Skeletal muscle GLUT-4 and postexercise muscle glycogen storage in humans

The purpose of this study was to examine the relationship between skeletal muscle GLUT-4 protein and postexercise glycogen storage in human subjects fed adequate carbohydrate. Eleven men completed 2 h of cycling, and a biopsy of the vastus lateralis was performed immediately after exercise cessation for the determination of muscle GLUT-4 protein and glycogen concentrations, glycogen synthase activity, and citrate synthase activity. The subjects ingested meals providing 2.0 g carbohydrate/kg body weight at 0, 2, and 4 h postexercise, and a second biopsy was performed 6 h postexercise. Muscle glycogen concentration increased significantly during the 6-h recovery period (glycogen immediately postexercise, 27.2 +/- 5.4 mmol/kg wet weight; glycogen storage, 52.4 +/- 2.9 mmol x kg wet weight-1 x 6 h-1; P<0.05). Glycogen storage during recovery was directly related to GLUT-4 protein (2.20 +/- 0.33 arbitrary standard units; r = 0.63; P<0.05) and inversely related to glycogen immediately postexercise (r = -0.70; P < 0.05). A direct correlation existed between glycogen storage during recovery and the activity of the I form of glycogen synthase (r = 0.60; P < 0.05). These results suggest that muscle GLUT-4 protein concentration, as well as factors relating to glucose disposal, may affect postexercise glycogen storage in humans fed adequate carbohydrate.     

Effect of epinephrine on muscle glycogenolysis during exercise in trained men

To test the hypothesis that an elevation in circulating epinephrine increases intramuscular glycogen utilization, six endurance-trained men performed two 40-min cycling trials at 71 +/- 2% of peak oxygen uptake in 20-22 degrees C conditions. On the first occasion, subjects were infused with saline throughout exercise (Con). One week later, after determination of plasma epinephrine levels in Con, subjects performed the second trial (Epi) with an epinephrine infusion, which resulted in a twofold higher (P < 0.01) plasma epinephrine concentration in Epi compared with Con. Although oxygen uptake was not different when the two trials were compared, respiratory exchange ratio was higher throughout exercise in Epi compared with Con (0.93 +/- 0.01 vs. 0.89 +/- 0.01; P < 0.05). Muscle glycogen concentration was not different when the trials were compared preexercise, but the postexercise value was lower (P < 0.01) in Epi compared with Con. Thus net muscle glycogen utilization was greater during exercise with epinephrine infusion (224 +/- 37 vs. 303 +/- 30 mmol/kg for Con and Epi, respectively; P < 0.01). In addition, both muscle and plasma lactate and plasma glucose concentrations were higher (P < 0.05) in Epi compared with Con. These data indicate that intramuscular glycogen utilization, glycolysis, and carbohydrate oxidation are augmented by elevated epinephrine during submaximal exercise in trained men.     

Effect of fluid ingestion on muscle metabolism during prolonged exercise

Five trained men were studied during 2 h of cycling exercise at 67% peak oxygen uptake at 20-22 degrees C to examine the effect of fluid ingestion on muscle metabolism. On one occasion, the subjects completed this exercise without fluid ingestion (NF) while on the other they ingested a volume of distilled deionized water that prevented loss of body mass (FR). No differences in oxygen uptake during exercise were observed between the two trials. Heart rate was lower (P < 0.01) throughout exercise when fluid was ingested, and rectal temperature after 2 h of exercise was lower (38.0 +/- 0.2 and 38.6 +/- 0.2 degrees C for FR and NF, respectively; P < 0.01), as was muscle (vastus lateralis) temperature (38.5 +/- 0.4 and 39.1 +/- 0.5 degrees C for FR and NF, respectively; P < 0.05). Resting muscle ATP, creatine phosphate, creatine, glycogen, and lactate levels were similar in the two trials, as were the postexercise ATP, creatine phosphate, and creatine levels. In contrast, muscle glycogen was higher (P < 0.05) and muscle lactate was lower (P < 0.05) after 2 h of exercise in FR compared with NF. Net muscle glycogen utilization during exercise was reduced by 16% when fluid was ingested (318 +/- 46 and 380 +/- 53 mmol/kg dry weight for FR and NF, respectively; P < 0.05). These results indicate that fluid ingestion reduces muscle glycogen use during prolonged exercise, which may account, in part, for the improved performance previously observed with fluid ingestion.     

