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Biomedical subjects

F Porro

Publications and source records attributed to F Porro.

At least 19 recordsLinked to original sources
PubMed2006

Cancer and thromboembolism: from biology to clinics.

The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. Recent studies evidenced that malignant growth has also been linked to activity of heparin-like glycosoaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression in addition with activation of coagulation and fibrinolysis. These evidences suggest that antithrombotic drugs may play an additional role in tumour cell growth and in cancer dissemination. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Antithrombotic drugs such as unfractioned heparin (UFH) and, particularly, low molecular weight heparins (LMWH) in addition with dicumaroids, are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompanies malignancies. The aims of the study are to review the pathogenetic mechanisms of thromboembolic disease in cancer patients, the efficiency of antithrombotic drugs in preventing and treating of cancer related thromboembolic complications and review the thromboprophylaxis strategies to prevent thromboembolic complications of cancer patients. Meta-analyses comparing UFH and LMWH for the treatment of deep vein thrombosis have shown better outcome with reduction of major bleeding complications in patients treated with LMWH. Many studies have demonstrated the efficiency and the safeness of antithrombotic agents in the prophylaxis and in the treatment of thromboembolic complication that accompanies malignancies. Many experimental studies, reviewed in this paper, support the hypothesis that antithrombotic agents, but especially heparins can affect cancer progression in many of the different steps of cancer biology. First of all, due to their anticoagulant effect, antithrombotic agents may interfere with thrombin generation and with fibrin formation induced by cancer cells, thus inhibiting the mechanism of metastasis.

Anticoagulants↗
PubMed2006

New antithrombotic agents.

The main clinical indications for anticoagulant agents are treatment and prophylaxis of venous and arterial thromboembolism and acute coronary syndromes. For decades, two anticoagulants, heparin and warfarin, have been the principal drugs available. Dicumaroid agents have serious limitations due to their narrow therapeutic range, needing close monitoring. The interaction with food and drugs and the numerous interindividual variations result in unstable effects on coagulation parameters. On the other side, heparins have an exclusive parenteral use and a risk of immunological adverse reactions. Heparin induced thrombocytopenia is the most serious complication. The limitations of existing oral and parenteral anticoagulant agents have prompted the search for alternative anticoagulant drugs. This paper reviews new anticoagulant agents describing their pharmacological and clinical properties. It focuses on the target of their anticoagulant action inside the coagulation pathway, and analyzes the clinical trials providing indications for new clinical anticoagulation strategies. Agents currently under study include direct thrombin inhibitors, indirect activated factor X inhibitors, and inhibitors of tissue factor and activated factor VII. The new anticoagulant agents may demonstrate improvements in effectiveness, safety convenience and cost-effectiveness compared with current anticoagulants.

Acute Disease↗
PubMed2003

Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope.

Syncope as an initial presentation of pulmonary embolism occurs in 10% of patients. We compared clinical and instrumental parameters in patients with syncope as the presenting symptom of pulmonary embolism and in patients with documented pulmonary embolism without syncope. Seventy patients with the diagnosis of pulmonary embolism and apparently stable clinical conditions were evaluated. They were divided in two groups: 10 patients with syncope as the presenting symptom of pulmonary embolism (group 1) and 60 patients without syncope (group 2). Patients with syncope showed a more pronounced tendency to present with main pulmonary artery embolus than patients without syncope (contingency coefficient = 0.301, p < 0.04; one-tailed). However, despite the evidence that patients with syncope have significant reductions in systolic and/or diastolic blood pressure, shock was not observed in any patient. In no case was thrombolytic treatment given and all patients received standard anticoagulation with unfractioned heparin and oral anticoagulant. We suggest that syncope in the setting of non-massive pulmonary embolism may be due to vaso-vagal mechanism that can lead to a reduction of arterial blood pressure when central artery thrombosis is involved.

Aged↗
PubMed2000

Mild spherocytic hereditary elliptocytosis and altered levels of alpha- and gamma-adducins in beta-adducin-deficient mice.

The membrane skeleton, a dynamic network of proteins associated with the plasma membrane, determines the shape and mechanical properties of erythrocytes. Deficiencies or defects in membrane skeletal proteins are associated with inherited disorders of erythrocyte morphology and function. Adducin is one of the proteins localized at the spectrin-actin junction of the membrane skeleton. In this work we show that deficiency of beta-adducin produces an 80% decrease of alpha-adducin and a fourfold up-regulation of gamma-adducin in erythrocytes. beta-Adducin or any other isoform generated by translation of abnormally spliced messenger RNAs could not be detected by our antibodies either in ghosts or in cytoplasm of -/- erythrocytes. Actin levels were diminished in mutant mice, suggesting alterations in the actin-spectrin junctional complexes due to the absence of adducin. Elliptocytes, ovalocytes, and occasionally spherocytes were found in the blood film of -/- mice. Hematological values showed an increase in reticulocyte counts and mean corpuscular hemoglobin concentration, decreased mean corpuscular volume and hematocrit, and normal erythrocyte counts that, associated to splenomegaly, indicate that the mice suffer from mild anemia with compensated hemolysis. These modifications are due to a loss of membrane surface and dehydration that result in an increase in the osmotic fragility of red blood cells. The marked alteration in osmotic fragility together with the predominant presence of elliptocytes is reminiscent of the human disorder called spherocytic hereditary elliptocytosis. Our results suggest that the amount of adducin remaining in the mutant animals (presumably alphagamma adducin) could be functional and might account for the mild phenotype. (Blood. 2000;95:3978-3985)

Animals↗
PubMed2000

Hypertension in beta-adducin-deficient mice.

