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  • Springer  (73)
  • BMJ Publishing  (4)
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  • 1
    Electronic Resource
    Electronic Resource
    Binding of [3H]ICIA 5165, an H2-receptor antagonist to guinea pig gastric mucosa (1986)
    Springer
    Inflammation research 18 (1986), S. 524-531 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ICIA 5165, 2-guanidino-4-[4-(2-cyano-3-methylguanidino)butyl] thiazole, a selective histamine H2-receptor antagonist was radiolabelled with tritium to a specific activity of 50.8 Ci/mmoll for use in binding studies. Radiolabelling did not impair bioactivity. Binding characteristics of [3H]ICIA 5165 to guinea pig gastric mucosa were determined. Ligand binding was rapid, reaching equilibrium within five minutes at 0°C, reversible and saturable. Specific [3H]ICIA 5165 binding had an equilibrium dissociation constant of 1.29×10−8 M, determined by Scatchard plot analysis, and of 1.02×10−8 M, calculated from the ratio of the dissociation to association rate constants. A Hill number, nH, of 1.02 was determined for the specific binding component. Specific binding of [3H]ICIA 5165 to gastric mucosal supernatant was not inhibited by methapyrilene, diphenhydramine, mepyramine, d-chlorpheniramine or I-chlorpheniramine (all at 10−7 M), or by atropine or propranolol (both at 10−6 M). Specific [3H]ICIA 5165 binding was inhibited in a concentration dependent manner by non-radioactive ICIA 5165 and tiotidine, as well as by a variety of other agents, with H2 agonist or H2 antagonist properties. In competition experiments, however, difficulties encountered in accurately defining the degree of specific binding indicate some reservation should be observed in interpreting these results.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01964958
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  • 2
    Electronic Resource
    Electronic Resource
    REV 5901 and Ly 171,883 protect rat gastric mucosa against ethanol-induced damage (1987)
    Springer
    Inflammation research 21 (1987), S. 320-322 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the leukotriene antagonist, Ly 171,883, or the 5-lipoxygenase inhibitor, REV 5901, on ethanol-induced gastric lesion formation in the rat was investigated. Pretreatment with REV 5901 resulted in a dose dependent decrease in lesion length. Doses of 32 and 64 mg/kg induced nearly complete protection against ethanol, while doses of 1 and 8 mg/kg were much less effective. With Ly 171,883, 32 and 64 mg/kg doses less dramatically reduced lesion length. These findings implicate products of the 5-lipoxygenase pathway in the production of ethanol-induced gastric lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01966503
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  • 3
    Electronic Resource
    Electronic Resource
    Renal function and insulin sensitivity during simvastatin treatment in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria (1993)
    Springer
    Diabetologia 36 (1993), S. 1079-1086 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; microalbuminuria ; glomerular filtration rate ; plasma lipoproteins ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of simvastatin (10–20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol ≥5.5 mmol·l−1). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n=8) for 36 weeks significantly reduced total cholesterol (6.7±0.3 vs 5.1 mmol·l−1 (p〈0.01)), LDL-cholesterol (4.4±0.3 vs 2.9±0.2 mmol·l−1 (p〈0.001)) and apolipoprotein B (1.05±0.04 vs 0.77±0.02 mmol·l−1 (p〈0.01)) levels as compared to placebo (n=10). Both glomerular filtration rate (mean±SEM) (simvastatin: 96.6±8.0 vs 96.0±5.7 ml·min−1·1.73 m−2, placebo: 97.1±6.7 vs 88.8±6.0 ml·min−1·1.73 m−2) (NS) and urinary albumin excretion rate (geometric mean x/÷ antilog SEM) (simvastatin: 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min−1, placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min−1)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin-and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0±0.1 vs 1.9±0.1 (NS) and 3.1±0.6 vs 3.1±0.7 mg·kg−1·min−1 (NS)) and the placebo group (1.9±0.1 vs 1.8±0.1 (NS) and 4.1±0.6 vs 3.8±0.2 mg·kg−1·min−1 (NS)). No different was observed in glucose storage or glucose and lipid oxidation before and after treatment. Further, the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin (−0.7±0.8 vs −0.7±0.5 mg·kg−1·min−1 (NS)). In conclusion, despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374502
