Studies of the mechanisms of carbohydrate-induced lipaemia in normal man.
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Adult↗
Biomedical subjects
M Mancini
Publications and source records attributed to M Mancini.
The metabolism of the apoprotein of plasma low density lipoprotein in familial hyperbetalipoproteinaemia in the homozygous form.
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Adult↗
Age-related changes in sulfide-silver stainable fibres in the rat cerebral cortex.
The present study was designed to assess the age-dependent changes in sulfide-silver stainable fibres in frontal, parietal and occipital cortex areas of the rat cerebral cortex. Male Sprague-Dawley rats of 2 months (young), 12 months (adult) and 24 months (aged) were used. Sulfide-silver stainable fibres, which represent predominantly zinc-containing associational fibres arising from local cortical interneurons, were visualized using the neo-Timm histochemical technique. The density of sulfide-silver stainable fibres within the neuropil of laminae I-III (upper zone) and of lamina V (lower zone) of the different cerebral cortex areas was assessed microdensitometrically. In the frontal and parietal cortices the density of sulfide-silver stainable fibres was higher in adult and in aged than in young rats both in the upper and in the lower zones. No significant differences were noticeable in the density of sulfide-silver stainable fibres between adult and old rats. In the occipital cortex the density of sulfide-silver stainable fibres was similar in young or adult rats. but was remarkably increased in old animals. The possibility that the increase in the density of sulfide-silver stainable fibres represents a compensatory mechanism in the cerebral cortex area showing the most consistent nerve cell loss is discussed.
Journal Article↗
Age-related changes in sulfide-silver staining in the rat neostriatum: a quantitative histochemical study.
The density and distribution of sulfide-silver staining in the neostriatum of 3-, 12-, and 24-month-old male Sprague-Dawley rats were analyzed using the neo-Timm sulfide-silver histochemical technique associated with microdensitometry. This technique stains zinc-containing terminals in the striatum and the density of neo-Timm staining is considered to be parallel to the density of synaptic boutons containing zinc. In the neostriatum sulfide-silver, staining was intense in the matrix, although the striosomes did not show appreciable reactivity. The density of sulfide-silver staining was significantly reduced (p less than 0.001) in the matrix of 12-month-old in comparison to 3-month-old rats. No further changes were noticeable between 24- and 12-month-old rats. In contrast, the area and the perimeter of neostriatum that were assessed by quantitative image analysis did not show age-related changes. The present results indicated that similar to the observations for a variety of neurochemical parameters of rat neostriatum such as local cerebral glucose utilization, cholinergic muscarinic receptors, and dopamine D-1 receptors, zinc-containing striatal terminal were primarily decreased between young and adult subjects but not between adult and aged animals.
Aging↗
Comparative studies on serum lipids and histochemical features of the arterial wall in animal species differently susceptible to experimental atherosclerosis.
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Animals↗
Recombinant hepatitis B surface antigen as a carrier of human immunodeficiency virus epitopes.
Eukaryotic cells transformed with a plasmid expression vector are able to synthesize and assemble HBsAg, a complex multimeric lipoprotein particle. Hybrid particles carrying HIV1 antigenic determinants were constructed and injected into monkeys. A complete immune response including neutralizing antibodies, proliferative and cytotoxic T-cell activities was obtained. Thus, such HIV/HBsAg hybrid particles could be a new approach to multivalent vaccination.
Acquired Immunodeficiency Syndrome↗
Measuring plasma fibrinogen to predict stroke and myocardial infarction.
Epidemiological observations indicate that high plasma fibrinogen levels are strongly correlated with the frequency of two major thrombotic complications of atherosclerosis, stroke and myocardial infarction. Thrombosis is increasingly recognized as a central mechanism in stroke and myocardial infarction, and fibrinogen is involved in events thought to play a major role in thrombosis. Therefore, elucidation of the relationship between fibrinogen and thrombosis may strengthen the predictive value of this protein and suggest new treatment to prevent stroke and myocardial infarction. The current data relating fibrinogen to thrombosis are not easy to reconcile with the available epidemiological observations. In addition, advances in understanding the atherogenic potential of several risk factors for coronary heart disease have used information on the measurement of the risk factors in population-based studies. Thus, measuring plasma fibrinogen to predict stroke and myocardial infarction may be important in gaining insight into the thrombogenic potential of this protein and in inspiring new strategies against the thrombotic complications of atherosclerosis.
Blood Vessels↗
Noninvasive ultrasound evaluation of pressure gradients in aortic root of homozygotes for familial hypercholesterolemia.