Oral tolerance induction with altered forms of ovalbumin

The mechanism of insulin resistance in obesity was examined in ten obese (BMI 33 +/- 1 kg/m2) and nine lean (BMI 22 +/- 1 kg/m2) Caucasian women during a hyperglycemic-hyperinsulinemic clamp using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy to measure rates of muscle glycogen synthesis and intramuscular glucose-6-phosphate (G-6-P) concentrations. Under similar steady-state plasma concentrations of glucose (approximately 11 mmol/l) and insulin (approximately 340 pmol/l), rates of muscle glycogen synthesis were reduced approximately 70% in the obese subjects (52 +/- 8 micromol/[l muscle-min]) as compared with the rates in the lean subjects (176 +/- 22 micromol/[l muscle-min]; P < 0.0001). Basal concentrations of intramuscular G-6-P were similar in the obese and lean subjects; but during the clamp, G-6-P failed to increase in the obese group (deltaG-6-P obese 0.044 +/- 0.011 vs. lean 0.117 +/- 0.011 mmol/l muscle; P < 0.001), reflecting decreased muscle glucose transport and/or phosphorylation activity. We conclude that insulin resistance in obesity can be mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis due to a defect in glucose transport and/or phosphorylation activity.     

Effects of medium-chain triglyceride ingestion on fuel metabolism and cycling performance

On three occasions separated by 10 days, six endurance-trained cyclists rode for 2 h at 60% of peak O2 uptake and then performed a simulated 40-km time trial (T-trial). During the rides, the subjects ingested a total of 2 liters of a [U-14C]glucose-labeled beverage containing a random order of either 10% glucose [carbohydrate (CHO)], 4.3% medium-chain triglycerides (MCTs); or 10% glucose + 4.3% MCTs (CHO+MCT). Although replacing CHO with MCTs slowed the T-trials from 66.8 +/- 0.4 (SE) to 72.1 +/- 0.6 min (P < 0.001), adding MCTs to CHO improved the T-trials from 66.8 +/- 0.4 to 65.1 +/- 0.5 min (P < 0.05). Faster T-trials in the CHO+MCT trial than in the CHO trial were associated with increased final circulating concentrations of free fatty acids (0.58 +/- 0.09 vs. 0.36 +/- 0.06 mmol/l; P < 0.05) and ketones (1.51 +/- 0.25 vs. 0.51 +/- 0.07 mmol/l; P < 0.01) and decreased final circulating concentrations of glucose (5.2 +/- 0.2 vs. 6.3 +/- 0.3 mmol/l; P < 0.01) and lactate (1.9 +/- 0.4 vs. 3.7 +/- 0.5 mmol/l; P < 0.05). Adding MCTs to ingested CHO reduced total CHO oxidation rates from 14 +/- 1 to 10 +/- 1 mmol/min at 2 h and from 17 +/- 1 to 14 +/- 1 mmol/min in the T-trial (P < 0.01), without affecting the corresponding approximately 5 and approximately 7 mmol/min rates of [14C]glucose oxidation. These data suggest that MCT oxidation decreased the direct and/or indirect (via lactate) oxidation of muscle glycogen. A reduced reliance on CHO oxidation at a given O2 uptake is similar to an endurance-training effect, and that may explain the improved T-trial performances.     

Expression of granulocyte-macrophage colony-stimulating factor receptors in human prostate cancer

This investigation examined the effects of NaHCO3 loading on lactate concentration ([La]), acid-base balance, and performance for a 603. 5-m sprint task. Ten greyhounds completed a NaHCO3 (300 mg/kg body weight) and control trial in a crossover design. Results are expressed as means +/- SE. Presprint differences (P < 0.05) were found for NaHCO3 vs. control, respectively, for blood pH (7.47 +/- 0.01 vs. 7.42 +/- 0.01), HCO-3 (28.4 +/- 0.4 vs. 23.5 +/- 0.3 meq/l), and base excess (5.0 +/- 0.3 vs. 0.2 +/- 0.3 meq/l). Peak blood [La] increased (P < 0.05) in NaHCO3 vs. control (20.4 +/- 1.6 vs. 16.9 +/- 1.3 mM, respectively). Relative to control, NaHCO3 produced a greater (P < 0.05) reduction in blood base excess (-18.5 +/- 1.4 vs. -14.1 +/- 0.8 meq/l) and HCO-3 (-17.4 +/- 1.2 vs. -12.8 +/- 0.7 meq/l) from presprint to postexercise. Postexercise peak muscle H+ concentration ([H+]) was higher (P < 0.05) in NaHCO3 vs. control (158.8 +/- 8.8 vs. 137.0 +/- 5.3 nM, respectively). Muscle [H+] recovery half-time (7.2 +/- 1.6 vs. 11.3 +/- 1.6 min) and time to predose values (22.2 +/- 2.4 vs. 32.9 +/- 4.0 min) were reduced (P < 0.05) in NaHCO3 vs. control, respectively. No differences were found in blood [H+] or blood [La] recovery curves or performance times. NaHCO3 increased postexercise blood [La] but did not reduce the muscle or blood acid-base disturbance associated with a 603.5-m sprint or significantly affect performance.     

