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Biomedical subjects

R J Barnard

Publications and source records attributed to R J Barnard.

At least 73 records · Page 4Linked to original sources

Effects of a high fat-sucrose diet on cortical bone morphology and biomechanics.

High fat-sucrose (HFS) diets can reportedly produce glucose intolerance and hyperinsulinemia that may indirectly have deleterious effects on bone. The effects of a high-fat diet on calcium absorption, bone calcium content, and bone mechanical properties, however, remain controversial. Thus, we examined the morphological and biomechanical adaptations in limb bones of rats that were fed a HFS diet. Female Sprague-Dawley rats (8 weeks old) were randomly assigned to two groups, either a control group (n = 9) fed a standard diet (low-fat complex-carbohydrate) or an experimental group (n = 9) fed a HFS diet for 10 weeks. The right tibia and second metatarsus (MT) were fractured in three-point bending, and contralateral bones were used for morphological and histological analyses. HFS tibias had significantly lower maximum load and failure energy, and tensile stress at the proportional limit for both HFS tibia and MT was significantly less than controls. In addition, the elastic modulus and density of the HFS MT was significantly lower than controls. Geometry of the tibial mid-diaphysial cross section did not differ for the two diets, but the cortical cross-sectional area of HFS MT increased significantly compared to control MT. The total number of osteons in the mid-diaphysis of HFS MT decreased, but tibial and MT porosities did not change with the HFS diet. Our results suggest that the deleterious effects of the HFS diet may be more related to changes in the material properties of the cortical bone rather than to osteoporotic changes in the bone.

Animals↗

Dietary regulation of fibrinolytic factors.

W examined the short-term effects of a high-complex carbohydrate, low fat diet on the plasmin-dependent fibrinolytic pathway. A population of 27 adult American Caucasians exposed to the diet for 3 weeks showed highly significant reductions in the levels of plasminogen (P = 0.0001), tissue plasminogen activator (tPA) (P = 0.0001) and plasminogen activator inhibitor (tPAI) (P = 0.0017). Fibrinogen levels also decreased, but the changes did not reach statistical significance (P = 0.07). In contrast, the levels of the Lpa(a) lipoprotein, a potential inhibitor of fibrinolysis, remained remarkably constant despite a marked decrease in the levels of apolipoprotein B, a major constituent of Lp(a). Correlations between the levels of tPA, tPAI and plasma triglyceride were observed among the individuals both before and after the dietary challenge. Although the mechanisms responsible for the effects are unknown, the dramatic responsiveness of the thrombolytic pathway to dietary challenge is likely to be of importance in understanding the etiology of coronary artery disease and other vascular disorders.

Apolipoproteins↗

Accuracy in staging carcinoma of the bladder by magnetic resonance imaging.

Thirty-four patients with a presumptive diagnosis of carcinoma of the bladder diagnosed at EUA and cystoscopy have been staged by MRI and the findings correlated with pathology in 15 patients and clinical follow-up, including repeat cystoscopy, in the remainder. MRI is accurate in identifying tumours confined to the bladder wall or extending beyond the wall to involve perivesical fat or adjacent organs. Whilst it is not possible to distinguish between T1, T2 or early T3a tumours they can be distinguished from advanced T3a lesions and this may affect management. MRI is superior to clinical staging, particularly in detecting lymphadenopathy and provides information for optimal radiotherapy planning. The problem of distinguishing between the effects of radiotherapy and suspected recurrent tumour is discussed.

Aged↗

Structural and mechanical adaptations of immature trabecular bone to strenuous exercise.

