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Biomedical subjects

M Tringali

Publications and source records attributed to M Tringali.

7 recordsLinked to original sources

The reduction of myocardial damage and leukocyte polymorphonuclear accumulation following coronary artery occlusion by the tyrosine kinase inhibitor tyrphostin AG 556.

We investigated the effects of tyrophostin AG 556, a tyrosine kinase inhibitor, on the phenomenon of leukocyte accumulation during ischaemia and reperfusion of the myocardium. Male anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK) serum Tumor Necrosis Factor (TNF-alpha) and Interleukin 6 (IL-6), cardiac intercellular adhesion molecule-1 (ICAM-1) and TNF-alpha expression and myocardial contractility (left ventricle dP/dt(max)) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity (196.5 +/- 19 U/100 ml, at the end of reperfusion) and myeloperoxidase activity (MPO, a marker of leukocyte accumulation) both in the area-at-risk (4.5 +/- 0.5 U/g/tissue) and in necrotic area (8.2 +/- 1.2 U/g/tissue), reduced myocardial contractility (1,706 +/- 52 mmHg/s, at the end of reperfusion) and induced a marked increase in the serum levels of TNF-alpha (1,950 +/- 97 pg/ml, at 1 h of reperfusion) and IL-6 (998 +/- 16 U/ml, at the end of reperfusion). Finally, myocardial ischaemia-reperfusion injury also increased cardiac mRNA for TNF-alpha and ICAM-1 in the myocardium-at risk. Tyrphostin AG 556 (0.5, 1 and 2 mg/kg subcutaneously 5 min after the onset of reperfusion) lowered myocardial necrosis and myeloperoxidase activity in the area-at-risk (1.5 +/- 0.2 U/g/tissue, following the highest dose) and in necrotic area (2.9 +/- 0.3 U/g/tissue following the highest dose), decreased serum CPK activity (96 +/- 9 U/100 ml, at the end of reperfusion), lowered serum TNF-alpha and IL-6, increased myocardial contractility (2,096 +/- 88 mmHg s, at the end of reperfusion) and reduced cardiac mRNA levels for TNF-alpha and ICAM-1. The present data suggest that tyrosine kinase inhibitors protect against myocardial ischaemia-reperfusion injury by reducing leukocyte accumulation to the ischaemic myocardium.

Animals↗

IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemia-reperfusion injury.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous rapid response transcription factor involved in inflammatory reactions which exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative stress causes NF-kappaB activation. IRFI 042 is a novel dual vitamin E-like antioxidant and we, therefore, investigated its ability to protect the heart from oxidative stress and to halt the inflammatory response in a model of myocardial ischaemia-reperfusion injury. METHODS: Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase content (an index of leukocyte infiltration), hydroxyl radical (OH&z.ccirf;) formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the at-risk myocardium were investigated. NF-kappaB activation and the inhibitory protein of NF-kappaB, I-kappaBalpha, were also studied in at-risk myocardium by using electrophoretic mobility shift assay (EMSA) and Western blot analysis, respectively. RESULTS: The ischaemia-reperfusion model produced wide heart necrosis (area at risk-necrotic area=52+/-5%; necrotic area-left ventricle=28+/-3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5+/-3.9 nmol/g tissue; necrotic area=80.3+/-5.1 nmol/g tissue), induced tissue neutrophil infiltration, and caused a marked decrease in endogenous antioxidants. Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1 immunostaining at 5 h of reperfusion. NF-kappaB activation was also evident at 0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-kappaBalpha was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h of reperfusion and thereafter it was gradually restored. Intraperitoneal administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced myocardial necrosis expressed as a percentage either of the area at risk (18+/-4%) or the total left ventricle (11+/-2%), and improved cardiac output. This treatment also limited membrane lipid peroxidation in the area at risk (MAL=14.3+/-2.5 nmol/g tissue) and in the necrotic area (MAL=26.5+/-3.7 nmol/g tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase, and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked the activation of NF-kappaB, reduced cardiac ICAM-1 expression, and blunted tissue elastase content, an index of leukocytes accumulation at the site of injury. CONCLUSIONS: Our data suggest that IRFI 042 is cardioprotective during myocardial infarction by limiting reperfusion-induced oxidative stress and by halting the inflammatory response.

