Search PubMed⌕ Search

Biomedical subjects

J Molinari

Publications and source records attributed to J Molinari.

At least 19 recordsLinked to original sources
PubMed2006

Effect of advanced glycation end-products on cell proliferation and cell death.

The effect of advanced glycation end products (AGE-s) was studied on the proliferation and cell death of human skin fibroblasts in culture. Several AGE-products were prepared from proteins, a peptide and amino acids, using Glucose or Fructose, with or without Fe2+. The AGE preparations increased cell death at the 7th day, after only 72 hours of incubation. Some of these glycation products modified also proliferation. This effect of AGE-s was even maintained without these products in fresh medium for a second period of incubation up to 10 days from the start of the experiment. In order to explore the role of AGE-receptors, especially of AGE-receptor and of growth factor receptors (fibroblast and epidermal growth factors receptors), antibodies to these receptors were added to cell cultures and their effect on both cell death and proliferation were determined as for the AGE-s. These anti-receptor antibodies imitated to some extent the results obtained with AGE-s, producing increase of cell death and proliferation, followed above a certain concentration of antibodies by a decrease and a new increase or plateau. This might correspond to the internalization of the receptors followed by a re-expression on the cell membrane. The role of receptor-mediated Reactive Oxygen Species-production was also explored using scavengers: N-acetyl-cysteine (NAC), L-Carnosine, superoxide dismutase (SOD) and Catalase. Several of these scavengers decreased cell death, suggesting that Reactive Oxygen Species-production is partially involved in the observed phenomena.

Antibody Formation↗
PubMed2006

Pharmacological properties of rhamnose-rich polysaccharides, potential interest in age-dependent alterations of connectives tissues.

Rhamnose-rich oligo- and polysaccharides (RROPs) were tested for their potential pharmacological properties using human skin fibroblasts in serial cultures. The substances tested were shown to stimulate cell proliferation, decrease elastase-type activity, stimulate collagen biosynthesis, and protect hyaluronan against free radical mediated degradation. These reactions appear to be triggered by the mediation of a specific alpha-L-rhamnose recognizing lectin-site acting as a receptor, transmitting signals to the cell-interior. The rapid increase of intracellular free calcium after addition of RROP-1 and preliminary data using micro arrays appear also to confirm this contention.

Adult↗
PubMed2006

Protection by rhamnose-rich polysaccharides against the cytotoxicity of Maillard reaction products.

Previous experiments have shown that AGE-products added to human skin fibroblast cultures increased the number of dead cells floating on top of the culture fluid and took up vital dye [1]. In these experiments, we tested several rhamnose-rich polysaccharides for protection against the cytotoxic effect of AGE-s. Added at relatively low concentrations (between 10 and 100 microg/ml) to the culture medium, several of the tested rhamnose-rich oligo- and polysaccharides (RROP-s) gave a significant protection against AGE-induced cytotoxicity. Their effect on cell proliferation was also tested. The number of cells at saturation density was also shown to be influenced by AGE-products added to the cultures. This effect was also, at least partially, corrected by the rhamnose-rich oligo- and polysaccharides. These substances might therefore be considered as of potential therapeutical interest against hyperglycemia induced cytotoxic effects as in type II-diabetes.

Cell Death↗
PubMed2005

Structural analysis of a set of proteins resulting from a bacterial genomics project.

The targets of the Structural GenomiX (SGX) bacterial genomics project were proteins conserved in multiple prokaryotic organisms with no obvious sequence homolog in the Protein Data Bank of known structures. The outcome of this work was 80 structures, covering 60 unique sequences and 49 different genes. Experimental phase determination from proteins incorporating Se-Met was carried out for 45 structures with most of the remainder solved by molecular replacement using members of the experimentally phased set as search models. An automated tool was developed to deposit these structures in the Protein Data Bank, along with the associated X-ray diffraction data (including refined experimental phases) and experimentally confirmed sequences. BLAST comparisons of the SGX structures with structures that had appeared in the Protein Data Bank over the intervening 3.5 years since the SGX target list had been compiled identified homologs for 49 of the 60 unique sequences represented by the SGX structures. This result indicates that, for bacterial structures that are relatively easy to express, purify, and crystallize, the structural coverage of gene space is proceeding rapidly. More distant sequence-structure relationships between the SGX and PDB structures were investigated using PDB-BLAST and Combinatorial Extension (CE). Only one structure, SufD, has a truly unique topology compared to all folds in the PDB.

Databases, Protein↗
PubMed1999

Coronary artery vasomotion and post-stenotic coronary artery blood flow after intracoronary lacidipine in patients with ischaemic heart disease: a pilot study.

