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Biomedical subjects

C Cortese

Publications and source records attributed to C Cortese.

At least 55 records · Page 3Linked to original sources
PubMed1991

Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia.

It is well known that hypercholesterolemia is correlated with coronary atherosclerosis, but no definite information is available on its association with cerebrovascular atherosclerosis. We studied 10 young patients (age 3-32 years) with homozygous familial hypercholesterolemia (FH), together with 3 normal relatives as healthy controls. Extra- and intracranial Doppler examination, MRI and cerebral blood flow by SPECT and 99mTc-HM-PAO were performed on all. Six out of 10 patients already had signs and symptoms of coronary heart disease, but all patients were free from ischemic brain lesions, as small as detectable at MRI, and had normal cerebral blood flow. Two patients presented significant stenosis of the carotid arteries at Doppler examination. Young patients with homozygous FH have early and clinically evident coronary atherosclerosis, while overt disease in the cerebral district is delayed despite the extremely elevated plasma cholesterol concentration. This was also confirmed by the autopsy of two patients, who died after the study and whose cerebral arteries were totally free from atherosclerotic lesions. The age, at which flow-reducing atherosclerotic lesions develop in hypercholesterolemic patients, differs with regard to the arterial district involved.

Adolescent↗
PubMed1991

Modulation of transforming growth factor-beta production in normal human osteoblast-like cells by 17 beta-estradiol and parathyroid hormone.

Although our laboratory has reported that normal human osteoblast-like (hOB) cells contain estrogen receptors, we have failed to find major effects of 17 beta-estradiol (E2) on modulation of proliferation of bone matrix protein production by hOB cells. Because the major effect of E2 in vivo is to decrease bone resorption and because transforming growth factor-beta (TGF-beta) has been reported to decrease osteoclast-mediated bone resorption, we have tested the hypothesis that the effect of E2 on osteoclast activity is, at least in part, indirectly mediated by enhancing production of TGF-beta by osteoblasts. We therefore have extended our studies to examine possible TGF-beta gene expression including the modulation of the release of TGF-beta by E2 in near homogenous populations of hOB cells. TGF-beta protein production was measured using growth inhibition of CCL-64 cells and verified by blocking effects with anti-TGF-beta antibodies. TGF-beta 1 messenger RNA (mRNA) steady state levels were assessed by northern blot analysis and quantitated by densitometric measurement using 18S ribosomal RNA as a reference. There was an E2 dose-dependent increase in TGF-beta protein production within 24 h of challenge with E2. Northern blots from these cells demonstrated a dose-dependent increase in steady state mRNA levels of TGF-beta 1 within 6 h of treatment. PTH was also a potent stimulator of TGF-beta protein and message levels in a dose-dependent manner. Interestingly, coincubation of equimolar concentrations of E2 and PTH (10(-8) M) abrogated the stimulation of TGF-beta 1 mRNA and protein. Decreasing the relative concentration of PTH in this coincubation with E2 increased TGF-beta 1 mRNA and protein levels. These data support the fact that E2 modulates TGF-beta production in osteoblasts. In this manner TGF-beta may mediate E2 inhibition of osteoclast activity.

Blotting, Northern↗
PubMed1990

Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia.

Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment.

Apolipoproteins↗
PubMed1990

Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia.

Repeat low density lipoprotein (LDL) apheresis and blood flow determinations in the forearm and leg were performed in 10 patients (age range, 13-49 years; four male, six female) with familial hypercholesterolemia (eight homozygous, two heterozygous). To perform LDL apheresis, plasma was first separated by a polysulphone hollow fiber filter; then, LDL was selectively removed from plasma by dextran sulphate cellulose beads packed in columns. Blood flows in the forearm and leg were determined at rest and during a reactive hyperemia test (peak flow). This test was performed noninvasively by a strain-gauge plethysmograph with semicontinuous registration of arterial blood flow variables before the first apheresis and 3 weeks after the last of six procedures for apheresis. Resting arterial blood flows in the forearm and leg were slightly increased after repeat LDL apheresis (p less than 0.05). Peak blood flow in the leg significantly increased (+34%, p less than 0.01). No change in peak blood flow in the forearm was observed. Systolic blood pressures were slightly but significantly reduced (p less than 0.05); forearm peripheral resistances were also reduced (p less than 0.05). Flow response was not related to LDL receptor status. Blood and plasma viscosities were determined before and 7 days after the last apheresis. Blood viscosity was significantly reduced after LDL apheresis at shear rates of 11.25-450 sec-1. Plasma viscosity did not change.

