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Biomedical subjects

G Nicoloff

Publications and source records attributed to G Nicoloff.

17 recordsLinked to original sources

Detection of free elastin-derived peptides among diabetic children.

Elastin breakdown products are found in the serum of all human subjects. The presence of these elastin-derived peptides (EDP) and the corresponding antibodies in circulation leads to formation of circulating immune complexes (CIC). The aim of this study was to determine if serum level of free-EDP (unbound in CIC) correlate with the development of microvascular complications in children with Type 1 (insulin-dependent) diabetes mellitus. To this end we used a method for detecting immune complexes (CIF-ELISA) in combination with an ELISA for detection of EDP. The levels of free EDP were studied in sera of 81 diabetic children (mean age 13.46+/-3.51 years, diabetes duration 5.17+/-4.21 years). Forty-two of the children had vascular complications (group 1) and 39 were without vascular complications (group 2). Twenty-one healthy children (mean age 12.6+/-2.47 years) were used as controls. Diabetics showed significantly higher levels of free EDP (68.1+/-25 ng/ml versus 51+/-12.5 ng/ml; p=0.003) compared to the control group. In group 1, free EDP showed significantly higher levels than controls (78.9+/-25.6 ng/ml versus 51+/-12.5 ng/ml; p=0.0001). About 38 of 81 (47%) patients were positive for free EDP (30/42--71% in group 1 and 8/39--21% in group 2). Free EDP levels in all diabetics showed a correlation with insulin dose (r=0.23; p=0.041), and microalbuminuria (r=0.57; p=0.0001). Patients who had vascular pathology showed a correlation of free EDP with microalbuminuria (r=0.41; p=0.0081), retinopathy (r=0.32; p=0.041), insulin dose (r=0.37; p=0.02), HbA1c (r=0.35; p=0.03), systolic blood pressure (r=0.30; p=0.045) and total cholesterol (r=0.36; p=0.02). These findings suggest that elevated levels of free EDP are associated with the development of diabetic vascular complications in children.

Adolescent↗

Serum AGE-elastin derived peptides among diabetic children.

The purpose of the study was to measure advanced glycated end products (AGE) of elastin in human serum. In the present study, we adapted an ELISA technique for the determination of AGE-elastin-derived peptides (AGE-EDP) in human sera of healthy and diabetic subjects. This test makes use of human aortic elastin hydrolyzed by a chemical procedure (alpha-elastin) and AGE-Hemocyanin. Polyclonal sera from rabbit against AGE-Hemocyanin and from sheep against alpha-elastin were obtained and their specificity was tested via direct and competitive ELISA. Sera of 60 Type 1 (insulin-dependent) diabetic children and 28 healthy subjects were tested. The patients with vascular complications showed significant higher levels of age, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure (DBP), dose, EDP and AGE-EDP than those without vascular complications. AGE-EDP concentrations of all diabetics correlated with triglycerides (r=0.19; p=0.04). The correlation was found between AGE-EDP and DBP in the subgroup of patients with microalbuminuria+retinopathy (r=0.94; p=0.0006). The subgroup of patients with microalbuminuria (n=19) showed correlation with age (r=0.24; p=0.008), AGE-EDP (r=0.65; p=0.0001), EDP (r=0.51; p=0.0001) and SBP (r=0.33; p=0.0003). Further studies are necessary to elucidate the relationship between the serum level of AGE-elastin degradation products and diabetic vascular complications. The measurement of non-invasive markers of elastin synthesis and degradation may be useful in monitoring development and therapeutic intervention in diabetic vascular complications.

Adolescent↗

Serum fibrillin-antifibrillin immune complexes among diabetic children.

