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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; biomechanics ; diabetic macrovascular disease ; collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The biomechanical properties of aortic samples from patients with Type 1 (insulin-dependent) diabetes mellitus and age- and sex-matched control subjects were analysed using a materials testing machine. The specimens were prepared from tissue outside areas of visible atherosclerosis in order to discriminate between primary Type 1 diabetic alterations in the aortae and secondary changes due to increased atherosclerosis. We paid special attention to the correction of biomechanical parameters for differences in wall thickness and registration of specimen length values. In the Type 1 diabetic aortae a marked reduction was found in the extensibility and an increase in their stiffness. The reduced extensibility was correlated significantly to the duration of Type 1 diabetes. The pronounced alterations in the mechanical properties could not be explained by the increase in the wall thickness which was observed among the Type 1 diabetic patients and the alterations could not be correlated to the grade of atherosclerosis in the thoracic aorta. The results of the present study, therefore, strongly suggest that Type 1 diabetic patients develop alterations in the arterial connective tissue independent of the presence of atherosclerosis. Such primary alterations in the vessel wall may play a role in the pathogenesis of large vessel disease among these patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; macrovascular disease ; atherosclerosis ; aorta ; tunica media ; glycosaminoglycans ; hyaluronic acid ; heparan sulphate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alterations in the connective tissue of the arterial wall have been suggested to play a role in the development of macrovascular disease in diabetes mellitus. The present study deals with changes in the content of GAG in aortic tunica media in human diabetes by separately analysing normal areas and areas with fibrous plaques. The thoracic aorta from 15 diabetic patients (7 with IDDM, 8 with NIDDM), and 30 sex- and age-matched non-diabetic subjects were collected at autopsy. Tunica intima was removed and GAG were isolated from the dried defatted and pulverized tunica media. GAG were quantified by uronic acid analysis and characterized by electrophoresis on cellulose acetate. Results showed that IDDM patients had a relative and absolute increase in hyaluronic acid in normal tunica media compared to non-diabetic subjects. There was a significant positive correlation between hyaluronic acid content of normal tunica media and duration of diabetes, but not between hyaluronic acid content and age. When tunica media from plaque areas was compared to normal areas the same pattern was evident in diabetic patients as in non-diabetic patients — significantly increased proportion of dermatan sulphate and reduced hyaluronic acid. The data agree with the notion that the arterial wall is subject to different pathological processes in diabetes, one of classical atherosclerosis with changes in GAG similar to non-diabetic subjects, and the other seen in areas without plaques with dissimilar alterations in GAG. These data therefore support the concept of the presence of a macrovascular disease in diabetes different from atherosclerosis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Angiotensin II ; polymerase chain reaction ; type IV collagen ; type V collagen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An insertion(I)/deletion(D) polymorphism in the angiotensin I-converting enzyme (ACE) gene seems to be associated with clinical heart disease in patients with diabetes mellitus. It is not known whether increased atherosclerosis or other factors among individuals with certain ACE-gene subtypes form the basis for the increased prevalence of heart disease among these subjects. We measured, at autopsy, the extent of macroscopically visible aortic atherosclerosis in 22 diabetic and 39 non-diabetic subjects and determined the ACE-genotype of all individuals by the polymerase chain reaction. The percentage of aortic surface area covered with atherosclerotic lesions was 29±8 (n=6), 71±7 (n=9), and 65±7 (n=5) in the II-, ID-, and DD-genotype subgroups, respectively, among diabetes patients (mean ± SEM) (2 p〈0.01, when comparing values from the ID and DD groups to the II group). The values were 37±9 (n=11), 40±5 (n=14) and 37±6 (n=11) in the II-, ID-, and DD-genotypes in the non-diabetic group. There were no differences in sex ratio or age in any of the ACE-gene subtypes. The previously described relationship between heart disease and the ACE-gene polymorphism in diabetes could thus be founded in an increased extent of atherosclerosis among patients with the ID- and DD-ACE-gene subtypes. Patients with diabetes have several alterations in the composition of the collagenous components in the arterial wall. We also analysed for associations between total collagen and type IV and type V collagen content in the aortic vessel wall and the ACE-gene subtypes. We were, however, not able to disclose correlations between the polymorphism and any of these parameters. In conclusion, our data show an association between the ACE-I/D polymorphism and the degree of aortic atherosclerosis in diabetes; however, we did not observe correlations between the polymorphism and data concerning arterial collagenous components.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 946-951 
