Biomedical subjects

S McLennan

Publications and source records attributed to S McLennan.

At least 19 recordsLinked to original sources

PubMed2004

Pancam multispectral imaging results from the Opportunity Rover at Meridiani Planum.

Panoramic Camera (Pancam) images from Meridiani Planum reveal a low-albedo, generally flat, and relatively rock-free surface. Within and around impact craters and fractures, laminated outcrop rocks with higher albedo are observed. Fine-grained materials include dark sand, bright ferric iron-rich dust, angular rock clasts, and millimeter-size spheroidal granules that are eroding out of the laminated rocks. Spectra of sand, clasts, and one dark plains rock are consistent with mafic silicates such as pyroxene and olivine. Spectra of both the spherules and the laminated outcrop materials indicate the presence of crystalline ferric oxides or oxyhydroxides. Atmospheric observations show a steady decline in dust opacity during the mission. Astronomical observations captured solar transits by Phobos and Deimos and time-lapse observations of sunsets.

Atmosphere↗

PubMed2004

Basaltic rocks analyzed by the Spirit Rover in Gusev Crater.

The Spirit landing site in Gusev Crater on Mars contains dark, fine-grained, vesicular rocks interpreted as lavas. Pancam and Mini-Thermal Emission Spectrometer (Mini-TES) spectra suggest that all of these rocks are similar but have variable coatings and dust mantles. Magnified images of brushed and abraded rock surfaces show alteration rinds and veins. Rock interiors contain </=25% megacrysts. Chemical analyses of rocks by the Alpha Particle X-ray Spectrometer are consistent with picritic basalts, containing normative olivine, pyroxenes, plagioclase, and accessory FeTi oxides. Mössbauer, Pancam, and Mini-TES spectra confirm the presence of olivine, magnetite, and probably pyroxene. These basalts extend the known range of rock compositions composing the martian crust.

Extraterrestrial Environment↗

PubMed2004

Pancam multispectral imaging results from the Spirit Rover at Gusev Crater.

Panoramic Camera images at Gusev crater reveal a rock-strewn surface interspersed with high- to moderate-albedo fine-grained deposits occurring in part as drifts or in small circular swales or hollows. Optically thick coatings of fine-grained ferric iron-rich dust dominate most bright soil and rock surfaces. Spectra of some darker rock surfaces and rock regions exposed by brushing or grinding show near-infrared spectral signatures consistent with the presence of mafic silicates such as pyroxene or olivine. Atmospheric observations show a steady decline in dust opacity during the mission, and astronomical observations captured solar transits by the martian moons, Phobos and Deimos, as well as a view of Earth from the martian surface.

Atmosphere↗

PubMed2000

Functional and structural abnormalities in the nerves of type I diabetic baboons: aminoguanidine treatment does not improve nerve function.

AIMS/HYPOTHESIS: To improve understanding of the pathophysiology of diabetic neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of the formation of advanced glycation end products) on nerve function. METHODS: Male baboons (Papio hamadryas) were assigned to four groups; control, diabetic, control and diabetic treated with aminoguanidine. Diabetes was induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminoguanidine (10 mg/kg) were injected subcutaneously daily. Motor and sensory nerve conduction velocity was measured using standard techniques. Autonomic function was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5.5 years) along with their age-matched controls. RESULTS: The diabetic groups were smaller in size with a mean HbA1c of 8.9 +/- 1.2%. The nerve conduction velocity and heart rate response was reduced in the diabetic groups. Morphometric analysis of the diabetic sural nerve showed smaller axon diameter (2.99 +/- 0.06 microns vs 3.29 +/- 0.06 microns; p < 0.01) accompanied by thinner myelin (1.02 +/- 0.02 microns vs 1.15 +/- 0.02 microns, p < 0.01) with no change in the axon density. Treatment with aminoguanidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contrary to the studies in rats. CONCLUSIONS/INTERPRETATION: These results show that the primate is a good model to study diabetic neuropathy and suggest that the accumulation of advanced glycation end products are not an early mechanism of nerve damage in this disorder.

Aging↗

PubMed1998

Topical plus subconjunctival anesthesia for phacotrabeculectomy: one year follow-up.

