Glomerular filtration and tubular reabsorption of albumin in preproteinuric and proteinuric diabetic rats

Microalbuminuria (26-250 mg/d) is considered to be an indicator of incipient diabetic nephropathy in humans in insulin-dependent diabetes (IDD). However, before microalbuminuria is observed, glomerular alterations, such as glycosylation of the glomerular basement membrane and glomerular hyperfiltration, in IDD may result in increased filtration of albumin before any observed increase in albumin excretion. Glomerular and tubular albumin kinetics were examined in streptozotocin (65 mg/kg body wt, i.v.) diabetic, Munich-Wistar rats at 7-10 (untreated) and 50-70 d (poorly controlled with small doses of insulin) after the onset of diabetes and compared with nondiabetic controls. Additional rats in each condition received acute lysine treatment to prevent tubular protein reabsorption. Urinary albumin excretion and nonvascular albumin distribution volumes were measured in the renal cortex and compared with morphometric measurements of interstitial space and the proximal tubule to assess intracellular uptake of albumin in the proximal tubule. Urinary albumin excretion under anesthesia was not different in 7-10-d IDD versus controls (19 +/- 3 vs. 20 +/- 3 micrograms/min) but increased in the 50-70-d IDD (118 +/- 13 micrograms/min, P < 0.05). Lysine treatment resulted in increased albumin excretion compared with respective nontreatment in 7-10-d IDD (67 +/- 10 micrograms/min, P < 0.05) but not in controls (30 +/- 6 micrograms/min) or in 50-70-d IDD (126 +/- 11 micrograms/min). Glomerular filtration rate was increased both in 7-10-d IDD (2.7 +/- 0.1 ml/min, P < 0.05) and in 50-70-d IDD (2.6 +/- 0.1 ml/min, P < 0.05) compared with control (2.2 +/- 0.1 ml/min). Calculated urinary space albumin concentrations increased early in IDD with 2.5 +/- 0.4 mg% in 7-10-d IDD and 4.9 +/- 0.6 mg% in 50-70-d IDD compared with control (1.4 +/- 0.3 mg%). The increase in filtration of albumin is in excess of that attributable to hyperfiltration before increased albumin excretion early in diabetes. In 50-70-d IDD, absolute tubular reabsorption of albumin is decreased, correlating to the decrease in brush border height of the proximal tubule.     

Tropical pasture hay utilization with slaframine and cottonseed meal: ruminal characteristics and digesta passage in wethers

Sixteen mature, ruminally cannulated wethers (average BW = 41 +/- 1 kg) were fed a low-quality hay diet with or without a cottonseed meal (CSM) supplement and the parasympathomimetic agonist slaframine (SF). Treatments were basal diet (Mitchell grass hay, 4.8% CP, 46.8% ADF) available on an ad libitum basis, basal diet plus SF (8 micrograms/kg BW, 2 x daily i.m. injection), basal diet plus CSM (41.0% CP; 100 g/d), or basal diet plus SF and CSM. Treatments were arranged as a 2 x 2 factorial within a replicated 4 x 4 Latin square with 20-d periods followed by a 10-d adjustment during which only the basal diet was fed. All measurements were performed within the final 10 d of each period. Slaframine increased salivary flow by 10 to 35% (P < .07), ruminal fluid dilution rate by 8 to 11% (P < .10), and pH by 3 to 4% (P < .001). A twofold increase (P < .05) in ruminal cellulolytic bacteria numbers occurred in SF-treated wethers. Despite these SF-induced changes in the ruminal environment, whole-tract apparent nutrient digestibility, N and mineral balance, and ruminal VFA concentrations were not changed. Cottonseed meal increased forage intake by 34 to 54% (P < .001) and DM digestibility by 30% (P < .001). Cottonseed meal supplementation of a Mitchell grass hay diet improved nutritional status and attenuated live weight loss.     

