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Biomedical subjects

M Cinquegrani

Publications and source records attributed to M Cinquegrani.

At least 19 recordsLinked to original sources

Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects.

This study was performed to determine whether the levels of soluble intercellular adhesion molecule-1 (sICAM-l) and soluble endothelial molecule-1 (sE-selectin) were elevated in subjects with hypercholesterolemia who presented with no other risk factors or evidence of atherosclerosis. The effects of administration of an HMG-CoA reductase inhibitor on the serum levels of these molecules were also examined. Forty hypercholesterolemic subjects (HCh) (19 males and 21 females), without hypertension or cardiovascular disease, received placebo for 4 weeks. The patients were then randomized in two groups; 20 of them (simvastatin group) were treated with simvastatin (20 mg/day) and the other 20 (placebo group) continued placebo administration. After 12 and 24 weeks of either simvastatin or placebo treatment, sICAM-1 and sE-selectin levels were measured. The same parameters were measured in 20 control subjects (C) with normal cholesterol levels, matched for sex and age. HCh had sICAM-1 basal values higher than C (352.4+/-57.9 ng/ml versus 114.9+/-89.6 ng/ml; P<0.001); however, sE-selectin basal values were not different in the two groups. No correlation was observed between HCh sICAM-1 levels and cholesterol levels (total and low-density lipoprotein). Furthermore, cholesterol-lowering treatment with simvastatin did not significantly diminish sICAM-1 levels. Our findings would support the hypothesis that patients with isolated hypercholesterolemia and without clinical atherosclerosis may be silent carriers of arterial subendothelial inflammation, expressed as an increase of sICAM-1.

Adult↗

Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection?

Our aims were to develop a noninvasive predictive tool to identify cirrhotic patients with esophageal varices and to evaluate whether portal Doppler ultrasonographic parameters may improve the value of other predictors. One hundred forty-three consecutive compensated cirrhotic patients underwent upper gastrointestinal endoscopy. Fourteen clinical, biochemical, ultrasonographic, and Doppler ultrasonographic parameters of each patient were also recorded. Esophageal varices were detected in 63 of the 143 patients examined (44%; 95% confidence interval [CI] 36.2-52.6). Medium and large esophageal varices were observed in 28 subjects (44%; 95% CI 31.4-58.4). Using stepwise logistic regression, presence of esophageal varices was independently predicted by prothrombin activity less than 70% (odds ratio [OR]: 5.83; 95% CI: 2.6-12.8), ultrasonographic portal vein diameter greater than 13 mm (OR: 2.92; 95% CI: 1.3-6.4), and platelet count less than 100 x 10(9)/L (OR: 2.83; 95% CI: 1.27-6.28). Variables included in the model were used to generate a simple incremental rule to evaluate each individual patient. The discriminating ability of the prediction rule was relevant (area under the curve: 0.80) and did not change by replacing ultrasonographic portal vein diameter with congestion index of portal vein. We concluded that compensated cirrhotic patients should be screened by upper gastrointestinal endoscopy when prothrombin activity less than 70%, platelet count less than 100 x 10(9)/L, and ultrasonographic portal vein diameter greater than 13 mm are observed, whereas those without any of these predictors should not undergo endoscopy. The contribution provided by portal Doppler ultrasonographic parameters does not appear of practical utility.

Aged↗

Effects of fluvastatin treatment on red blood cell Na+ transport systems in hypercholesterolemic subjects.

