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Biomedical subjects

M Romano

Publications and source records attributed to M Romano.

At least 163 records · Page 9Linked to original sources
PubMed2000

Fluvastatin reduces soluble P-selectin and ICAM-1 levels in hypercholesterolemic patients: role of nitric oxide.

BACKGROUND: Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. Adhesion molecules, regulating interactions between vascular and circulating cells, may play a central role in the pathogenesis of atherosclerosis and related complications. In the present report we examined the impact of the HMG-CoA reductase inhibitor fluvastatin on plasma levels of P-selectin and ICAM-1. METHODS: Plasma levels of P-selectin and ICAM-1 were determined using an enzyme immunoassay in 26 patients with type IIa hypercholesterolemia randomized to treatment with either fluvastatin (80 mg/d) or placebo in a double blind fashion for 12 weeks. RESULTS: Fluvastatin administration reduced either P-selectin (118 +/- 63 vs 81 +/- 36 ng/mL [-31%], P = 0.0015) or ICAM-1 (264 +/- 75 vs 228 +/- 68 ng/mL [-13.7%], P = 0.0033) levels. Fluvastatin also lowered urinary 11-dehydro-TXB2 (1396 +/- 536 vs 1009 +/- 378 pg/mg creatinine [-27%], P = 0.0015) and von Willebrand Factor levels (1456 +/- 716 vs 1203 +/- 527 U/L [-17.4%], P = 0.0275), and a direct correlation was observed between P-selectin and 11-dehydro-TXB2 levels (r = 0.588, P = 0.0033). Patients treated with fluvastatin displayed an increase in nitric oxide (NO) generation, evaluated with measurements of serum NO2-/NO3-, (4.7 +/- 1 vs 8.9 +/- 3.1) mumol/L [98%], P = 0.0046). Moreover, an inverse correlation was observed between NO2-/NO3- and P-selectin (r = -0.420; P = 0.0343), 11-dehydro-TXB2 (r = -0.511; P = 0.0106), or LDL (r = -0.742; P = 0.0002) levels. CONCLUSIONS: These results may provide novel biochemical basis for the beneficial clinical effects of HMG-CoA reductase inhibitors in hypercholesterolemia.

Adult↗
PubMed2000

[Comparison of segmental wall motion in electrocardiogram-gated myocardial scintigraphy and transthoracic echocardiography].

ECG-gated myocardial scintigraphy (Gspect) is a recent method of assessing myocardial perfusion, left ventricular ejection fraction and regional wall motion in a single investigation. It reduces the time required for the evaluation of coronary patients by radionucleide cardiology. Many reports have validated the measurement of the left ventricular ejection fraction compared with other methods. However, there are fewer series reporting the results of regional wall motion. The authors compared segmental wall motion by Gspect after injecting Thallium or Mibi and by transthoracic echocardiography in 47 patients or 423 myocardial segments. The concordance of score (normal, hypokinetic, akinetic, dyskinetic) was 75% (Kappa = 0.538). If analysis was limited to a normal-abnormal differentiation (binary analysis) it increased to 83%. When perfusion was taken into consideration, it was 81% (normal perfusion), 63% (mild hypoperfusion) and 70% (moderate and severe hypoperfusion). This concordance improved in binary analysis respectively to 85, 74 and 86% respectively. When the typs of segment was taken into consideration, concordance varied from 57 to 100%. The concordances were 74% for Thallium and 78% for Mibi scintigraphy, improving to 82% and 85% respectively in binary analysis. Thus, analysis of LV regional wall motion by Gspect is comparable to transthoracic echocardiography. This result, completed by measurement of LV ejection fraction and of myocardial perfusion, provides a method of evaluation of coronary patients in a single investigation.

Aged↗
PubMed2000

[Relationship between exercise capacity and left ventricular function at rest in patients with heart insufficiency: radionuclide continuous monitoring of left ventricular function].