Adolescent↗
PubMed1989

Plasma lipids and geriatric assessment in a very aged population of south Italy.

A very old population of a rural area of Southern Italy with a mean age of 87 years was investigated in order to evaluate serum lipid levels and their possible association with health conditions, such as mental status, social behaviour and physical autonomy. Among 101 subjects with ages above 82 years, 73 were investigated (participation rate 72%, 31 men and 42 women). Mean +/- SD serum cholesterol level was 199 +/- 36 and 210 +/- 40 mg/dl and mean serum triglyceride level was 107 +/- 43 and 148 +/- 74 mg/dl (P less than 0.05) in men and women, respectively. Mean high density lipoprotein (HDL)-cholesterol level was 49 mg/dl in both sexes. All subjects were investigated by means of geriatric and neuropsychometric scales such as Sandoz Clinical Assessment Geriatric Scale (SCAGS), Hachinski Dementia Scale (HDS), Plutchik Geriatric Rating Scale (PGRS) and Indexes of Activity of Daily Living (ADL). When subjects were divided into 3 groups according to levels of serum lipids, HDL-cholesterol appeared to be better related to clinical conditions than total serum cholesterol: the group with the higher HDL-cholesterol level presented better scores at all the administered assessment scales when compared to the groups with lower and modal levels (P range between less than 0.05 and less than 0.001). Subjects in the higher serum cholesterol group presented better scores at PGRS only (P less than 0.01). No relation was observed between serum total triglyceride levels and geriatric assessment scores.

Activities of Daily Living↗
PubMed1989

Short-term effects of moderate alcohol consumption on lipid metabolism and energy balance in normal men.

The short-term effects of moderate alcohol consumption on energy balance, serum lipids, and lipoproteins were studied in eight healthy middle-aged men (age 30 to 47 years and body mass index 23.1 to 27.7 w/h2). A crossover dietary trial included two isocaloric periods without (20% protein, 50% carbohydrate, 30% fat) or with alcohol (12% protein, 29% carbohydrate, 25% fat, 75 g of alcohol as red wine). Each period lasted 2 weeks. The body weight of the subjects remained stable over the study. Fasting blood glucose, serum insulin, total cholesterol, and LDL cholesterol were similar at the end of both dietary periods. Mean values of serum total triglyceride (108 +/- 18 v 85 +/- 24 mg/dL, P less than 0.05), VLDL-Tg (88 +/- 24 v 73 +/- 16 mg/dL, NS), and total HDL cholesterol (49.4 +/- 6.0 v 43.4 +/- 5.5 mg/dL, P less than 0.05) were higher after the diet with alcohol than without alcohol. The increase of HDL cholesterol was primarily due to that of HDL2 cholesterol (10.4 +/- 5.1 v 5.7 +/- 3.9 mg/dL, P less than 0.05). The concentration of apoprotein A-I, A-II, and B averaged 104 +/- 17 v 89 +/- 16 mg/dL, 33 +/- 4 v 28 +/- 8 mg/dL, P less than 0.02, and 111 +/- 24 v 105 +/- 33 mg/dL after the diets with and without alcohol, respectively. Adipose tissue LPL activity increased in six of the eight volunteers during the diet with alcohol. Resting metabolic rate, postprandial energy expenditure, and postprandial responses of blood glucose, serum insulin, triglyceride, and plasma FFA were similar after the both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Abnormalities in serum lipoprotein composition in patients with premature coronary heart disease compared to serum lipid matched controls.

Serum lipoprotein composition was examined in 18 male patients (mean age 44 +/- 0.9 years) who had undergone coronary artery by-pass surgery because of premature coronary heart disease (PCHD) and in 18 control subjects, matched with patients for sex, age, body mass index and serum cholesterol and triglyceride. Cholesterol, triglyceride and apolipoprotein B (apo B) concentrations in very low density lipoprotein (VLDL) and in low density lipoprotein (LDL) did not differ in the two groups, but high density lipoprotein (HDL)-cholesterol was significantly lower in PCHD patients (P less than 0.02). Cholesterol/apo B, triglyceride/apo B and phospholipid/apo B ratios in VLDL were significantly higher in patients than in controls (P less than 0.05, P less than 0.01 and P less than 0.001, respectively). The relative VLDL enrichment in cholesterol was mainly due to the non-esterified moiety (P less than 0.01). These VLDL abnormalities as well as the low HDL-cholesterol suggest an impairment of VLDL catabolism in PCHD patients.

Adult↗
PubMed1988

Extracoronary atherosclerosis in familial hypercholesterolemia.