PURPOSE: To evaluate the results of topical plus subconjunctival anesthesia for phacotrabeculectomy surgery and postoperative glaucoma control over 1 year. SETTING: Pacific Eye Center, Brisbane, Australia. METHODS: In this retrospective study of consecutive patients with glaucoma and cataract, topical plus subconjunctival anesthesia was used for combined phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy (phacotrabeculectomy). Patients with proliferative diabetic retinopathy or neovascular glaucoma were excluded. RESULTS: Thirty-eight eyes had phacotrabeculectomy using topical plus subconjunctival anesthesia over 2 years. Patients reported no discomfort intraoperatively or postoperatively, and none required intravenous sedation. Eighty-one percent of patients achieved a best corrected visual acuity of 20/40 or better 6 months after surgery. Mean drop in intraocular pressure (IOP) was 5.91 mm Hg at 3 months and 5.86 mm Hg at 12 months, at which time IOP was controlled without additional medication in 72% of patients. There were no serious complications postoperatively. CONCLUSION: In this series, no patient reported intraoperative or postoperative discomfort and surgical results were excellent in terms of visual outcome and IOP control.

Administration, Topical↗

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↗

PubMed1990

The effects of dietary n - 3 fatty acid in animal models of type 1 and type 2 diabetes.

We studied the incorporation of dietary n - 3 fatty acids from marine oils into red cell membranes, using animal models of type 1 diabetes (streptozotocin-treated Wistar rats) and type 2 diabetes (gold-thioglucose-injected CBA/T6 mice). In type 1 diabetic rats, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were higher following marine oil supplementation, and the increase in EPA was significantly greater than in non-diabetic animals (3.4 +/- 1.4% vs. 0.8 +/- 1.6%). Marine oil supplementation also resulted in higher levels of EPA and DHA in mice, but the increases were quantitatively similar with and without type 2 diabetes. Improvement in glycosylated haemoglobin following n - 3 fatty acid feeding was only found in type 2 diabetes (6.5 +/- 2.9% vs. 9.5 +/- 1.2%). This was associated with a higher plasma insulin concentration (170 +/- 40 vs. 136 +/- 41 mU/ml). The theory that n - 3 fatty acids improve insulin sensitivity would have predicted a decrease in plasma insulin levels. Our results suggest that n - 3 fatty acids may modify insulin secretion.

Animals↗

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↗

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↗

PubMed1986

The prevention and reversibility of tissue non-enzymatic glycosylation in diabetes.

The time course of non-enzymatic glycosylation (NEG) of liver, kidney, tail collagen, and haemoglobin was studied in diabetic rats. Increased NEG of liver, kidney, and collagen was detectable within 4 weeks of diabetes. The abnormal NEG of liver, kidney, and haemoglobin present after 4 weeks of untreated diabetes could be normalized by 4-8 weeks of intensive insulin therapy given by continuous subcutaneous infusion. However, the same treatment was ineffective in reversing the abnormal NEG and thermal stability of tail collagen. The differences in the development and reversibility of these tissue changes may be due to different tissue turnover rates. Insulin therapy, given from the onset of diabetes, was effective in preventing the development of collagen abnormalities. This suggests that early and vigorous treatment of diabetes is necessary to prevent collagen changes which are potentially irreversible.

Animals↗

PubMed1986

Abnormalities of granulation tissue and collagen formation in experimental diabetes, uraemia and malnutrition.

The formation of granulation tissue and collagen was studied in rats made diabetic with streptozotocin. Granulation tissue was harvested from the inside of steelmesh cylinders implanted in the back of diabetic and control animals. Four weeks after implantation there was a reduction in the quantity of granulation tissue and its collagen content in diabetic animals compared to controls. Rats with renal failure or malnutrition but no diabetes also formed less granulation tissue but in these animals the content of collagen in the granulation tissue was normal. These results suggest that the decrease of collagen, but not granulation tissue, in diabetes is a relatively specific phenomenon which was not due to the toxic effects of streptozotocin as the changes were prevented by insulin treatment. The hydroxyproline/proline ratio of diabetic collagen was found to be normal, excluding defective hydroxylation of proline as an important factor in the reduction of collagen in diabetes. Treatment with an aldose reductase inhibitor did not prevent the abnormalities of granulation tissue and collagen in diabetes, making it unlikely that increased activity of this enzyme played an important pathogenetic role. The observed reduction of granulation tissue mass and collagen content in diabetes may be important factors in the impairment of wound healing in diabetes.

Aldehyde Reductase↗

PubMed1985

The effects of cyclooxygenase and lipoxygenase inhibitors on the collagen abnormalities of diabetic rats.

