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Biomedical subjects

J R Turtle

Publications and source records attributed to J R Turtle.

At least 55 records · Page 3Linked to original sources
PubMed1989

Adrenal function in patients with active tuberculosis.

Although tuberculosis is a recognised cause of adrenal insufficiency, little is known about adrenal function in patients with active tuberculosis. Ninety Melanesian adults with active tuberculosis (30 pulmonary, 30 miliary, 30 extrapulmonary) had adrenal function assessed prospectively before and three to four weeks after starting antituberculous chemotherapy. Basal serum cortisol concentrations were normal in 55 (61%) and raised in 35 (39%) of the subjects. No patient had a low basal cortisol concentration. After Synacthen stimulation, cortisol responses were normal in 81 (92%) of the patients and subnormal in seven (8%). After antituberculous chemotherapy the response to Synacthen stimulation was normal in all but one patient. It is concluded that adrenal dysfunction is an uncommon problem in patients with active tuberculosis, and that, contrary to recent reports, antituberculous chemotherapy regimens that include rifampicin do not have an adverse effect on adrenal function.

Adrenal Glands↗
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

Chronic stimulation of human fetal pancreas with phorbol inhibits insulin secretion.

Acute exposure to agents that activate protein kinase C is known to cause insulin release both from the fetal and adult pancreas. These experiments were designed to test the effect of chronic exposure of the human fetal pancreas to such agents. Nine to twelve days after commencement of culture of this tissue, exposed to 0.165-1.3 microM 12-O-tetradecanoylphorbol-13-acetate, insulin secretion was reduced and remained less than that for controls thereafter. Exchange of the test for the control medium resulted in partial recovery of insulin release. Insulin content of the treated explants was also significantly reduced. The insulinogenic response to an acute challenge of either 20 mM glucose or 10 mM theophylline/2.8 mM glucose at the end of the culture was no different from that for controls.

Enzyme Activation↗
PubMed1988

Proteinuria and renal function in diabetic patients fed a diet moderately restricted in protein.

Protein restriction has been used in the treatment of renal disease and may also be beneficial in the management of diabetic nephropathy. We evaluated the effects of moderate protein restriction (0.6 g/kg ideal body weight per day) for a 3-mo period on renal function in seven diabetic patients. Moderate protein restriction led to a decrease of approximately 50% in the albumin excretion rate in patients with overt proteinuria or microalbuminuria. This decrease occurred in some patients without a decrease in glomerular filtration rate, renal plasma flow, or plasma albumin concentration and may reflect subtle changes in filtration properties or permeability of glomeruli. In this pilot study moderate protein restriction has marked effects on albumin excretion irrespective of the initial degree of renal impairment. It is therefore suitable for longer-term study of its effects on the progression of renal disease in both patients with overt and incipient diabetic nephropathy.

Adult↗
PubMed1988

Activators of protein kinase C stimulate insulin secretion from the human fetal pancreas.

The human fetal pancreas, like the adult pancreas, releases insulin in response to agents that increase intracellular levels of calcium and cyclic AMP. It differs from the adult pancreas in that glucose causes either minimal or no insulin secretion from it. Whether activation of protein kinase C will cause release of insulin from this immature cell, as it does from the adult pancreas, is unknown. This was the phenomenon examined in the experiments below. Activators of protein kinase C, 1.3 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) and 25.1 microM 1-oleoyl-2-acetylglycerol, caused significant release of insulin from cultured explants of human fetal pancreas. Lower concentrations of TPA--0.65 microM or less--had no such effect. Agents that are known to inhibit protein kinase C, 100 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, 2 mM polymyxin B, and 1 mM dibucaine, caused abolition of the insulinogenic effect of 1.3 microM TPA. Glucose, at 2.8, 5, and 10 mM, also inhibited the positive effect of TPA. However, when the concentration of glucose was increased to 20 or 30 mM, stimulation of insulin secretion returned to levels achieved with TPA alone. These levels were significantly higher than the minimal response achieved with 20 mM glucose. Such data support the involvement of protein kinase C activation in insulin secretion from the human fetal pancreas. It is postulated that this involvement may occur physiologically.

Enzyme Activation↗
PubMed1988

Recovery of human fetal pancreas after one year of implantation in the diabetic patient.

Between one and six cultured human fetal pancreata were allografted into five insulin-dependent diabetic recipients and their progress monitored for a year on each occasion. To prevent rejection the tissue was cultured for 1-3 weeks before transplantation, the HLA-DR antigens of the donor tissue were matched with those of the recipient when a single pancreas was used, and four of the recipients were immunosuppressed, three because of coexisting renal grafts. Graft function was observed transiently in one of the recipients. In three others human fetal pancreas was recovered 9-14 months after transplantation, although it was being slowly rejected during this time. Beta cells were present in the graft but did not function adequately to enable immunoreactive C-peptide to be measured in peripheral blood. The issues of rejection and immaturity of the human fetal pancreas will need to be surmounted if the potential of the human fetal pancreas to normalize blood glucose levels in diabetic man is ever to be realized.

C-Peptide↗
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↗
PubMed1988

Comparison of different models of diabetes care on compliance with self-monitoring of blood glucose by memory glucometer.