The fibrillins are large glycoproteins components of 10-nm microfibrils found in the extracellular matrix of most tissues. Microfibrils play a role in elastic fiber assembly and serve to link cells to elastic fibers in the extracellular matrix. Fibrillin-1 (FBN-1) and -2 (FBN-2) are large, secreted glycoproteins known to be components of extracellular matrix microfibrils located in the vasculature, basement membrane, and various connective tissues and are often associated with a superstructure known as the elastic fiber. Anti-fibrillin antibodies found in some autoimmune diseases could form circulating immune complexes (CIC) with corresponding antigens. Type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease leading to formation of different types of autoantibodies. To determine the possible presence of FBN-anti-FBN CIC (IgG and IgM) were studied by modified version of ELISA 35 children with Type 1 diabetes mellitus (mean age--12.37+/-3.77 years, diabetes duration 4+/-3.5 years). Eight of the diabetics had vascular complications. Twenty healthy children (mean age--11.58+/-2.89 years) were used as controls. Diabetics showed statistically significant higher levels of FBN-anti-FBN-2 CIC - IgG (0.303+/-0.076 vs. 0.252+/-0.029; p=0.029) and IgM (0.415+/-0.085 vs. 0.348+/-0.069; p=0.018) compared to the control group. FBN-anti-FBN-1 CIC IgM correlate with diabetes duration (r=0.52; p=0.0015) and BMI (r=0.33, p=0.053) while FBN-anti-FBN-1 CIC IgG correlate with serum Zinc (r=0.49, p=0.006). FBN-anti-FBN-2 CIC IgG correlate with microalbuminuria (r=0.65, p=0.0046) and retinopathy (r=0.61, p=0.0001). This study suggests that there may be a relationship of levels of FBN-anti-FBN-2 CIC IgG with the development of diabetic microangiopathy. Of course the number of the tested patients is limited for definitive conclusions. Although the meaning of these results is still being determined, the measurement of FBN-anti-FBN CIC may represent immunologic markers of FBN metabolism.

Antigen-Antibody Complex↗

Serum antibodies to collagen type IV and development of diabetic vascular complications in children with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study.

Thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. To monitor the metabolism of the basement membrane protein collagen type IV (CIV) in diabetes mellitus, serum levels of IgG, IgM and IgA to CIV were measured using an ELISA method in 28 children with Type 1 diabetes mellitus over a period of 6 years. These values were compared to serum antibodies to CIV in 24 age- and sex-matched controls. At the end of the study, 11 children had diabetic microangiopathy. IgG to CIV was associated with age (r = .33, P = .026), diabetes duration (r = .32, P = .021), HbA1c (r = .31, P = .019), microalbuminuria (r = .32, P = .022) and anti-AGE antibodies (r = .47, P = .0007). IgM to CIV correlated with age (r = .46, P = .001), diabetes duration (r = .45, P = .001), HbA1c (r = .26, P = .038) and anti-AGE antibodies (r = .26, P = .038) and IgA to CIV with triglycerides (r = .29, P = .038) and anti-AGE antibodies (r = .44, P = .0025). We suggest that serum levels of IgG to CIV can be used as a marker for the development of diabetic microalbuminuria.

Adolescent↗

Antibodies to advanced glycation end products in children with diabetes mellitus.

The tissue accumulation of advanced glycation end products (AGE) alters the structure and function of long-lived proteins. A number of studies have shown that tissue accumulation of AGE correlates with the severity of diabetic complications. Proteins containing AGE are highly immunogenic and anti-AGE antibodies were found in sera of diabetic rats and human. Considering the potential use of anti-AGE antibodies as a marker of AGE deposition during diabetes, we have investigated, by competitive ELISA, the presence of anti-AGE antibodies in sera of 58 children with Type 1 diabetes mellitus. The patients were studied for the period of 5 years. Positive for anti-AGE antibodies were 19 children with diabetes. Fourteen of them showed initial data for vascular complications. Anti-AGE antibodies were related to age (r = .25, P = .024), duration of diabetes (r = .41, P = .0001), HbA1c (r = .27, P = .016), microalbuminuria (r = .41, P = .0001), retinopathy (r = .35, P = .001), triglycerides (r = .27, P = .016), and total cholesterol (r = .19, P = .05). In conclusion, our study showed that the investigation of the levels and dynamics of anti-AGE antibodies might give the possibility for early diagnosis and prognosis of the severity of diabetic late complications.

Adolescent↗

Detection of serum collagen type IV in children with type 1 (insulin-dependent) diabetes mellitus--a longitudinal study.

The basement membrane is a major focus of scientific interest because of its role in a variety of diseases. In diabetes mellitus, a thickening of the capillary basement membrane results in microangiopathic lesions. To monitor the metabolism of the basement membrane protein collagen type IV (CIV) in diabetes mellitus, serum levels of CIV were measured using an enzyme-linked immunosorbent assay (ELISA) method in 28 children with type 1 diabetes mellitus over a period of 6 years. These values were compared to serum CIV levels in 24 age and sex matched controls. In the first 3 years, serum CIV levels were normal. In the 4th year, 1 patient and in years 5 and 6, 4 patients had increased CIV serum levels. At the end of the investigation, 3 children had developed retinopathy, 6 microalbuminuria, and 2 both microalbuminuria and retinopathy. Only those patients with microalbuminuria had increased CIV serum levels. In conclusion, we suggest that CIV serum levels can be used as a marker for the development of diabetic microalbuminuria.