The aim of this study was to measure noninvasively by Doppler ultrasound the blood flow velocity at the level of the aortic root in patients with homozygous familial hypercholesterolemia (FH) to detect abnormal pressure gradients. Seven patients with homozygous FH and seven healthy controls matched for age and sex were included in the study. Continuous-wave Doppler (2 MHz) was used to measure the highest detectable velocity from the aortic root; the probe was positioned in the suprasternal notch. When an abnormal velocity was detected, the corresponding pressure drop was calculated from the formula: Delta P = 4Vmax2. Each FH patient had an abnormal aortic velocity consistent with a pressure gradient across the valvular area. All the controls had normal aortic velocities (p less than 0.01). The measurement of the pressure drop across the aortic valvular area in FH patients gives an estimate of the lesions produced by cholesterol deposition in a crucial area of the cardiovascular system near the origin of coronary arteries. The noninvasivity of this method makes it an excellent method for obtaining parameters for follow-up and clinical trials.
Adolescent↗
Impaired glucose tolerance and risk factors for atherosclerosis.
This study attempts to evaluate whether the putative excess risk of cardiovascular disease in individuals with impaired glucose tolerance (IGT) can be explained by the clustering of other major cardiovascular risk factors after controlling for obesity. The study population was 1376 male and female employees of a Naples telephone company who had participated in a health survey in which an oral glucose tolerance test (OGTT) was given. After excluding treated hypertensives, we recruited all 65 individuals with IGT and 125 euglycemic controls matched for gender, age, and weight. Systolic and diastolic blood pressure was significantly higher in individuals with IGT (134 +/- 16 vs 127 +/- 15 mm Hg, p less than 0.001; 87 +/- 10 vs 84 +/- 8 mm Hg, p less than 0.05 (M +/- SD). Blood lipids were similar in the two groups (total cholesterol was 214 +/- 34 vs 218 +/- 40 mg/dl; HDL cholesterol was 39 +/- 9 vs 40 +/- 10 mg/dl; total triglyceride was 145 +/- 58 vs 135 +/- 63 mg/dl). Serum insulin values (fasting or at 1 or 2 hours after 75 g of oral glucose) were also similar. The number of persons currently smoking was significantly lower among individuals with IGT (30% vs 47%, p less than 0.025) but the percentage of exsmokers was identical in the two groups. We conclude that, among the possible cardiovascular risk factors investigated, blood pressure is the only one significantly associated with IGT independent of matched variables and antihypertensive treatment.
Adult↗
Premature development of iliac artery stenosis in asymptomatic type II hyperlipoproteinemia.
There is conflicting evidence on the relationship between increased low density lipoprotein (LDL) concentration in Type II hyperlipoproteinemia and premature development of peripheral atherosclerosis of the lower limbs. We evaluated the early signs of iliac artery involvement in patients with asymptomatic Type II hyperlipoproteinemia. Of these, 23 were Type IIA, 12 were Type IIB. Thirty-five consecutive patients, ages 40 to 60 years, with asymptomatic Type II hyperlipoproteinemia (LDL cholesterol greater than or equal to 3.80 mmol/liter, 147 mg/dl) and 54 normocholesterolemic controls (plasma cholesterol less than 5.70 mmol/liter, 220.6 mg/dl) from a random sample of clinically healthy, 50-year-old men had a noninvasive examination to detect common and external iliac artery stenosis. Both Type II patients and the controls were examined by the echo-Doppler technique (Duplex Scanner III-ATL Mark V) with spectral analysis of the Doppler signals. This method is sensitive not only to severe stenosis or occlusion but also to non-flow-reducing stenosis (less than 50% narrowing of the lumen diameter) and to minor wall irregularities (1%-15% stenosis). In Type II patients, 19 of 70 limbs (27%) were abnormal as compared to 6 of 108 limbs (6%) in the controls (p less than 0.001). The premature development of an obliterating disease of the iliac arteries was demonstrated in persons asymptomatic for Type II hyperlipoproteinemia.
Adult↗
Increased fibrinogen binding to platelets from patients with familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is a disease marked by a high incidence of thrombotic episodes and hypersensitivity of the patients' platelets to naturally occurring aggregating agents. Prostaglandin/thromboxane (PG/Tx) formation, adenosine 5'-diphosphate (ADP) secretion, and fibrinogen binding to platelets are all believed to be involved in the mechanisms of platelet aggregation. Therefore, we studied the interrelated roles of these processes in the platelets of nine FH patients and 10 controls. In response to ADP, collagen, or thrombin, FH platelets bound about twice as much 125I-fibrinogen as controls. This ratio did not change after suppression of PG/Tx formation by aspirin. With or without aspirin, FH platelets always aggregated in response to significantly lower concentrations of these agents than did platelets from normal controls. After stimulation with thrombin or collagen, the hyperaggregable platelets from FH patients were shown to bind significantly more fibrinogen than control platelets even when PG/Tx formation was suppressed (aspirin) and secreted ADP was scavenged (apyrase). To determine whether the increased fibrinogen binding observed in FH platelets is due to a qualitative or quantitative abnormality of the platelet receptor, we used a monoclonal antibody (B79.7) that is specific for the receptor. The amount of B79.7 that bound to platelets from control and FH subjects was similar. In addition (as in normal individuals), the antibody inhibited aggregation and fibrinogen binding of FH platelets.