The importance of cyclooxygenase and lipoxygenase pathways in the determination of collagen abnormalities in diabetes was investigated. Pharmacological agents with antiprostaglandin activity, such as indomethacin, naproxen, and aspirin, were able to prevent the rise in thermal rupture time of tail collagen in diabetic rats. Paracetamol was without effect. The action of indomethacin on diabetic collagen was abolished by concurrent administration of sodium benoxaprofen, an inhibitor of lipoxygenase, to the diabetic rats. Collagen abnormalities in diabetes may be regulated by a balance of the cyclooxygenase and lipoxygenase pathways. Antiprostaglandin agents may have a role in the prevention of some diabetic complications.

Acetaminophen↗

PubMed1984

The effect of salicylates on nonenzymatic glycosylation and thermal stability of collagen in diabetic rats.

The effects of glucose on the nonenzymatic glycosylation and thermal rupture time of rat tail collagen were examined by (1) in vitro incubation of collagen fibers in glucose and (2) in vivo in diabetic rats. In vitro, glucose caused a dose-dependent rise in both nonenzymatic glycosylation and thermal rupture time and there was a good correlation between these two parameters (r = 0.68, P less than 0.0001). Aspirin, a known inhibitor of nonenzymatic glycosylation, was effective in preventing the glucose-induced rise in nonenzymatic glycosylation and thermal rupture time when present at concentrations of 0.78, 1.56, and 3.12 mM. Sodium salicylate at concentrations of 1.56 and 3.12 mM was also effective. In vivo, the nonenzymatic glycosylation and thermal rupture time of collagen fibers were both increased by 2-3-fold in rats with streptozotocin-induced diabetes of 4 wk duration. Aspirin or sodium salicylate treatment for 4 wk (240 mg/kg/day) from the onset of diabetes was able to prevent the rise in thermal rupture time without affecting nonenzymatic glycosylation of collagen or glycosylated hemoglobin levels. Aspirin or sodium salicylate treatment did not have detectable effect on properties of collagen in normal rats. The in vitro findings are consistent with the hypothesis that nonenzymatic glycosylation leads to the increased thermal stability of collagen fibers. The significance of nonenzymatic glycosylation in vivo is less certain, as thermal rupture time can be altered independently. The action of aspirin and sodium salicylate in vivo suggests new therapeutic options in the prevention and treatment of diabetic complications.

Animals↗

PubMed1983

Non-enzymatic glycosylation of tissue protein in diabetes in the rat.

Non-enzymatic glycosylation of tissue and haemolysate proteins has been studied in normal and diabetic rats by reduction with tritiated sodium borohydride (NaB3H4) alone or in combination with chromatography on m-aminophenylboronic acid coupled to Biogel P-6. With NaB3H4 reduction alone, there was a linear relationship between plasma glucose and tritium incorporation into haemolysate protein. However, increased non-enzymatic glycosylation of tissue protein could not be demonstrated with NaB3H4 reduction alone. Tritiated glycosylated amino acids could be selectively removed by m-aminophenylboronic acid immobilized on Biogel P-6, then eluted by acidification and the radioactivity in the acidic peak used to estimate non-enzymatic glycosylation. Using the combined techniques, an increase in non-enzymatic glycosylation was observed in heart, kidney and liver obtained from rats with diabetes of 18 weeks duration.

Animals↗

PubMed1983

The thermal stability of collagen in diabetic rats: correlation with severity of diabetes and non-enzymatic glycosylation.

The thermal stability of collagen fibres from rat tail tendon was studied in both normal and diabetic rats. Results were correlated with the age of the animals, glycosylated haemoglobin level and the degree of non-enzymatic glycosylation of the collagen. Age was found to be the most important single determinant of the thermal rupture time of collagen fibres (r = 0,87, p less than 0.005). Thermal rupture time was also increased in diabetes and showed good correlation with glycosylated haemoglobin (r = 0.69, p less than 0.005) and non-enzymatic glycosylation of collagen (r = 0.51, p less than 0.005). The correlation of glycosylated haemoglobin level and thermal rupture time was significant, independent of age and non-enzymatic glycosylation of collagen. Experiments in vitro showed that incubation of collagen fibres with glucose increased the thermal stability of collagen. These results demonstrated an independent effect of severity of diabetes on the physical properties of collagen. The role of non-enzymatic glycosylation in causing the changes in collagen properties in diabetes remains to be fully elucidated.

Aging↗