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; glycation ; cross-links ; vascular stiffening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that biomechanical analysis of aorta from diabetic subjects reveals a marked increase in stiffness compared to aorta from age-matched control subjects. In the present paper we have proposed that this increased stiffness can be attributed to glycation-induced inter-molecular cross-links based on a direct analysis of the two known glycation cross-links, the fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant difference in the increase in concentration of both cross-links with increasing age for both the intima (p〈0.0025) and the media (p〈0.0005) from the diabetic compared to the control subjects, but no correlation with the mature enzymic cross-link hydroxylysyl-pyridinoline. Finally, we have obtained a significant correlation of stiffness with both glycation cross-links (NFC-1, r=0.86; p〈0.005 and pentosidine r=0.75, p〈0.05), but the concentration of NFC-1 is about 50 times greater than that of pentosidine, indicating that it is the major glycation cross-link responsible for the stiffening of the aorta.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Angiotensin II ; polymerase chain reaction ; type IV collagen ; type V collagen.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An insertion(I)/deletion(D) polymorphism in the angiotensin I-converting enzyme (ACE) gene seems to be associated with clinical heart disease in patients with diabetes mellitus. It is not known whether increased atherosclerosis or other factors among individuals with certain ACE-gene subtypes form the basis for the increased prevalence of heart disease among these subjects. We measured, at autopsy, the extent of macroscopically visible aortic atherosclerosis in 22 diabetic and 39 non-diabetic subjects and determined the ACE-genotype of all individuals by the polymerase chain reaction. The percentage of aortic surface area covered with atherosclerotic lesions was 29 ± 8 (n = 6), 71 ± 7 (n = 9), and 65 ± 7 (n = 5) in the II-, ID-, and DD-genotype subgroups, respectively, among diabetes patients (mean ± SEM) (2 p 〈 0.01, when comparing values from the ID and DD groups to the II group). The values were 37 ± 9 (n = 11), 40 ± 5 (n = 14) and 37 ± 6 (n = 11) in the II-, ID-, and DD-genotypes in the non-diabetic group. There were no differences in sex ratio or age in any of the ACE-gene subtypes. The previously described relationship between heart disease and the ACE-gene polymorphism in diabetes could thus be founded in an increased extent of atherosclerosis among patients with the ID- and DD-ACE-gene subtypes. Patients with diabetes have several alterations in the composition of the collagenous components in the arterial wall. We also analysed for associations between total collagen and type IV and type V collagen content in the aortic vessel wall and the ACE-gene subtypes. We were, however, not able to disclose correlations between the polymorphism and any of these parameters. In conclusion, our data show an association between the ACE-I/D polymorphism and the degree of aortic atherosclerosis in diabetes; however, we did not observe correlations between the polymorphism and data concerning arterial collagenous components. [Diabetologia (1996) 39: 696–700]
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 39 (1996), S. 946-951 
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; glycation ; cross-links ; vascular stiffening.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that biomechanical analysis of aorta from diabetic subjects reveals a marked increase in stiffness compared to aorta from age-matched control subjects. In the present paper we have proposed that this increased stiffness can be attributed to glycation-induced inter-molecular cross-links based on a direct analysis of the two known glycation cross-links, the fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant difference in the increase in concentration of both cross-links with increasing age for both the intima (p 〈 0.0025) and the media (p 〈 0.0005) from the diabetic compared to the control subjects, but no correlation with the mature enzymic cross-link hydroxylysyl-pyridinoline. Finally, we have obtained a significant correlation of stiffness with both glycation cross-links (NFC-1, r = 0.86; p 〈 0.005 and pentosidine r = 0.75, p 〈 0.05), but the concentration of NFC-1 is about 50 times greater than that of pentosidine, indicating that it is the major glycation cross-link responsible for the stiffening of the aorta. [Diabetologia (1996) 39: 946–951]
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus, macrovascular disease, atherosclerosis, aorta, tunica media, glycosaminoglycans, hyaluronic acid, heparan sulphate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alterations in the connective tissue of the arterial wall have been suggested to play a role in the development of macrovascular disease in diabetes mellitus. The present study deals with changes in the content of GAG in aortic tunica media in human diabetes by separately analysing normal areas and areas with fibrous plaques. The thoracic aorta from 15 diabetic patients (7 with IDDM, 8 with NIDDM), and 30 sex- and age-matched non-diabetic subjects were collected at autopsy. Tunica intima was removed and GAG were isolated from the dried defatted and pulverized tunica media. GAG were quantified by uronic acid analysis and characterized by electrophoresis on cellulose acetate. Results showed that IDDM patients had a relative and absolute increase in hyaluronic acid in normal tunica media compared to non-diabetic subjects. There was a significant positive correlation between hyaluronic acid content of normal tunica media and duration of diabetes, but not between hyaluronic acid content and