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Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 145 records · Page 8Linked to original sources
PubMed1996

Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study.

PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

Anticholesteremic Agents↗
PubMed1996

Antihypertensive and renal effects of acute and chronic therapy with a dihydropyridine Ca-antagonist in patients with different salt sensitivity.

We evaluated the effect of the dihydropyridine Ca-channel blocker nitrendipine on blood pressure (BP) and electrolyte urinary excretion after acute and chronic therapy in 33 patients with different NaCl sensitivity as assessed by a modification of the test of Grim and colleagues. Acute nitrendipine administration significantly reduced BP in the group as a whole, although the hypotensive effect was greater in patients with greater NaCl sensitivity; this difference was still evident after 1 month of chronic therapy. Furthermore, urinary sodium and calcium excretion significantly increased in the 3 h after nitrendipine administration during both acute and chronic therapy: these effects on electrolyte excretion were independent of the NaCl sensitivity of the subject.

Adult↗
PubMed1996

Plasma lipoprotein(a) levels in subjects attending a metabolic ward. Discrimination between individuals with and without a history of ischemic stroke.

In this cross-sectional study we compared the abilities of lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (TPA) to discriminate between individuals with and without a history of stroke from among subjects in a metabolic ward. A total of 210 subjects (108 men and 102 women; mean age, 63.8 years; range, 31 to 86 years) provided plasma and DNA samples for the study. Of these, 51 men and 50 women had a history of ischemic stroke. The 109 subjects without a history of stroke were compared with those with such a history for major risk factors for ischemic events. Mean plasma TPA and PAI-1 levels significantly (P < .001) discriminated among subjects younger than 70 years with a history of stroke. The mean plasma Lp(a) level of stroke subjects (21.9 mg/dL) did not differ significantly from that of control subjects (15.2 mg/dL). However, among individuals < 70 years old, Lp(a) plasma levels > 50 mg/dL were more common among stroke patients (8 with versus 1 without, P < .01 by chi 2 test). A molecular variation in the 5' flanking region of the apo(a) gene that has been related to elevated Lp(a) plasma levels (G/A-914) was not strongly correlated with circulating levels of Lp(a), nor did Lp(a) levels correlate with a polymorphism of the apo(a) gene (G/A-21), which is strongly linked (P < .001) to the G/A-914 variation. In this setting, the relation between Lp(a) and cerebral ischemia appears to be limited to individuals below 70 years with elevated (> 50 mg/dL) plasma levels of the lipoprotein.

Adult↗
PubMed1996

Comparison of plasmid DNA preparation methods for direct gene transfer and genetic immunization.

Plasmid DNA is widely used for direct gene transfer in animals to study gene therapy, gene regulation, drug delivery and genetic immunization. Here we compare cesium chloride and anion-exchange purified plasmid DNA for direct gene transfer in mouse muscle and show no differences in efficiency of transfection with reporter genes or in humoral response to DNA-based immunization.

Animals↗
PubMed1996

Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia.

OBJECTIVE: The aim of this study was to evaluate the long-term (6-month) effects of moderate fish oil supplementation on insulin sensitivity and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: The study has been performed according to a randomized double-blind placebo-controlled design with a parallel group sequence. After a washout period of 4 weeks and a run-in period of 3 weeks, 16 NIDDM patients with hypertriglyceridemia (triglyceride [TG], 2.25-5.65 mmol/l) were randomly assigned to either fish oil (2.7 g/day eicosapentaenoic plus docosahexaenoic acid for 2 months, then 1.7 g/day for 4 more months) (n = 8) or placebo (n = 8). Diet and hypoglycemic drugs remained unchanged throughout the whole experiment. At baseline and after 6 months, insulin sensitivity was measured by euglycemic hyperinsulinemic clamp (insulin infused, 2.0 mIU.kg-1 body wt.min-1). At the same time, blood glucose control, fasting and postprandial serum insulin and nonesterified fatty acid (NEFA) concentrations, and fasting plasma lipoprotein concentrations were evaluated. RESULTS: In the group treated with fish oil compared with the baseline, there was: 1) a significant reduction in both plasma TG (2.92 +/- 0.23 vs. 3.85 +/- 0.32 [mean +/- SE] mmol/l, P < 0.001) and VLDL-TG (2.35 +/- 0.24 vs. 4.25 +/- 0.66 mmol/l, P < 0.01), without significant changes in blood glucose control; 2) a significant reduction in fasting NEFA concentrations (572 +/- 100 vs. 825 +/- 131 mumol/l, P < 0.01); and 3) a significant enrichment in long-chain omega-3 fatty acids of erythrocyte membrane phospholipids. In the placebo group, there were no changes in any of the variables analyzed. The insulin-mediated glucose uptake was unchanged in both groups (fish oil, 4.04 +/- 0.82 mg.kg-1.min-1 at baseline and 3.96 +/- 0.50 mg.kg-1.min-1 at 6 months; placebo, 3.51 +/- 0.62 mg.kg-1.min-1 at baseline and 4.09 +/- 0.49 mg.kg-1.min-1 at 6 months). CONCLUSIONS: In NIDDM patients with hypertriglyceridemia, moderate amounts of fish oil induce a long-term significant reduction in plasma triglycerides, VLDL triglycerides, and NEFA and a significant enrichment in the erythrocyte phospholipid content of long-chain omega-3 fatty acids, without deteriorating blood glucose control. However, this amount of omega-3 fatty acids was unable to improve insulin sensitivity in this group of patients.