Protein-calorie malnutrition does not predict subtle vitamin K depletion in hospitalized patients

OBJECTIVE: Recent studies suggest that subtle vitamin K depletion has far-reaching consequences. As this entity is not associated with prothrombin time elevation, it is important to determine whether alternate methods can help identify it. We investigated subtle vitamin K depletion in a hospital setting and determined whether protein calorie malnutrition predicts its presence. DESIGN, SETTING, SUBJECTS: Using a high-pressure liquid chromatography (HPLC) assay of plasma phylloquinone and a food frequency questionnaire for phylloquinone intake, we examined the phylloquinone status of 27 hospitalized patients with normal coagulation parameters, no liver disease, and no recent warfarin use. We assessed protein-calorie nutritional status with Reilly's criteria and anthropometrics. RESULTS: 51% of patients (95% CI = 31% to 70%) had evidence of subtle vitamin K depletion as defined by a subnormal plasma phylloquinone concentration. Patients whose phylloquinone intake was less than the Recommended Daily Allowance (RDA) over the preceding year had lower plasma phylloquinone concentrations when compared to other patients: median (range) 0.106 nmol/l (0.022-0.461) versus 0.301 nmol/l (0.067-3.928), respectively (P = 0.023). Plasma phylloquinone concentrations were no different, however, between well-nourished and malnourished patients: median (range) 0.245 nmol/l (0.022-0.522) versus 0.188 nmol/l (0.067-3.928), respectively (P=0.782). CONCLUSIONS: Subtle vitamin K depletion is common among hospitalized patients and protein-calorie malnutrition does not predict its presence.     

Influence of ovariectomy and estradiol treatment on calcium homeostasis during aging in rats

Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.     

Folate status response to controlled folate intake in pregnant women

A metabolic study (84-d) was conducted to investigate the folate status response of pregnant subjects (n = 12) during their second trimester and nonpregnant controls (n = 12) to folate intakes approximating the current (400 microg/d) and former (800 microg/d) recommended dietary allowance (RDA). The overall goal of the study was to provide metabolic data to assist in the interpretation of the current RDA for folate. Subjects were fed a controlled diet containing 120 +/- 15 microg/d (mean +/- SD) folate and either 330 or 730 microg/d synthetic folic acid. Outcome variables between and within supplementation groups were compared at steady state. Serum folate was higher (P 0.05) were detected in serum folate between pregnant and nonpregnant women within the same supplementation group. Urinary 5-methyl-tetrahydrofolate excretion was greater (P 0.05) in 5-methyl-tetrahydrofolate excretion were detected between pregnant and nonpregnant women within supplementation groups. Differences (P 相似文献   

Influence of circulating epinephrine and norepinephrine on insulin-like growth factor binding protein-1 in humans

The aim of the present study was to investigate the influence of circulating epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol.kg.min Epi iv (n = 6), 0.5 nmol.kg.min Norepi iv (n = 7), or saline (n = 5) during 30 min. Arterial blood samples were obtained before, during, and 120 min after infusion. During the catecholamine infusion arterial Epi and Norepi plasma concentrations reached 6.35 +/- 0.53 and 15.65 +/- 2.71 nmol/L, respectively, which resulted in significant increases in glucose concentrations. When Epi was infused, IGFBP-1 increased from 45 +/- 6 micrograms/L to 76 +/- 10 micrograms/L (P < 0.05) 60 min after the infusion. Epi was also followed by increases in insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in circulating IGFBP-1 (43 +/- 6 to 54 +/- 8 nmol/L, NS). The findings suggest that Epi, at plasma concentrations similar to those reached during physical stress, stimulates the production of IGFBP-1 in humans.     

Markers of bone turnover in hyperthyroidism and the effects of treatment

Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary pyridinoline cross-link (Pyr) excretion, reflecting bone resorption, have been measured in 27 patients with hyperthyroidism and 30 age-matched controls using direct and novel immunoassays. Hyperthyroid patients had higher (P < 0.001) levels of all 3 markers compared with control values: Pyr, 246 +/- 181 nmol/mmol creatinine vs. 40 +/- 12 (+515%); OC, 55 +/- 23 vs. 23 +/- 7.4 micrograms/L (+139%); and B-ALP, 22 +/- 17 vs. 10.0 +/- 5.0 micrograms/L (+120%). OC and Pyr levels were elevated above the normal range in most patients and were significantly correlated with serum free T3 concentrations (r = 0.53; P < 0.01 and r = 0.76; P < 0.001; for OC and Pyr, respectively). B-ALP levels were elevated in 11 of the 27 patients and did not correlate with serum thyroid hormone concentrations. After therapy for hyperthyroidism, Pyr and OC levels returned to normal within 1 month, whereas B-ALP transiently increased after 1 month before falling to baseline levels. The relapse of hyperthyroidism observed in 1 patient was associated with a steep increase in bone markers. These results indicate that Pyr, measured using a new and convenient immunoassay, is a highly sensitive marker for altered bone metabolism in hyperthyroidism. The increases in OC and B-ALP were less impressive, suggesting an imbalance between resorption and formation with subsequent rapid bone loss in untreated hyperthyroidism. OC and B-ALP also appear to reflect different aspects of osteoblast metabolism during the treatment of hyperthyroid patients.     