This study was performed to ascertain the effects of short-term cholesterol-lowering therapy with fluvastatin on red blood cells Na+ transport systems. Forty familial hypercholesterolemic subjects (FH; 19 men and 21 women) without hypertension or cardiovascular disease were given a placebo for 4 weeks, and then randomized in two groups. Twenty (fluvastatin group) were given fluvastatin (40 mg/day), and the other 20 (placebo group) continued placebo administration. After the placebo period and after 4 and 12 weeks of placebo or fluvastatin treatment, we measured Na+/K+ pump activity, Na+/K+ cotransport (Na+/K+ Ct), Na+/Li+ countertransport (Na+/Li+ Cnt), passive Na+ permeability (Na+PP), and internal Na+ content (Na+i). The same parameters were measured in 23 control subjects (C) with normal cholesterolemic values, who were matched for sex and age. FH had higher Na+/Li+ Cnt values than C (193.2 +/- 59.4 vs. 139.8 +/- 48.7 microM cells/h; p < 0.01), an increase in Na(+)PP (0.034 +/- 0.012/h vs. 0.018 +/- 0.004/h; p < 0.001), and higher Na(+)i (7.5 +/- 1.5 vs. 6.2 +/- 0.9 mM cells; p < 0.001). In hypercholesterolemic subjects, Na(+)i values were correlated with cholesterol (total and LDL) and apo B levels, whereas an inverse correlation was found for HDL-c and apo AI levels. Reduced total and LDL cholesterol and apo B levels after fluvastatin treatment caused a decrease in both Na(+)/Li(+) Cnt (from 186.1 +/- 60.5 to 125.1 +/- 34.0 microM cells/h; p < 0.001) and Na(+) PP (from 0.035 +/- 0.013/h to 0.02 +/- 0.016/h; p < 0.01), and an increase in Na+/K+ pump activity (from 1,549.0 +/- 507.7 to 1,894.2 +/- 536.2 microM cells/h; p < 0.04), with a significant reduction in the internal Na+ content (from 7.5 +/- 1.6 to 5.8 +/- 2.4 mM cells; p < 0.001). Our findings show that hypercholesterolemia affects red blood cell Na+ transport systems, with an increase in Na+/Li+Cnt, Na+PP, and the internal Na+ content. Cholesterol-lowering treatment with fluvastatin influences Na+ transport systems and reduces the internal Na+ content. This might also be responsible for the greater vascular reactivity observed in hypercholesterolemic patients, and its amelioration after a reduction in cholesterol levels.

Adult↗

Gastric permeability to sucrose is increased in portal hypertensive gastropathy.

BACKGROUND: Portal hypertensive gastropathy (PHG) is frequently found among patients with hepatic cirrhosis and at present the only way to detect and follow PHG is via endoscopy. OBJECTIVE: To assess gastric and intestinal permeability and investigate its relationship to endoscopic findings and indices of portal hypertension and hepatic function. DESIGN AND METHODS: Thirty-one non-diabetic patients with hepatic cirrhosis and PHG (PHG+) were studied and compared with 17 cirrhotic patients without PHG (PHG-). All patients underwent endoscopy for the assessment of PHG and Helicobacter pylori status, ultrasound determination of the diameters of spleen and portal vein, and, subsequently, an oral load of sucrose, lactulose, and mannitol. Sugar concentrations were determined in 6-h urine specimens and expressed as a percentage of the orally administered dose or as lactulose/mannitol ratio. RESULTS: The urinary sucrose excretion was significantly elevated in patients with PHG compared to those without (PHG+, 0.20% +/- 0.03; PHG-, 0.07% +/- 0.01; P< 0.001). No difference was found for the small intestinal probes lactulose and mannitol. Gastric sucrose permeability correlated positively with the endoscopic lesion score (P < 0.001), but not with other parameters of portal hypertension or hepatic function. H. pylori status did not influence gastric permeability. The sensitivity of this test reached 100% for PHG scores > 2. CONCLUSIONS: Gastric permeability to sucrose is increased in patients with PHG, independently of the presence of H. pylori. Sucrose permeability may be useful for the follow-up of patients with PHG.

Female↗

Erythrocyte passive potassium flux is increased in patients with ischemic coronary disease (ICD) and in subjects with family history of ICD.

BACKGROUND: It has been proposed that ischemic coronary disease (ICD) associated potassium loss could be due to modifications of potassium permeability. We investigated whether a positive family history of ICD can influence this parameter. We have compared potassium permeability in erythrocytes from ICD patients and from positive family history subjects (FICD) with control subjects. METHODS: All patients and subjects were carefully selected for the absence of hypertension and dysmetabolic pathologies. ICD group: 24 patients (19 males, 5 females; ages 43 to 69) all affected by ischemic coronary disease, under no drug treatment; FICD group: 18 subjects (all males, ages 27 to 42) with a verified positive ICD family history, without hypertensive family history and cardiovascular pathology; control group: 16 subjects (11 males, 5 females; ages 28 to 48) without positive family history of ICD. Passive potassium efflux (PPE) was spectrophotometrically measured in K-free medium containing ouabain and bumetanide. The kinetic constant was calculated by dividing PPE by the erythrocyte potassium concentration. RESULTS: No statistically significant differences were noted between the intracellular potassium content of the three groups. However, (1) the passive potassium permeability of the ICD group was significantly higher (kK=0.055 +/- 0.021 h(-1), n=24) than that of the control group (kK=0.023 +/- 0.008 h(-1), n= 16; p<0.00001), (2) the FICD group was higher (kK=0.036 +/- 0.012 h(-1), n=18) than the control group (p<0.001), and (3) the ICD group was higher than the FICD group (p<0.001). CONCLUSIONS: Our results suggest an inheritability of ICD, paralleling the familial aggregation of the pathology. Erythrocyte potassium permeability could represent an early marker of ischemic coronary disease and be used as a prophylactic tool.

