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Biomedical subjects

P Marraccini

Publications and source records attributed to P Marraccini.

At least 37 records · Page 2Linked to original sources

[Quantitative evaluation of the dynamics of the coronary wall in man: description of a new method based on tridimensional time-dependent reconstruction of intravascular ultrasonographic images].

BACKGROUND: Intravascular ultrasound imaging provides information on vascular lumen and arterial wall structure and it has potential application in arterial wall dynamic study. The aim of this study was to develop a computer assisted system for analysing digitised cross sectional ultrasound images of coronaries to easily display and quantify coronary dynamic and its relationship with arterial wall morphology. METHODS AND RESULTS: To extract the anatomical regions of interest from the digitised sonograms, automatic image segmentation and interactive procedures for manual correction were implemented. This step included the recognition of the lumen edge and an analysis of gray level intensity of the wall. Subsequently, a virtual 3D reconstruction of lumen and vessel wall was done in a Cartesian system where the XY plane was parallel to each cross-sectional sonogram, while the Z axis corresponded to the acquisition time. The baricentre of vascular lumen was used as a reference for alignment. We obtained a cylinder-like solid representing the behavior of the arterial cross-sectional sonogram in time, with the possibility to look either at the wall or at the lumen. In this virtual solid it was possible to measure the variation of lumen area and of 16 hemidiameters; in addition, the derivatives of these values, allowing an estimate of the velocity of events, can be obtained. CONCLUSIONS: The described computerised system for the analysis of intravascular ultrasound images could become a very useful tool for 3D representation and quantitative monitoring of coronary compliance and their relationship with segmental arterial wall morphology.

Coronary Vessels↗

Adenosine-induced renal vasoconstriction in man.

OBJECTIVE: The aim of the study was to evaluate the effects of adenosine on renal blood flow in humans. METHODS: Eleven normotensive patients (mean age 53 +/- 11 years) with normal renal angiograms were enrolled in the study. Arterial blood pressure, one ECG lead and arterial renal blood flow velocity, by intravascular Doppler catheter, were monitored throughout the procedure. Incremental doses (10(-5), 10(-4), 10(-3), 2 x 10(-3), 5 x 10(-3), 10(-2), 10(-1), 1 mg) were selectively injected, at 5-min intervals, in a renal artery. RESULTS: Adenosine administration had no significant effects on blood pressure, heart rate and atrio-ventricular conduction. A progressive reduction in renal blood flow velocity (from 16.36 +/- 1.9 to 3.9 +/- 0.8 cm/s, P < 0.0001) was observed. Following adenosine the decrease of flow velocity was immediate and its duration was proportional to dosage (from 0.5 +/- 0.4 s at 10(-5) mg to 31 +/- 6.5 s at 1 mg). Renal angiography, repeated in four patients during flow velocity decrement, showed no changes in vessel diameter. CONCLUSIONS: Exogenous adenosine-induced a marked and transient reduction in renal blood flow in man. This effect suggests that adenosine or its metabolites may be directly implicated in rapid and powerful mechanisms of cardiac output redistribution. Thus endogenous adenosine could have a role in regulating renal blood flow in physiological and pathological situations like strenuous exercise, hemorrhage shock and cardiac failure.

Adenosine↗

[Usefulness of pirenzepine in the study of the upper digestive tract and the large intestine with double contrast media: comparison with scopolamine methylbromide].

The purpose of the present study is to assess the importance of pirenzepine, a selective M1 antimuscarinic drug, as hypotonic agent for diagnostic double-contrast studies of the upper gastrointestinal tract and for double-contrast barium enema studies of the large bowel. Pirenzepine and scopolamine methylbromide (SMB) (Buscopan) were compared in a single blind randomized trial. One hundred-thirty consecutive patients were enrolled in the study. Seventy of them underwent double-contrast studies of the stomach and duodenum and sixty double-contrast barium enema studies of the large bowel. Visceral distension and painting of stomach, duodenal bulb and large bowel and global quality of the images were blindly evaluated by 4 independent observers by means of a numerical score (1 to 4). Quantitative analysis of bowel distension was done measuring the maximum diameter of the transverse colon before and after drug administration. No differences were found in the diagnostic performance between the two drugs in the study of the duodenal bulb (2.8 +/- 0.8 vs 2.9 +/- 0.7, p = NS) and of the large bowel (3.0 +/- 0.6 vs 3.1 +/- 0.6, p = NS). Under SMB, slightly but significantly better results were obtained in the stomach (3.0 +/- 0.6 vs 2.7 +/- 0.6, p = 0.01). However, large bowel distension was slightly but significantly improved with Pirenzepine (68 +/- 12 vs 65 +/- 8 mm, p = 0.02). Heart rate and rhythm during the study were recorded by ECG. SMB induced tachycardia in all patients while pirenzepine did not. Moreover, after SMB, 3 patients exhibited faintness, some patients complained of visual accommodation defects, dryness of the mouth and dizziness. Under pirenzepine, no side-effects were reported. To conclude, pirenzepine gives good results in double contrast studies, as good as SMB but with no adverse effects; thus, it could be proposed as the hypotonic agent of choice in upper gastrointestinal and large bowel examinations.

