Biomedical subjects

Jordi Bozzo

Publications and source records attributed to Jordi Bozzo.

7 recordsLinked to original sources

PubMed2006

Serotonergic mechanisms: a potential link between affective disorders and cardiovascular risk.

Cardiovascular disease and major depression are highly prevalent disorders in our society. Evidence has been found that confirms a reciprocal relationship between mechanisms of depression and those of cardiovascular pathology. This possible feedback between both pathologies is a subject of great concern. In recent years some studies suggest that platelets and serotonergic mechanisms could be involved in both conditions. The present review seeks a better understanding of the mechanisms that could link depression with an enhanced cardiovascular risk.

Journal Article↗

PubMed2006

Spotlight on tNOX: a tumor-selective target for cancer therapies.

Tumor-associated NOX (tNOX) is a novel cell surface ECTO-NOX protein that represents a promising target for selective antitumor therapy. Studies have confirmed the unique presence of tNOX on the cell surface of invasive human cancers and in the sera of cancer patients. Furthermore, as there is a resolute difference between tNOX and the drug-resistant constitutive NOX isoform constitutive NOX, it represents an attractive target for drug, vaccine and diagnostic strategies for cancer. Interestingly, several products currently utilized or under development for cancer display tNOX inhibition as one of their underlying mechanisms, these include non- steroidal antiinflammatory drugs, (-)-epigallocatechin gallate, phenoxodiol and doxorubicin hydrochloride (Adria- mycin). This spotlight article will also highlight tNOX inhibitors under preclinical development and new lines of research to target tNOX for cancer therapeutics.

Antineoplastic Agents↗

PubMed2006

Argatroban: a direct thrombin inhibitor with reliable and predictable anticoagulant actions.

Pharmacological strategies aimed at the prevention of thrombotic complications are in continuous development. Argatroban is a synthetic small molecule derived from l-arginine with specific antithrombotic activity. Argatroban is a direct thrombin inhibitor that binds avidly and reversibly to the catalytic site of thrombin and that does not require other cofactors to exert its antithrombotic action. Due to its selective inhibitory mechanism, argatroban blocks both circulating and clot-bound thrombin. A rapid onset of its anticoagulant action is achieved after intravenous administration. The short elimination half-life of argatroban (52+/-16 minutes) ensures a rapid restoration of hemostasis upon cessation of treatment. Argatroban produces a predictable dose response, and its anticoagulant actions can be monitored easily through the routine coagulation tests activated partial thromboplastin time (aPTT) and activated clotting time (ACT). The specific mechanism of action and favorable pharmacokinetic profile of argatroban suggest that it could be beneficial in all indications where other intravenous anticoagulants are used. Results from clinical studies performed to date show that, when administered to patients with heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITTS) in two large-scale, nonrandomized, prospective trials, argatroban reduced a combined endpoint of morbidity and mortality when compared with historical controls. Argatroban was well tolerated in clinical trials of patients with HIT and caused no increase in bleeding risk compared with historical controls. Argatroban does not induce the formation of antibodies that can neutralize its anticoagulant effect, prolong its half-life or enhance its activity. The U.S. Food and Drug Administration has approved the use of this drug as an alternative antithrombotic treatment for patients with HIT as well as for patients with or at risk for HIT undergoing percutaneous coronary interventions. In 2004 (Sweden), 2005 (Germany, the Netherlands, Austria and Iceland) and 2006 (Denmark) argatroban was approved for anticoagulation in adult patients with heparin-induced thrombocytopenia type II who require parenteral antithrombotic therapy.

Animals↗

PubMed2006

Chronicles in drug discovery.

Chronicles in Drug Discovery features special interest reports on advances in drug discovery and development. This month we focus on the progress of the ongoing search for safe and effective chemopreventive agents. Chemoprevention is a strategy to decrease the risk of developing cancer by using agents that prevent or abrogate carcinogenic processes. Bowman- Birk inhibitor concentrate, budesonide, NCX-4016 and statins are all undergoing investigation in the clinical setting as potential chemopreventive agents for head and neck, lung, colon and breast cancers, respectively.

Animals↗

PubMed2005

Serotonergic mechanisms: a potential link between affective disorders and cardiovascular risk.

Antidepressive Agents↗

PubMed2004

Biocompatibility of cellulosic and synthetic membranes assessed by leukocyte activation.