Adult↗

Effects of picotamide on release of endothelin-1, thromboxane and prostacycline after treadmill stress in patients with peripheral artery disease.

To assess the effects of picotamide, an antithromboxane receptor and antithromboxane synthase drug, on vascular function and endothelin-1 release, 20 patients with peripheral arterial disease, without hypertension or diabetes mellitus, receiving placebo and picotamide (900 mg/day) were studied. The modifications of vascular parameters were evaluated by arterial distensibility index and postischemic hyperemia test (postischemic perfusion index and recovery time). Endothelin-1, prostacycline, and thromboxane B2 were determined under resting conditions and after treadmill test. Picotamide treatment caused a decrease of resting thromboxane B2 and endothelin-1 concentrations, produced an improvement of the vascular function as seen by the increase of vascular parameters reported, and attenuated the ischemic treadmill-induced increase of thromboxane B2, but not of endothelin-1. These data confirm that the picotamide improved vascular flow by the reduction of thromboxane-mediated effects, reduced resting endothelin-1 levels, but did not attenuate endothelin-1 concentrations induced by the treadmill stress.

Aged↗

Effects of cloricromene on the levels of endothelin and on the microcirculatory function in peripheral atherosclerotic arteriopathies.

The effects of cloricromene on plasma endothelin-1 (ET-1) levels and on microcirculatory function in 9 patients with peripheral atherosclerotic arteriopathy (PAA) and in healthy control subjects were studied. ET-1 levels and microcirculatory function were evaluated both under basal conditions and 30, 60, and 90 min after acute administration of cloricromene (30 mg i.v.). PAA patients had significantly increased levels of ET-1 and impaired vascular parameters (studied by means of Winsor's Index, Gosling's Index, postischemic perfusion index and recovery time) when compared to control subjects. The acute administration of cloricromene (30 mg i.v.) did not change plasma ET-1 both in control subjects and in patients with PAA. In contrast, cloricromene produced a significant improvement in the postischemic perfusion index and in recovery time in arteriopathic patients. Control subjects and patients with PAA also underwent a cold pressor test (CPT) under basal conditions and (72 h later) 30 min after an acute intravenous administration of cloricromene (30 mg i.v.). CPT caused a higher increase in ET-1 in the patients with PAA compared to the control group, and a reduction in the vascular flow at the femoral level, while the pretreatment with cloricromene prevented both the increase in the levels of ET-1 and the reduction of the femoral vascular flow observed after the cold stimulus in patients with PAA. Our data show that cloricromene, besides ameliorating the microcirculatory function, is able to interfere with dynamic mechanisms, such as those induced by the CPT, capable of stimulating the release of ET-1 at the vascular level.

Aged↗

Acute cardiovascular effects of salmeterol in subjects with stable bronchial asthma.

The airway response and cardiovascular effects of salmeterol (SM) and salbutamol (SB) given as a single dose from metered-dose inhalers were studied in 10 patients with mild asthma. In a double-blind, randomized, cross-over, placebo-controlled study, the subjects received SM 100 micrograms (four puffs, 25 micrograms per actuation), SB 200 micrograms (four puffs, 50 micrograms per actuation) or placebo (P) (four puffs). SM caused a greater and longer lasting increase of peak expiratory flow rate (PEFR) value than SB and P. There was no significant difference either with P or the study drugs in heart rate, PR interval, QT interval corrected for heart rate (QTc), incidence of ventricular and supraventricular ectopics, and in echocardiogram evaluation. These findings show that at dosages based on those used in clinical practice salmeterol causes cardiovascular effects comparable to those induced by salbutamol and confirm the favourable cardiac safety profile of this drug.

Administration, Inhalation↗

[Transmembrane sodium transport systems in various forms of hyperlipoproteinemia].

