PubMed Health⌕ Search

Biomedical subjects

G Ruotolo

Publications and source records attributed to G Ruotolo.

At least 37 records · Page 2Linked to original sources

The effect of cigarette-smoking on cardiovascular risk factors: a study of monozygotic twins discordant for smoking.

The association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age +/- SD: 47.4 +/- 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 +/- 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants alpha 1-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4% (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p < 0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.

Adult↗

Lipoprotein profile after combined kidney-pancreas transplantation in insulin dependent diabetes mellitus.

In order to evaluate the effect of a combined kidney-pancreas (KP) transplantation in insulin-dependent diabetes mellitus (IDDM) patients on the lipid and lipoprotein profile, 15 KP patients were compared with 11 kidney (K)--transplanted IDDM patients, 19 IDDM patients on hemodialysis (HD), and 15 nondiabetic control subjects. Cholesterol, triglycerides, apo AI, and apo B were measured in total plasma and in VLDL, LDL, and HDL of all participants. VLDL cholesterol, VLDL-triglycerides, and VLDL-apo B were significantly lower in KP patients, but not in K patients, than in HD patients. In addition, patients in the K, but not in the KP, group showed high levels of apo B in LDL and an increased triglyceride/apo B ratio in VLDL, compared with patients in the HD group. The percentage of apo AI associated with HDL was significantly higher in both transplanted groups than in the HD group. However, compared with a nondiabetic control population, an increase in VLDL particles and in triglyceride content in LDL and HDL still persisted following combined KP transplantation. Insulin resistance (probably due to steroid therapy) associated with high peripheral and potentially low hepatic insulin levels (due to the systemic drainage of the transplanted pancreas) could be the main causes of the remaining lipoprotein abnormalities.

Adult↗

Prevalence of NIDDM and impaired glucose tolerance in Italy: an OGTT-based population study.

To provide complete prevalence data on diabetes mellitus in Italy (diagnosed and undiagnosed), a population survey was performed in the Health District of Cremona, a representative area of the Po river (north Italy). The survey is characterised by particular attention being paid to methodology, non-responders being investigated for possible selection biases affecting diagnosed and undiagnosed diabetes prevalence estimations. Out of a population aged 44 years or older from three municipalities, a random sample of 3097 subjects was selected to undergo an oral glucose tolerance test. In addition, past medical history, clinical and laboratory data were collected. A total of 1797 subjects participated (58%), and information on known diabetes status was obtained for 2618 persons (85%), also including 826 interviewed non-participating subjects. Overall rates were age-standardised according to the 1991 Italian census. Overall prevalence and 95% confidence interval of diagnosed diabetes was 8.5% (6.9-10.1) in males and 7.9% (6.7-9.3) in females over the age of 44 years; previously undiagnosed diabetes was 2.5% (1.4-3.6) in males and 3.4% (2.1-4.7) in females; glucose intolerance was 7.7% (5.7-9-7) in males and 8.9% (7.0-10.8) in females. Total diabetes prevalence above age 44 years, developed-world age, and sex standardised, was 10.7%. This study provides the first reliable prevalence estimation of impaired glucose tolerance, diagnosed and undiagnosed diabetes in Italy, according to World Health Organization criteria, and one of the few figures for Southern Europe. The role of body mass index on both prevalence of diabetes and cluster of cardiovascular risk factors is considered, with implications for prevention.

Age Factors↗

Evidence that apolipoprotein(a) phenotype is a risk factor for coronary artery disease in men < 55 years of age.