Effects of two low-fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free-living hypercholesterolaemic men

Diet enriched with polyunsaturated fat may increase the susceptibility of LDL to oxidation. Therefore the effects of two low-fat diets on plasma lipid peroxides in free-living mildly hypercholesterolaemic men (n = 37) were investigated in a randomized single-blind 28-week study. Composition of the diets were (1) American Heart Association (AHA) type 32/10:8:8 (indicating percentages of energy from total fat/saturated fat:monoenes:polyenes in actual diet); (2) low-fat 30/12:8:3. The subjects kept 3-day dietary records five times during the study to estimate the intake of nutrients. Plasma lipid peroxides were measured photometrically as the thiobarbituric-acid reactive substances (TBARS). Levels of serum vitamin E during the study were also determined. Mean change (+/- SD) in serum low density lipoprotein (LDL) cholesterol was similar in both groups (-0.32 +/- 0.76 vs -0.32 +/- 0.87 mmol/l) (AHA type vs low-fat). Level of TBARS decreased (P < 0.05) during the AHA type diet (-8.4 +/- 37.1%) (mean +/- SD) and increased (P = 0.228) during the low-fat diet (+8.7 +/- 27.0%) from 0 to 6 months. The mean intake of total active tocopherols was greater (14.7 +/- 3.7 mg) during the AHA type diet compared to the low-fat diet (7.8 +/- 2.1 mg). Serum vitamin E to LDL cholesterol ratio increased from 8.9 +/- 2.9 to 9.6 +/- 2.4 nmol/mmol (0 vs 6 months) (P = 0.07) during the AHA type diet and from 8.6 +/- 2.6 to 9.3 +/- 2.4 nmol/mmol (P = 0.159) during the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vitamin A inhibits radiation-induced pneumonitis in rats

Radiation-induced lung injury frequently limits the total dose of thoracic radiotherapy that can be delivered, and the determinants of host susceptibility are poorly understood. To test the hypothesis that vitamin A status may be an important, modifiable host determinant of radiation-induced lung injury, we determined the effect of altered vitamin A status on radiation-induced lung inflammation in rats. WAG-Rij Y rats were fed a diet deficient in or supplemented with vitamin A (0 units/kg or 80,000 units/kg diet). After 5 wk of consuming the prescribed diet, rats were irradiated with 15 Gy of 250 kV X-rays to the whole thorax. At 4-5 wk post-irradiation, there were significantly fewer neutrophils on bronchoalveolar lavage in rats fed the vitamin A-supplemented diet (8.8 +/- 1.2% neutrophils) compared with those fed the vitamin A-deficient diet (20.8 +/- 3.4% neutrophils, P < 0.01). At the termination of the experiment, 4-5 wk postradiation, lung retinol levels of the vitamin A-supplemented group were 19.6 +/- 1.8 nmol/g, whereas those in the vitamin A-deficient group were significantly lower, 1.7 +/- 0.5 nmol/g (P < 0.01). These findings suggest that supplemental vitamin A may reduce lung inflammation after thoracic radiation and be an important modifiable radioprotective agent in the lung.     

Differences in corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol before and after weight loss