BACKGROUND: The calcium antagonist lacidipine has been shown to be highly vasoselective and to improve myocardial perfusion in hypertensive patients. However, its effects on coronary artery vasomotility and on post-stenotic coronary flow reserve in patients with atherosclerotic heart disease are unknown. OBJECTIVES: This study was designed to investigate the acute direct effects of repeated infusions of lacidipine on epicardial coronary artery vasomotion and on post-stenotic coronary artery blood flow in patients with stable angina pectoris and angiographic evidence of coronary heart disease. METHODS: In 8 patients with stable angina and moderate to severe stenosis of the left coronary artery, measurements of epicardial dimensions (quantitative angiography) and of coronary blood flow (Doppler guidewire) distal to a stenosis were performed at baseline and after 3 repeated intracoronary boluses of 12 microg of lacidipine. Results were compared with those obtained after 10 mg of intracoronary papaverine. RESULTS: The intracoronary administration of lacidipine was well tolerated, without any adverse effects. Lacidipine significantly increased the minimal luminal diameter of the lesion (peak relative increase of 43.7%), without significant changes in heart rate and systolic aortic pressure. Intracoronary lacidipine caused a dose-dependent increase in coronary flow reserve. Maximal vasodilatory effects were equivalent to those obtained with intracoronary papaverine. CONCLUSIONS: These results suggest that lacidipine acts directly as a potent vasodilator in stenotic epicardial vessels and improves myocardial perfusion distal to a moderately severe stenosis in patients with stable angina.

Aged↗
PubMed1997

The use of mediation to manage patient-staff conflict in the dialysis clinic.

The use of mediation to manage a disruptive incident between a staff nurse and a hemodialysis patient is the focus of this multidisciplinary case review. The growing interest in techniques to manage disruptive patient behavior in the dialysis clinic is analyzed. A mediation model designed for the dialysis clinic is presented for the reader. This case presentation also examines the experience of conflict from several perspectives including the patient, the nurse, the nurse manager, and the social worker. This discussion is intended to provide the reader with support for viewing conflict as unavoidable in the chronic dialysis treatment environment and for enlisting the support of the patient when responding to disruption in the treatment relationship.

Adult↗
PubMed1995

Maximal myocardial perfusion by videodensitometry in the assessment of the early and late results of coronary angioplasty: relationship with coronary artery measurements and left ventricular function at rest.

In the assessment of the acute results of percutaneous transluminal coronary angioplasty (PTCA), myocardial perfusion at maximal vasodilatation theoretically has fewer limitations than the coronary flow reserve measurements and quantitative coronary angiography. The purpose of this study was to compare the myocardial perfusion to the measurements of the severity of the lesion (minimal luminal diameter and percent area stenosis) and to relate it to the changes of left ventricular function after PTCA. Regional myocardial perfusion was assessed during intracoronary papaverine, using the inverse mean transit time of contrast medium (1/Tmn), before, 15 min after, 18-24 hr after, and 6 months after successful single-vessel PTCA in 14 patients with stable angina. Left ventricular angiography (before angioplasty, 18-24 hr after, and 6 months later) was analysed by area-length and centerline methods. Immediately after PTCA, 1/Tmn increased from 0.14 +/- 0.07 sec-1 to 0.21 +/- 0.09 sec-1 (P = .001). Maximal myocardial perfusion remained higher than the pre-PTCA value the day after angioplasty (1/Tmn of 0.23 +/- 0.09 sec-1), while it reduced to near pre-PTCA values at follow-up (1/Tmn of 0.16 +/- 0.05 sec-1). Before PTCA, three out of ten patients had ejection fraction of < 65%, and seven had mild-to-moderate hypokinesis. The day after PTCA the ejection fraction and the regional dysfunction improved significantly. The change in ejection fraction 18-24 hr after PTCA did not correlate with minimal luminal diameter and percent area stenosis and correlated slightly with the improvement of perfusion (r = 0.54, P = .10). At follow-up left ventricular function deteriorated in the whole group, despite the persistence of angiographic success of PTCA, possibly because of changes in the loading condition. Coronary artery stenosis measurements and 1/Tmn failed to correlate with the left ventricular function. Given the difficulties in routine application of the analysis of time-density curves, the measurement of minimal luminal diameter remains a more practical assessment of the results of the intervention. However, the improvement of myocardial perfusion may give more information than coronary artery dimensions of the early recovery of left ventricular function.

Adult↗
PubMed1994

Coronary vasoconstriction in response to acetylcholine after balloon angioplasty: possible role of endothelial dysfunction.

