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Biomedical subjects

M Cassader

Publications and source records attributed to M Cassader.

At least 55 records · Page 3Linked to original sources
PubMed1997

Qualitative analysis of the carbohydrate composition of apolipoprotein H.

The specific binding of digoxigenin-labeled lectins to carbohydrate moieties is used to characterize the carbohydrate chains bound to apolipoprotein H. Our results show that apolipoprotein H is rich in sialic acid linked alpha(2-6) to galactose or N-acetylgalactosamine. Sialic acid is not alpha(2-3)-linked to galactose. Galactose is beta(1-4)-linked to N-acetylglucosamine and beta(1-3)-linked to N-acetylgalactosamine. High-mannose N-glycan chains are barely detectable. After N-glycosidase F treatment the molecular weight is substantially reduced. The main band is 32,500 daltons. Carbohydrate O-linked chains, which are mainly represented by sialic acid, are alpha(2-6)-linked to galactose or N-acetylgalactosamine. Galactose is also organized in O-linked chains and it is beta(1-4)-linked to N-acetylglucosamine and beta(1-3)-linked to acetylgalactosamine. Biochemical analysis of carbohydrate structures reveals that no specific carbohydrate complex is bound to a single isoform.

Acetylgalactosamine↗
PubMed1997

Influence of APOH protein polymorphism on apoH levels in normal and diabetic subjects.

Apolipoprotein (apo)H (also known as beta 2 glycoprotein-I) is a glycoprotein synthesized by liver cells and it is present in the blood associated with plasma lipoproteins. APOH displays a genetically determined structural polymorphism: three alleles (APOH*1, APOH*2, APOH*3) at a single locus on chromosome 17 code for different isoforms, and population studies have shown that APOH*2 is the most frequent allele. This paper assesses the relation between APOH phenotypes and plasma apoH levels in a population composed of 278 healthy subjects (243 H2/2, 32 H3/2, 2 H3/3, 1 H2/1; allele frequencies APOH*1 0.002, APOH*2 0.934, APOH*3 0.064) and 245 diabetics (212 H2/2, 30 H3/2, 3 H3/3; allele frequencies APOH*2 0.927 and APOH*3 0.073). Determination of apoH levels by competitive ELISA gave a mean value of 26.3 +/- 9.8 mg/dl for all subjects, 22.6 +/- 7.7 in normals vs 30.6 +/- 10.3 in diabetics (p = 0.0001), and 23.0 +/- 7.9, 19.3 +/- 5.4 and 18.5 +/- 3.5 mg/dl for H2/2, H3/2 and H3/3 in normals and 31.1 +/- 10.1, 28.2 +/- 10.8 and 15.7 +/- 9.0 mg/dl in diabetics, respectively. ANCOVA of the adjusted data revealed a significant difference in apoH levels for the three phenotypes in both the normal subjects (p = 0.01) and the diabetics (p = 0.02). ANCOVA of the whole samples of subjects, controlling for diabetes as well as age, sex and total cholesterol, indicated a substantial effect of phenotype, independent of the other variables (p = 0.0007).

Adult↗
PubMed1996

Postprandial triglyceride-rich lipoprotein changes in elderly and young subjects.