Adolescent↗
Short-term effect of natural disasters on coronary heart disease risk factors.
In this analysis of the data from a longitudinal study on coronary heart disease risk factors, it was found that participants screened a few weeks after a major disaster (earthquake) had a higher heart rate, serum cholesterol levels, and serum triglyceride levels than matched participants that were screened shortly before the catastrophic event. The two groups of participants did not differ with regard to their characteristics at the baseline examination carried out 5 years previously. The lack of difference in blood pressure between exposed and nonexposed participants could be explained by the lag-time between the earthquake and the blood pressure measurements. We conclude that the acute stress associated with major disasters can influence risk factors for coronary heart disease. Permanent elevation of these risk factors due to the disruption of the social environment of the individuals affected by major disasters might be responsible for the apparent long-term adverse effects on cardiovascular mortality discussed previously in the literature.
Body Weight↗
Association between retinopathy and impaired peripheral arterial circulation in insulin-dependent diabetic patients.
This study was undertaken to investigate whether, in insulin-dependent diabetic patients, an association exists between microangiopathy (evaluated as retinopathy) and macroangiopathy (evaluated as impaired arterial circulation of the lower limbs). A total of 38 diabetic outpatients with either background (n = 25) or proliferative (n = 13) retinopathy, plus 18 diabetic outpatients of similar age (46.8 +/- 13.4 vs. 43.0 +/- 11.0 yrs) and duration of diabetes (16.8 +/- 5.8 vs. 14.8 +/- 15.1 yrs) without retinopathy were studied. Retinopathy was defined according to fluorescein angiography. The arterial circulation of the lower limbs was evaluated by the ankle/arm systolic pressure index with ultrasonic Doppler end-point detection and echo-Doppler examination of the pelvic vessels. The ankle/arm index was significantly lower in diabetic patients with retinopathy (0.98 +/- 0.16 vs. 1.12 +/- 0.11, p less than 0.002) and the percentage of persons with definitely impaired arterial circulation of the legs (ankle/arm systolic blood pressure less than 0.95) was significantly higher in this group (36.8% vs. 5.5%, p = 0.038). Of 14 patients with retinopathy and peripheral arterial disease, only three (21%) had detectable stenoses of the pelvic vessels. The overall profile of cardiovascular risk factors was similar in the two groups. The multivariate analysis indicated that retinopathy was the best correlate of impaired peripheral arterial circulation. In conclusion, in our study population, an association between retinopathy and impaired peripheral arterial circulation of the legs existed independently of major cardiovascular risk factors.
Adult↗
Left ventricular mass reduction during salt depletion in arterial hypertension.
Long-term therapy with antihypertensive agents that reduce sympathetic nervous system activity has been demonstrated by echocardiographic measurements to reverse left ventricular hypertrophy. This investigation evaluated the effects of salt depletion obtained by both chlorthalidone (25 mg/day) and severe restriction of salt intake (about 1016 mg Na+/day) on left ventricular mass (LVM) in as short a time as 12 weeks. Before the study, the patients had been off medication and on a balanced diet without salt restriction for at least 2 weeks; they were then randomly allocated to either the diuretic or low-salt regimen for 6 weeks and finally to alternative treatment according to a crossover model. Blood pressure, body weight, myocardial mass, and noninvasive measurements of left ventricular function (LVF) were determined at baseline and at the end of both periods of treatment. Results were evaluated by two-way analysis of variance in randomized blocks. Systolic and diastolic blood pressure and LVM were significantly and similarly reduced by diuretic therapy or salt restriction. A significant correlation was demonstrated between noninvasive measurements of LVM, expressed as cross-sectional area, and systolic blood pressure. No impairment of LVF could be detected over the treatment period.
Adult↗
Carotid atherosclerosis in familial hypercholesterolemia.
Common and internal carotids have been studied by noninvasive method (echo-Doppler) in 30 normotensive patients with familial hypercholesterolemia (FH). Vascular lesions were detected in 14 patients (46%), who presented one or more lesions of different degree (between 1-15% and 16-49%). In one case, only one carotid had stenosis greater than 50%. Severity and number of stenosis were related to age and levels of hypercholesterolemia. FH patients with carotid lesions showed a significantly higher LDL-cholesterol (p less than 0.01) and plasma apolipoprotein B (p less than 0.001) concentrations and a significantly lower HDL-cholesterol (p less than 0.05) and plasma apolipoprotein A (p less than 0.001) levels as compared to those with normal echo-Doppler findings. These data indicate that investigation of arterial districts other than coronaries are useful in quantitative evaluation of atherosclerotic involvement.