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  • 4
    Electronic Resource
    Electronic Resource
    Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity (1995)
    Springer
    Diabetologia 38 (1995), S. 565-572 
    Details
    ISSN: 1432-0428
    Keywords: Insulin resistance ; hyperinsulinaemia ; glucose tolerance ; chronic renal failure ; aerobic work capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml·min−1·1.73 m−2 (11–43) (median, range) and 15 sex, age, and body mass index matched control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p〈0.01) and during the test (p〈0.02). The tissue sensitivity to insulin, expressed by the amount of glucose infused during the last 60 min of a 120-min hyperinsulinaemia euglycaemic clamp (M-value) and the M/I ratio, was significantly lower in the patients than in the control subjects (M-value 404±118 vs 494±85 mg glucose/kg body weight, p〈0.02) (M/I ratio 1.77±0.71 vs 2.57±0.70 (mg/(kgBW·min) per pmol/l·100, p〈0.001). The maximal aerobic work capacity was significantly lower in the patients than in the control subjects (24±8 vs 32±11 ml O2/(kg body weight·min), p〈0.02) and positively correlated to the M-value and the M/I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting that these patients might benefit from physical training programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400725
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  • 5
    Electronic Resource
    Electronic Resource
    Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet (1995)
    Springer
    Diabetologia 38 (1995), S. 1069-1075 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; microalbuminuria ; blood pressure ; monounsaturated fat diet ; olive oil ; diet ; metabolic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50% carbohydrate, 30% fat [10% monounsaturated fat]) vs a diet rich in monounsaturated fat (30% carbohydrate, 50% fat [30% monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean±SD: 145/78±25/10 vs 143/79±19/10 mmHg (NS) and the monounsaturated fat diet: 140/78±16/8 vs 143/79±15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean ×/÷ tolerance factor) 32.4×/÷2.1 to 36.0×/÷1.9 Μg/min (NS) vs from 34.2×/÷1.9 to 32.1×/÷2.1 Μg/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p〈0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients. Moreover, glycaemic control and lipoprotein levels were unchanged, although a potential beneficial effect on the LDL/HDL-cholesterol ratio was noted. Monounsaturated fat represents an alternative in the diets of NIDDM patients especially when caloric intake is not a concern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402177
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  • 6
    Electronic Resource
    Electronic Resource
    Insulin resistance in relatives of NIDDM patients: the role of physical fitness and muscle metabolism (1996)
    Springer
    Diabetologia 39 (1996), S. 813-822 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin resistance ; relatives ; non-insulin-dependent diabetes mellitus ; oral glucose tolerance test ; physical fitness ; forearm blood flow ; muscle metabolism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary First degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) are often reported to be insulin resistant. To examine the possible role of reduced physical fitness in this condition 21 first degree relatives of NIDDM patients and 22 control subjects without any history of diabetes were examined employing a 150-min hyperinsulinaemic (0.6 mU insulin · kg–1· min–1) euglycaemic clamp combined with the isotope dilution technique (3-3H-glucose, Hot GINF), the forearm technique and indirect calorimetry. During hyperinsulinaemia glucose disposal (Rd) and forearm glucose extraction were significantly diminished in the relatives (p 〈 0.01 and p 〈 0.05), but glucose oxidation and the suppressive effect on hepatic glucose production were normal. Arteriovenous differences across the forearm of the gluconeogenic precursors lactate, alanine and glycerol as well as the increments in forearm blood flow during hyperinsulinaemia were similar in the two groups. Maximal oxygen uptake (VO2 max) was lower in the relatives than in the control