Effects of strenuous exercise on immature bone were examined in two clinically important regions, femoral neck (FN) and lumbar vertebra (L6). Female Sprague-Dawley rats (n = 20, 8 wk of age, 150-170 g) were exercised progressively 5 days/wk for approximately 1 h/day for 10 wk at 75-80% of maximum oxygen capacity on a motor-driven treadmill. Caged age-matched rats served as controls (n = 20). Rat FNs were tested in cantilever bending, and vertebral bodies were compressed to 50% of their initial height at a fast strain rate. In response to the strenuous exercise, the relative area of the FN trabecular core increased significantly at the expense of the cortical shell. With that structural change, the exercised FN had significantly less energy to proportional limit than controls. The FN material properties (normal stresses at proportional limit and maximum) were significantly diminished after 10 wk of strenuous exercise. At the same time, no differences were found in vertebral geometry or structural and material properties. In the immature rate, the differential responses of the FN vs. L6 may relate to load history rather than a general systemic response to the strenuous exercise.

Adaptation, Physiological↗

Effects of streptozotocin-induced diabetes on glucose transport in skeletal muscle.

Female Sprague-Dawley rats were injected with streptozotocin (45 mg/kg) to induce mild diabetes (glucose, greater than 13 mM). Half of the animals received daily insulin injections to reduce hyperglycemia. After 10 weeks, sarcolemmal membranes were isolated from hindlimb muscles to study glucose transport, and the number of glucose transporters was assessed by cytochalasin-beta binding. Both glucose transport (19.2 +/- 1.6 vs. 31.93 +/- 3.29 pmol/mg protein.15 sec) and cytochalasin-beta binding (3.06 +/- 0.28 vs. 6.14 +/- 0.59 pmol/mg protein) were significantly (P less than 0.05) reduced in the diabetic untreated rats compared to control values. Daily insulin injections restored both (P less than 0.05) basal transport (33.22 +/- 3.62 pmol/mg protein.15 sec) and cytochalasin-beta binding (5.52 +/- 0.66 pmol/mg protein) to control levels. Maximum insulin stimulation (1 U/kg, iv) significantly increased (P less than 0.05) both glucose transport (30.18 +/- 3.76 vs. 96.48 +/- 4.21 pmol/mg protein.15 sec) and cytochalasin-beta binding (4.38 +/- 0.29 vs. 9.40 +/- 0.42 pmol/mg protein) in the untreated diabetic and control rats. However, the stimulation in the untreated diabetic rats only reached basal control levels, which was significantly (P less than 0.05) below the insulin-stimulated value for the controls. In the rats receiving daily insulin injections, maximum insulin stimulation increased (P less than 0.05) both glucose transport (58.67 +/- 15.24 pmol/mg protein.15 sec) and cytochalasin-beta binding (6.4 +/- 0.7 pmol/mg protein), but both transport and binding were significantly (P less than 0.05) below insulin-stimulated values for the control rats. These data show that insulin deficiency adversely affected the glucose transport system in skeletal muscle. Both basal and maximum insulin-stimulated transport and the number of transport molecules were reduced. Daily insulin treatment corrected some of the defects, but maximum insulin stimulation was still significantly below values for control animals.

Animals↗

Assessment of the nephron segments involved in post-obstructive diuresis in man, using lithium clearance.

The phenomena of post-obstructive diuresis and natriuresis have been studied using the lithium clearance technique in 10 patients with high pressure chronic retention. Following relief of obstruction there was a significant increase in both sodium and water excretion. There was a coincident reduction in the fractions of sodium and water reabsorbed in both proximal and distal nephron segments. This study demonstrates for the first time that following relief of chronic obstructive uropathy in man, changes in sodium and water excretion are due to altered handling in both proximal and distal nephron segments.

Aged↗

Exercise and insulin stimulate skeletal muscle glucose transport through different mechanisms.