Blood Glucose↗
PubMed1996

The presence of arterial anatomical variations can affect the results of duplex sonographic evaluation of penile vessels in impotent patients.

PURPOSE: Since penile arterial communications are present in a significant percentage of impotent patients, we evaluated whether peak systolic cavernous blood velocity after intracavernous prostaglandin E1 injection might be different in patients with and without arterial variants. MATERIALS AND METHODS: Cavernous blood flow was assessed with echo color Doppler ultrasound before and after intracavernous injection of prostaglandin E1 in 63 impotent patients. The penile shaft was accurately evaluated to detect arterial anatomical variants. Clinical erectile response was assessed by visual inspection and palpation. RESULTS: Of 23 patients who obtained a full erection with full rigidity after prostaglandin E1 injection the cavernous peak blood velocities in 11 with penile arterial communications were significantly less than those in 12 without arterial communications. CONCLUSIONS: The generally accepted limit of normal for cavernous peak blood flow obtained after prostaglandin E1 injection (greater than 25 to 30 cm. per second) must be interpreted carefully because lower peak blood velocities may be found in subjects with a full erectile response if arterial communications are present.

Alprostadil↗
PubMed1996

Clinical and cytologic characteristics of blastic phase in Ph-positive chronic myeloid leukemia treated with alpha-interferon.

We report 72 blastic crises (BC), occurring in 238 Ph+ chronic myeloid leukemia (CML) patients treated in chronic phase (CP) with alpha-interferon (IFN) for a median time of 51 months (range 7-96). The 238 patients were grouped by Sokal's risk at diagnosis in low- (LR), intermediate- (IR) and high-risk (HR), and by CP treatment. Group 1: 160 patients (57% LR, 31% IR, 12% HR) given IFN alone in early CP. Group 2: 31 patients (65% LR, 32% IR, 3% HR) given IFN alone in late CP. Group 3: 23 patients (78% LR, 22% IR) given IFN before and after autologous stem cell transplantation (ASCT). Group 4: 24 patients (83% LR, 17% IR) given IFN after ASCT. Of the 72 BC, 52 (72%) were myeloid (My), and 20 (28%) lymphoid (Ly). Overall BC incidence was similar in all CP treatment groups, although with a prevalence of Ly BC in groups 3 + 4 vs groups 1 + 2, (p = NS); the incidence of BC was higher in HR patients (P = NS), but on the whole it was lower than expected on the basis of historical controls. Lymphoid BC was more frequent in LR than in IR + HR patients (P < 0.05), and was more frequent in responders to IFN, than in non-responders (P < 0.05). In conclusion, a subset of patients with low risk at diagnosis, better response to IFN and proneness to evolve into Ly BC can be identified. The role played by IFN in this context remains to be defined.

Adolescent↗
PubMed1996

[The Mediterranean diet in the prevention of arteriosclerosis].