subjects (36.8 ± 1.9 vs 42.1 ± 2.0 ml · kg–1· min–1; p = 0.03). There was a highly significant correlation between Rd and VO2 max in both relatives and control subjects (r = 0.68 and 0.66, respectively; both p 〈 0.001). Comparison of the linear regression analyses of insulin-stimulated Rd on VO2 max in the two groups showed no significant differences between the slopes (0.10 ± 0.03 vs 0.09 ± 0.02) or the intercepts. In stepwise multiple linear regression analyses with insulin-stimulated Rd as the dependent variable VO2 max significantly determined the level of Rd (p 〈 0.01), whereas forearm blood flow and anthropometric data did not. In conclusion, the insulin resistance in healthy first degree relatives of patients with NIDDM is associated with a diminished physical work capacity. Whether, this finding is ascribable to environmental or genetic factors (e. g. differences in muscle fibre types, capillary density etc) remains to be determined. [Diabetologia (1996) 39: 813–822]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050515
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  • 7
    Electronic Resource
    Electronic Resource
    Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity (1995)
    Springer
    Diabetologia 38 (1995), S. 565-572 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin resistance ; hyperinsulinaemia ; glucose tolerance ; chronic renal failure ; aerobic work capacity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml · min−1· 1.73 m−2 (11–43) (median, range) and 15 sex, age, and body mass index matched control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p 〈 0.01) and during the test (p 〈 0.02). The tissue sensitivity to insulin, expressed by the amount of glucose infused during the last 60 min of a 120-min hyperinsulinaemia euglycaemic clamp (M-value) and the M/I ratio, was significantly lower in the patients than in the control subjects (M-value 404 ± 118 vs 494 ± 85 mg glucose/kg body weight, p 〈 0.02) (M/I ratio 1.77 ± 0.71 vs 2.57 ± 0.70 (mg/(kgBW · min) per pmol/l · 100, p 〈 0.001). The maximal aerobic work capacity was significantly lower in the patients than in the control subjects (24 ± 8 vs 32 ± 11 ml O2/(kg body weight · min), p 〈 0.02) and positively correlated to the M-value and the M/I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting that these patients might benefit from physical training programmes. [Diabetologia (1995) 38: 565–572]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400725
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  • 8
    Electronic Resource
    Electronic Resource
    Urinary albumin excretion rate and 24-h ambulatory blood pressure in NIDDM with microalbuminuria: effects of a monounsaturated-enriched diet (1995)
    Springer
    Diabetologia 38 (1995), S. 1069-1075 
    Details
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus; microalbuminuria ; blood pressure ; monounsaturated fat diet ; olive oil ; diet ; metabolic control.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that unsaturated fat-enriched diets may have a beneficial effect on blood pressure in non-insulin-dependent diabetic (NIDDM) patients, whereas little is known about the effects on albuminuria. In a 3-week cross-over design we compared the effects of a currently recommended high-carbohydrate diet (50 % carbohydrate, 30 % fat [10 % monounsaturated fat]) vs a diet rich in monounsaturated fat (30 % carbohydrate, 50 % fat [30 % monounsaturated fat]) on urinary albumin excretion rate, 24-h ambulatory blood pressure and metabolic control in ten NIDDM patients with persistent microalbuminuria. The 24-h ambulatory blood pressure was similar before and after both the high-carbohydrate diet (mean ± SD: 145/78 ± 25/10 vs 143/79 ± 19/10 mmHg (NS) and the monounsaturated fat diet: 140/78 ± 16/8 vs 143/79 ± 15/8 mmHg (NS). No changes were observed in day or night-time blood pressures. Urinary albumin excretion rate was unaffected after 3 weeks' treatment by the diets: from (geometric mean ×/7 tolerance factor) 32.4 ×/72.1 to 36.0 ×/7 1.9 μg/min (NS) vs from 34.2 ×/7 1.9 to 32.1 ×/7 2.1 μg/min (NS). Fasting plasma glucose, serum fructosamine and HbA1c as well as lipid and lipoprotein concentrations were stable during both diets. Compared to the high-carbohydrate diet a reduction in the LDL/HDL cholesterol ratio was observed during the monounsaturated fat diet (p 〈 0.03). In conclusion, compared to a high-carbohydrate diet, 3 weeks' treatment with a monounsaturated fat diet did not affect the levels of 24-h ambulatory blood pressure or albuminuria in microalbuminuric NIDDM patients. Moreover, glycaemic control and lipoprotein levels were unchanged, although a potential beneficial effect on the LDL/HDL-cholesterol ratio was noted. Monounsaturated fat represents an alternative in the diets of NIDDM patients especially when caloric intake is not a concern. [Diabetologia (1995) 38: 1069–1075]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402177
