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Biomedical subjects

L Rossi

Publications and source records attributed to L Rossi.

At least 271 records · Page 15Linked to original sources

Red blood cells as an antigen-delivery system.

The use of adjuvants is usually required to induce strong immunological responses to protein antigens. However, in many cases these adjuvants cannot be extensively applied in human and veterinary vaccinations because of associated inflammatory reactions or granuloma formation. We show here that protein antigens (bovine serum albumin, hog liver uricase, and yeast hexokinase), coupled to autologous red blood cells by way of a biotin-avidin-biotin bridge, elicit an immunological response in mice similar to or higher than that obtained by the use of Freund's adjuvant. Quantities as low as 0.5 micrograms/mouse are high enough to generate these immunological responses. Furthermore, splenocytes of mice immunized by red blood cell-coupled antigens can be used to generate hybridomas secreting monoclonal antibodies. Thus, the delivery of antigens by autologous red blood cells is an effective way to avoid the use of adjuvants for producing anti-peptide antibodies and possibly to generate peptide vaccines.

Animals↗

Evaluating the patient with coronary artery disease.

The evaluation of patients with suspected or known CAD involves a comprehensive diagnostic workup. Careful analysis of pain and the factors that influence it is a key factor in differentiating CAD from other cardiovascular and noncardiac diagnoses. The assessment of pain also serves as an important guide for the identification of appropriate diagnostic tests. An evaluation of lifestyle patterns is helpful in identifying behaviors associated with a high risk of CAD. FHP serves as a useful categorization for documentation and provides data that are complementary to the physician's traditional review of systems. The ECG is the most common initial diagnostic test; however, cardiac catheterization remains the most definitive source for the diagnosis of CAD. The sequence and use of diagnostic tests proceeds according to the patient's physiologic stability, with consideration to the risks and benefits to the individual patient. The nurse has an important role in the evaluation for CAD. The initial encounter provides an opportunity to promote the patient's full participation in treatment as well as to establish a commitment to ongoing evaluation. The nurse must be prepared to explain not only the process for the evaluation but also the sometimes unclear results to the patient. In this way, patients can be better prepared to meet the challenges of daily living with CAD.

Clinical Laboratory Techniques↗

[Hemosiderosis in thalassemia major. Quantitative study with magnetic resonance (MR)].

Hemosiderosis, which results from transfusional therapy and from increased absorption of dietary iron, is a severe complication of thalassemia major. The complication is also very difficult to manage. An accurate determination of the total amount and of the distribution of body iron stores is essential for prognostic purposes and to evaluate the efficacy of chelation therapy. Therefore, a suitable tool for the noninvasive depiction of iron overload is to be hoped for. MR imaging has been usefully employed, of late, to this purpose. Sixteen thalassemic patients have been studied to evaluate iron depositions using a 1.5 T magnet. Signal intensities from liver, pancreas, spleen, bone marrow, and heart were considered. The signals were dramatically lower than the normal values obtained in a sex- and age-matched group; the differences were due to the iron. Iron distribution appeared inhomogeneous, with the highest overload in liver and bone marrow. Since cardiomyopathy represents the first cause of death in thalassemic patients, the relationship between cardiac function and iron overload in the heart has been thoroughly investigated. Finally, the authors conclude that MR will become a widely employed method for assessing iron overload and will contribute to improve the management of thalassemia major.

Adolescent↗

Acetaldehyde, ethanol and acetone concentrations in blood of alcohol-treated mice receiving aldehyde dehydrogenase-loaded erythrocytes.

Blood levels of acetaldehyde (ACh), ethanol and acetone were investigated in mice treated with ethanol for 6 months and receiving compatible erythrocytes (RBCs) overloaded with aldehyde dehydrogenase (AlDH). Following an acute dose of ethanol, ACh levels were significantly lower in these animals than in alcohol-treated mice receiving AlDH-unloaded RBCs, and were similar to the ACh levels of normal mice. The peak ethanol concentration was higher in normal mice than in both groups of alcohol-treated animals, while acetone concentrations were not significantly different in the three groups of animals.

Acetaldehyde↗

Increased glucose metabolism by enzyme-loaded erythrocytes in vitro and in vivo normalization of hyperglycemia in diabetic mice.