To determine whether an increased risk for atherosclerosis in older humans is related to changes in postprandial lipoprotein metabolism, we compared the dynamic profiles (0-10 hours) of triglyceride (Tg)-rich lipoproteins and the Tg content in VLDL subfractions in elderly and young subjects after an oral fat load. The plasma Tg response curves displayed significant differences between the groups at all times. Postprandial triglyceridemia was quantified from the plasma response curves as an incremental area, and was significantly different in the two groups (young subjects 231.9 +/- 199.6 vs elderly subjects 511.0 +/- 305.6 mg/dL x 10 hr, p = 0.036). The more scattered VLDL-Tg values were significantly different compared to values at baseline and 6 hours after fat load. Tg baselines in the four VLDL subfractions (expressed as percentages) were higher in the larger particles (B Sf = 175-400) in the elderly subjects, and in the smaller, denser particles (D Sf = 20-100) in the young subjects. In both groups, postprandial hyperlipidemia increased the Tg content of the larger, less dense particles (Sf more than 400), and reduced that of the denser particles. These variations usually coincided with the plasma Tg and VLDL peaks: 63% to 70% above the Tg baseline between the 2nd and 4th hour in all the young subjects: 48% to 68% above the baseline between the 4th and the 6th hour in all the elderly subjects. Total cholesterol variations showed no significant differences between the two groups at any time. All subjects tested for the missense mutation at codon 188 of the human lipoprotein lipase (LPL) gene resulted noncarriers of LPL mutant alleles. Our data show that, after a fatty meal, healthy elderly subjects tend to present prolonged postprandial hypertriglyceridemia, suggesting an atherogenic behavior of their lipid metabolism.

Adult↗
PubMed1996

Insulin resistance shows selective metabolic and hormonal targets in the elderly.

There has been no simultaneous evaluation of different aspects of insulin action in ageing. We studied 12 elderly (77 +/- 2 years) and 12 young (26 +/- 1 years) subjects with normal glucose tolerance and matched for sex, body mass index, lean body mass (LBM), blood pressure and physical activity, using a euglycaemic-hyperinsulinaemic clamp at about 350 pmol L-1 in combination with [3H]-glucose infusion. In the elderly group, hepatic glucose production was normal, fasting serum insulin and C-peptide were significantly increased (P = 0.001) and glucose utilization (34.4 +/- 2.4 vs. 44.4 +/- 3.2 mumol kg-1 LBM min-1, P = 0.02) and the percentage maximal suppression of C-peptide (58 +/- 6% vs. 79 +/- 5%, P = 0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and glycerol levels were similar in the two groups, but their percentage maximal suppression during the clamp was reduced in the elderly group (FFA 45 +/- 5% vs. 77 +/- 6%, P = 0.001; glycerol 43 +/- 5% vs. 76 +/- 3%, P = 0.001). Branched-chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar in the two groups, both while fasting and during the clamp. Thus, insulin resistance in ageing appears selective on glucose utilization, inhibition of lipolysis and feedback inhibition of the B-cell secretion.

Adult↗
PubMed1996

Apolipoprotein H: a two-step isolation method.

A new method for the purification of apolipoprotein H by affinity chromatography followed by continuous-elution electrophoresis is described. It is both simpler and less complicated than the chromatographic and electrophoretic methods usually used. In addition, apolipoprotein H is isolated in a pure, structurally uncleaved form. This is of importance, as impairment has been detected in commercial preparations. The separation and purification of apolipoprotein H is a necessary prelude to its quantitative determination and phenotyping, and hence the clarification of its physiopathological mechanisms in lipid metabolism.

Amino Acid Sequence↗
PubMed1995

Apolipoprotein E allele frequencies in an Italian population: relation to age and lipid profile.

Apo E phenotype and plasma Tg, Chol, LDL-Chol, HDL-Chol and Apo B levels were determined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93. The allele frequencies were: epsilon 2 = 0.070; epsilon 3 = 0.829; epsilon 4 = 0.101 (among the lowest values in the literature). Division of the sample into four age groups indicated that epsilon 4 frequency decreased with age to 0 in persons aged over 75. Covariance analysis of the influence of each allele on plasma lipids showed that epsilon 4 was significantly associated with the highest Chol, LDL-Chol and Apo B levels. These data are evidence of the influence of epsilon 4 on Chol metabolism in an Italian population. They also show that its frequency decreases with age.

Adolescent↗
PubMed1994

Influence of apolipoprotein H polymorphism on levels of triglycerides.