Polymorphic variants of the cytoskeletal protein adducin have been associated with hypertension in humans and rats. However, the direct role of this protein in modulating arterial blood pressure has never been demonstrated. To assess the effect of beta-adducin on blood pressure, a beta-adducin-deficient mouse strain (-/-) was studied and compared with wild-type controls (+/+). Aortic blood pressure was measured in nonanesthetized, freely moving animals with the use of telemetry implants. It is important to note that these mice have at least 98% of C57Bl/6 genetic background, with the only difference from wild-type animals being the beta-adducin mutation. We found statistically significant higher levels of systolic blood pressure (mm Hg) (mean+/-SE values: -/-: 126.94+/-1.14, n=5; +/+: 108.06+/-2. 34, n=6; P:</=0.0001), diastolic blood pressure (-/-: 83.54+/-1.07; +/+: 74.87+/-2.23; P:</=0.005), and pulse blood pressure (-/-: 43. 32+/-1.10; +/+: 33.19+/-1.96; P:</=0.001) in beta-adducin-deficient mice. Western blot analysis showed that as a result of the introduced genetic modification, beta-adducin was not present in heart protein extracts from -/- mice. Consequently, this deficiency produced a sharp decrease of alpha-adducin and a lesser reduction in gamma-adducin levels. However, we found neither cardiac remodeling nor modification of the heart function in these animals. This is the first report showing direct evidence that hypertension is triggered by a mutation in the adducin gene family.

Animals↗
PubMed1998

Expression of RGD minus fibronectin that does not form extracellular matrix fibrils is sufficient to decrease tumor metastasis.

Fibronectin (FN) is a plasma and extracellular matrix (ECM) glycoprotein, the expression of which may modulate the invasive and metastatic abilities of cancer cells. LMM3 is a cell line derived from the highly metastatic mouse mammary adenocarcinoma MM3 and is unable to express FN both at protein and mRNA levels. To study the role of FN in the metastatic process, LMM3 cells were stably transfected with 2 variants (wt and RGD-minus) of a full length human FN cDNA. All analyzed clones secreted recombinant FN and although none assembled FN in the ECM they showed an in vitro reduced migratory ability and an increased adhesive capacity. FN-producing cells were assayed for experimental and spontaneous metastasis. All clones tested showed a significant reduction in the number of experimental lung metastasis when compared with a control clone. Similar trends were observed for spontaneous metastatic ability. Our results indicate that the expression of FN that lacks the well-recognized RGD cell-binding site and that does not form ECM fibrils, is sufficient to decrease the metastatic potential of cancer cells. Our results also suggest that an RGD-independent mechanism may be acting in the prevention of metastasis.

Adenocarcinoma↗
PubMed1995

A new epitope presenting system displays a HIV-1 V3 loop sequence and induces neutralizing antibodies.

The principal neutralizing domain, IGPGRAF sequence, from the V3-loop of HIV-1 was inserted in two positions on the surface of the protein that makes up the capside shell of the insect Flock House Virus. The hybrid proteins were expressed in insect cells via recombinant baculoviruses. Three different hybrids were used as immunogens: two with a single copy of the insert in different positions of the carrier protein and a third with two copies of the insert at the same positions as before. All hybrid proteins induced strong and broad specific immune response in guinea pigs against different V3-loop sequences. However, only one of the hybrid proteins was able to induce a strong neutralizing response against MN and IIIB HIV-1 isolates. Our results demonstrate that a very short peptide sequence of HIV-1 can constitute a valuable immunogen able to induce a neutralizing response if presented to the immune system in the context of the FHV capsomer structure.

Amino Acid Sequence↗
PubMed1995

[Reliability of clinical parameters in the diagnosis of pulmonary thromboembolism at an emergency department].