Importance of substrate changes in the decrease of hepatic glucose cycling during insulin infusion and declining glycemia in the depancreatized dog

We wished to determine whether the elevated glucose cycling (GC) between glucose and glucose-6-phosphate (G<-->G6P) in diabetes can be reversed with acute insulin treatment. In six insulin-deprived, anesthetized, depancreatized dogs, insulin was infused for 6-9 h at a starting dose of 45-150 pmol.kg-1.min-1 to normalize plasma glucose from 23.9 +/- 1.4 to 5.0 +/- 0.4 mmol/l and gradually decreased to and maintained at a basal rate (1.7 +/- 1.0 pmol.kg-1.min-1) during the last 3 h. GC, measured with [2-3H]- and [6-3H]glucose, fell markedly from 15.3 +/- 2.7 and normalized at 1.3 +/- 0.6 mumol.kg-1.min-1 (P < 0.001). This occurred because total hepatic glucose output fell much more (from 41.2 +/- 3.1 to 11.6 +/- 1.2) than did glucose production (from 25.9 +/- 1.9 to 10.3 +/- 1.0 mumol.kg-1.min-1) (both P < 0.01). Freeze-clamped liver biopsies were taken at timed intervals for measurements of hepatic enzymes and substrates. The elevated hepatic hexose-6-phosphate levels decreased with insulin infusion (151 +/- 24 vs. 71 +/- 13 nmol/g, P < 0.01). Maximal activities of glucose-6-phosphatase (G6Pase) (from 17.6 +/- 0.8 to 19.6 +/- 2.6 U/g) and glucokinase (from 1.1 +/- 0.2 to 1.0 +/- 0.2 U/g) did not change. Insulin infusion resulted in a threefold increase (P < 0.05) in the activity of glycogen synthase (active form), but had no effect on hepatic glycogen content.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative toxicity of 2-hydroxy-3-alkyl-1,4-naphthoquinones in rats

The outcome and metabolic control was studied in 60 critically ill patients with acute renal failure (ARF) treated by continuous arteriovenous hemodiafiltration (CAVHD) in a single surgical intensive care unit. Mean age (+/- SEM) was 60 +/- 2 years with a male predominance (80%). The majority of patients required mechanical ventilation (83%) and/or vasopressor support (70%) and suffered from multiorgan failure [mean number of organ system failures 3.3 +/- 0.3 (range 1-6)]. CAVHD resulted in a rapid decline of serum urea and creatinine levels during the first 72 h (urea 47.4 +/- 2.3 to 30.3 +/- 1.4 mmol/l, p < 0.05, and creatinine 572 +/- 27 to 361 +/- 23 mumol/l, p < 0.05); thereafter, controlled steady-state levels were achieved with serum urea levels kept below 30 mmol/l with full protein alimentation and often despite hypotension, surgery and septicemia. Significant electrolyte derangements could be easily corrected and maintained within normal limits. Bicarbonate homeostasis could be restored within 48 h in patients with severe metabolic acidosis (HCO3- < 20 mmol/l) with use of bicarbonate as a buffering anion (17 +/- 0.5 to 23.2 +/- 0.6, p < 0.05). CAVHD allowed rapid removal of excess body and lung water (up to 5 liters/day) without hemodynamic instability. Despite a mean pretreatment APACHE II score of 26.5, 26 patients (43%) survived until discharge from the intensive care unit, of whom 23 (38%) survived to leave hospital. Requirement of mechanical ventilation or vasopressor support, higher APACHE II scores and septicemia were all associated with a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of glucose supplement timing on protein metabolism after resistance training