Journal Article↗

Relationship between elastin-derived peptides and the development of microvascular complications: a longitudinal study in children with Type 1 (insulin-dependent) diabetes mellitus.

Levels of elastin-derived peptides (EDP) were determined by enzyme-linked immunosorbent assay (ELISA) in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5.1+/-2.5 years). None of the children had clinical or laboratory evidence of vascular complications. The children were followed over a period of 6 years, and 24 healthy children of similar age and sex served as a control group. During the investigative period, 10 diabetic patients had increased EDP levels, with 9 having been diabetic for more than 5 years and 1 patient less than 5 years. Seven of these patients developed diabetic microvascular complications. In this group, EDP were independently associated with age (r=.39, P=.047), retinopathy (r=.48, P=.034), and antibodies to advanced glycation endproducts (AGE) (r=.52, P=.018). The data of this pilot study are not strong enough to appear that EDP are a useful predictor of subsequent development of microvascular complications. This may be due to the small number of subjects, short duration of the study, manner in which EDP or the endpoints were measured, or frequency of which EDP measurements were made. Further prospective and longer studies of larger populations are needed to identify the role of EDP as an early marker for the development of diabetic microvascular complications.

Adolescent↗

An association of anti-elastin IgA antibodies with development of retinopathy in diabetic children.

An important factor in the development of vascular wall alterations is degradation of the elastic fiber major protein-elastin. Elastin peptides derived from this degradation are present in the circulating blood and they are a stimulus for increased production of anti-elastin antibodies (AEAb). The aim of the present study was to examine the possible association between serum elastin AEAb and the development of diabetic vascular complications. Levels of AEAb (IgG, IgM and IgA) were determined by ELISA in sera of 28 children with Type 1 (insulin-dependent) diabetes mellitus (mean age 11.6+/-2.8 years, diabetes duration 5.1+/-2.5 years). None of the children had clinical or laboratory evidence of vascular complications. The children were followed over a period of 7 years, and 24 healthy children of similar age and sex served as a control group. During the study, four diabetics developed retinopathy, six microalbuminuria and two both retinopathy and microalbuminuria. Anti-elastin IgG showed correlation with diabetes duration (r=.48, P=.0007), HbA1c (r=.28, P=.05), triglycerides (r=.28, P=.05) and antibodies to advanced glycation endproducts (AGE) (r=.41, P=.005). Anti-elastin IgM correlated with HbA1c (r=.26, P=.038) and IgA with retinopathy (r=.32, P=.017). Our results suggest an association between the level of anti-elastin IgA antibodies and the development of diabetic retinopathy.

Adolescent↗

Age-related changes in the levels of IgG, IgM and IgA antibodies to type I collagen in the sera of normal human subjects.

Serum samples from healthy subjects of different ages (within the age range of 1-75 years) were tested for the presence of anti-type I collagen (anti-CI) IgG, IgM and IgA by enzyme-linked immunosorbent assay (ELISA). All the tested sera showed anti-CI antibodies from the three immunoglobulin classes with the following age-related regularities: 1. Anti-CI IgG and IgM showed statistically non-significant changes up to the age of 60 decreasing thereafter. 2. Anti-Ci IgA changed negligibly up to the age of 40 increasing with age thereafter. The established age-related changes in the levels of anti-CI antibodies may serve as a basis for future studies of normal and pathological turnover of type I collagen.

Adolescent↗

Age-dependent changes in the level of antielastin antibodies of different immunoglobulin classes (IgG, IgM, IgA and IgD) in the human serum.

Serum samples from healthy subjects of different ages (within the age range 1-75 years) were tested for the presence of antielastin IgG, IgM, IgA and IgD by an enzyme-linked immunosorbent assay, utilizing insoluble human aortic elastin. All the tested sera showed detectable levels of antielastin antibodies of the four classes with the following regularities in changing their level with age. Antielastin IgG and IgM showed relatively high levels in the serum of children, growing even higher in the serum of subjects 18-20 years old. Then their levels were stabilized in the serum of 30-60 year olds for IgG and of subjects 30-50 years old for IgM and gradually decreased thereafter. The antielastin IgA showed non-significant changes with age up to the age of 40 and then its level gradually increased. The antielastin IgD showed statistically non-significant changes with age and a tendency to decrease after the age of 60.