BACKGROUND: Abnormal endothelium-dependent vasomotion has frequently been observed early after coronary angioplasty. The aim of this study was to investigate endothelium-mediated coronary vasomotion caused by increasing intracoronary infusions of acetylcholine into epicardial coronary arteries 3-6 months after coronary angioplasty in patients without restenosis (50% luminal diameter reduction). METHODS: Intracoronary acetylcholine was infused during follow-up coronary angiography followed by an intracoronary bolus of 250 g nitroglycerin in 18 patients who had undergone successful angioplasty of 21 isolated coronary artery lesions. Using an automated edge-detection program, coronary artery measurements were performed in the proximal reference segment, in the proximal part of the angioplasty site, at the site of previous maximal stenosis, in the distal part of the angioplasty site, and in the distal reference segment. RESULTS: In the segments of the coronary artery not manipulated by balloon catheter, acetylcholine did not produce significant luminal diameter changes (+2 +/- 23% in the proximal segment and -3 +/- 27% in the distal segment at 10(-4) mol/l). All the angioplasty vessel segments, excluding the proximal reference segments, showed an abnormal dose-related reactivity to the acetylcholine. Maximal vasoconstriction was observed at 10(-4) mol/l and was 4.9 +/- 11.1% in the proximal reference segment, 9.3 +/- 19.1% in the proximal angioplasty site (P = 0.0314), 20.3 +/- 24.1% at the site of previous maximal stenosis (P = 0.0005), 10.7 +/- 16.8% at the distal angioplasty site (P = 0.0098), and 9.3 +/- 14.1% in the distal reference segment (P = 0.0032). The maximal response of the angioplasty site to acetylcholine and to nitroglycerin did not correlate either with the time to follow-up or with the follow-up stenosis. Nitroglycerin-induced vasodilation was significant in all segments, but was lower in the lesion-related segments. Acetylcholine evoked the same effect on both the vessels that were manipulated and those that were not. CONCLUSIONS: Three to 6 months after coronary angioplasty, endothelium-dependent vasodilation was impaired not only at the site of previous maximal stenosis, but also in segments directly injured by balloon inflation. In contrast, endothelium-independent vasodilation by nitroglycerin is maintained in all segments. These observations suggest that the endothelium is still functionally impaired in the area of balloon dilation.

Acetylcholine↗
PubMed1994

[Coronary recanalization: rationale for stents].

Coronary stenting is a technique complementary to coronary angioplasty, because it is successful in the management of the two major limitations of conventional balloon dilation, i.e. the acute or threatened closure and the restenosis. The currently available intracoronary stents are far from being ideal, mainly for their thrombogenicity. During abrupt closure, the bailout stenting has, in most of the cases, offered a valuable alternative to emergency coronary artery bypass surgery. The major complications after stent insertion are the result of an inadequate stent placement, of persistence of intra and/or poststent obstruction and of the ineffective anticoagulant therapy. The mechanical support (scaffolding) provided by the stent after dilation significantly reduces the amount of elastic recoil, and, improving laminar flow, eliminates arterial wall shear stress that may contribute to an increase in intimal thickening. Moreover, the reduction of arterial cyclical stretching may reduce the rate of neointimal proliferation. By sealing the exposed subintimal spaces, stents may minimise the formation of local thrombi, and thus also limit their later organization and fibrous conversion into part of the restenotic lesion: two recently completed randomized trials (STRESS and BENESTENT) confirm the lower rate of restenosis in patients treated with single stent placement in de-novo lesions as compared with standard balloon angioplasty. The mechanism of stent benefit in reducing restenosis rate seems to be the wider initial lumen, which can accommodate a greater degree of intimal hyperplasia. In the near future, the improvements of the blood and tissue compatibility of the stents, may allow easier management.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1993

[Endothelial dysfunction in ischemic syndromes].

Several studies have shown evidence of the key role of the endothelium in modulating the tone of epicardial coronary vessels, in the different manifestations of coronary artery disease. Recently, the role of endothelium-dependent vasodilation has been focused, because clinical observations have suggested that myocardial ischemia might be caused or aggravated by inappropriate vasoconstriction of resistance vessels. An abnormal endothelium-dependent vasodilation, either of epicardial and of coronary microvasculature, has been documented in patients with syndrome X and in patients with history of hypertension and left ventricular hypertrophy. Vasoconstriction of the small coronary vessels is probably the mechanism underlying the impaired increase of coronary blood flow during atrial pacing and the wide variations of the ischemic threshold in some patients with chronic stable angina. In patients with variant angina, the endothelial function seems abnormal only in the conductance vessels. It is likely that the endothelial dysfunction of the small coronary arteries be present in many clinical situations in which a discrepancy between a mild atherosclerosis of epicardial coronary artery and signs of ischemia exists, as it has been observed early after successful angioplasty and after coronary artery reperfusion during acute myocardial infarction.

Coronary Vessels↗