We determined the effect of the timing of glucose supplementation on fractional muscle protein synthetic rate (FSR), urinary urea excretion, and whole body and myofibrillar protein degradation after resistance exercise. Eight healthy men performed unilateral knee extensor exercise (8 sets/approximately 10 repetitions/approximately 85% of 1 single maximal repetition). They received a carbohydrate (CHO) supplement (1 g/kg) or placebo (Pl) immediately (t = 0 h) and 1 h (t = +1 h) postexercise. FSR was determined for exercised (Ex) and control (Con) limbs by incremental L-[1-13C]leucine enrichment into the vastus lateralis over approximately 10 h postexercise. Insulin was greater (P < 0.01) at 0.5, 0.75, 1.25, 1.5, 1.75, and 2 h, and glucose was greater (P < 0.05) at 0.5 and 0.75 h for CHO compared with Pl condition. FSR was 36.1% greater in the CHO/Ex leg than in the CHO/Con leg (P = not significant) and 6.3% greater in the Pl/Ex leg than in the Pl/Con leg (P = not significant). 3-Methylhistidine excretion was lower in the CHO (110.43 +/- 3.62 mumol/g creatinine) than P1 condition (120.14 +/- 5.82, P < 0.05) as was urinary urea nitrogen (8.60 +/- 0.66 vs. 12.28 +/- 1.84 g/g creatinine, P < 0.05). This suggests that CHO supplementation (1 g/kg) immediately and 1 h after resistance exercise can decrease myofibrillar protein breakdown and urinary urea excretion, resulting in a more positive body protein balance.     

Loss of the signature six carboxyl amino acid tail from ovine interferon-tau does not affect biological activity

Interferon-tau (IFN-tau) is a type I IFN that is secreted from conceptuses of Bovidae (sheep, cattle, and related ruminant ungulates) for a few days during early pregnancy. It acts to prolong the life span of the corpus luteum. All secreted forms of IFN-tau, like the related IFN-omega, are 172 amino acids in length and differ from IFN-alpha and -beta by the presence of six additional amino acids at their carboxyl termini. The aim of this study was to determine whether this carboxyl tail was important for biological activity of IFN-tau, particularly for its antiluteolytic function in ewes. Full-length ovine IFN-tau (p3) and a mutated form truncated by six amino acids at its carboxyl terminal (p3Trn6, 166 amino acids) were produced in Escherichia coli. Both proteins had similar antiviral activities (2.12 +/- 0.92 x 10(8) IU/mg for p3; 1.96 +/- 0.58 x 10(8) IU/mg for p3Trn6) when tested on Madin-Darby bovine kidney (MDBK) cells. Antiproliferative activity, as measured on human Daudi cells by determining the protein concentration required to inhibit growth by 50%, was slightly higher (p < 0.05) for p3Trn6 (7.36 +/- 0.46 pM) than for p3 (13.99 +/- 0.85 pM). Most importantly, p3 and p3Trn6 were equally capable of prolonging the life span of the corpus luteum of nonpregnant ewes when the proteins were administered at doses of either 60 or 300 microg/day into the uterine lumen through indwelling uterine cannulae from Day 10 to Day 18 postestrus. Therefore, the carboxyl-terminal amino acid extension for IFN-tau does not appear to serve a functional role in the action of these proteins.     

The breast cancer screening controversy and the National Institutes of Health Consensus Development Conference on Breast Cancer Screening for Women Ages 40-49

PURPOSE: Unaccustomed exercise is associated with an elevated plasma creatine kinase (CK), myofibrillar inflammation, and delayed onset muscle soreness (DOMS). Nonsteroidal antiinflammatory drugs (NSAID) may attenuate DOMS and indirect indices of inflammation in humans. METHODS: We studied the effects of an NSAID (naproxen sodium (500 mg, 2 times a day for 48 h)) taken before and after resistance exercise in eight healthy, moderately trained men in a randomized, double-blind trial. The exercise consisted of unilateral knee concentric/eccentric weight lifting with 6 sets x 10 repetitions at 80-85% of the 1 repetition maximal contraction. Muscle biopsies of each vastus lateralis (EX = exercised/REST = control) were taken 24 h after exercise for immunohistochemical staining of inflammatory cells (leukocyte common antigen). At 24 and 48 h postexercise, we also determined DOMS, plasma CK activity, and knee extensor muscle torque. RESULTS: Exercise resulted in an increased CK activity at +24 and +48 h (vs preexercise: P < 0.01), with no treatment effect. There were no treatment effects for any of the measured variables except for a return of voluntary knee extension torque to baseline by +48 h postexercise for NSAID treatment (P < 0.05). CONCLUSIONS: NSAID administration did not alter CK rise, muscle force deficit at 24 h postexercise, nor perceived muscle pain. In addition, the increased CK at 24 h postexercise was not associated with an acute myofibrillar inflammatory cell infiltrate in moderately trained men after resistance exercise.     