The possible interrelationships between the erythrocytic transport systems of Na+ (Na+/K+ pump, Na+/K+ cotransport, Na+/Li+ countertransport, Na+ passive permeability) and the plasmatic lipids (cholesterol, triglycerides, HDL, LDL, apoprotein A1, apoprotein B) were studied in 42 normotensive subjects with different forms of hyperlipoproteinaemia and with a negative familiarity for arterial hypertension. In subjects with hypercholesterolaemia (hyperlipoproteinaemia II A and II B) an elevated activity of the Na+/K+ pump was noticed, while in subjects with hypertriglyceridaemia (type IV) an increase in Na+ passive permeability and Na+/Li+ countertransport with a lower level of intraerythrocytic Na+ was shown. A negative correlation was observed between the total efflux of Na+ and Na+/K+ pump and the levels of cholesterol (r = -0.43, p < 0.04 and r = -0.41, p < 0.05) and the apoprotein B/A ratio (r = 0.42, p < 0.05 and r = -0.50, p < 0.01). A negative correlation was also noticed between the Na+/K+ pump and the levels of apoprotein B (r = -0.41, p < 0.05). The Na+/K+ cotransport appeared inversely correlated with the levels of HDL cholesterol (r = -0.42, p < 0.05), while the Na+ passive permeability was negatively correlated with the levels of LDL (r = -0.43, p < 0.04) and positively correlated with the plasmatic triglycerides (r = +0.54, p < 0.01). Such data show that the plasmatic lipids can influence the systems of transmembrane ionic transport of Na+ and play an important role also this way, in cardiovascular pathology.

Adult↗

[Evaluation of the anti-arrhythmic action of propafenone treatment and its influence on left ventricular function].

Twelve patients (9 males, 3 females, mean age 59.2 +/- 7.0 years) with hyperkinetic ventricular arrhythmias were treated for 30 days with 150 mg propafenone three times daily; the daily dosage was raised to 900 mg in non responders (< 85% reduction of ectopic ventricular beats/h). A 24-hour ECGD and mono- and bidimensional echocardiography were carried out at baseline, after 30 days on 450 mg, 30 days on 900 mg propafenone, and one week after drug withdrawal. Propafenone treatment was found to reduce significantly ectopic ventricular beats, especially with the higher dosage (44.9% reduction under 450 mg; 88.8% reduction under 900 mg). At the lower dosage, 25% of patients responded, under the higher dosage 88.9%; the latter dosage also induced a significant reduction of Lown class. Propafenone treatment was also accompanied by a reduction of maximum and mean heart rate, and by a lengthened PR interval which was almost always within the normal range, without changes of QTc. The two months of propafenone treatment did not induce significant changes of cardiac volume or left ventricular function; on the contrary, at the end of the treatment period an increase, albeit not a significant one, of the ejection fraction and a shortening of the circumference inversely proportional to the reduction in ectopic ventricular beats could be noted. In conclusion, propafenone was found to have a valid antiarrhythmic effect, especially at the 900 mg/day dosage without interfering with left ventricular function which was even found to improve under chronic treatment, probably as a result of improved compliance thanks to the reduction of ventricular ectopic beats.

Aged↗

Macrophage activation induced by different carbon fiber-epoxy resin composites.

The activation of cells by interaction with solid surfaces is important in many settings, including the response of tissue to implanted materials. However, few comprehensive studies of both cell migration and activation have been performed so that the connection between these events and immunological activation against foreign material is not well understood. In the present study, synthesis and expression of Ia antigens by peritoneal exudate macrophages after implantation of different carbon fiber composites in the rat peritoneal cavity have been investigated in order to determine whether the type of material implanted affected the composition of Ia-bearing cells of the exudate. The results have confirmed the low level of expression of Ia on resident peritoneal macrophages; while we have found that macrophages, harvested after implantation, express a different amount of Ia related to the different cure cycles of the composite material used.

Animals↗

Rat peritoneal immune response to carbon fibre reinforced epoxy composite implants.

The aim of this paper was to evaluate the histocompatibility of differently cured carbon fibre reinforced epoxy composites, studying their potential to induce an intolerance reaction in neighbouring tissues after peritoneal implantation in the rat. According to the microscopic and scanning electron microscope findings, the inductive capacity to generate connective tissue and cellular reaction was greatest in the partially cured material compared to the fully cured material. In addition, only the partially cured material implants appeared totally coated by macrophages at various stages of activation. The differences in the cellular reactions and scar tissue deposition in the interstices of these two composites are probably related to the chemical surface properties rather than to the structural characteristics of the materials.