Human apolipoprotein H (apo H) displays a genetically determined structural polymorphism: three alleles (H*1, H*2 and H*3) on chromosome 17 code for the six phenotypes (three homozygotes and three heterozygotes). The effect of apolipoprotein polymorphism on individual variations in plasma lipoprotein levels has been underscored in recent years. Since apo H is involved in metabolism of triglycerides (Tg), its phenotype could affect Tg levels. This paper reports an investigation of apo H phenotypes in a sample of 217 subjects of the Italian population by means of isoelectrofocussing followed by immunoblotting. The levels of the main lipid parameters were evaluated in relation to phenotype and other influential factors. Analysis of covariance disclosed a significant association between Tg levels (log transformed) and phenotype (F = 8.27, P = 0.004). Comparison of Tg levels between bearers of the two most frequent phenotypes (H2/2 and H3/2) divided by sex and age classes revealed significantly higher levels in male H3/2 heterozygotes (P = 0.0053) and in H3/2 subjects aged less than 50 (P = 0.0095). Our data support the view that there is an association between hypertriglyceridaemia and apo H polymorphism, especially with the H*3 allele.

Apolipoproteins↗
PubMed1994

Serum glucose, insulin and C-peptide response to oral glucose after intravenous administration of hydrocortisone and methylprednisolone in man.

Glucocorticoid-induced glucose intolerance and insulin resistance are dependent on the type of steroid, its dose and route of administration. Although the intravenous (i.v.) route is used mainly, the effects of different steroids have so far been compared using the oral route. The present study was therefore planned to compare the effects on glucose metabolism of hydrocortisone (HC) and methylprednisolone (MP) administered i.v. at equivalent antiinflammatory doses in healthy subjects. Eighteen healthy volunteers with normal glucose tolerance, divided into three groups (A,B,C) matched for age, sex and body mass index were subjected to oral glucose tolerance tests (oGTT) 12 h after HC or MP i.v. injection. The two tests were performed at a 1-month interval and in random sequence. Group A received low doses (HC 100 mg, MP 20 mg), group B intermediate doses (HC 200 mg, MP 40 mg) and group C high doses (HC 400 mg, MP 80 mg). Serum glucose, insulin and C-peptide were measured during both fasting and oGTT. Serum glucose values were not significantly different after HC or MP, during both fasting and oGTT. However, there was a positive correlation between fasting serum glucose or the area under the glucose curve and the dose.kg-1 body weight of HC (r = 0.748; r = 0.462) and MP (r = 0.708; r = 0.736). Serum insulin values were significantly higher after MP than after HC when fasting (A: 115 vs 223; B: 95 vs 215, C: 158 vs 268 pmol.l-1) and as area under the oGTT curve (A: 57.8 vs 87; B: 48.5 vs 92.1; C:57.8 vs 94.5 pmol.l-1 x 2 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Total parenteral nutrition in critical patients. The metabolic-nutritional aspects and effects on immune function of 2 different isocaloric-isonitrogenous regimens].