Whereas the importance of plasma lipoprotein(a) [Lp(a)] levels as a risk factor for premature coronary artery disease (CAD) is certain, it is not clear if the apolipoprotein(a) [apo(a)] phenotype plays an additional and independent role. To investigate the possible effect of apo(a) phenotype on premature CAD (in patients < 55 years of age), plasma Lp(a) concentrations, the apo(a) phenotypes, and their relation with many recognized CAD risk factors were examined in 96 non-diabetic male patients with angiographically defined CAD and in 83 age-matched male control subjects with no angiographic evidence of CAD. Results demonstrate that patients with premature CAD are characterized by higher Lp(a) levels (24 +/- 21 vs 17 +/- 15 mg/dl, p < 0.01) and a higher frequency of S2 phenotype (32% vs 15%, p < 0.01). Patients with an S2 phenotype exhibited significantly higher plasma Lp(a) concentrations than control subjects with the same isoform (37 +/- 22 vs 22 +/- 17 mg/dl, p < 0.05). A significant correlation was found between apo B and Lp(a) levels in patients with an S2 phenotype. In addition, patients had a low frequency of S1 and S4, and a high frequency of double-band phenotypes of apo(a). Multivariate analysis did not demonstrate an independent role for apo(a) phenotype as a risk factor for premature CAD. In conclusion, CAD patients < 55 years of age have a very different pattern of apo(a) phenotypes than subjects with no angiographic evidence of CAD; this study confirms the hypothesis that apo(a) phenotype may play an additional role in the etiology of premature CAD.

Apolipoproteins↗

Normalization of lipoprotein composition by intraperitoneal insulin in IDDM. Role of increased hepatic lipase activity.

OBJECTIVE: To characterize the effects of intraperitoneal insulin pump therapy on lipoprotein composition and lipolytic enzyme activity in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Ten IDDM patients were studied 3 times: when receiving conventional subcutaneous insulin therapy and at 3 and 9 months from the initiation of intraperitoneal insulin regimen. Ten nondiabetic subjects matched for age, sex, and body weight were studied as controls. Levels of cholesterol, triglycerides, apolipoprotein A-I (apoA-I) and B (apoB) were measured in total plasma and lipoprotein fractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]: HDL2 and HDL3). Postheparin plasma lipoprotein lipase and hepatic lipase activities were determined by an immunochemical method. RESULTS: IDDM patients showed higher levels of HDL3 and lower levels of HDL2 particles during intraperitoneal insulin therapy in comparison with subcutaneous insulin therapy. Both cholesterol and apoA-I significantly increased in HDL3 and decreased in HDL2 during intraperitoneal treatment. Plasma total cholesterol significantly decreased in the diabetic patients at 3 months of intraperitoneal insulin therapy compared with both subcutaneous insulin regimen and control subjects. IDL triglyceride concentrations during intraperitoneal treatment were significantly lower than those seen with subcutaneous therapy. Furthermore, triglyceride:apoB ratio in VLDL and cholesterol:apoB ratio in LDL significantly decreased in IDDM patients treated by intraperitoneal insulin. A significant increase in the activity of hepatic lipase with intraperitoneal insulin therapy by 9 months compared with subcutaneous insulin therapy has been shown. CONCLUSIONS: The increased activity of hepatic lipase after intraperitoneal insulin administration in IDDM patients appears to be one of the main determinants of lipoprotein changes observed, resulting in the normalization of lipoprotein composition during this mode of therapy. The normal inverse relationship between VLDL triglycerides and HDL cholesterol, which was not present in IDDM patients with subcutaneous therapy, was restored with intraperitoneal insulin regimen.

Adult↗

Acute presentation of Tangier polyneuropathy: a clinical and morphological study.

We describe a patient with Tangier disease and a peripheral neuropathy with an unusual acute onset. The morphological studies of sural nerve biopsy revealed both axonal degeneration and demyelination, and the fiber loss was preferentially restricted to two of ten nerve fascicles. The cytoplasm of Schwann cells, fibroblasts, macrophages and pericytes were vacuolated because of the presence of numerous lipid droplets. The clinical and morphological findings are consistent with the possibility that ischemia plays a major role in causing this neuropathy.

Female↗

[The diagnosis and therapy of hyperprolactinemia].