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  • 9
    Electronic Resource
    Electronic Resource
    Transcapillary escape rate and albuminuria in Type II diabetes. Effects of short-term treatment with low-molecular weight heparin (Short Communication) (1999)
    Springer
    Diabetologia 42 (1999), S. 60-67 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Transcapillary escape rate of albumin ; microalbuminuria ; albuminuria ; low-molecular weight heparin ; heparin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relation between urinary albumin excretion rate (UAE), transcapillary escape rate of albumin (TERalb), haemostatic factors, ambulatory blood pressure, and metabolic variables was investigated in 45 Type II (non-insulin-dependent) diabetic patients without overt nephropathy or uncontrolled blood pressure. We enrolled 44 patients in a placebo controlled study to test the effects of 3 week long treatment with low-molecular weight heparin (tinzaparin) on the same variables. BMI, 24 h systolic and diastolic blood pressure, plasma concentrations of triglycerides, fasting glucose, factor VIII, von Willebrand factor (vWf), fibrinogen, α-2 macroglobulin, and fibronectin were notably higher in patients with increased albuminuria compared with normoalbuminuric patients, whereas the TERalb was similar in the two groups. TERalb correlated with fasting plasma glucose. UAE correlated more closely than TERalb with 24 h ambulatory blood pressure, vWf, and factor VIII. Urinary albumin excretion rate was unchanged during tinzaparin [28.9 ± 5.6 vs 28.1 ± 6.0 μg/min (geometric mean (antilog SD)] vs placebo (18.0 ± 5.4 vs 17.6 ± 5.3 μg/min), and no change was found in TERalb [6.3 ± 1.6 vs 6.0 ± 1.5 %/h (means ± SD), and 6.3 ± 1.5 vs 5.6 ± 1.8 %/h; tinzaparin versus placebo, respectively]. Only minor changes were observed in blood pressure, lipids, glycaemic control and haemostatic factors. This study shows no correlation between albuminuria and transcapillary escape rate in Type II diabetic patients without overt nephropathy or uncontrolled blood pressure. UAE is related to markers of atherosclerosis, endothelial injury and dysfunction, and haemostatic factors. Moreover, UAE correlates much more than TERalb with 24 h ambulatory blood pressure, von Willebrand factor, and factor VIII. Finally, short-term treatment with tinzaparin does not change the transvascular or glomerular leakage of albumin. These results indicate that TERalb is not a sensitive marker of microvascular dysfunction in such patients and that factors other than abnormal glycosaminoglycan metabolism may contribute to the vascular damage of these patients. [Diabetalogia (1999) 42: 60–67]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051114
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  • 10
    Electronic Resource
    Electronic Resource
    The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics (1976)
    Springer
    Diabetologia 12 (1976), S. 161-166 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic microangiopathy ; early diabetes ; influence of metabolic regulation ; microvascular permeability of small and large molecules
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and β2-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and β2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was determined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured by single shot 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC for 51Cr-EDTA was determined in the hyperaemic anterior tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic — histologically demonstrated — diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i. e. the concept of plasmatic vasculosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428983
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