Adult↗

Selection of medical treatment in stable angina pectoris: results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.

Angina Pectoris↗

Effect of phosphotyrosine phosphatase over-expression on glutathione metabolism in normal and oncogene-transformed cells.

We measured the level of reduced glutathione (GSH) and oxidized glutathione (GSSG) in normal and oncogene-transformed NIH/3T3 fibroblasts and 32D hematopoietic cells. NIH/3T3 cells transformed by the activated oncogenes erbB, src, and raf, showed increased levels of GSH with concomitant alterations in the levels of GSH-related enzymes. Transfection and over-expression of a synthetic gene coding for a phosphotyrosine protein phosphatase (PTPase), which inhibited the proliferation of normal and transformed NIH/3T3 cells, was accompanied by a decrease in GSH levels in normal and erbB-transformed fibroblasts, and by an increase in src and raf transformants. Among GSH-related enzymes, only gamma-glutamylcysteine synthetase was altered in normal and erbB-transformed NIH/3T3 fibroblasts following PTPase transfection. Therefore, tyrosine phosphorylation could be selectively involved in the regulation of GSH metabolism in normal and oncogene-transformed NIH/3T3 fibroblasts, possibly by a dual-type effect on receptor/oncoprotein-mediated mitogenic signal transduction. However, no relationship was observed between the GSH and PTPase effect on cell growth, either after oncogene transfection or PTPase transfection. Moreover, the changes in GSH metabolism were specifically related to cell lineage. In fact GSH and related enzymes did not change in 32D hematopoietic cells transformed by the same activated erbB oncogene and in those--normal or transformed--over-expressing the PTPase: in these cells also, over-expression of the PTPase gene was not accompanied by growth inhibition.

3T3 Cells↗

Glutathione metabolism in Crohn's disease.

A statistically significant decrease of glutathione (GSH) and an increase of GSH disulfide (GSSG) both in healthy and ill ileum of patients with Crohn's disease in comparison with the controls (without this pathology) is demonstrated. However, the lowering of these levels was more remarkable in ill ileum in which high levels of GSSG were detected, too. These alterations may be in part explained by the changes obtained in GSH-related enzyme levels. Finally, considering the results that others and we obtained by studies on GSH oral absorption in rat intestine, an oral therapy of GSH in Crohn's disease is suggested.

Administration, Oral↗

Adrenergically mediated coronary vasoconstriction in patients with syndrome X.

Several studies have shown that coronary vasodilator reserve is impaired in some patients with chest pain and angiographically normal coronary arteries. In a subgroup of these patients, who additionally show ST depression on the electrocardiogram during exercise and are generally labelled as having Syndrome X, the impairment of coronary flow reserve is associated with metabolic and functional signs consistent with an increased sympathetic drive. The aim of the present investigation was to ascertain whether the impairment of coronary vasodilator reserve in patients with Syndrome X is due to adrenergically mediated vasoconstriction of coronary microcirculation. Myocardial blood flow (MBF), at baseline and following intravenous infusion of dipyridamole (0.56 mg/kg over 4 minutes), was measured by means of 13N-ammonia and dynamic positron emission tomography in 10 females (mean age 52 +/- 8 years) with a chest pain history, ST-segment depression during exercise, and angiographically normal coronaries. The first MBF study was performed while the patients were off therapy; a repeat MBF study was performed following 1 week of treatment with the alpha-1 blocker doxazosin (2 mg/day). Off therapy MBF was 1.13 +/- 0.25 ml/min/g at baseline and increased to 2.35 +/- 0.66 ml/min/g following dipyridamole. Coronary vasodilator reserve (dipyridamole/baseline MBF) was 2.18 +/- 0.56. During treatment with doxazosin, baseline MBF was not different from the control value (1.25 +/- 0.50 ml/min/g), while added dipyridamole significantly increased MBF to 3.52 +/- 1.20 ml/min/g (p < 0.01 vs. off therapy). Coronary vasodilator reserve was significantly increased (2.91 +/- 0.92, p < 0.01 vs. control value) by doxazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗

Investigation into vanadate-induced potentiation of smooth muscle contractility in the rabbit isolated ileum.