Hyperprolactinaemia is the most common result of pituitary dysfunction and is characterized by alteration on the reproductive function. After a review of the hypothalamic control mechanisms and of the local paracrine and autocrine factors regulating prolactin secretion, the most common physiological, pharmacological and pathological causes of hyperprolactinaemia are described. The clinical pictures of hyperprolactinaemia in man and woman are then summarized. The diagnostic protocol used in this Institute is then described: confirmation of the existence and entity of hyperprolactinaemia by means of a prolactin profile; exclusion of pharmacological or extra pituitary causes (cirrhosis, primitive hypothyroidism, chronic renal failure, etc.); neuro-radiological evaluation of the sella region, by means of standard X-ray, computer tomography scan, nuclear magnetic resonance. The drugs commonly used in medical treatment of hyperprolactinaemia such as a bromocriptine, other-derived compounds and then recent CV 205-502, and the surgical approaches (trans-sphenoidal and transcranial routes) are reported. The indication of medical or surgical treatment and the relevance of radiotherapy are finally considered.

Combined Modality Therapy↗

Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet.

The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL-decreasing effect of this dietary change.

Adult↗

Protocol for the study of the metabolism of retinyl esters in plasma lipoproteins during postprandial lipemia.

An efficient protocol is described for the study of the kinetics of retinyl esters in whole plasma and several lipoprotein fractions following the consumption of an oral fat load containing vitamin A (retinol). To allow for a more complete characterization of the kinetics of retinyl esters in different lipoprotein fractions, a simplified two-step ultracentrifugation procedure is reported for the efficient and reproducible isolation of triglyceride-rich chylomicrons from nonfasting subjects, VLDL-sized lipoprotein particles, and the triglyceride-poor lipoprotein fraction. The present method for the determination of retinyl esters is based on the direct application of the lipid fraction onto a normal phase HPLC column without requiring the lipid extract to be desiccated and resolubilized. All of the commonly occurring esters of retinol elute as a single peak with a retention time of 1.6-1.8 min followed by retinyl acetate (serving as the internal standard) and retinol with retention times of 2-2.5 min and 5-5.5 min, respectively. With this system, a new sample can be processed every 10 min and a complete set of 60 samples from a typical oral fat load can analyzed in one working day with minimal technical interaction. By normalizing to the area under the internal standard to correct for variability in the injected volume, the coefficient of variability for the concentration retinyl esters within a single run is less than 5% and less than 10% between runs.

Chemical Fractionation↗

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus.

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo(a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo(a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276 +/- 78 vs 149 +/- 46 units/l). Type 2 diabetic patients had considerably higher levels of apo(a) than matched controls (471 +/- 89 vs 221 +/- 61 units/l, P = 0.06), though the difference was not statistically significant. However, concentrations of apo(a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo(a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo(a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo(a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.

Adult↗

Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes.

In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential.

Adult↗

Energy expenditure in humans: effects of dietary fat and carbohydrate.

A high-dietary fat intake may be an important environmental factor leading to obesity in some people. The mechanism could be either a decrease in energy expenditure and/or an increase in caloric intake. To determine the relative importance of these mechanisms we measured 24-h energy expenditure in a whole body calorimeter in 14 nondiabetic subjects and in six subjects with non-insulin-dependent diabetes mellitus, eating isocaloric, weight-maintenance, high-fat, and high-carbohydrate diets. All subjects were Pima Indians. In nondiabetics, the mean total 24-h energy expenditure was similar (2,436 +/- 103 vs. 2,359 +/- 82 kcal/day) on high-fat and high-carbohydrate diets, respectively. The means for sleeping and resting metabolic rates, thermic effect of food, and spontaneous physical activity were unchanged. Similar results were obtained in the diabetic subjects. In summary, using a whole body calorimeter, we found no evidence of a decrease in 24-h energy expenditure on a high-fat diet compared with a high-carbohydrate diet.

Adult↗

Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians.

The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio.

Apolipoproteins B↗