PURPOSE: To evaluate the relationship of systolic and diastolic function at rest to exercise capacity. MATERIAL AND METHODS: Seventeen patients with ischemic heart failure were included in the study. Ambulatory left ventricular monitoring at rest and during upright exercise with combined analysis of pulmonary gas exchange was performed. Ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, and peak filling rate were measured. RESULTS: Significant positive correlations were found between rest ejection fraction and peak oxygen consumption (r = .60, p < .01), peak cardiac output (r = .77, p < .0001), peak stroke volume (r = .67, p < .005), and peak ejection fraction (r = .69, p < .005). On the other hand, peak filling rate at rest showed a significant inverse correlation with peak end-diastolic (r = -.48, p < .05) and end-systolic (r = -.66, p < .005) volumes. The patients were then subgrouped into two groups according to their rest ejection fraction (lower or higher than 40%). In the group with ejection fraction less than 40% a significant correlation was observed between rest ejection fraction and both peak stroke volume (r = .66, p < .05) and peak ejection fraction (r = .69, p < .05). In the same group of patients an inverse correlation was found between peak filling rate and both end-diastolic (r = -0.65, p < .05) and end-systolic (r = -.82, p < .005) volumes. CONCLUSIONS: The results of the present study suggest that exercise capacity is related to left ventricular function at rest and that rest diastolic function might be a determinant of left ventricular function during exercise in patients with heart failure.

Exercise Tolerance↗
PubMed1999

Exercise capacity in hypertrophic cardiomyopathy depends on left ventricular diastolic function.

Some studies have demonstrated that left ventricular (LV) diastolic function is the principal determinant of impaired exercise capacity in hypertrophic cardiomyopathy (HC). In this study we sought the capability of echocardiographic indexes of diastolic function in predicting exercise capacity in patients with HC. We studied 52 patients with HC while they were not on drugs;12 of them had LV tract obstruction at rest. Diastolic function was assessed by M-mode and Doppler echocardiography by measuring: (1) left atrial fractional shortening, and the slope of posterior aortic wall displacement during early atrial emptying on M-mode left atrial tracing; and (2) Doppler-derived transmitral and pulmonary venous flow velocity indexes. Exercise capacity was assessed by maximum oxygen consumption by cardiopulmonary test during cycloergometer upright exercise. Maximum oxygen consumption correlated with the left atrial fractional shortening (r = 0.63, p <0.001), the slope of posterior aortic wall displacement during early atrial emptying (r = 0.55, p <0.001), age (r = -0.50; p <0.001), pulmonary venous diastolic anterograde velocity (r = 0.41, p <0.01), and the systolic filling fraction (r = -0.43; p <0.01). By stepwise multiple linear regression analysis, left atrial fractional shortening and the pulmonary venous systolic filling fraction were the only determinants of the maximum oxygen consumption (multiple r = 0.70; p <0.001). Exercise capacity did not correlate with Doppler-derived transmitral indexes. Thus, in patients with HC, exercise capacity was determined by passive LV diastolic function, as assessed by the left atrial M-mode and Doppler-derived pulmonary venous flow velocities.

Adolescent↗
PubMed1999

The myoglobin of Emperor penguin (Aptenodytes forsteri): amino acid sequence and functional adaptation to extreme conditions.

In the framework of a study on molecular adaptations of the oxygen-transport and storage systems to extreme conditions in Antarctic marine organisms, we have investigated the structure/function relationship in Emperor penguin (Aptenodytes forsteri) myoglobin, in search of correlation with the bird life style. In contrast with previous reports, the revised amino acid sequence contains one additional residue and 15 differences. The oxygen-binding parameters seem well adapted to the diving behaviour of the penguin and to the environmental conditions of the Antarctic habitat. Addition of lactate has no major effect on myoglobin oxygenation over a large temperature range. Therefore, metabolic acidosis does not impair myoglobin function under conditions of prolonged physical effort, such as diving.

Adaptation, Physiological↗
PubMed1999

Molecular response of gastric epithelial cells to Helicobacter pylori-induced cell damage.