Formulation and in vitro and in vivo availability of diclofenac sodium enteric-coated beads

OBJECTIVE: The beneficial effects of weight loss with a very-low-calorie diet (VLCD) on cardiovascular risk factors have been reported at the end of energy restriction. As the effects, especially on blood pressure, may not remain constant during weight maintenance, we studied the longer-term effects of weight loss on 24h ambulatory blood pressure (ABP), lipids, glucose and insulin. DESIGN: Prospective study of a 17-week weight loss programme containing an eight-week VLCD period and follow-up visit at one-year. SUBJECTS: Twenty-nine moderately obese, normotensive or mildly hypertensive women. The mean +/- s.d. body mass index (BMI) was 36.0 +/- 2.6 kg/m2 and mean age 40.3 +/- 8.3 y. RESULTS: In the last week of the VLCD, the mean (s.d.) weight loss was 12.4 +/- 3.3 kg (P < 0.001), at the end of the programme 15.1 +/- 4.4 kg (P < 0.001 vs baseline), and at one-year follow-up 10.7 +/- 7.6 kg (P < 0.001 vs baseline). Mean 24 h ABP decreased 8.0/4.6 mmHg (P < 0.001 for both) on the last week of the VLCD, at the end of the programme, the systolic ABP decrease was 4.7 mmHg (P < 0.01 vs baseline) and diastolic 2.1 mmHg (not statistically significant (NS) vs baseline). At one-year follow-up, the mean systolic ABP decrease was 4.1 mmHg (P < 0.01 vs baseline) and mean diastolic 3.0 mmHg (P < 0.05 vs baseline). Sodium excretion decreased 55 mmol/24 h in the last VLCD week (P < 0.01) and returned to baseline after that. At the one-year follow-up, beneficial changes, compared with baseline, were observed in mean serum glucose (-0.28 mmol/l, P < 0.05), triglyceride (-0.35 mmol/l, P < 0.01) and HDL cholesterol (+0.16 mmol/l, P < 0.001). CONCLUSIONS: This weight loss programme with a VLCD enabled obese subjects to lose weight and decrease cardiovascular risks. Despite some regain in weight during follow-up, the beneficial effects were overall maintained over the year. Sodium intake tended to increase during follow-up. Information on sodium restriction should be included in weight loss programmes.     

Preservation of physiological responses to hypoglycemia 2 days after antecedent hypoglycemia in patients with IDDM

OBJECTIVE: To assess the effects of short-term antecedent hypoglycemia on responses to further hypoglycemia 2 days later in patients with IDDM. RESEARCH DESIGN AND METHODS: We studied eight type I diabetic patients without hypoglycemia unawareness or autonomic neuropathy during two periods at least 4 weeks apart. On day 1, 2 h of either clamped hyperinsulinemic (60 mU.m-2.min-1) hypoglycemia at 2.8 mmol/l or euglycemia at 5.0 mmol/l were induced. Hyperinsulinemic hypoglycemia was induced 2 days later with 40 min glucose steps of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/l. Catecholamine levels and symptomatic and physiological responses were measured every 10-20 min. RESULTS: When compared with the responses measured following euglycemia, the responses of norepinephrine 2 days after hypoglycemia were reduced (peak, 1.4 +/- 0.4 [mean +/- SE] vs.1.0 +/- 0.3 nmol/l [P < 0.05]; threshold, 3.4 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l glucose [P < 0.01]). The responses of epinephrine (peak, 4.0 +/- 1.4 vs. 3.5 +/- 0.8 nmol/l [P = 0.84]; threshold, 3.8 +/- 0.1 vs. 3.6 +/- 0.1 mmol/l glucose [P = 0.38]), water loss (peak, 194 +/- 34 vs. 179 +/- 47 g-1.m-2.h-1 [P = 0.73]; threshold, 2.9 +/- 0.2 vs. 2.9 +/- 0.2 mmol/l glucose [P = 0.90]), tremor (peak, 0.28 +/- 0.05 vs. 0.37 +/- 0.06 root mean square volts (RMS V) [P = 0.19]; threshold, 3.2 +/- 0.2 vs. 3.1 +/- 0.2 mmol/l glucose [P = 0.70]), total symptom scores (peak, 10.6 +/- 2.1 vs. 10.8 +/- 1.9 [P = 0.95]; threshold, 3.3 +/- 0.2 vs. 3.6 +/0 0.1 mmol/l glucose [P = 0.15]), and cognitive function (four-choice reaction time: threshold, 2.9 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l glucose [P = 0.69]) were unaffected. CONCLUSIONS: The effect on hypoglycemic physiological responses of 2 h of experimental hypoglycemia lasts for 1-2 days in these patients with IDDM . The pathophysiological effect of antecedent hypoglycemia may be of shorter duration in IDDM patients, compared with nondiabetic subjects.     