Apolipoproteins↗
Measurement of the cost of screening for cervical cancer in the district of Florence, Italy.
AIMS AND BACKGROUND: To estimate the cost per woman examined and per CIN II or more severe lesion detected in a population-based cytologic screening program for cervical cancer prevention. An organized cytologic screening program has been ongoing in the Florence District since 1973, and a call-recall system using mail invitation has been ongoing since 1980. Smear reading and assessment of screening positives is centralized at the screening unit. METHODS AND STUDY DESIGN: All relevant resources (costs) consumed by the program were listed and measured. The unit cost per examined woman and per each CIN II or more severe lesion detected was estimated for each screening phase (recruitment, screening, assessment). RESULTS: The cost per examined woman was $24.60, whereas that per CIN II or more severe lesion detected was $13,600. Staff accounted for 80% of total amount. CONCLUSIONS: Although the cost for a single procedure is low, the cost per detected lesion is quite remarkable due to the low detection rate in a population screened for a long time. Different approaches and longer interval screening tests are discussed.
Adult↗
Peripheral arterial circulation in individuals with impaired glucose tolerance.
Employees of a telephone company in Naples (N = 1376) were screened by oral glucose tolerance test (OGTT, 75 g). All those with impaired glucose tolerance (IGT) (N = 69) plus 138 normoglycemic controls, matched by sex, age, and body mass index (BMI, kg/m2), were selected to participate in this study. All participants were retested by OGTT under the same conditions as the first test. The prevalence of signs of impaired peripheral arterial circulation (IPAC) were investigated by different methods: Rose questionnaire on intermittent claudication, digital pulse plethysmography (inclination time), and ankle blood pressure measurement (ankle/arm systolic blood pressure). Very few persons had symptoms of IPAC: 2 (3.1%) and 3 (2.4%), respectively, in IGT subjects and controls. No difference in the prevalence of abnormal vascular parameters was detected between IGT and normoglycemic individuals according to either digital pulse plethysmography (6.1% versus 8.8%, P = 0.36) or ankle blood pressure measurement (10.8% versus 9.6%, chi 2 = 0.06, NS); similar results were obtained when the prevalence of abnormalities was evaluated according to both methods combined (16.9% versus 16.8%). The finding remained very much the same after controlling for the effect of smoking. Individuals with IGT at both OGTTs were compared with individuals with normoglycemia at both tests: once again no significant difference was detected between the two groups in the prevalence of abnormal vascular findings (22.6% versus 16.7%, chi 2 = 0.66, NS). This suggests that IGT is not associated with increased prevalence of atherosclerotic peripheral arterial disease.
Adult↗
Uteroglobin and transglutaminase modulate human sperm functions.
During the process of capacitation, spermatozoa undergo significant changes in membrane composition, including removal of decapacitating factors (DFs), which are present in seminal plasma, that lead to increased sensitivity to physiological stimuli of the acrosome reaction. In the present study we investigated the presence, localization, and effects on human spermatozoa of 2 proteins of seminal plasma origin, uteroglobin (UG) and transglutaminase (TG). These 2 proteins interact with one another because TG promotes covalent links of UG to sperm surface proteins. We found that UG is localized around the entire surface of ejaculated human sperm, whereas TG is predominantly localized in the neck. FACScan analysis confirmed the surface localization of both antigens and demonstrated that swim-up selection of spermatozoa was associated with a significant reduction in the contents of the 2 substances when compared with unselected samples. Western blot analysis of UG in total sperm lysates confirmed the lower content of the protein in swim-up-selected sperm. Swim-up-selected sperm were characterized by their ability to undergo a spontaneous, time-dependent increase of capacitation-characteristic chlortetracycline pattern of fluorescence and increase in responsiveness to progesterone. Such changes were not observed in unselected sperm. Exogenous addition of TG, together with recombinant rabbit UG, prevented the spontaneous increase in responsiveness to progesterone (acrosome reaction and intracellular calcium) at 24 hours in swim-up-selected sperm, suggesting the occurrence of a capacitation-inhibiting activity of the 2 substances. In addition, we found that endogenous UG and TG contents, as determined by FACScan analysis, were negatively correlated (P < .0001) with sperm motility and that exogenous addition of the 2 substances resulted in a substantial reduction of progressive motility (P < .01). Collectively, these data indicate that TG and UG represent 2 DFs, and contribute to understanding the biochemical mechanisms that characterize the process of capacitation.
Blotting, Western↗