Infection with the Gram-negative bacterium Helicobacter pylori leads to different clinical and pathological outcomes in humans, including chronic gastritis, peptic ulcer disease and adenocarcinoma of the stomach. H. pylori-induced damage to gastric mucosal cells is controlled by bacterial virulence factors encoded by genes of the cag pathogenicity island, which trigger the inflammatory response of the host through the activation of nuclear factor kappaB-dependent gene transcription. Also, H. pylori infection impairs the processes of gastric mucosal healing through inhibition of epidermal growth factor receptor-dependent signal transduction pathways and induction of apoptosis. H. pylori infection may influence the progression from chronic gastritis to gastric adenocarcinoma by stimulating cell proliferation and growth factor expression, inhibiting apoptosis and increasing the DNA mutation rate of infected gastric mucosa.

Adenocarcinoma↗
PubMed1999

Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9.

The rate of exon 9 exclusion from the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA is associated with monosymptomatic forms of cystic fibrosis. Exon 9 alternative splicing is modulated by a polymorphic polythymidine tract within its 3' splice site. We have generated a minigene carrying human CFTR exon 9 with its flanking intronic sequences and set up an in vivo model to study the cis-acting DNA elements which modulate its splicing. Transfections into human cell lines showed that T5, but not T9 or T7 alleles, significantly increases the alternative splicing of exon 9. Moreover, we found that another polymorphic locus juxtaposed upstream of the T tract, and constituted by (TG)(n)repeats, can further modulate exon 9 skipping but only when activated by the T5 allele. Then, we extended our studies to the mouse CFTR exon 9 which does not show alternative splicing. Comparison of human and mouse introns 8 and 9 revealed a low homology between the two sequences and the absence of the human polymorphic loci within the mouse intron 3' splice site. We have tested a series of constructs where the whole human exon 9 with its flanking intronic sequences was replaced partially or completely by the murine counterpart. The transfections of these constructs in human and murine cell lines reveal that also sequences of the downstream intron 9 affect exon 9 definition and co-modulate, with the UG/U 3' splice site sequences, the extent of exon 9 skipping in CFTR mRNA.

Alternative Splicing↗
PubMed1999

Nutritional management of chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction (CIP) is a gastrointestinal motility disturbance characterized by recurrent episodes of postprandial nausea and bloating in the absence of mechanical obstruction of the small bowel or colon. Weight loss and severe malnutrition are often seen in advanced stages of the disorder. This article discusses the nutritional management of patients with CIP, focusing on general dietary as well as enternal and parenternal nutritional support. Enteral access methods and various enteral formulas used in CIP are also discussed.

Chronic Disease↗
PubMed1999

Hepatocytes are a rich source of novel aspirin-triggered 15-epi-lipoxin A(4).

Novel aspirin (ASA)-triggered 15-epi-lipoxins (ATL) comprise new potent bioactive eicosanoids that may contribute to the therapeutic effect of this drug. ATL biosynthesis is initiated by ASA acetylation of cyclooxygenase (COX)-2 and was originally identified during the interaction of leukocytes with either endothelial or epithelial cells. Here, we examined ATL biosynthesis in rat hepatocytes either alone or in coincubation with nonparenchymal liver cells (NPC) and in liver homogenates from ASA-treated rats. Rat hepatocytes and CC-1 cells, a rat hepatocyte cell line, displayed COX-1 but not COX-2 mRNA expression and predominantly produced thromboxane A(2) (TXA(2)) and 15-hydroxyeicosatetraenoic acid (15-HETE). In these cells, ASA shifted the arachidonic acid metabolism from TXA(2) to 15-HETE in a concentration-dependent manner. In contrast, neither indomethacin, ibuprofen, valeryl salicylate, nor nimesulide was able to trigger 15-HETE biosynthesis. SKF-525A, a cytochrome P-450 inhibitor, significantly reduced the effect of ASA on 15-HETE biosynthesis. Furthermore, phenobarbital, a potent inducer of cytochrome P-450 activity, further increased ASA-induced 15-HETE production. ASA treatment of hepatocyte-NPC coincubations resulted in the generation of significant amounts of ATL. In addition, in vivo experiments demonstrated augmented hepatic levels of 15-epi-lipoxin A(4) in ASA-treated rats. Taken together and considering that ASA is hydrolyzed on its first pass through the portal circulation, these data indicate that, during ASA's consumption, liver tissue generates biologically relevant amounts of ATL by COX-2-independent mechanisms.

Animals↗
PubMed1999

Transcellular regulation of eicosanoid biosynthesis.