The aim of this investigation was to compare, in a randomized short-term study the effects on some parameters evaluating lipid metabolism, nutritional status and immune function of two different patients. Particularly, the influence of the intravenous (i.v.) infusion of a fat emulsion on above-mentioned parameters was evaluated. The two regimens (G and GL) were isocaloric (about 30 kcal.kg-1.d-1 non protein energy) and isonitrogenous (about 0.27 g.kg-1.d-1 nitrogen); the only difference was the source of non-protein calories administered. Regimen G consisted of glucose-based TPN (100% of non-protein energy as glucose) whereas, in regimen GL (glucose-lipid-based TPN), the 55% of non-protein caloric supply was given as glucose and 45% as lipids. 9 of the patients were randomly assigned to receive regimen GL (group GL) and 8 to receive regimen G (group G). TPN was delivered through a central vein catheter for 8 days; during this period no hepatic or metabolic complications have been observed. Clinical and laboratory tests were performed at day 0 (enrollment), at day 4 (after 4 days of TPN) and at day 8 (at the end of TPN). Both regimens of TPN were able to induce an improvement of the nutritional status and serum prealbumin (TBPA) significantly increased in all patients (p < 0.05). The results of the immune measurements showed that no significant change in immune function during the administration of either regimen occurred. However, in group GL, we observed a slight, non significant change in the percentage numbers of T-cells subpopulations that resulted in a decrease in the ratio of helper to suppressor T-cells (H:S). Serum lipids and lipoprotein profile didn't change significantly in group GL. On the contrary, in group G, we observed a significant decrease in serum concentrations of HDL cholesterol (p < 0.05), LDL cholesterol and apo A1 (p < 0.01) while total cholesterol remained unchanged; a non significant rise in serum triglyceride also occurred, These results show that the two regimens had a similar impact on nutritional status in both groups. The i.v. infusion of the fat emulsion didn't alter lipid profile and was not associated with an impairment of some aspects of the immune function. In conclusion, our results confirm that fat emulsions represent an important component of i.v. nutritional support regimens and should continue to be used when and where indicated in short-term TPN. However, long-term effects of i.v. infusion of fat emulsions on the immune systems should be further investigated, in a more substantial number of patients.

Adult↗
PubMed1993

Feedback inhibition of insulin and glucagon secretion by insulin is altered in abdominal obesity with normal or impaired glucose tolerance.

We investigated the feedback inhibition of insulin and glucagon secretion during euglycemic-hyperinsulinemic clamp at about 350 pmol/l in 16 patients with abdominal obesity [8 with normal glucose tolerance (oNGT), 8 with impaired glucose tolerance (oIGT)] and 8 normal-weight subjects matched for age, sex and blood pressure. In oNGT and oIGT, fasting plasma C-peptide levels were twice those in the controls (962 +/- 51 and 915 +/- 85 vs 439 +/- 28 pmol/l, P < 0.001) and their suppression was lower than in the controls, both in absolute terms (155 +/- 19 and 185 +/- 17 vs 274 +/- 18 pmol/l, P < 0.001) and as a percentage decline from basal levels (16 +/- 2% and 21 +/- 2% vs 63 +/- 2%, P < 0.001). Fasting plasma glucagon levels were similar in the patients and in the controls, but were less suppressed during clamp in oNGT and oIGT, both in absolute terms (7.0 +/- 0.9 and 5.6 +/- 0.6 vs 13.2 +/- 1.2 pmol/l, P < 0.001) and as a percentage change from basal levels (23 +/- 3% and 19 +/- 2% vs 44 +/- 4%, P < 0.001). These results suggest that the insulin feedback on B and A cells is impaired in abdominal obesity, and that this defect is of similar degree in oNGT and oIGT. These alterations could be implicated in the pathogenesis of hyperinsulinemia in obesity.

Adult↗
PubMed1993

Hypercholesterolemia in non-insulin-dependent diabetes mellitus: different effect of simvastatin on VLDL and LDL cholesterol levels.

Non-insulin-dependent diabetes mellitus (NIDDM) is often characterized by an increase in VLDL-triglyceride, VLDL-cholesterol, LDL-cholesterol and a reduction in HDL-cholesterol. HMG-CoA reductase inhibitors significantly lower cholesterol rates and have an indirect effect on the LDL receptor. We measured the effect of simvastatin in 28 hypercholesterolemic subjects, including 14 with NIDDM in good metabolic control (HbAIc 7.8% +/- 1.3%). A 24-week treatment with 10 mg/day (weeks 1-4), 20 mg/day (weeks 5-8) and 40 mg/day (weeks 9-24) simvastatin revealed different responses in diabetic and non-diabetic patients. Total cholesterol, LDL-cholesterol and apo B decreased significantly in both groups (less in the diabetics), whereas only NIDDM patients displayed a significant reduction in VLDL-cholesterol and VLDL-apo B. In the non-diabetics, the reduction in plasma cholesterol was mainly confined to the LDL fraction (276 +/- 65 vs. 132 +/- 28 mg/dl), whereas a significant fall in VLDL-cholesterol (45 +/- 19 vs. 21 +/- 10 mg/dl) was more evident in the NIDDM patients. Simvastatin also influenced plasma apo B levels (221 +/- 33 vs 134 +/- 23 mg/dl in non-diabetics and 182 +/- 44 vs. 134 +/- 30 mg/dl in diabetics). Significant reduction of apo B, LDL-apo B (205 +/- 39 vs. 128 +/- 23 mg/dl) in the non-diabetics and VLDL-apo B (16 +/- 5 vs. 9 +/- 2 mg/dl) in the diabetics, indicates that the VLDL are primarily concerned when statins are administered in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1993