Sixty-two patients (31 males, 31 females) with familial hypercholesterolemia (FH) underwent a vascular examination by Doppler ultrasound. The ankle/arm systolic pressure index was determined, and serum lipoproteins were analyzed. Eight of 124 legs examined (6.5%) showed an ankle/arm pressure index less than 0.95, suggesting flow reducing stenosis. Common carotid, internal carotid, and iliac arteries were evaluated by echo Doppler examination with spectral analysis. Forty-five of the 372 arteries examined (12.1%) had detectable abnormalities at echo Doppler examination. Iliac and internal carotid artery lesions were significantly (P less than 0.01) more frequent among FH patients than in a control group (30 men, 20 women) comparable for sex and age. The mean age of the patients with heterozygous FH and detectable arterial lesions was 45.3 years and that of those without lesions 30.7 years (P less than 0.05). When 14 patients with heterozygous FH and arterial lesions were compared to another 14 without lesions and matched for age and gender, it was found that patients with lesions had on average lower concentrations of HDL-cholesterol, and that 10 of 14 cases were actual smokers.

Adolescent↗
PubMed1988

Acute and chronic effects of dihydropyridines on triglycerides in humans.

Several drugs used in the treatment of hypertension have been shown to affect lipid metabolism. A few studies have examined in detail the effects of calcium antagonists on blood lipids. We investigated the effects of nifedipine and nitrendipine on blood lipids using two experimental protocols. The first study was a double-blind, randomized, placebo-controlled trial to assess the effects of acute oral administration of nifedipine 10 mg on blood lipids in 10 patients (9 males, 1 female; age range 26-50 years) with mild hypertriglyceridemia. Serum triglycerides were not significantly affected (from 310 +/- 120 to 280 +/- 110 mg/dl 2 h after nifedipine) but a slight decrease was observed in patients with higher baseline levels. In the second study, an intravenous fat tolerance test (ivFTT, Intralipid 10%, 1 ml/kg body weight, as a bolus) was performed before and after chronic oral administration of nitrendipine 10 mg b.i.d. in 10 mild to moderate hypertensive patients (7 males, 3 females; age range 40-60 years). After nitrendipine treatment, the fractional removal rate (K2) of the lipid emulsion was significantly increased from 3.1 +/- 0.9 to 3.8 +/- 0.9% min (p less than 0.05). The main findings of these studies suggest that the secretion of lipoprotein lipase might be stimulated by calcium antagonists. Alternatively, the vasodilation produced by these compounds may influence triglyceride removal by expanding the capillary bed where the enzyme exerts its activity. In conclusion, calcium antagonists do not seem to cause unwanted side effects on blood lipids and apparently enhance triglyceride removal.

Adult↗
PubMed1988

Very low density lipoprotein. Qualitative abnormalities in patients with premature coronary heart disease and in patients with insulin dependent diabetes.

VLDL composition has been investigated in two groups of patients: one with Premature Coronary Heart Disease (PCHD) and another one with Insulin Dependent Diabetes Mellitus. Both groups showed abnormal VLDL composition. PCHD patients had VLDL significantly enriched in free cholesterol and triglycerides in comparison with a group of controls matched with patients for sex, age, BMI, serum cholesterol and TG. This VLDL composition indicates a prevalence of big particles, which can be found at the beginning of the lipolytic cascade. On the other hand VLDL of diabetic patients were enriched in cholesterol, especially esterified cholesterol, and apo B in comparison with the respective control group suggesting an increase of smaller VLDL, considered more atherogenic. In conclusion these two studies demonstrate that VLDL compositional abnormalities can be found in two different groups of patients even in the absence of hyperlipidemia.

Adult↗
PubMed1988

Blood and plasma viscosity after acipimox treatment in hypertriglyceridemic patients.

Acipimox, a nicotinic acid analog, is known to reduce the plasma lipid concentration in hyperlipidemic patients. In a study to check whether the drug improved hemo-rheological parameters, 21 patients (17 M, 4 F) with asymptomatic hypertriglyceridemia were treated with acipimox (250 b.i.d.) for 30 days. Plasma lipid concentrations were measured before and after therapy, together with blood and plasma viscosity. Mean plasma cholesterol and triglyceride levels decreased from 234 +/- 51 (SD) mg/dl to 202 +/- 53 mg/dl (p less than 0.01) and from 515 +/- 231 mg/dl to 298 +/- 130 mg/dl (p less than 0.01) respectively. Blood viscosity decreased (p less than 0.05 and less than 0.01) (range of reduction 6-20%) at all shear rates examined (from 2.25 s-1 to 450 s-1); plasma viscosity was significantly reduced only at lower shear rates (2.25 and 4.50 s-1). Changes in blood and plasma viscosity after acipimox treatment were not related to changes in plasma triglycerides. Acipimox seems to act beneficially on hemo-rheological parameters, independently of its hypolipidemic effect and could be usefully prescribed to patients with clinical signs of arteriosclerosis.