The modern management of diabetes relies heavily on self-monitoring of blood glucose (SMBG), and therefore SMBG records are an important source of clinical data for management decision making. The development of a memory Glucometer has provided the opportunity to verify the validity of glucose records thus generated and observe the effects of different educational approaches on compliance with SMBG. Thirty-four patients without previous experience of SMBG were randomized into one of the following experimental groups differing in the model of diabetes care: mutual decision making, didactic, and authoritarian. Patients, unaware of the memory capacity of the glucose meter, were required to perform four glucose measurements per day over a 14-day observation period. Patient-generated blood glucose records were then compared with objective records stored in the glucose-meter memory. Patients with gestational diabetes mellitus recorded a lower proportion of correct results (63 vs. 79%, P = .049) and exhibited a tendency to invent results with lower blood glucose levels (5.3 vs. 7.5 mM, P less than .0001) than the results omitted compared with patients with non-insulin-dependent diabetes mellitus. Predictors of greater validity of records were perceived intelligence of the subject (chi 2 = 4.56, P less than .02) and private health-insurance status (chi 2 = 4.52, P less than .04), whereas the experimental group assignment was not significant. These findings reflect potential motivational and sociodemographic limitations in the validity of SMBG recordings within the management and education of patients with gestational and nongestational diabetes.

Blood Glucose Self-Monitoring↗
PubMed1987

The activity of the pyruvate dehydrogenase complex in heart and liver from mice during the development of obesity and insulin resistance.

The amount of pyruvate dehydrogenase in the active form (PDHa) was increased 1.7-fold compared with controls in heart muscle of mice 1 week after induction of obesity with a single injection of gold-thioglucose. At 4 weeks post injection, the amount of PDHa was decreased to 32% of control, a value which was observed in later stages of the obesity syndrome. In contrast, liver PDHa was increased and remained at an increased activity during the development of obesity. Despite normal post-prandial serum insulin contents, liver membrane insulin-receptor numbers were decreased 1 week after gold-thioglucose injection, and there was no change in receptor affinity. The decrease in heart PDHa in the obese animals was reversed by a single dose of 2-tetradecylglycidic acid, but this inhibitor of mitochondrial fatty acid oxidation did not affect liver PDHa in these animals. These early and diverse changes in PDHa argue for a multifactorial aetiology in the development of the whole-body insulin resistance seen in older gold-thioglucose-treated obese animals.

Animals↗
PubMed1987

Effect of phorbol and glucose on insulin secretion from the human fetal pancreas.

It has been reported previously that 12-0-tetradecanoylphorbol-13-acetate is capable of stimulating the release of insulin from adult and neonatal pancreatic tissue. The data from this study show that this agent at a concentration of 1.3 uM, in the presence of 2.8 mM glucose, was unable to cause significant secretion of insulin from cultured human fetal pancreatic explants. By contrast 20 mM glucose was able to cause a small but significant immediate increase in secretion of insulin, but was unable to maintain this response beyond ten minutes. When the two agents were combined, a synergistic effect was seen throughout the entire 50 minute period of stimulation. The reason for this synergism is unclear since, whilst both secretagogues were able to cause a rise in the levels of diacylglycerol, together no extra effect was observed.

Arachidonic Acid↗
PubMed1987

Effects of experimental diabetes, uremia, and malnutrition on wound healing.

The strength of linear wounds was studied in normal and diabetic rats in the first 8 wk after wounding. The strength of wounds from diabetic animals was found to be reduced compared with normal controls but could be improved by insulin treatment, especially when excellent metabolic control was achieved. There appeared to be both quantitative and qualitative defects in the formation of wound tissues in diabetic animals, because wound strength was not normalized when the thinner skin of diabetic animals was taken into consideration. This was different from the findings in rats with renal failure or malnutrition: in these two conditions, wound strength appeared reduced but was normalized when adjusted for skin thickness. Increased activity of aldose reductase did not appear to be an important factor in the impairment of wound healing in diabetes, because wound strength was not corrected by treatment with sorbinil, an aldose reductase inhibitor. The precise mechanism of abnormal wound strength in diabetes remains to be studied further, but careful control of diabetes, maintenance of nutrition, and treatment of systemic illness are important factors in the promotion of wound healing.

Animals↗
PubMed1987

The effect of diet composition on weight gain and pyruvate dehydrogenase activity in heart muscle in the gold thioglucose obese mouse.

Pyruvate dehydrogenase complex activity is the major determinant of glucose oxidation in animal cells. Tissue glucose oxidation is reduced in obesity and states of insulin resistance and alternate fuels are utilized for energy and pyruvate dehydrogenase activity is reduced in cardiac muscle in obesity. The effect of four different diets (standard laboratory chow, high-carbohydrate, high-protein and high-fat) on weight gain, cardiac pyruvate dehydrogenase activity (PDHa) and serum insulin, glucose and free fatty acids was studied in the gold thioglucose obese mouse. All four diets produced significant weight gain in the gold thioglucose injected animal. Cardiac PDHa was influenced by both obesity and diet composition. The obese chow-fed animals had significantly reduced PDHa. On high-carbohydrate and high-protein feeding lean controls had a significant decrease in cardiac PDHa compared to chow-fed controls, but only in high-carbohydrate-fed animals was this further reduced by obesity. High-fat feeding produced a rapid and almost complete suppression of PDHa in both lean and obese animals. Serum insulin, glucose and free fatty acids were also affected by diet as well as obesity. The highest serum insulins were found in chow-fed obese animals whereas the highest serum glucoses were in high-carbohydrate-fed obese animals. Hyperinsulinaemia did not develop in the high-fat-fed obese animal, but the highest serum free fatty acids were found in high-fat feeding. It is concluded that both diet composition and obesity affect cardiac PDHa and therefore glucose utilization in this tissue. Insulin resistance in the acute stages of obesity development is also affected by diet composition.

Animals↗