It is well-known that mortality from coronary heart disease (CHD) is much lower in Italy and the Mediterranean countries than in Northern Europe and United States. Diet is one of the major environmental factors playing an important etiological role in different CHD incidence rates in these areas. The Seven Countries Study demonstrated that the average consumption of saturated fatty acids and cholesterol was directly related to CHD death rates, these being higher in Northern Europe and United States and lower in the Mediterranean countries and the Far East. Olive oil, particularly rich in oleic acid, could play a beneficial role in CHD prevention, as reported in the Italian Nine Communities Study carried out in the early 80s. Another multicenter study, the Intersalt Study, has clearly shown lower blood pressure in participants with lower intake of both sodium and alcohol and higher intake of potassium. Recent findings have also shown that two helping of fish per week and antioxidant vitamins, particularly vitamin E and beta carotene, are related to lower CHD incidence rate in the Mediterranean area compared to other countries. In conclusion, based on the reported findings, the Mediterranean diet represents an useful and effective mean for the prevention of CHD.

Alcohol Drinking↗
PubMed1996

[LDL oxidation in homozygous familial hypercholesterolemia: effects of selective LDL-apheresis treatment].

Homozygous familial hypercholesterolemia (HFH) results from a mutation affecting both the structure and function of a cell surface receptor that removes low density lipoproteins (LDL) from plasma. The disorder is characterized by autosomal dominant inheritance, a lifelong elevation in the concentration of LDL-bound cholesterol in blood and by cholesterol deposits that form xanthomas and early coronary artery disease. HFH patients, as a result of the increased levels and prolonged residence time of LDL in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall causing premature atherosclerosis. Selective LDL-apheresis (LA) on dextran/sulphate cellulose columns is the best therapy reducing mortality of these patients. We previously showed that prolonged lifelong enhanced LDL oxidation in HFH. LDL undergo oxidation before being taken up by macrophages then transformed into foam cells. At the present time, the relevance of the in vitro macrophages studies to the accumulation of cholesterol esters in scavenger cells of HFH patients is not yet established. The aim of this study was to investigate LDL oxidation, induced by xanthine (2 mM)+xanthine oxidase (100 mU), and cholesterol esterification in macrophages, in 8 HFH patients before and after LA. LDL peroxidation by conjugated-diene absorbance showed an increased resistance against oxidation after LA: lag time 129 +/- 25 vs 112 +/- 27 min, p < 0.05; diene production 9.1 +/- 2.1 vs 13.9 +/- 2.5 nM/min/mg LDL, p < 0.01. Peroxidation was also evaluated from lipid peroxides (158 +/- 34 vs 57 +/- 18 nM/mg protein after LA, p < 0.05) and malonyldialdehyde (38 +/- 12 vs 27 +/- 8 nM/mg protein after LA, p < 0.05) content. When oxidized LDL was run on polyacrylamide gel extensive apo-B100 fragmentation was observed in LDL before LA, vs a less fragmentation after LA. A similar reduction was obtained in LDL agarose mobility after LA (1.7 +/- 0.2 vs 2.5 +/- 0.2, p < 0.05). Cholesterol esterification in mouse peritoneal macrophages was also decreased after LA (8.5 +/- 1.8 vs 14.6 +/- 2.7 nM/mg cell protein/12 hours, p < 0.05). Vitamin E content of LDL (mg/g protein) was increased after LA (4.44 +/- 1.0 vs 3.9 +/- 1.2, p < 0.05). Thus, selective LA, not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation and decreased high cholesterol esterification in macrophages. The prevention of these mechanisms by LA contributes actively to retard atherogenesis in HFH patients.

Analysis of Variance↗
PubMed1995

A comparative transcriptional map of a region of 250 kb on the human and mouse X chromosome between the G6PD and the FLN1 genes.

The transcriptional organization of the region of the mouse X chromosome between the G6pd and the Fln1 genes was studied in detail, and it was compared with the syntenic region of the human chromosome. A cosmid contig of 250 kb was constructed by screening mouse cosmid libraries with probes for human genes and with whole cosmids. Overlapping cosmids were aligned by comparing EcoRI and rare-cutter restriction enzyme digestions. The gene order and the orientation of transcription were determined by hybridization with fragments from the 5' and 3' moieties of each cDNA. Our work demonstrates that all of the new genes identified in human are present in the mouse. The size of the region, 250 kb, is also very similar, as are gene order and gene organization: the transcriptional organization in "domains" described in human is found to be identical in the mouse. The major difference detected is the much lower content in rare-cutter restriction sites, which is related to the lower G+C and CpG content of mouse DNA. The very high conservation that we have described suggests that a potent selective pressure has contributed to such conservation of gene organization.