Models for in vivo scenarios of transcellular biosynthesis provide invaluable information about the regulation of eicosanoid biosynthesis that is likely to occur during multicellular events in vivo. The experimental approach of studying eicosanoid generation during cell-cell interactions and receptor-mediated cell activation represents a significant advancement beyond initial observations of eicosanoid formation and bioaction in isolated cell types that were activated under less physiologically relevant conditions. The experimental models reviewed in this chapter should be viewed as specific examples or as approaches to the study of cell-cell interactions. These examples may serve as guidelines to investigate novel cell-cell scenarios (see Fig. 3) and advance the emerging area of transcellular biosynthesis of bioactive lipid mediators.

Aspirin↗
PubMed1999

A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1.

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propan oic acid) dose-dependently inhibited MCP-1 and TNF-alpha production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1alpha and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.

Animals↗
PubMed1999

Haematologic pattern in healthy elderly subjects.

BACKGROUND: A more prolonged life expectancy is associated with an increased morbidity rate with marked alterations of physiologic and metabolic functions in the body. The haematologic pattern can be modified during ageing because of reduced cellular replication and enhanced fibrosis in the bone marrow. Nevertheless it is not clear whether ageing represents the cause or the result of these phenomena. METHODS: In order to evaluate wide variation of data on the haematologic pattern in elderly subjects, we studied one hundred eight healthy subjects (27 males, 81 females; ranging from 50 to 99 years), living in their home. RESULTS: We observed a reduction in serum iron and transferrin and an increase in serum ferritin levels during ageing, with a consequential iron tissue stores increase. CONCLUSIONS: Our data suggested that senescence was associated with an increased incidence of anemia, which cannot be considered a normal feature of aging, the physicians must investigate each cause of anemia in elderly subjects. Haematological pattern is in the normal range in healthy elderly subjects, even if we found significant age-linked changes. We conclude that a progressive impairment of bone marrow functions is the most important factor in determining significant changes of hematopoiesis in healthy elderly subjects.

Aged↗
PubMed1999

Morphological imaging of thymic disorders.

The thymus is a bilobed lymphoid organ the morphology of which varies considerably with age as a result of a process of fatty infiltration occurring after puberty. Although several diseases can arise in the thymic parenchyma, including germ cell and neuroendocrine tumours, primitive epithelial neoplasms (thymomas) are the most common neoplasms and account for almost 10% of mediastinal masses. Thymomas are usually benign but can be locally invasive. Up to 30% of patients with a thymoma have myasthenia gravis, which is more commonly associated with thymic hyperplasia. The latter results in a symmetric diffuse enlargement of the thymus. However, thymic hyperplasia can be histologically found in up to 50% of normal-sized thymuses on computed tomography (CT). CT is much more accurate in detecting thymomas than it is in detecting thymic hyperplasia, although CT findings may be unspecific. CT can be exhaustive in the case of an encapsulated thymoma (65% of all thymomas), which appear as a solid homogeneous mass with a slight contrast enhancement and a well-defined surrounding fat plane. These tumours rarely recur after surgery. CT can also accurately detect a spread through the capsule into the adjacent mediastinal fat, which characterizes invasive thymomas (35%). These, however, are best evaluated by magnetic resonance imaging (MRI). On T1-weighted MR scans the thymus is well delineated against the mediastinal fat, whereas marked inhomogeneity of the signal may appear on T2-weighted images as a result of areas of cystic degeneration in the tumour mass. The superior contrast resolution of MRI and the multiplanar images that can be produced with it are well suited for documenting the mediastinal spread of invasive thymomas. MRI depicts accurately pleural and/or pericardial implants as well as the involvement of great vessels, offering considerable aid in the planning of surgery.

Adult↗
PubMed1999

[Postoperative infections after heart surgery under extracorporeal circulation].

