that was reversed by treatment with either tolrestat or myo-inositol. In contrast, AA supplementation normalized plasma AA concentrations while further increasing urinary AA excretion. The abnormality of AA metabolism was less severe in galactose-fed rats, which had normal plasma AA levels and only minor increases in urinary AA excretion. These studies demonstrated a disturbance in the regulation of plasma and urinary AA concentration in experimental diabetes and confirmed the relationship of AA with the polyol pathway. Because AA has many important biological functions, abnormalities of AA metabolism could be important in the pathogenesis of some diabetic complications. The interaction of the polyol and AA pathways suggests that this could be another site of action for aldose reductase inhibitors.

Aldehyde Reductase↗
PubMed1988

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities.

The plasma and tissue concentration of ascorbic acid (AA) is reduced in diabetes. This study was designed to investigate the mechanism and significance of this phenomenon. The low plasma AA concentration of diabetic rats can be normalized by dietary AA supplement (20-40 mg/day), a dosage approximately equal to the maximal synthetic rate of this substance in the rats. Treatment of diabetic rats with this regime prevented the decrease in activity of granulation tissue prolyl hydroxylase (PRLase), an AA-dependent enzyme required for maintaining the normal properties of collagen. The decreased plasma AA concentration and granulation tissue PRLase activity in diabetes can also be normalized by the aldose reductase inhibitor tolrestat. We conclude that in diabetic animals there is a true deficiency of AA that may be responsible for some of the changes of collagen observed in diabetes. Treatment with AA or an aldose reductase inhibitor may prevent some of the diabetic complications with underlying collagen abnormalities.

Aldehyde Reductase↗