The action of sodium orthovanadate (Na3VO4) on spontaneous mechanical activity of the longitudinal muscle was investigated in isolated segments of rabbit distal ileum. Vanadate (0.3-1000 microM) concentration-dependently enhanced the amplitude of phasic contractions (pendular movements) and caused the muscle tone to slightly increase at the highest concentrations. Both these effects were mimicked by the Ca2+ channel activator BAY K 8644 (10-1000 nM). Vanadate- and BAY K 8644-induced potentiation of mechanical activity was antagonized by the Ca2+ entry blocker nifedipine (3 nM). In Ca(2+)-free, K(+)-depolarized preparations, vanadate (100 microM) failed to contract the musculature, but potentiated the contractile response to applied calcium (CaCl2: 30-300 microM). The action of vanadate was similar to that of BAY K 8644 (3 nM) and was antagonized by nifedipine (0.1 nM). These results suggest that extracellular calcium is required for vanadate-induced smooth muscle excitation which, at least in part, appears to arise from facilitation of calcium influx through voltage-dependent Ca2+ channels.

Animals↗

Light-regulated promoters from Synechocystis PCC6803 share a consensus motif involved in photoregulation.

A library of Synechocystis PCC6803 (S.6803) DNA cloned in front of the promoterless cat reporter gene of the plasmid pFF11 was used to transform S.6803 to high light-dependent resistance to chloramphenicol. In five clones harbouring a stably replicating pFF11-derived plasmid, this phenotype occurred independently of the photosystem II electron transport and resulted from the correlated increase of CAT activity level and cat mRNA accumulation. The five promoter inserts contained no Escherichia coli sigma 70 promoter element, in agreement with their lack of activity in this organism, but shared two conserved motifs. Two secondary mutations, which restored light-regulated promoter activity to an inactive mutant of the smallest insert, mapped within one of the common motifs, emphasizing the probable involvement of this element in photoregulation.

Base Sequence↗

Age and GSH metabolism in rat cerebral cortex, as related to oxidative and energy parameters.

A comprehensive study on GSH metabolism in relation to some markers of oxidative and energy status in rat cerebral cortex as a function of age was performed. Reduced GSH, total GSH and the GSH Redox Index decreased both during growth (defined as the period between 1 and 5 months) and during aging (defined as the period between 5 and 27 months) while GSSG levels increased during the two periods, but most significantly during aging. Also GSH-associated enzymes and adenine-pyridine nucleotide levels show age characteristic changes. The obtained results suggest that decreases in oxidative and energy metabolism occur during aging. They probably contribute to decreases in the activity of the biosynthetic processes (i.e., NADP+(H) and GSH synthesis) and in the antioxidant capacity of the GSH system. However, the oxidative stress does not seem to be a typical characteristic of the aging period; as an oxidative status is present during the growth period too. Typical parameters of aging process are mainly the low levels of reduced GSH, total GSH and GSH Redox Index and the high levels of GSSG as well as the high levels of GSH peroxidase and GSH transferase and the low levels of gamma-glutamylcysteine synthetase.

Adenosine Diphosphate↗

Altered metabolism of glutathione in cells transformed by oncogenes which cause resistance to ionizing radiations.

We measured glutathione (GSH) metabolism in normal NIH/3T3 fibroblasts, and in cells transformed by the oncogenes sis, erbB, src, ras, dbl, and raf.erbB,src,ras and raf, but not sis and dbl transformants, showed increased level of total and reduced GSH as compared with normal NIH/3T3 fibroblasts; oxidized GSH was elevated only in src- and ras-transformed cells. Increased total GSH content was associated with decreased activity of the synthetic enzyme gamma-glutamylcysteine synthetase, and oxidized GSH level with increased activity of GSH reductase. These data suggest that GSH synthesis was selectively enhanced in cells transformed by specific oncogenes, with resulting down-regulation of its synthetic enzyme; alterations of GSH metabolism appeared to be peculiar of transformation by specific oncogenes, and not trivial epiphenomena of neoplastic transformation. Oncogenic transformants that presented elevated level of GSH were also those reported to be resistant to antineoplastic drugs and ionizing radiations, thus confirming a possible link between altered GSH metabolism and resistance to antineoplastic treatment.

3T3 Cells↗

A conjugative plasmid vector for promoter analysis in several cyanobacteria of the genera Synechococcus and Synechocystis.

A promoter-probe vector, pSB2A, based on the plasmid RSF1010 and the promoterless chloramphenicol acetyl transferase (cat) reporter gene, has been constructed. pSB2A appeared to be most efficiently transferred by conjugation to the widely used cyanobacteria Synechocystis strains PCC6803 (S.6803) and PCC6714 (S.6714) and Synechococcus strains PCC7942 (S.7942) and PCC6301 (S.6301), where it replicates stably even though it contains no cyanobacterial DNA. Using pSB2A we found that (1) a light-regulated promoter from S.6803 remains controlled by light intensity in S.7942 while it is silent in Escherichia coli, and (2) the E. coli tac promoter behaves as a strong and light-independent promoter in the four cyanobacterial hosts tested.