Bezafibrate affects lipid, lipo- and apolipoprotein pattern in non-insulin-dependent diabetic patients.

To assess bezafibrate efficacy in a diabetic population a single-blind randomized study was performed in 32 diet-resistant type IIb hyperlipidaemic non-insulin-dependent (NID) diabetic patients in good metabolic control (HbA1c < 8%) compared to a placebo group. In our diabetic patients one month treatment of 400 mg/day bezafibrate lowered plasma C (-14%) and TG (-37%) and globally reduced the VLDL particles and VLDL lipids (-37% for C, -56% for TG and -25% for PL), raising VLDL C/TG ratio (+46%), redistributing TG from VLDL to LDL (+10%) and mainly in HDL (+49%), lowered LDL-C and Apo B levels and increased HDL-C together with Apo A1 (+19% and +13%) and Apo A1/Apo B (+72%). PL were raised by bezafibrate treatment and were redistributed from VLDL (-25%) to LDL (+25%) and HDL (+18%), while PL/C ratio increased in VLDL and in LDL (+18% and +50% respectively). Bezafibrate use was safe and improved the lipid pattern and the apolipoprotein and lipid distribution in the lipoproteins, producing a less atherogenic pattern in our NID diabetics.

Apolipoproteins↗
PubMed1992

The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study.

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1991

Lipoprotein-apolipoprotein changes in renal transplant recipients: a 2-year follow-up.

Renal transplantation modifies the dyslipidemia characteristic of chronic renal failure (CRF). The change in lipoprotein and lipid values of 51 transplant recipients, on cyclosporine and corticosteroid treatment, was studied during 2 years after transplantation to examine the short- and medium-term variations of lipid metabolism. Compared with control values of (all in mg/dL) triglycerides (Tg) 111 +/- 44, very-low-density lipoprotein (VLDL) Tg 69 +/- 18, total cholesterol (Chol) 201 +/- 32, VLDL-Chol 32 +/- 9, low-density lipoprotein (LDL) Chol 118 +/- 28, and high-density lipoprotein (HDL) Chol 50 +/- 10, uremic patients pretransplantation exhibited values of Tg 200 +/- 82 (P less than .001), VLDL-Tg 133 +/- 70 (P less than .001), Chol 193 +/- 51 (NS), VLDL-Chol 52 +/- 16 (P less than .001), LDL-Chol 100 +/- 37 (P less than .007), HDL-Chol 40 +/- 16 (P less than .001), which changed to Tg 118 +/- 18 (P less than .001), VLDL-Tg 64 +/- 45 (P less than .001), Chol 223 +/- 48 (P less than .006), VLDL-Chol 26 +/- 33 (P less than .001), LDL-Chol 134 +/- 43 (P less than .001), at HDL-Chol 63 +/- 21 (P less than .001) at 3 months and Tg 135 +/- 76, VLDL-Tg 81 +/- 62, Chol 218 +/- 55, VLDL-Chol 22 +/- 20, LDL-Chol 139 +/- 46, and HDL-Chol 58 +/- 18 at 24 months without evidence of a significative variations in the 3- to 24-month posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