BACKGROUND/AIMS: The contact of blood with artificial surfaces may activate blood leukocytes and platelets and initiate the leukocyte inflammatory response. We have investigated the effect of a hemodialysis (HD) with a cellulosic- and a synthetic-based membrane on circulating leukocyte activation. METHODS: Samples were obtained from patients with ESRD at baseline, and at 15 and 120 min of a hemodialysis session from both the arterial and venous lines. Leukocyte respiratory burst was analyzed by luminol chemiluminescence. Actin polymerization, expression of CD11b, and heterotypic aggregation were studied by flow cytometry, leukocyte labeling with NBD phallacidin and monoclonal antibodies, respectively. RESULTS: HD with a cellulosic membrane induced a transient fall in neutrophil (1.2 +/- 0.5 x 10(9) vs. 3.6 +/- 0.6 x 10(9) cells/l; p < 0.05) and monocyte counts (0.2 +/- 0.1 x 10(9) vs. 0.7 +/- 0.1 x 10(9) cells/l; p < 0.05). There was also an increase in respiratory burst in the venous line during a HD with a cellulosic membrane, at 15 and 120 min (100 +/- 41 and 143.2 +/- 45.3 vs. 23.8 +/- 15.7; p < 0.05). Polymerized actin, expressed as fluorescence arbitrary units, was increased in baseline samples from uremic patients versus control subjects (327.8 +/- 60.8 for a cellulosic membrane, p < 0.005, and 205 +/- 26.5 for a synthetic one, p < 0.05 vs. 97.8 +/- 27.6 in controls). The percentage of CD11b+ cells increased in samples during a HD with a cellulosic membrane at the venous line at 15 and 120 min (9.6 +/- 4.5 and 18.4 +/- 7.1% vs. 3.3 +/- 1.9%; p < 0.05%). Changes in heterotypic aggregation during HD did not reach statistical significance, but levels were higher in patients treated with a cellulosic membrane at all points than in patients dialyzed with a synthetic one. CONCLUSION: There is evidence of a priming state of leukocytes from uremic patients, which is more evident in patients dialyzed with a cellulosic membrane. Cellulosic membranes also induce greater leukocyte activation than synthetic membranes during hemodialysis.

Adult↗

PubMed2002

Possible hemostatic effect of synthetic liposomes in experimental studies under flow conditions.

BACKGROUND AND OBJECTIVES: The possibility of developing synthetic platelet substitutes is a subject of current interest. We explored the possible hemostatic effect of synthetic phospholipid incorporated in multilamellar vesicles (MLVs) or intermediate unilamellar vesicles (IUVs) using a well-characterized experimental system with circulating human thrombocytopenic blood (10 min, 250 s(-1)). DESIGN AND METHODS: The ability of the liposomes containing different combinations of dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (PE) and dipalmitoylphosphatidylserine (DPPS) to promote fibrin formation (%F) on the damaged subendothelium was morphometrically evaluated. Generation of thrombin in the system was monitored through prothrombin fragment F1+2 determination. RESULTS: IUV liposomes containing DPPC, 1DPPS:9DPPC, 1DPPS:3DPPC, 1PE:1DPPC increased fibrin deposition on the subendothelium (53.87 +/- 11.0%; 39.76 +/- 6.75%; 40.69 +/- 10.54% and 32.22 +/- 7.35%, respectively vs. thrombocytopenic blood 11.5 +/- 1.2%; p<0.05), while 9PE:1DPPS IUV liposome failed to promote a procoagulant effect. MLV liposomes containing DPPC alone, 1DPPS:3DPPC and 1PE:1DPPC showed a positive effect on fibrin deposition (85.50 +/- 5.95%, 59.86 +/- 11.55% and 43.73 +/- 7.84% respectively; p<0.05). However, no effect was observed in those experiments performed with liposomes containing 3DPPS:1DPPC. After perfusion experiments, the coagulation system became activated, but differences were not statistically significant vs. control experiments, except for MLV liposomes containing DPPC alone (p<0.05). INTERPRETATION AND CONCLUSIONS: These results confirm that, at an experimental level, liposomes containing phospholipids could potentially be used to improve hemostasis in patients with quantitative or qualitative platelet disorders.

Animals↗