This study was designed to examine the effects of acute exercise, insulin stimulation, and their combination on the kinetics of glucose transport in rat skeletal muscle. Sarcolemmal (SL) membranes were isolated from control (C), acute exercise (E), insulin-stimulated (I), and combined (E + I) rats. Michaelis-Menten kinetics indicated that the Vmax for glucose transport was increased after each perturbation compared with C but were not different from each other (E, 4,334 +/- 377; I, 4,424 +/- 668; E + I, 4,338 +/- 602; and C, 1,366 +/- 124 pmol.mg protein-1.s-1). The apparent Km was unchanged. Scatchard plots of cytochalasin B binding sites indicated that both I and E + I increased the number of binding sites compared both E and C (9.4 +/- 0.5 and 7.8 +/- 0.5 vs. 5.1 +/- 0.2 and 5.5 +/- 0.3 pmol/mg protein) without altering the dissociation constant. The increase in Vmax was greater than the increase in cytochalasin B binding sites indicating that both I and E + I caused an increase in the turnover rate of transport molecules as well as an increase in the total number of transport molecules. Because there was no change in the Km for glucose transport and no increase in cytochalasin B binding sites after exercise, the increase in Vmax was due solely to an increased turnover rate of existing transport molecules.

Animals↗

Beta-adrenergic receptors are not responsible for exercise stimulation of glucose transport.

This study was designed to examine whether the increased glucose transport after acute exercise in rat skeletal muscle is mediated via beta-adrenergic receptor stimulation. Sarcolemmal (SL) membranes were isolated from three groups: control (C), acute exercise (E), and exercise + propranolol (E+P). The acute exercise bout was performed on a treadmill and consisted of a 45-min run until near exhaustion. E+P received an intravenous propranolol injection (0.8 mg/kg) 10 min before the exercise session. Michaelis-Menten kinetics at 1.5 s indicated that the Vmax for glucose transport was increased after each perturbation compared with C but were not different from each other (E, 4,334 +/- 377; E+P, 4,824 +/- 357; and C, 1,366 +/- 124 pmol.mg protein-1.s-1). The apparent Km's were similar in all groups. Scatchard plots for the D-glucose inhibitable class of cytochalasin B binding sites indicated no differences in either the total number of binding sites in the SL vesicles (C, 5.5 +/- 0.3; E, 5.1 +/- 0.2, and E+P, 5.1 +/- 0.3 pmol/mg protein) or in their dissociation constant (Kd) (C, 46 +/- 3; E, 48 +/- 3; and E+P, 49 +/- 2 nM). The increase in Vmax for transport was similar between E and E+P, indicating that exercise does not stimulate glucose transport via the beta-adrenergic receptor.

Animals↗

Characterization of rat skeletal muscle sarcolemmal insulin receptors and a sarcolemmal insulin binding inhibitor.

When insulin receptors of rat skeletal muscle sarcolemmal vesicles were solubilized with Triton X-100, the specific binding of 125I-labeled insulin increased by more than 10-fold over that seen in the intact vesicles. Partial purification of the skeletal muscle insulin receptors on wheat germ agglutinin affinity columns increased the total insulin binding activity by 7-fold and reduced the Kd for insulin binding from 1.92 to 0.20 nM, suggesting that an inhibitor of insulin binding was removed by this purification step. This was confirmed when the unbound fractions of the affinity column were dialyzed and reconstituted with the insulin receptors. The inhibitory activity in the sarcolemmal extract could not be accounted for by the presence of Triton X-100. The skeletal muscle inhibitor was more potent in inhibiting insulin binding to skeletal muscle insulin receptors than to liver or adipose receptors. The inhibitor was very effective in inhibiting insulin binding to wheat germ agglutinin-purified IM-9 receptors, but had negligible effects on insulin binding to intact IM-9 cells. The properties of the alpha and beta subunits of the skeletal muscle insulin receptors appear to be the same as those of insulin receptors of other tissues: cross-linking of 125I-labeled insulin to the receptor revealed a band of 130,000 daltons, and insulin stimulated the phosphorylation of bands of 90,000 and 95,000 daltons in the receptor preparation. The skeletal muscle insulin binding inhibitor elutes from molecular sieves in a major 160,000-dalton peak and minor 75,000-dalton peak. The binding inhibitor is not inactivated by heat, by mercaptoethanol, or by trypsin, pepsin, or proteinase K. Collectively, these data suggest that the inhibitor may be a small molecule that aggregates with itself, with larger proteins, or with detergent micelles.