Postoperative infection is still an important cause of mortality and morbidity after cardiac surgery. The aim of this study was to assess its incidence and causes in order to optimise treatment. Between January 1996 and December 1997, 1,000 consecutive patients (253 women and 747 men) were operated for cardiac aortic pathology under cardiopulmonary bypass. The mean age was 66 +/- 11 years. The initial pathology was coronary artery disease (N = 663), valvular heart disease (N = 193), an association of the two (N = 94), thoracic aortic pathology (N = 38) or other pathologies (N = 12). The global postoperative infection rate was 4.9% (N = 49). The incidence of sternal and/or mediastinal infections was 0.7%, of bronchopneumonia 0.9%, urinary infection 2.1%, and septicaemia 1.7%. Nine patients died of the consequences of an infection. The hospital stay was significantly longer in infected patients, irrespective of the site of infection. Statistical analysis of the whole population did not show any predictive factor related to the preoperative clinical status of the patients. The only predictive factor demonstrated was the day on which surgery was performed: the infection rate in patients operated during the first 4 days of the week was 2.2% compared with 7.3% for the patients operated during the last 3 days (p = 0.004, odds ratio (OR) = 3.57). In those patients who had an urinary infection, the two identified risk factors were the female gender (p = 0.006, OR = 3.34) and an operation performed at the end of the week (p = 0.017, OR = 3.77). In patients with sternal and medistinal infections, the only identified predictive factor was combined coronary artery and valvular surgery (p = 0.009, OR = 7.43). With respect to pulmonary infections, the only predictive factor was recent preoperative myocardial infarction (< 1 month) (p = 0.004, OR = 7.5). Finally, no predictive risk factors were identified in those patients who developed septicaemia. In conclusion, this study showed that postoperative infection remains a serious complication of cardiac surgery. The prevention of these complications should be a priority for quality health care.

Adult↗
PubMed1998

The hemoglobins of the antarctic fishes Atedidraco orianae and Pogonophryne scotti. Amino acid sequence, lack of cooperativity, and ligand binding properties.

The oxygen-transport system of two species of Antarctic fishes belonging to the family Artedidraconidae, Artedidraco orianae and Pogonophryne scotti, was thoroughly investigated. The complete amino acid sequence of the alpha and beta chains of the single hemoglobins of the two species was established. The oxygen-binding properties were also investigated, and were found not to differ significantly from those shown by blood, intact erythrocytes, and unstripped hemolysates. Both hemoglobins have unusually high oxygen affinity and display a relatively small Bohr effect; the Root effect is elicited only by organophosphates and is also reduced. Remarkably, the Hill coefficient is close to one in the whole pH range, indicating absence of cooperative oxygen binding which, in A. orianae hemoglobin, could be ascribed to the subunit heterogeneity shown upon oxygen dissociation. In comparison with the other families of the suborder Notothenioidei, the oxygen-transport system of these two species of Artedidraconidae has unique characteristics, which raise interesting questions on the mode of function of a multisubunit molecule and the relationship with cold adaptation.

Amino Acid Sequence↗
PubMed1998

Helicobacter pylori up-regulates cyclooxygenase-2 mRNA expression and prostaglandin E2 synthesis in MKN 28 gastric mucosal cells in vitro.

Helicobacter pylori has been suggested to play a role in the development of gastric carcinoma in humans. Also, mounting evidence indicates that cyclooxygenase-2 overexpression is associated with gastrointestinal carcinogenesis. We studied the effect of H. pylori on the expression and activity of cyclooxygenase-1 and cyclooxygenase-2 in MKN 28 gastric mucosal cells. H. pylori did not affect cyclooxygenase-1 expression, whereas cyclooxygenase-2 mRNA levels increased by 5-fold at 24 h after incubation of MKN 28 cells with broth culture filtrates or bacterial suspensions from wild-type H. pylori strain. Also, H. pylori caused a 3-fold increase in the release of prostaglandin E2, the main product of cyclooxygenase activity. This effect was specifically related to H. pylori because it was not observed with Escherichia coli and was independent of VacA, CagA, or ammonia. H. pylori isogenic mutants specifically lacking picA or picB, which are responsible for cytokine production by gastric cells, were less effective in the up-regulation of cyclooxygenase-2 mRNA expression and in the stimulation of prostaglandin E2 release compared with the parental wild-type strain. This study suggests that development of gastric carcinoma associated with H. pylori infection may depend on the activation of cyclooxygenase-2-related events.

Adenocarcinoma↗