Alterations in glucose metabolism in patients with Alzheimer's disease

OBJECTIVE: To determine the alterations in glucose metabolism that occur in patients with Alzheimer's Disease (AD). DESIGN: Cross-sectional comparison of AD and healthy controls. SETTING: A University teaching hospital. PATIENTS: Healthy controls (n = 14, BMI: 24.9 +/- 0.5 kg/M2, age 73 +/- 1 years) and patients with AD (n = 12, BMI: 23.9 +/- 1.0 kg/M2, age 72 +/- 1 years). All controls and patients with AD had a normal history and physical examination, a negative family history of diabetes, and took no medications. MEASUREMENTS: All patients and controls underwent an assessment of their dietary intake and physical activity, a 3-hour oral glucose tolerance test (OGTT), and a 2-hour hyperglycemic glucose clamp study. RESULTS: Total caloric intake (AD: 27.1 +/- 1.3 kcal/kg/day; Control: 23.6 +/- 1.6 kcal/kg/day; P = ns) and intake of complex carbohydrates (AD: 5.9 +/- 0.4 kcal/kg/day; Control: 6.5 +/- 0.3 kcal/kg/day; P = ns) were not different between groups. Leisure time physical activity was greater in controls (AD: 2970 +/- 411 kcal/week; Control: 5229 +/- 864 kcal/week; P < 0.05). Patients with AD had higher fasting glucose (AD: 5.9 +/- 0.2 mmol/L; Control: 5.1 +/- 0.1 mmol/L; P < 0.01) and insulin (AD: 144 +/- 20 pmol/L; Control: 100 +/- 6 pmol/L; P < 0.05) values. In response to the OGTT, the area under the curve for glucose and insulin was similar in both groups. During the hyperglycemic clamp, steady-state glucose values were higher in the Alzheimer's patients (AD: 11.5 +/- 0.2 mmol/L; Control: 10.9 +/- 0.1 mmol/L, P < 0.01). First- and second-phase insulin responses were similar in each group. The insulin sensitivity index (units: mL/kg.min per pmol/L x 100), a measure of tissue sensitivity to insulin, was reduced in the patients with AD (AD: 0.59 +/- 0.06; Control: 0.79 +/- 0.07; P < 0.05). CONCLUSIONS: We conclude that early AD is characterized by alterations in peripheral glucose metabolism, which may relate, in part, to alterations in physical activity.     

Use of an AC induction motor system for producing finger movements in human subjects

Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm3 respectively; P < 0.0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1.5+/-0.8 years and 0%) than in those with a macroadenoma (0.7+/-0.6 years and 40%; P < 0.05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134+/-78 and 130+/-7 ng/l respectively) than in those with microadenoma (52+/-28 and 56+/-19 ng/l, P < 0.05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3.4+/-0.3 mmol/l and 1273+/-401 lymphocytes/mm3) than in those with microadenoma (3.8+/-0.3 mmol/l and 1852+/-668 lymphocytes/mm3 P < 0.05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28+/-24%, compared with 62+/-39% in those with microadenoma; P < 0.05), less suppression of plasma cortisol by high doses of dexamethasone (-30+/-14%, compared with -61+/-25%; P < 0.05), and a reduced concentration ratio of mean basal cortisol to ACTH (7+/-3, compared with 12+/-5; P < 0.05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0.4+/-0.2 x 10(3) IU/I and 2.3+/-1.8 mIU/I, compared with 1.8+/-0.6 x 10(3) IU/I and 5.2+/-1.6 mUI/l; P < 0.05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions.     