Adipose Tissue↗

Effect of low-fat, high-carbohydrate, high-fiber diet on fecal bile acids and neutral sterols.

The effect of a diet low in total fat and high in complex carbohydrates on the excretion of bile acids and neutral sterols and on serum lipids was studied in women, 46-47 years old, who were consuming a mixed Western diet. Participants kept an initial 3-day food record while consuming their normal diet (pre-diet period). During the dietary intervention period (experimental diet) which lasted for 26 days, all volunteers consumed a low-calorie, low-fat (less than 10% of total calories), high-fiber (37 g/day, high-carbohydrate diet. At the 1-year follow-up, the participants completed another 3-day food record, which indicates that these volunteers maintained their caloric and fat intake at levels slightly higher than the experimental diet, but lower than the pre-diet period. Individual 24-hr fecal samples for 2 days and blood samples were collected from the volunteers during each dietary period. Fecal samples were analyzed for neutral sterols and bile acids, and blood samples were analyzed to ascertain cholesterol and triglyceride levels. There were no significant differences in the excretion of neutral sterols between the dietary periods. Fecal secondary bile acids were significantly lower during the experimental and follow-up diet periods compared with the pre-test diet period. Serum cholesterol levels were significantly lower during the experimental and follow-up diet periods than during the pre-test diet period. These results suggest that switching from a high-fat, low-fiber diet to a low-fat, high-fiber diet can reduce the excretion of bile acids which are thought to be involved in the promotion of colon cancer.

Aged↗

Peripheral insulin sensitivity as modified by diet and exercise training.

To determine which component of a high-fat sucrose diet (HFS) caused insulin resistance and whether exercise training or fiber could prevent it, six dietary treatments were tested in rats: low-fat complex carbohydrate (LFCC); high-fat complex carbohydrate (HFCC); low-fat sucrose (LFS); high-fat sucrose (HFS); HFS plus fiber (HFS + F); and HFS plus exercise training (HFS + EX). After 10 wk rats were subjected to an intravenous glucose-tolerance test. The HFS and HFS + F groups developed glucose intolerance, as indicated by significantly greater areas under their glucose curves compared with the LFCC group's areas. The LFS, HFS, HFS + F, and HFS + EX groups developed insulin resistance, as indicated by significantly greater areas under their insulin curves compared with the LFCC and HFCC groups' areas. Either the presence of sucrose or the absence of complex carbohydrates, not high fat, was responsible for the insulin resistance and it was not improved by adding fiber to the diet or by exercise training.

Animals↗

The biphasic nature of renal functional recovery following relief of chronic obstructive uropathy.

Twenty-one patients with chronic obstructive uropathy due to high pressure chronic retention of urine underwent renal functional assessment both during the period of obstruction and repeatedly up to 3 months following its relief. Glomerular filtration rate (GFR) was determined using clearance of 99mTc-DTPA and iohexol. Creatinine, water, urea and electrolyte excretion was assessed from timed urine collections. Excretion of water, urea and electrolyte was normal during obstruction but increased dramatically immediately following relief (e.g. sodium 110 to 234 mmol/24 h). Values returned to normal by 2 weeks (sodium excretion 148 mmol/24 h). No further significant changes occurred up to 3 months. Mean 99mTc-DTPA and iohexol clearances during obstruction were 59.0 and 50.5 ml/min respectively. Following relief of obstruction, no significant improvement occurred at 2 weeks but did at 3 months (mean = 68.4 and 55.7 ml/min). Mean creatinine clearance during obstruction was 32.5 ml/min. This improved 2 days following relief to 46 ml/min. No further improvement was seen until 3 months (mean = 57.3 ml/min). It was concluded that recovery of renal function from obstructive injury occurs in two phases, an early tubular phase lasting up to 2 weeks and a later, predominantly glomerular phase, between 2 weeks and 3 months. There is some disparity between creatinine clearance and more accurate measurements of GFR which may be explained by tubular excretion of creatinine in the early phase of recovery.