Little is known about the effects of intentional weight loss on the function of the hypothalamic-pituitary-adrenal (HPA) axis of obese individuals. We studied the HPA axis of 34 healthy obese women (body mass index, 40.2 +/- 7.9 kg/m2) before and after a 21.0 +/- 7.9-kg weight loss induced by a 26-week weight loss program that included 12 weeks of a 3350 kJ/day (800 Cal/day) liquid formula diet, 6 weeks of gradual refeeding, and 6 weeks of caloric stabilization at 5020-6280 kJ/day (1200-1500 Cal/day). Obese subjects were evaluated twice: before caloric restriction and during the last 3 weeks of caloric stabilization with a 3-h evening 1 microg/kg ovine CRH (oCRH) stimulation test. CRH-stimulated ACTH and cortisol values were compared to those of a control group of 12 normal weight women. Before caloric restriction, both ACTH and cortisol responses to oCRH were similar in obese women and normal weight controls. Weight loss did not significantly alter the ACTH response to oCRH; however, the total plasma cortisol response to oCRH decreased significantly with weight loss (area under the curve, 96,320 +/- 21,040 nmol/L x min before weight loss; 82,450 +/- 22,460 nmol/L x min after weight loss; P < 0.001). Cortisol-binding globulin also decreased significantly after weight loss (2,270 +/- 1,050 nmol/L) compared either to values obtained before weight loss (3,590 +/- 1,360 nmol/L; P < 0.001) or to those of normal weight controls (3,910 +/- 1,400 nmol/L; P < 0.001). Assay for plasma free cortisol, either before or 180 min after oCRH treatment, showed no significant changes in cortisol responses resulting from weight loss. As plasma free cortisol was not altered by weight reduction, the decrease in the total cortisol response to oCRH after weight loss appears to be secondary to significant decreases in cortisol-binding globulin. We conclude that when obese women lose large amounts of weight with a 3350 kJ/day, very low energy diet, such weight reduction does not significantly affect the HPA axis.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Maternal folate status during extended lactation and the effect of supplemental folic acid

BACKGROUND: Folate requirements during lactation are not well established. OBJECTIVE: We assessed the effects of dietary and supplemental folate intakes during extended lactation. DESIGN: Lactating women (n = 42) were enrolled in a double-blind, randomized, longitudinal supplementation trial and received either 0 or 1 mg folic acid/d. At 3 and 6 mo postpartum, maternal folate status was assessed by measuring erythrocyte, plasma, milk, and dietary folate concentrations; plasma homocysteine; and hematologic indexes. Infant anthropometric measures of growth, milk intake, and folate intake were also assessed. RESULTS: In supplemented women, values at 6 mo for erythrocyte and milk folate concentrations and for plasma homocysteine were not significantly different from those at 3 mo. In supplemented women compared with unsupplemented women at 6 mo, values for erythrocyte folate (840 compared with 667 nmol/L; P < 0.05), hemoglobin (140 compared with 134 g/L; P < 0.02), and hematocrit (0.41 compared with 0.39; P < 0.02) were higher and values for reticulocytes were lower. In unsupplemented women, milk folate declined from 224 to 187 nmol/L (99 to 82 ng/mL), whereas plasma homocysteine increased from 6.7 to 7.4 micromol/L. Dietary folate intake was not significantly different between groups (380+/-19 microg/d) and at 6 mo was correlated with plasma homocysteine in unsupplemented women (r = -0.53, P < 0.01) and with plasma folate in supplemented women (r = 0.49, P < 0.02). CONCLUSIONS: A dietary folate intake of approximately 380 microg/d may not be sufficient to prevent mobilization of maternal folate stores during lactation.     

Consequences of hyperhomocyst(e)inemia on vascular function in atherosclerotic monkeys

Moderate elevation of plasma homocyst(e)ine is associated with increased risk for atherosclerotic vascular disease. In a previous study, we observed impaired vascular function in nonatherosclerotic monkeys with moderate hyperhomocyst(e)inemia. In this study, we tested the hypothesis that dietary intervention to lower plasma homocyst(e)ine corrects vascular dysfunction in atherosclerotic monkeys. Cynomolgus monkeys were fed an atherogenic diet that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. After 17 months, the atherogenic diet was supplemented with B vitamins (5 mg folic acid, 400 micrograms vitamin B-12, and 20 mg vitamin B-6 daily) for 6 months. Total plasma homocyst(e)ine decreased from 12.8 +/- 2.8 to 3.5 +/- 0.3 mumol/L (n = 9; mean +/- SE; P < .01) after vitamins were added to the diet, but plasma cholesterol remained elevated (522 +/- 63 versus 514 +/- 41 mg/dL; P > .05). In response to intra-arterial infusion of collagen, blood flow to the leg decreased by 30 +/- 3% and 38 +/- 5%, respectively, before and after vitamin supplementation (P > .05). In vivo responses of resistance vessels to endothelium-dependent vasodilators (acetylcholine or ADP) were impaired at baseline and did not improve after vitamin supplementation. In carotid artery studied ex vivo, relaxation to low doses of acetylcholine improved after vitamin supplementation, but maximal relaxation remained impaired. Ex vivo thrombomodulin anticoagulant activity was threefold higher in monkeys fed the atherogenic diet (with or without B vitamins) than in normal monkeys (P < .05). We conclude that normalization of plasma homocyst(e)ine is insufficient to restore normal vascular function in atherosclerotic monkeys with persistent hypercholesterolemia and that atherosclerosis, with or without hyperhomocyst(e)inemia, is associated with elevated thrombomodulin activity.     