BACKGROUND: Pulmonary thromboembolism (PTE) mortality rate is four times greater among non-diagnosed than among diagnosed and hence suitably treated patients. Diagnosis, however, may be difficult due to the aspecific and polymorphic clinical picture of the disease. OBJECTIVE: We made a comparison between two groups of patients with PTE. In the first group the diagnosis was immediately suspected, in the second group it was delayed. The aim of our work was to identify any clinical or laboratory feature which may be helpful (singularly or jointly considered) to immediately recognize PTE in the Emergency Department. MATERIALS AND METHODS: 62 patients with PTE were studied retrospectively in 5 consecutive years. They came to E.D. because of symptoms and signs of cardiorespiratory failure. Pulmonary embolism was demonstrated in 60 cases by high probability pulmonary scan; in 2 cases (who suddenly died after the first visit) by autopsy. They were divided in two groups according to the first provisional diagnosis made after the first visit: group A (n 33 = 53.2%) with assumed pulmonary embolism; group B (n 29 = 46.8%) with other diagnosis. History, clinical findings, ECG, chest X-ray, blood gas analysis and routine laboratory tests were then compared between group A and group B patients. RESULTS: No differences were observed between diagnosed and non-diagnosed patients, except for a significantly higher rate of clinically overt deep venous thrombosis in group A. Three main clinical pictures were detected among our patients: 1-circulatory collapse syndrome: n = 20 (32.3%), of whom 8 in group A and 12 in group B (p = n.s.); 2-pulmonary infarction syndrome: n = 12 (19.4%), of whom 5 in group A and 7 in group B (p = n.s.); 3-uncomplicated embolism syndrome: n = 30 (48.4%), of whom 20 in group A and 10 in group B (p = n.s.). CONCLUSIONS: In our study, history and signs of deep vein thrombosis were the only clues significantly more represented in early diagnosed cases. The possibility of thromboembolic accident should never be dismissed, even despite lack of a proven emboligenous cause in patients with unexplained chest pain or cardiorespiratory failure.

Adult↗
PubMed1994

Immunoreactivity of chimeric proteins carrying the HIV-1 epitope IGPGRAF. Correlation between predicted conformation and antigenicity.

Sera from HIV-1 infected individuals were examined for their reactivity to the principal neutralizing domain, IGPGRAF sequence, of the V3-loop of HIV-1. Four hybrid proteins carrying this sequence inserted in four different outer loops of a protein that makes up the capsid of an insect virus were used as antigen in a Western blot assay for this survey. All the four antigens showed different activity: sera that recognise all antigens to sera that reacted with only one of them. Competition experiments indicated that the antibodies recognised these proteins with different affinity. Molecular modelling of the hybrid proteins predicted that the inserted sequence adopted different conformations in each position. Comparison of predicted most stable conformations for IGPGRAF indicated that there is a close relationship between conformational similarity to a V3-loop reference structure and the degree of reactivity with sera.

Amino Acid Sequence↗
PubMed1983

A polygraph study of ischemic heart disease: behavior of systolic times in acute myocardial infarction.

The authors investigated systolic time intervals in 28 cases of acute myocardial infarction (AMI). Polygraph recordings were made on the first day of illness and repeated at two, three, five, and seven hospital days. The patients were divided into two groups: one with a contributory history of ischemic and/or hypertensive heart disease (Group PH for "positive history") and one without such history (Group NH for "negative history"). The influence of numerous variables on systolic times were explored in both groups, and the emerging data were processed by multiple stepwise regression analysis. The results show that the left ventricular ejection time (LVET) is invariably shortened in AMI, whereas the pre-ejection indices (PEP and ICT) afford definite differentiation of patients of Group PH (with lengthened PEP and ICT values) from those of Group NH (shortened PEP and ICT). The authors emphasize the importance of obtaining polygraph recordings very early in the course of AMI and of taking into account the patient's history in view of a correct assessment of pre-ejection times.

Aged↗
PubMed1983

[Methodological survey of erythrocyte filtration time].

We measured the whole blood filtration time of 30 healthy subjects. The influence of hematocrit, fibrinogen, leucocyte and platelet count on filtration time was also evaluated. Multiple regression analysis did not demonstrate any effect of the above-mentioned parameters when they were separately considered. We have subsequently taken from the entire population a group of 14 subjects in which were simultaneously found values of hematocrit greater than or equal to 41%, fibrinogen greater than or equal to 210 mg/100 ml and platelet count greater than or equal to 250,000/mm3. The filtration time was significantly higher in this group (69 +/- 4 sec) than in the remaining 16 normal subjects (56 +/- 4 sec), p less than 0.05. These data suggest that the simultaneous variation of several parameters could modify the whole blood filtration time, while these parameters have no effect when taken separately.

Adult↗
PubMed1982

A polygraph study of ischemic heart disease: short-term prognosis of acute myocardial infarction based on early modifications of isometric contraction time.

The authors have explored the early modifications of systolic time intervals in 90 patients hospitalized as emergency cases for acute myocardial infarction. From analysis and interpretation of the collected data they conclude that such modifications have considerable prognostic value. All patients fitting the specifications of NYHA classes I and II, but at the same time showing a shortening of the isometric contraction time to less than 39 +/- 1.4 ms turned out to constitute a high-risk group for the development of major mechanical and electrical complications in the next 2 weeks.

Aged↗