Adolescent↗
PubMed1985

Are plasma lipoprotein cholesteryl esters utilized for biliary cholesterol and bile acid production in man?

Studies were carried out to determine whether or not plasma lipoprotein cholesteryl esters are available to the liver for biliary cholesterol and bile acid production in humans with intact biliary tracts. Six healthy males were given intravenous infusions of autologous high-density (d, 1.063-1.21; n = 2), low-density (d, 1.019-1.063; n = 2) or intermediate-density (d, 1.006-1.019; n = 2) lipoproteins that had been labelled in vitro with radioactive cholesteryl linoleate (n = 5) or cholesteryl oleate (n = 1). Duodenal contents were continuously aspirated via the intermediate and distal ports of a triple-lumen tube (mean recovery, 64 per cent), through the proximal port of which was infused an amino-acid solution. During 5-6 hours only moderate fluctuations were observed in bile acid and cholesterol secretion rates, implying the existence of near steady-state conditions. In all subjects radioactivity rapidly appeared in both biliary cholesterol and bile acids, and continued to be secreted for the duration of the experiment. The total radioactivity recovered from cholesterol averaged 0.27 per cent of the administered dose; the corresponding figure for bile acids was 11.2 per cent. These results indicate that lipoprotein cholesteryl esters are readily available for biliary lipid production in humans.

Adolescent↗
PubMed1985

An alternative procedure for incorporating radiolabelled cholesteryl ester into human plasma lipoproteins in vitro.

A simple method has been developed for labelling human plasma lipoproteins to high specific radioactivity with radioactive cholesteryl esters in vitro. After isolation by preparative ultracentrifugation, the selected lipoprotein was incubated for 30 min at 4 degrees C in human serum (d greater than 1.215) that had been prelabelled with [4-14C]cholesteryl oleate or [1,2-3H]cholesteryl linoleate, and was then re-isolated by ultracentrifugation. All major lipoprotein classes were labelled by the procedure. Specific radioactivities of up to 18 d.p.m. . pmol-1 (46 d.p.m. . ng-1) were achieved. When radiolabelled high-density lipoprotein was infused intravenously, the radioactive cholesteryl ester behaved in vivo indistinguishably from endogenous cholesteryl esters produced by the lecithin (phosphatidylcholine): cholesterol acyltransferase reaction.

Carbon Radioisotopes↗
PubMed1985

Molecular cloning of human LDL apolipoprotein B cDNA. Evidence for more than one gene per haploid genome.

We have isolated an apolipoprotein B (apo B) clone (pXB1) from a human liver cDNA expression library, by immunoselection with a polyclonal antibody to human low density lipoprotein. pXB1 was used to isolate 3 clones (pB2, pB3 and pB4), containing cDNA inserts spanning a region of 3.75 kbp, from a second human liver cDNA library. We report the sequence of 1359 nucleotides at the 3' end of the pB4 cDNA insert and the amino acids encoded by this sequence. The cDNA inserts of pBX1 and pB2 overlapped the sequenced portion of pB4. pB2 contained an EcoR1 restriction site (resulting in a Glu-Lys replacement) which is not present in pB3 or pB4 and pB3 contained an MspI site not present in pB2 or pB4. Since all 3 clones were derived from the mRNA of a single human liver, we suggest that the human haploid genome contains more than one functional apo B gene. Labelled probes spanning almost the whole of the pB4 cDNA insert hybridized with RNA from human liver and small intestine, showing that the apo B mRNAs from these two tissues have nucleotide sequences in common. The nucleotide sequence in human liver apo B mRNA is probably longer than 12 kb, showing that the MW of monomeric apo B is at least 350kd. Clone pB4 hybridized with mRNA of similar length in rabbit liver and small intestine. These results raise the possibility that the low MW apo B synthesized in the intestine (B-48) and the high MW apo B synthesized in the liver (B-100) are translated from the same mRNA. The expression products of fragments of pB4 cloned into an expression vector were blotted with monoclonal antibodies to human LDL. The results suggest that the cDNA insert in pB4 encodes a part of apo B common to B-48 and B-100 and a region close to the recognition site for the LDL receptor.

Animals↗