Total intravenous anaesthesia with sufentanil-midazolam for major abdominal surgery

Haemodynamic and endocrine stress responses were compared during total intravenous anaesthesia with sufentanil and midazolam or fentanyl and midazolam in patients undergoing elective major abdominal surgery. Twenty-two ASA I and II patients were allocated randomly to receive sufentanil (induction 1.5 micrograms kg-1 plus infusion 1.5 micrograms kg-1 h-1) or fentanyl (induction 10 micrograms kg-1 plus infusion 10 micrograms kg-1 h-1) supplemented with 0.15 microgram kg-1 sufentanil or 1 microgram kg-1 fentanyl as necessary. Midazolam was infused to obtain plasma concentrations of 500-600 ng ml-1. Ventilation was with oxygen-enriched air. The opioid infusion was reduced post-operatively by half and benzodiazepine effects were reversed by titration with flumazenil. Mean arterial pressure, heart rate and cardiac index decreased in both groups after induction (cardiac index: sufentanil 4.94 +/- 0.45 to 2.99 +/- 0.18 litre min-1; fentanyl 4.97 +/- 0.45 to 3.71 +/- 0.36 litre min-1), but all returned to baseline during surgery. With sufentanil; mean arterial pressure was lower throughout the study period, and heart rate was lower intra-operatively. Oxygen uptake decreased in both groups after induction (sufentanil 289 +/- 29 to 184 +/- 21 ml min-1; fentanyl 318 +/- 32 to 216 +/- 32 ml min-1) and remained low with sufentanil until flumazenil was given. Adrenaline concentrations increased in both groups but there was no intergroup difference. The median noradrenaline concentration was lower intra-operatively with sufentanil (0.47 nmol litre-1 (range 0.06-6.77)) than with fentanyl (0.73 nmol litre-1 (0.07-4.58)). Cortisol, glucose and lactate concentrations increased in both groups. Bradycardia occurred in four patients with sufentanil and in three with fentanyl. There were two cases of marked thoracic rigidity with sufentanil and one with fentanyl.     

1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled NIDDM

OBJECTIVE: To evaluate the usefulness of plasma 1,5-anhydro-D-glucitol (1,5-AG) as a possible marker for daily glycemic excursion, we measured plasma 1,5-AG, HbA1c, fasting plasma glucose (FPG) level, and daily excursion of glycemia, from which the M-value (after Schlichtkrull) was calculated as an index of daily glycemic excursion. RESEARCH DESIGN AND METHODS: The subjects were 76 patients with well-controlled non-insulin-dependent diabetes mellitus (NIDDM) treated with diet therapy only (diet, n = 17), oral hypoglycemic agents (OHA, n = 28), conventional insulin therapy (CIT, n = 16), or multiple insulin injection therapy (MIT, n = 15). RESULTS: HbA1c values were similar among all the groups (diet, 6.9 +/- 0.6; OHA, 7.2 +/- 0.5; CIT, 7.1 +/- 0.6; MIT, 7.2 +/- 0.5%). The MIT group showed a significantly higher 1,5-AG concentration (11.5 +/- 5.3 micrograms/ml), a significantly lower M-value (9.2 +/- 5.2), and little risk of hypoglycemia ( < 4 mmol/l) and hyperglycemia ( > 10 mmol/l) (1.3 +/- 1.1 times/24 h) compared with the CIT group (6.9 +/- 3.3 micrograms/ml, 15.7 +/- 8.9, 2.2 +/- 1.6 times/24 h, respectively). Insulin doses (22.4 +/- 4.5 vs. 22.0 +/- 8.9 U/day), FPG (6.6 +/- 2.2 vs. 7.4 +/- 2.4 mmol/l), and HbA1c concentrations were not significantly different between the CIT and MIT groups. M-values significantly correlated with 1,5-AG concentrations (r = 0.414, P < 0.05), but not with HbA1c concentrations. CONCLUSIONS: The findings suggest that the plasma 1,5-AG concentration can be a useful index of the daily excursion of blood glucose, especially in patients with well-controlled NIDDM.     