Evidence suggesting an additional control mechanism regulating episodic secretion of luteinizing hormone and follicle stimulating hormone in pre-pubertal children and post-menopausal women

The possible differential regulation of pulsatile follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion in pre-pubertal children and in post-menopausal women was investigated. Children were studied for 4 h and post-menopausal women for 6 h; blood samples were taken every 10 min. Post-menopausal women were studied before and 21 days after administration of a single i.m. dose of gonadotrophin-releasing hormone (GnRH) analogue. Eight post-menopausal women and 18 children (nine boys and nine girls) were enrolled. The children were divided into two groups: A, at Tanner stages 0-1 (four boys and three girls); B, at Tanner stage 2-3 (five boys and six girls). Plasma LH and FSH concentrations were determined using an immunofluorimetric assay. Time series were analysed and the specific concordance (SC) index was computed to determine the degree of concordance between episodes of LH and FSH secretion. While children of group A had LH concentrations below the minimal detectable dose of 0.1 IU/l, group B showed measurable LH plasma concentrations (1.4 +/- 0.3 IU/l, mean +/- SEM). Plasma FSH concentrations were detectable in both groups. Group A showed FSH plasma concentrations significantly lower than those of group B (0.75 +/- 0.2 and 1.95 +/- 0.4 IU/l respectively; P < 0.05), but FSH pulse frequency was higher in group A (P < 0.05). Children of group B showed significant concomitance of LH and FSH secretory events at time 0 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential regulation of genes encoding 1-aminocyclopropane-1-carboxylate (ACC) synthase in etiolated pea seedlings: effects of indole-3-acetic acid, wounding, and ethylene

OBJECTIVE: To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS: Thirty-nine IDDM patients (age, 39.4 +/- 1.5 years; sex ratio, 22M/17W; BMI, 24.4 +/- 0.4 kg/m2; diabetes duration, 22.5 +/- 1.6 years) who were treated by external pump for 5.1 +/- 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0-5 min (LP) or 20-30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS: The decrease in HbA1c was more pronounced with LP than with ACT (-0.62 +/- 0.13 vs. -0.09 +/- 0.15%, P = 0.01). BG levels were lower with LP (7.93 +/- 0.15 vs. 8.61 +/- 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 +/- 0.19 vs. 9.90 +/- 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 +/- 0.10 vs. 3.80 +/- 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 +/- 0.10 vs. 3.84 +/- 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 +/- 0.94 vs. 7.94 +/- 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 +/- 0.05 vs. 0.47 +/- 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS: When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.     

Hyperhydration: tolerance and cardiovascular effects during uncompensable exercise-heat stress

This study examined the efficacy of glycerol and water hyperhydration (1 h before exercise) on tolerance and cardiovascular strain during uncompensable exercise-heat stress. The approach was to determine whether 1-h preexercise hyperhydration (29.1 ml H2O/kg lean body mass with or without 1.2 g/kg lean body mass of glycerol) provided a physiological advantage over euhydration. Eight heat-acclimated men completed three trials (control euhydration before exercise, and glycerol and water hyperhydrations) consisting of treadmill exercise-heat stress (ratio of evaporative heat loss required to maximal capacity of climate = 416). During exercise ( approximately 55% maximal O2 uptake), there was no difference between glycerol and water hyperhydration methods for increasing (P < 0.05) total body water. Glycerol hyperhydration endurance time (33. 8 +/- 3.0 min) was longer (P < 0.05) than for control (29.5 +/- 3.5 min), but was not different (P > 0.05) from that of water hyperhydration (31.3 +/- 3.1 min). Hyperhydration did not alter (P > 0.05) core temperature, whole body sweating rate, cardiac output, blood pressure, total peripheral resistance, or core temperature tolerance. Exhaustion from heat strain occurred at similar core and skin temperatures and heart rates in each trial. Symptoms at exhaustion included syncope and ataxia, fatigue, dyspnea, and muscle cramps (n = 11, 10, 2, and 1 cases, respectively). We conclude that 1-h preexercise glycerol hyperhydration provides no meaningful physiological advantage over water hyperhydration and that hyperhydration per se only provides the advantage (over euhydration) of delaying hypohydration during uncompensble exercise-heat stress.     