Conjugation, Genetic↗

Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia. BACKGROUND: After infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown. METHODS: Coronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries. RESULTS: Basal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 +/- 0.91 vs. 2.89 +/- 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 +/- 0.82 and 2.73 +/- 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 +/- 0.13 and 3.67 +/- 0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 +/- 0.98 (p < 0.01) vs. values in remote regions). During pacing there was net lactate release in diseased regions (-18 +/- 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 +/- 17%) and in normal control subjects (26 +/- 11%). Glucose and alanine extraction were increased in diseased (8 +/- 6% and 6 +/- 6%) and remote regions (6 +/- 3% and 4 +/- 3%), compared with values in normal control subjects (2 +/- 3% and -1 +/- 3%, both p < 0.05 vs. diseased and remote regions). CONCLUSIONS: Coronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium.

Aged↗

Methylene chloride exposure in industrial workers.

Methods of environmental and biological monitoring were applied in order to evaluate exposure to methylene chloride in workers operating in a factory where this substance was used as a solvent. For the measurement of methylene chloride in environmental concentration, the ambient air was sampled by using personal passive dosimeters. The activated charcoal was desorbed with CS2 and injected into a gas chromatograph connected with a mass spectrometer. The biological monitoring of exposed workers was performed by determining the concentration of CO in alveolar air (CA, ppm) and methylene chloride in urine (Cu, mu/L). Immediately after the end of the exposure, a urine sample was collected avoiding solvent loss and using gas-tight samplers. Excretion level in urine was determined by using headspace gas chromatography linked to a mass spectrometer. The CO was determined at the end of the shift by using a portable instrument. A group of 20 workers (12 smokers and 8 nonsmokers) in the manufacturing plant were monitored. No significant correlation was observed among the CO of all subjects and the concentration of methylene chloride in ambient air. When those workers who smoked were removed from the analysis, a correlation between the methylene chloride concentration in air and the CO concentration in alveolar air was found. Significant linear correlation was found between the environmental concentration of methylene chloride in the breathing zone and methylene chloride concentration in urine.

Adult↗

Bronchial reactivity to methacholine in HIV-infected individuals without AIDS.

To evaluate bronchial reactivity to methacholine in human immunodeficiency virus (HIV) infection, we submitted 25 HIV-seropositive subjects without full-blown AIDS and 25 HIV-seronegative subjects, all inmates in a drug rehabilitation center for previous intravenous drug abuse, to interview and to bronchial challenge with methacholine. Four (16 percent) HIV-seropositve and three (12 percent) HIV-seronegative subjects noted bronchospastic symptoms. Baseline FEV1 and MEF50 percent were within the normal range in every patient. Bronchial hyperreactivity to methacholine (PD20FEV1 < 1,400 micrograms) was found in two (8 percent) HIV-seropositive and in four (16 percent) HIV-seronegative subjects, with no significant difference in the frequency between the two groups. We conclude that HIV infection without AIDS in intravenous drug users does not appear to be associated with an increased frequency of bronchospastic disorders and to bronchial hyperreactivity to methacholine.

Acquired Immunodeficiency Syndrome↗

Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia.

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gallopamil and diltiazem: a double-blind, randomized, cross-over trial in effort ischaemia.

The aim of this study was to evaluate the efficacy and possibly the mechanism of action of gallopamil and diltiazem in a double-blind crossover trial in patients with effort ischaemia. Twenty male patients (mean age 57 +/- 6 years) with documented coronary atherosclerosis and exercise-induced ischaemia (ST depression greater than or equal to 0.15 mV) completed the study, which consisted of four 7 day periods. At the end of each period a multistage bicycle exercise stress test was performed under placebo (first and third periods) and randomly under gallopamil (50 mg t.i.d.) or diltiazem (90 mg t.i.d.) in the second and fourth periods. Both drugs significantly increased time to ischaemia (0.15 mV ST depression) as compared to placebo, from 7.9 +/- 1.7 min to 8.9 +/- 1.1 min (diltiazem) and 9.1 +/- 1.6 min (gallopamil) with no significant difference between the two drugs, and reduced the maximal extent of ST shift from 0.18 +/- 0.08 mV to 0.13 +/- 0.04 mV (diltiazem) and 0.12 +/- 0.05 mV (gallopamil). Analysis of the results from the whole population showed that the beneficial effect did not appear to be related to any specific parameter. Individual analysis showed that 13/20 patients under gallopamil and 13/20 under diltiazem increased time to ischaemia, while this was unchanged or reduced in the remainder. A positive correlation between changes in time to ischaemia and changes in rate x pressure product at ischaemia was found in both those administered gallopamil (R 0.80, P less than 0.01) and diltiazem (R 0.65, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