Adsorption↗

[Changes in the QT interval caused by autonomic cardiovascular involvement in diabetes mellitus].

The aim of the study was to assess the role of altered autonomic regulation on changes in the QT interval. Fifty-three diabetic patients, comprising 32 men and 21 women with a mean age of 49.4 +/- 15.9 years (range 13-73 years), underwent sympathetic and parasympathetic stimulatory tests (changes in heart rate between clino- and orthostatism, lying to standing, while deep breathing, Valsalva's manoeuvre, changes of arterial pressure related to posture) to study cardiovascular reflexes. Patients who were positive for at least two of the tests were considered to be affected by autonomic neuropathy. Ten non-diabetic age-matched subjects (44.8 +/- 14.8 years) with no cardiovascular diseases were included in the study as a control group. The QTc interval was measured in basal conditions and during sympathetic and parasympathetic stimulatory tests, in clino- and orthostatism, during deep breathing and Valsalva's manoeuvre. A significantly greater QTc interval (p less than 0.05) was found in neuropathic patients compared to controls and non-neuropathic patients both in basal conditions and following stimulatory tests at the lowest heart rate (phase IV of Valsalva's manoeuvre and slow exhalation during deep breathing), while at a higher heart rate (orthostatism, L-S, deep inhalation during deep breathing, phase II of Valsalva's manoeuvre) there was no difference in QTc between controls, and neuropathic and non-neuropathic patients due to a lesser extension of the QTc in neuropathic patients. This difference appears to be the expression of autonomic dysregulation in neuropathic patients, given the lack of correlation with diabetes or duration of disease, and is only conditioned by the presence or absence of autonomopathic damage. Among other causes, the observed extension of the QT interval might therefore justify the increased frequency of sudden death in diabetic patients with cardiovascular autonomic neuropathy.

Adolescent↗

[Clinical-instrumental evaluation of the effects of quinapril treatment in mild-to-moderate hypertension].

Eleven patients with uncomplicated mild-to-moderate hypertension (diastolic pressure 95-115 mmHg) were treated for four weeks with daily single quinapril doses of 20-40 mg. Already during the second week a significant reduction in blood pressure was observed without increase of heart rate; 27.3% of patients responded to the lower dose (diastolic blood pressure [90 mmHg], and 54.6% responded to the higher dose. Drug treatment led to reduced pressure increase in response to cold stimulation without influencing the adrenergic response both in basal conditions and after cold pressor test. The drug brought about peripheral vasodilatation as shown by increased perfusion index during Doppler ultrasound examination, and improved arterial reactivity with increased perfusion index and reduced recovery time after ischemia. The reduction of angiotensin and aldosterone plasma levels during treatment was not correlated to diminished blood pressure values, indicating that the antihypertensive effect can occur via pathways different from ACE inhibition. Tolerance was excellent as shown both by clinical and laboratory evidence.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of calmodulin and calcium channel blockers on the Ca2+ induced outflow of K+ in intact red blood cells of patients with essential hypertension.

The correlation between the alterations of free intracellular calcium concentrations and the essential arterial hypertension has been largely investigated. Calmodulin, a cytoplasmic protein with low molecular weight, is one of the factors known to be able to affect the activity of calcium-dependent enzymes. The authors have investigated the effect of calcium and calmodulin on the plasmatic membrane of intact erythrocytes in a group of patients with essential arterial hypertension. To this purpose, the ionophor A23187, propranolol at low concentrations and a few calcium channel blocking drugs, alone or associated with calmodulin have been used. The results demonstrate that calmodulin, capable of blocking calcium outside the cell, can exert its effect only when propranolol is also present in the erythrocytes of normotensive but not in the hypertensive patients. The authors discuss some pathogenetic hypotheses.

Adult↗

[Systemic cardiorespiratory effects induced by doxofylline].

The authors evaluated the clinical effectiveness and tolerability of doxofylline, a new methyl-xanthinic derivative with peculiar pharmacodynamic properties. 13 patients affected with chronic obstructive lung disease (mean age +/- 54 years) were studied. Doxofylline (200 mg) and theophylline (240 mg) were randomly administered by intravenous route in 60'. Arterial haemogasanalysis, FEV1 and ECG data were obtained after the infusion. Doxofylline proved to possess an equal therapeutic efficacy in comparison to theophylline, with a better clinical tolerability. In conclusion, doxofylline is a new and effective drug for the treatment of bronchostructive disorders.

Cardiovascular System↗