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

Sensory neuropeptides, released from the peripheral nervous system, might modulate glucose homeostasis by antagonizing insulin action. The effects of de-afferentation of functional small diameter unmyelinated C-fibres (sensory nerves) on in vivo insulin-mediated intracellular glucose metabolism were investigated by using euglycaemic insulin (6 and 18 mU/kg x min) clamps with [3-(3)H]-glucose infusion in 24 adult rats, treated neonatally with either capsaicin (CAP) (50 mg/kg) or vehicle (CON). Following the clamp, skeletal muscle groups, liver and adipose tissue were freeze-clamped. At plasma insulin levels of approximately 90 mU/l, CAP-rats showed a 21% increase in whole body glucose uptake compared with CON (24.4 +/- 1.6 vs 20.1 +/- 0.8 mg/kg min, p < 0.02), which was paralleled by a 20% increase in whole body glycolysis (12.6 +/- 0.8 vs 10.5 +/- 0.5 mg/ kg.min p < 0.05) (concentration of 3H2O in plasma). Whole body skeletal muscle glycogenesis was increased by 80% in CAP-rats (5.7 +/- 0.7 vs 3.1 +/- 0.7 mg/kg x min, p < 0.05) with increased muscle glycogen synthase activity. Whole body (muscle, liver and adipose tissue combined) de novo lipogenesis also was increased in CAP-rats compared with CON (0.69 +/- 0.10 vs 0.44 +/- 0.06 mg/kg x min, p < 0.05) (incorporation of [3-(3)H]-glucose counts into glycogen or fat). Hepatic glucose production was lower in CAP-rats compared with CON (0.6 +/- 0.6 vs 2.1 +/- 0.7 mg/kg x min, p < 0.05). Plasma glucagon, corticosterone, epinephrine and norepinephrine levels were reduced in CAP-rats: 43 +/- 2 compared with 70 +/- 6 pg/ml, 855 +/- 55 compared with 1131 +/- 138 nmol/l, 513 +/- 136 compared with 1048 +/- 164 pmol/l and 928 +/- 142 compared with 1472 +/- 331 pmol/l, respectively, p < 0.05. At plasma insulin levels of approximately 400 mU/l, CAP-rats showed no differences in peripheral and hepatic insulin action compared with CON. We conclude that the removal of endogenous sensory neuropeptides, by de-afferentation of capsaicin-sensitive sensory nerves, increases in vivo insulin sensitivity, but not responsiveness: 1) primarily through an increased sensitivity of skeletal muscle glycogen synthesis to insulin; 2) through a reduction in the levels of counter-regulatory hormones, thereby creating a milieu which favours overall in vivo insulin sensitivity with respect to glucose uptake, glucose production, glycolysis, glycogenesis and lipogenesis.     

Effects of hypertonic sodium lactate dextran resuscitation in severely burned dogs

12 dogs with 35% TBSA third degree burns received HLD resuscitation (HLD group, n = 6) or LR resuscitation (LR group, n = 6). Fluid resuscitation started one hour postburn. The amount of fluid infused with HLD resuscitation was calculated by that after giving HLD 19.6 ml/kg in 3 hours and 6 ml/kg/% TBSA lactate Ringer's solution followed. The amount of fluid infused with LR resuscitation was calculated by 8 ml/kg/% TBSA lactate Ringer's solution. Infusion of lactated Ringer's solution in both groups was adjusted by maintaining urinary output 0.5-1 ml/kg/h. The volume of fluid infused in HLD group (5.05 +/- 1.11 ml/kg/% TBSA) was much less than that of LR group (10.03 +/- 1.30 ml/kg/%TBSA) (P < 0.01). There was no significant difference in urinary output, serum Na+ and albumin, and plasmacrystalloid osmolarity between two groups. Plasma level of MDA decreased after resuscitation with HLD, which (0.81 +/- 0.20 mmol/g Hb) was much lower than that (1.39 +/- 0.44 mmol/g Hb) of LR group 4 hours postburn (P < 0.05). Plasma SOD activity (7.22 +/- 0.68 u/g Hb) of HLD group were much higher than that of LR group (4.86 +/- 0.53 u/g Hb) 4 hours postburn (P < 0.05). HLD resuscitation could significant reduce the amount of fluid infused comparing with lactate Ringer's solution. HLD resuscitation could attenuate postburn damage to tissue induced by lipid peroxide by elevating plasma SOD activity.