The use of antibiotic-impregnated cement in infected reconstructions after resection for bone tumours

Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic fractures are recognized in postmenopausal women with weight loss. Because a high-calcium intake suppresses bone loss in peri- and postmenopausal women, the present randomized, double-blind, placebo-controlled study was designed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women. Subjects were placed on a moderate energy-restricted diet and either calcium supplementation (1 g/day) or placebo for 6 months. Body weight, bone turnover markers (pyridinium cross-links), osteocalcin, and parathyroid hormone (PTH) were measured at treatment weeks 1-5, 7, 10, 13, 16, 20, and 25. Total body BMD, insulin-like growth factor, 25-hydroxyvitamin D, and sex hormone binding globulin (SHBG) were measured at baseline and week 25. The calcium supplemented (n = 15; age 60.9 +/- 9.4 years, body mass index [BMI] 33.2 +/- 4.6 kg/m2) and placebo (n = 16; age 55.8 +/- 8.3 years, BMI 32.9 +/- 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 +/- 5.3% vs. 10.0 +/- 5.2%) and both groups increased SHBG (p < 0.001). There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross-links, osteocalcin, and PTH (p < 0.05, < 0.01, and < 0.05, respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p < 0.08) after weight loss. One gram per day calcium supplementation normalizes the increased calcium-PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women.     

Annual variations in serum thyroid-stimulating hormone and thyroid hormones and in their responses to thyrotrophin-releasing hormone in the reindeer

The reindeer in its natural habitat is subject to great annual variations in ambient temperature, illumination and nutrition. To ascertain the effect of these environmental factors on thyroid function, serum thyroid-stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) concentrations were measured four times a year (2 June, 8 October, 21 November, and 24 February) in 14 animals housed outdoors at latitude 69 degrees 10'N. They all showed statistically significant (P < 0.05) seasonal changes. Serum TSH and T4 were highest in February (623 +/- 30 ng/ml and 287 +/- 19 nmol/l respectively). TSH was lowest in October (318 +/- 47 ng/ml) and T4 in November (199 +/- 19 nmol/l). The T3 concentration was highest in November (3.0 +/- 0.3 nmol/l) and lowest in June (1.8 +/- 0.2 nmol/l). In contrast, rT3 was highest in June (3.6 +/- 1.2 nmol/l) and lowest in November (1.9 +/- 0.6 nmol/l). Thus, there was an inverse relationship between T3 and rT3 (linear regression r = -0.406, P < 0.01). TSH, T4, T3 and rT3 responses to exogenous thyrotrophin-releasing hormone (synthetic TRH; 500 micrograms i.m.) were determined in ten animals. The magnitude of their response to TRH was significantly (P < 0.05) dependent on the time of year. When compared with the control level all the parameters rose significantly (P < 0.05). The greatest rise in serum TSH occurred in October (219 +/- 151%) and the smallest in February (66 +/- 53%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of ovariectomy on bone metabolism in very old rats

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.     

The trans-syn-I thymine dimer bends DNA by approximately 22 degrees and unwinds DNA by approximately 15 degrees

Chromium metabolism of lactating women was evaluated by measuring diet, breast milk, urine, and serum chromium in 17 subjects 60 d postpartum. Breast milk chromium concentration was similar for the 3 d of collection with a mean +/- SE concentration of 3.54 +/- 0.40 nmol/L (0.18 ng/mL). Dietary intake and urinary chromium values were also similar for each of the 3 collection days. Total chromium intake of lactating mothers (0.79 +/- 0.08 mumol/d) was greater than that of reference female subjects (0.48 +/- 0.02). There was a significant correlation (r = 0.84) between serum chromium and urinary chromium excretion. If a breast milk volume of 715 mL is assumed, chromium intake of exclusively breast-fed infants is < 2% of the estimated safe and adequate daily intake of 10 micrograms. In summary, breast milk chromium content is independent of dietary chromium intake and serum or urinary chromium values. Chromium intake also did not correlate with serum or urine chromium but there was a significant relationship between serum and urinary chromium concentrations.     

Zinc balance in adolescent females consuming a low- or high-calcium diet

There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.