age. When tunica media from plaque areas was compared to normal areas the same pattern was evident in diabetic patients as in non-diabetic patients – significantly increased proportion of dermatan sulphate and reduced hyaluronic acid. The data agree with the notion that the arterial wall is subject to different pathological processes in diabetes, one of classical atherosclerosis with changes in GAG similar to non-diabetic subjects, and the other seen in areas without plaques with dissimilar alterations in GAG. These data therefore support the concept of the presence of a macrovascular disease in diabetes different from atherosclerosis. [Diabetologia (1994) 37: 286–292]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Atherosclerosis ; diabetic complications ; extracellular matrix ; elastin ; non-enzymatic glycation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Structural alterations in arterial extracellular matrix components have been suggested to play a role in the development of arterial disease among patients with diabetes mellitus. This study examines the quantity and quality of collagenous components in aortas from diabetic patients. In order to obtain data about the arterial tissue concentration of type IV and V collagen in diabetic and non-diabetic patients, aortas from 21 patients with diabetes (9 with Type 1 (insulin-dependent) diabetes and 12 with Type 2 (non-insulin-dependent) diabetes), were collected at autopsy together with aortas from groups of sex- and age-matched patients. Intima and media samples from normal and fibrous plaque areas from the individual vessels were evaluated. Pulverized, dried and defatted tissue samples were subjected to chemical solubilization with cyanogen bromide and subsequent immunochemical quantitation of the dissolved type IV and V collagen in an ELISA. It was found that the concentration of type IV collagen was increased in the tunica media both in plaque and non-plaque areas in the samples from the diabetic patient groups as compared to the non-diabetic groups. No consistent differences in type IV collagen concentrations were found between diabetic and non-diabetic patients in tunica intima. The type V collagen concentrations and the total collagen content were not altered in the diabetic samples. The fraction of the total collagen that was solubilized during cyanogen bromide treatment was determined, and it was found that this fraction was decreased in most tissue areas in the diabetic patient groups. These findings suggest that patients with diabetes develop alterations in arterial collagenous components that may play a role in the development of arterial disease in diabetes.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1988), S. 549-555 
    ISSN: 1432-1041
    Keywords: verapamil ; sustained release formulation ; hypertension ; renal disease ; kidney function ; angiotensin II ; aldosterone ; arginine vasopressin ; atrial natriuretic peptide ; lipids and lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 14 patients with arterial hypertension secondary to chronic renal parenchymal disease and impaired renal function, 24-h ambulatory and casual blood pressure readings plasma, angiotensin II, aldosterone, arginine vasopressin and atrial natriuretic peptide, creatinine clearance, plasma lipids and lipoproteins, and body weight were determined after consecutive 3-week periods on placebo and sustained release verapamil 240 mg/day. Verapamil reduced the mean 24-h ambulatory blood pressure from 152/104 to 142/97 mm Hg. Blood pressure was significantly reduced during the daytime and the evening, but not at night. Casual blood pressure was also significantly reduced from 176/106 mm Hg to 154/96 mm Hg. No significant changes were found in the hormones, creatinine clearance, plasma lipids and lipoproteins, heart rate or body weight. The atrial natriuretic peptide level was significantly correlated with the calculated creatinine clearance (r=−0.797). Thus, sustained release verapamil 240 mg as a single daily dose had a moderate hypotensive effect in patients with chronic renal disease without inducing tachycardia, activation of the renin-angiotensin-aldosterone system, or increasing body weight, and without altering renal function and plasma lipids and lipoproteins. The negative correlation between atrial natriuretic peptide and glomerular filtration rate supports the hypothesis that the extracellular volume increases during progression of renal disease.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract Saccharomyces cerevisiae was inoculated into a yeast nitrogen base with either glycerol or glucose as carbon source. Cell proliferation was followed by colony counts on agar medium. Cells in the glycerol-supplemented medium divided less than once in 10 days. When glucose, 6-deoxy-glucose or protoporphyrin IX was added, the cells had doubling times of about 24 h and increased in number to about 0.5 × 106 cells ml−1 Addition of either of the protein kinase C activators oleoyl-acetylglycerol or phorbol-12-myristate-13-acetate did not activate cell proliferation in the glycerol medium. However, when (i) glucose was combined with either protoporphyrin IX or chlorophyllin, or (ii) either protoporphyrin IX or chlorophyllin was combined with either of the protein kinase C activators, the cells had doubling times of about 12 h. Hence, (i) glucose can act as both a carbon source and a signalling molecule for proliferation, and (ii) two systems are involved in activating cell proliferation in S. cerevisiae: one operating through a protein kinase C system and another through a guanylate cyclase system.
    Type of Medium: Electronic Resource
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