Adolescent↗

Immunological investigations on the antigenic changes of human aortic elastin in aging and atherosclerosis.

Alpha-elastin of human aorta was investigated by an enzyme-linked immunosorbent assay (ELISA) on the material isolated from aborted human fetuses and healthy subjects killed by accident, assigned to 7 age groups. Samples up to the age of 55 were taken only from regions without detectable changes in the arterial wall, in the 60-75-year age group--both from normal areas and atherosclerotic plaques of the same aortas. An immune serum against alpha-elastin isolated from the normal aortic areas of a 61-year-old subject was produced in sheep. Testing with this serum showed the existence of some antigenic changes in the elastins from different age groups. A prevalence of the species-specific antigenic determinants was observed in alpha-elastin from fetal aorta while in alpha-elastin from the atherosclerotically altered human aorta the cross-reacting antigenic determinants prevailed in its antigenic structure.

Adolescent↗

Detection of elastin-antielastin circulating immune complexes (CIC) in diabetic patients with vascular damage.

Healthy subjects aged between 25 and 60 (20 cases) and between 61 and 65 (5 cases), and diabetic patients with vascular damage, aged between 24 and 62 (6 cases), were tested by a new method for the detection and identification of elastin-antielastin circulating immune complexes (CIC) in human sera. Such immune complexes were found in all patients' sera and only in one of the controls (at the age of 65). Among different patients, the elastin-antielastin CIC varied in size and elastin content, showing some correlation between these two characteristics and the existence of microvascular complications, as proved by the clinical and paraclinical investigation of the patients.

Adult↗

Age-related changes in anti-elastin antibodies in serum from normal and atherosclerotic subjects.

A modified version of the enzyme-linked immunosorbent assay (ELISA), utilising human insoluble aortic elastin, was used for determination of anti-elastin antibodies in serum from normal and atherosclerotic subjects. The age-related changes in their level among healthy persons were investigated. Anti-elastin antibodies were found in all the tested human sera, showing the highest level at the age of 18-20 and the lowest at the age over 60 and especially among atherosclerotic patients. The possible role of the immune system in the turnover of elastin is discussed.

Adolescent↗

Age-related changes in the level of circulating elastin-derived peptides in serum from normal and atherosclerotic subjects.

The level of the circulating elastin-derived peptides (CEDP) in the serum is believed to reflect the activity of the degradation of the elastic structures. This paper reports a new method, based on the 'sandwich' version of the enzyme-linked immunosorbent assay (ELISA), for the detection and quantification of CEDP in human serum. By this method we investigated the age-related changes in their level among healthy subjects within the age range of 1 and 75 years and among atherosclerotic subjects aged 50 to 75 years. The highest level of CEDP was found in the serum of the atherosclerotic patients, and the lowest, among the healthy subjects between 18 and 50 years of age.

Adolescent↗

Serum cobalt in children with essential hypertension.

The effect of cobalt on the cardiovascular system is one of many aspects of cobalt metabolism in humans. Elastin and collagen are the main proteins of the vascular wall. The aims of this study were: 1) to determine serum cobalt concentrations in children with hypertension; and 2) to study the correlation between serum cobalt and some biological markers of the extracellular matrix of the vascular wall, i.e., anti-elastin and anti-collagen type IV antibodies. Patients showed statistically significant higher levels of systolic and diastolic blood pressure, and significantly lower serum cobalt concentrations, than controls. Children with hypertension showed significantly higher levels of total cholesterol (P = 0.0003) and collagen type IV IgM (P = 0.04). Collagen type IV IgG levels (P = 0.027) were lower than in controls. Serum cobalt in patients showed a correlation with systolic blood pressure (r = -0.44, P = 0.05), elastin IgM (r = 0.60, P = 0.007), and collagen type IV IgG (r = -0.46, P = 0.04). Our data suggest the existence of a correlation between changes in levels of serum cobalt, total cholesterol, anti-collagen type IV antibodies, and essential hypertension in children. This is the first study of serum cobalt in children with essential hypertension.

Adolescent↗