Animals↗
PubMed1995

DNA-mediated immunization to the hepatitis B surface antigen in mice: aspects of the humoral response mimic hepatitis B viral infection in humans.

Intramuscular injection of plasmid DNA expression vectors encoding the three envelope proteins of the hepatitis B virus (HBV) induced humoral responses in C57BL/6 mice specific to several antigenic determinants of the viral envelope. The first antibodies appeared within 1-2 weeks after injection of DNA and included antibodies of the IgM isotype. Over the next few weeks, an IgM to IgG class switch occurred, indicating helper T-lymphocyte activity. Peak IgG titers were reached by 4-8 weeks after a single DNA injection and were maintained for at least 6 months without further DNA injections. The antibodies to the envelope proteins reacted with group- and subtype-specific antigenic determinants of the HBV surface antigen (HBsAg). Expression vectors encoding the major (S) and middle (preS2 plus S) envelope proteins induced antibodies specific to the S protein and preS2 domain, and preS2 antibodies were prominent at early time points. In general, the expression vectors induced humoral responses in mice that mimic those observed in humans during the course of natural HBV infection.

Animals↗
PubMed1995

Effect of long-term treatment with the dihydropyridine-type calcium channel blocker darodipine (PY 108-068) on the cerebral capillary network in aged rats.

The effects of treatment with the dihydropyridine Ca+2 antagonist darodipine (PY 108-068) on age-related changes in the cerebral capillary network was studied using alkaline phosphatase histochemistry with quantitative image analysis. The investigation was performed on male Wistar rats of 12 months (adult reference group) and 27 months. The 27-month-old rats consisted of two groups, the first of control untreated animals and the second of rats receiving an oral dose of 5 mg/kg/day of darodipine from the 21st to the 27th month. The cerebral areas examined included the frontal cortex, the occipital cortex, Ammon's horn of the hippocampus, and the dentate gyrus. The number and the average length of alkaline phosphatase-positive capillaries were decreased in old rats, when compared with adult rats. The intercapillary distance, which is considered as a sensitive parameter for capillary density was increased in aged rats in comparison to adult rats. The capillary diameter was increased slightly or unchanged in old rats. The Ammon's horn and the frontal cortex were the cerebral areas most affected by age-dependent changes of the capillary network. Treatment with darodipine increased the number and the average length of alkaline phosphatase-reactive capillaries and reduced the intercapillary distance and the diameter of cerebral capillaries in old rats. The pericapillary microenvironment of the Ammon's horn was the most sensitive to treatment with darodipine. The above results showed that treatment with darodipine is capable of counteracting some microvascular changes occurring in the brain of aged rats. This suggests that the blockade of dihydropyridine-type Ca2+ channels has a positive effect on the brain microvascular system and may counteract the impairment of pericapillary microenvironment occurring with aging.

Aging↗
PubMed1995

Effect of treatment with the dihydropyridine-type calcium antagonist darodipine (PY 108-068) on the expression of calbindin D-28K immunoreactivity in the cerebellar cortex of aged rats.

The influence of long term treatment with the dihydropyridine-type Ca2+ antagonist darodipine (PY 108-068) on age-dependent changes in calbindin D-28K immunoreactivity in the cerebellar cortex of male Wistar rats was assessed. In 12-month-old rats used as an adult reference group, specific calbindin D-28K immunoreactivity was found within the cytoplasm of Purkinje neurons and their dendritic processes. The number of Purkinje neurons displaying calbindin D-28K immunoreactivity was decreased in the cerebellar cortex of aged in comparison with adult rats. The pattern of calbindin D-28K immunoreactivity was similar in the cerebellar cortex of 24-month-old rats (aged), although a significant decrease in the intensity of immunoreactivity was noticeable. Treatment of aged rats with darodipine for 6 months increased the percentage of immunoreactive Purkinje neurons and the intensity of calbindin D-28K immunoreactivity in the cytoplasm of Purkinje neurons. Calbindin D-28K is a Ca2+ binding protein probably involved in the modulation of Ca2+ homeostasis. The observation of a positive effect of darodipine treatment on calbindin D-28K immunoreactivity in the cerebellar cortex suggests that manipulation of dihydropyridine-type Ca2+ channels may contribute to counter age-dependent changes of Ca2+ homeostasis.

Aging↗
PubMed1995

Factors affecting lipoprotein lipase in hypertensive patients.