Adult↗

Mechanism of insulin action on glucose transport in rat skeletal muscle.

This study was designed to examine the effect of insulin stimulation on glucose transport in rat skeletal muscle. Sarcolemmal vesicles (SL) were isolated from the gastrocnemius-plantaris and quadriceps muscles from insulin-stimulated and control groups. The insulin-stimulated group received an intravenous insulin injection (1 U/kg) 10 min before isolation. The early time course of specific D-glucose transport was linear through 2 s. Michaelis-Menten kinetics at 1.5 s indicated that the Vmax for glucose transport was increased after insulin stimulation compared with controls (4,424 +/- 668 vs. 1,366 +/- 124 pmol.mg protein -1.s-1), whereas the Km remained unchanged (19.4 +/- 0.6 vs. 21.6 +/- 3.1 mM). Scatchard plots for the D-glucose-inhibitable class of cytochalasin B binding sites indicated that insulin stimulation increased the number of binding sites in the SL vesicles (9.3 +/- 0.6 vs. 5.5 +/- 0.3 pmol/mg protein) without altering the Kd (48 +/- 3 vs. 46 +/- 3 nM). That the increase in Vmax was greater than the increase in cytochalasin B binding sites indicates that insulin stimulation caused an increase in the turnover rate of existing transport molecules as well as an increase in the total number of SL glucose transport molecules.

Animals↗

Reversible hypertension associated with unrecognised high pressure chronic retention of urine.

The cardiovascular effects of relief of obstruction were examined in 21 patients with painless urinary retention and hydronephrosis and hydroureter associated with hypertension (diastolic blood pressure 95-120 mm Hg, mean 107, 11 patients), severe peripheral oedema (8 patients), raised jugular venous pressure (5 patients), or clinical evidence of pulmonary oedema (5 patients). Before relief of obstruction fractional sodium excretion was appropriate for the reduced rate of glomerular filtration. After urethral catheterisation blood pressure fell (p less than 0.001) and the other cardiovascular abnormalities were rapidly reversed without further therapeutic measures. This improvement was associated with an increase (p less than 0.05) in both absolute and fractional urinary sodium excretion that was greatest at 24 h. 5% of patients undergoing surgery for obstructive disorders of the lower urinary tract have hydronephrosis and hydroureter. Hypertension related to chronic urinary tract obstruction may be the commonest form of surgically correctable renal hypertension.

Adult↗

Management of colovesical fistula.

The clinical presentation and management of 24 patients treated for colovesical fistula were reviewed. It is concluded that an aggressive investigative approach in the management of patients with suspected colovesical fistula is rewarding. Cystoscopy and barium enema appear to be the most useful investigative tools. Once found the fistulae should be managed surgically. Radical excision of the sigmoid colon with primary anastomosis is the treatment of choice and is accompanied by no mortality and a very low complication rate.

Adult↗

Effects of a low-fat, low-cholesterol diet on serum lipids, platelet aggregation and thromboxane formation.

The purpose of this study was to test the effects of a low-fat, low-cholesterol diet on serum lipids, platelet aggregation, thromboxane formation and blood pressure. Fifteen hyperlipidemic males with normal blood pressure were treated for 2 weeks. Resting supine blood pressure, total serum cholesterol, HDL-cholesterol, the ratio of total cholesterol/HDL-cholesterol and triglycerides all were significantly reduced. The maximum aggregation and velocity of aggregation for isolated platelets stimulated with either ADP or collagen was significantly reduced. Thromboxane formation during 5 min of platelet aggregation with collagen or ADP was also significantly reduced. These results have important implications for hypertension and atherosclerotic cardiovascular disease.

Blood Pressure↗