Analysis of Variance↗

[Internet biomedical databases: the MEDLINE paradigm. Users' guide].

The Medline database is now available into a wide number of biomedical websites. Clinicians and scientists can now access the most important bibliographic file in medicine directly from their desktop. Medline availability on the Internet can enhance effectiveness and efficiency of medical activities. Real usefulness of Medline and other databases stands on the relevance and validity of the information content that can be obtained at the least work (and cost) for the user. In order to retrieve really useful information, knowledge of some methodological issues related to bibliographic searching is mandatory to the final user. The rising number of Medline providers on Internet occurring during 1996 and 1997 is a proof that the "ideal" world-wide-Medline has not arrived yet.

Information Storage and Retrieval↗

[Presence of HLA-DRB1 alleles in a group of patients with rheumatoid arthritis treated with low doses of sodium aurothiomalate].

The good results of a therapy with small doses of sodium aurothiomalate (20 mg/month) in 17 patients suffering from rheumatoid arthritis are reported. The mean age +/- ESM at the beginning of treatment was 59.9 +/- 3.2 years, the mean duration of disease was 1.3 +/- 0.5 years. The lowest grade of disease activity (1) according to Mallya and Mace's (1981) criteria was observed in 12 patients (70%) after a period of 1.7 +/- 0.6 years (mean +/- ESM). This grade of activity persisted in 11 patients and remained for 3 years in 1 patient. In the other 5 patients a low or middle activity of disease persisted. The relationship between therapeutic results and HLA DRB1 prevalence was investigated. The LLEQRRAA and LLEQKRAA sequences are present in 3 patients, i.e. 17.9%. This frequency is not significantly different from the frequency (28.6%) observed in a control group of healthy subjects. Therefore these sequences, at least in Italian people, cannot be considered a factor of susceptibility to RA. They may be a factor of evolution to a more severe disease. Dermatological side effects were evident only in 2 patients; one of these patients was HLA DR5 positive. The results observed in DR7 positive patients were not different from the results observed in the other patients; therefore, DR7 positive patients could responders to gold treatment, even with low doses.

Adult↗

[The Internet and clinical medicine. An introduction to the biomedical information services available in electronic form on the "net of all nets"].

Clinical users expectations from medical informatics are evolving due to the wide availability of biomedical information services on the Internet. Thanks to hypertexts and advanced browsing tools users with no informatical expertise can travel on the Internet and easily gain access to textual databases. With a multimedia computer other kinds of information can be grabbed: images, sounds and audiovisual documents. Basic Internet services (electronic mail, discussion lists, file transfer protocol, terminal emulation) can be accessed from a wide range of hardware equipment. However, the real power of a world-scale computer network like the Internet will be unleashed only when its global connectivity will be linked to the powerful retrieval ability of existing clinical and related databases. While biomedical journals editors and other medical information providers are in the way to offer electronic versions of their paper-based products, at the leading edge of this world-scale process is the USA National Library of Medicine, with the Internet-compatible version of its Grateful Med software which is expected to be launched during 1996.

Computer Communication Networks↗

[The utilization of Medline for the solution of real clinical problems. A prospective study in Italy].

AIM: Measure of usefulness of Medline searches requested for clinical problems. METHODS: open prospective uncontrolled study lasted for 3 months. Collection of online or CD-ROM Medline searches operated by clinicians or librarians at 5 biomedical libraries. User interviews about use and usefulness of Medline, recorded with a closed-answer self-administered questionnaire, adapted from a U.S. National Library of Medicine product. RESULTS: Of the 6 participating libraries, one was excluded from analysis from data collection inadequacies. Among 668 searches, 55 (8.2%) were produced for real patients. Physicians judgement about clinical usefulness of their searches (available for 46 cases) indicate a significant importance for diagnostic evaluation (23%) and therapy administration (46%). After applying search results into clinical practice, clinicians think that positive outcomes are achieved in the doctor-patient-family relationship area (19%), a better use of health care system facilities is obtained (26%) and, less consistently, positive effects are perceived on longevity (5%), abnormality correction (10%), symptomatic relief (7%) and functional recovery (6%). CONCLUSION: Physicians judge that Medline searches actually can contribute to diagnosis and treatment of real patients, with significant benefits on the process of care, on doctor-patient relationship and on patient's health.

CD-ROM↗