Arterial hypertension is frequently associated with serum lipid abnormalities. Lipid metabolism can also be affected by antihypertensive treatment, possibly via an interference with lipoprotein lipase (LPL) activity. The aims of this study were to investigate the metabolic and hemodynamic factors that can interfere with plasma postheparin LPL activity in a sample of 13 patients with mild, uncomplicated arterial hypertension. The effects of vasodilator administration (prazosin and hydralazine) alone or in combination with a beta-blocker (propranolol) were also studied. A direct correlation between serum insulin levels and LPL activity was found during placebo treatment. This was confirmed by multiple regression analysis, which also showed a positive correlation of LPL activity with aortic flow velocity and plasma adrenaline (F significance = 0.0007, R2 = .905). Serum insulin was also directly correlated with cholesterol in high-density lipoproteins (HDLs) and in the HDL2 subfraction. A significant decrease in LPL activity was observed during the addition of propranolol to vasodilators as compared with vasodilators alone. A positive correlation was found between LPL and adrenaline changes induced by the combined treatment. These data suggest that LPL may play a role in the pathophysiologic connections between insulin action, the adrenergic nervous system (ANS), and lipid metabolism.

Blood Pressure↗
PubMed1995

Age-related changes in brain microanatomy: sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068).

The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 108-068) on the age-related microanatomical changes of rat brain were studied in male Wistar rats treated from the 18th to the 24th month of age with an oral dose of 5 mg/kg/day of darodipine. Twelve-month-old untreated rats were used as an adult reference group. A decreased number of nerve cells and of alkaline phosphatase-positive capillaries and an increased lipofuscin deposition were observed in the frontal and occipital cortex, in the hippocampus, and in the cerebellar cortex of rats of 24 months in comparison with 12-month-old animals. The number of nerve cells was higher in the occipital cortex and in the hippocampus, but not in the frontal cortex and in the cerebellar cortex, of darodipine-treated rats in comparison with age-matched untreated animals. Lipofuscin deposition is reduced in all the brain areas investigated. The density of alkaline phosphatase-reactive capillaries is also increased in the frontal and occipital cortex and in the hippocampus of aged rats treated with darodipine. The above results suggest that treatment with darodipine is able to counter some microanatomical changes occurring in the brain of aged rats and involving not only microvascular parameters. The occipital (visual) cortex and the hippocampus were the cerebral areas more sensitive to treatment with darodipine. The possible relevance of these findings is discussed.

Aging↗
PubMed1995

'White-coat' hypertension in patients with newly diagnosed hypertension: evaluation of prevalence by ambulatory monitoring and impact on cost of health care.

To evaluate the prevalence of 'white-coat' hypertension in patients with newly diagnosed hypertension, 255 subjects (131 males and 124 females) underwent 24-h ambulatory blood pressure monitoring. Patients with 24-h systolic and diastolic blood pressure < 135/85 mmHg were classified as white-coat hypertensives and the remaining as sustained hypertensives. On the assumption that white-coat hypertensives may not need to take antihypertensive medication, we evaluated the impact on cost of health care of two strategies based essentially on treating all patients according to casual blood pressure, or ambulatory blood pressure monitoring, followed by drug treatment in sustained hypertensives only. Of the 255 hypertensives studied, 54 (21%), confidence interval 16%, 26%, were classified as white-coat hypertensives. The age, sex-ratio and body mass index did not differ between the white-coat and the sustained hypertensive subjects. The strategy of monitoring all patients and of treating only the sustained hypertensives resulted in a substantial coat saving, which was calculated to be about 110,000 U.S.A. dollars over a period of 6 years. In conclusion, white-coat hypertensives are frequent among patients with newly diagnosed hypertension, and they do not differ from sustained hypertensives as regards demographic data. Ambulatory blood pressure monitoring, when used to decide whether or not to treat pharmacologically, increases the cost-effectiveness of treatment for hypertension and reduces the cost of health care.

Adult↗
PubMed1995

Lipid-lowering treatment: effects on endothelial dysfunction.

An association has been demonstrated between the extent of atherosclerotic involvement and vasodilatory capacity in coronary and cerebral circulation. Impairment of endothelium-dependent relaxation is inversely related to HDL concentrations in plasma. Angiographic studies in humans have shown improved vasodilation capacity of the coronary arteries after lipid-lowering treatment.

Animals↗