The main metabolic properties of human red blood cells (RBC) overloaded with glucose catabolizing enzymes such as hexokinase and glucose oxidase were evaluated. Human erythrocytes loaded with human hexokinase metabolized 3.1 +/- 0.2 mumol/h/ml RBC of glucose, an amount double that consumed by normal and unloaded cells (1.46 +/- 0.16 mumol/h/ml RBC), while glucose oxidase-loaded erythrocytes consumed up to 5.5 +/- 0.5 mumol/h/ml RBC of glucose but with a time-dependent increase in methemoglobin formation due to the H2O2 produced in the glucose oxidase reaction. This methemoglobin production was greatly reduced while glucose consumption was increased (8.1 +/- 0.4 mumol/h/ml RBC) by coentrapment of hexokinase and glucose oxidase. Similar results were obtained in mouse red blood cells, although the role of hexokinase was less pronounced due to a higher basal level of this enzyme. When administered to diabetic mice the hexokinase/glucose oxidase-overloaded erythrocytes had a circulating half-life of 5 days and were able to regulate blood glucose at near physiological levels. A single intraperitoneal administration of 500 microliters of enzyme-loaded cells maintained a near-normal blood glucose concentration for 7 +/- 1 days, while repeated administrations at 10-day intervals were effective in the regulation of blood glucose levels for several weeks. These results suggest that enzyme-loaded erythrocytes can behave as circulating bioreactors and can provide a new way to reduce abnormally elevated blood glucose.

Animals↗

[The effect of a territorial health emergency service on the delay in the hospitalization of patients with an acute myocardial infarct].

In July 1987 a prehospital emergency medical service (EMS) was activated in Verona (Italy) and a broad educational campaign was introduced. Prehospital care is delivered by emergency physicians and/or qualified nursing staff, who travel by ambulance or helicopter and have radio contact with the hospital alarm centre. During a 1-year period before the activation of the EMS, 476 patients with acute myocardial infarction (AMI) were admitted to the coronary care unit (CCU) of Verona, with a median delay time of 4 hours. In the period between July 1990 and June 1991, 412 patients were admitted, with a median delay time of 3 hours. Age, gender, previous AMI and infarct location were not related to delay time. In the second period, 34% patients used the EMS, while 66% used their own transport. In patients who used the EMS, median delay time was 2 hours (1 hour and 20 min shorter, p < 0.01, than in patients who did not). The time between symptoms onset and reaching the decision that medical care should be sought (1 hour and 18 min) was the longest component of the total delay time. The time from EMS call to hospital arrival was 25 min and the time which elapsed in the Emergency Department before reaching the CCU was 15 min. In these patients, decision time and Emergency Department time were significantly shorter (p < 0.01) than in patients who did not use the EMS. We conclude that the EMS is effective in reducing delay time in patients with AMI.

Aged↗

Regulation of the expression of the sex-specific isoforms of cytochrome P-450 in rat liver.

The hepatic metabolism of steroid hormones and of xenobiotics frequently depends on the expression of the sex-specific isoforms of cytochrome P-450 and on differences in sex hormones. Following biochemical, immunological and molecular biological investigations, it was shown that in adult rat liver there exist at least four male-specific and one female-specific isoforms of cytochrome P-450. The designation of these sex-specific genes is IIC11, IIIA2, IIC13 and IIA2 in males, and IIC12 in females. The irreversible programming of the expression of these isoforms of cytochrome P-450 in adulthood occurs during the perinatal period of life, and is named enzyme imprinting. One of the main factors that regulates the expression of the sex-specific isoforms of cytochrome P-450 is the level of androgens in the blood. Castration of adult rats decreased the level of the male isoforms of cytochrome P-450 and the activity of the monooxygenase enzyme system that remained higher than in intact females. The mechanism of enzyme imprinting can be explained as follows: neonatal androgens program the secretion of hypothalamic hormones, somatostatin and growth-hormone-releasing factor. These factors determine the type of growth hormone secretion in adult rats, and this controls the type of sex-specific isoforms of cytochrome P-450 expressed in adulthood. Metabolic regulation similar to that outlined above was shown to occur for several metabolism-dependent chemical carcinogens. Such a pathway may explain the different sensitivity displayed by male and female rats to treatment with these carcinogenic agents. One possible way of modulating the expression of some isoforms of cytochrome P-450 in adult rats is by treating neonates with specific xenobiotics that change the constitutive expression of neonatal androgens. It appears that this enzyme imprinting plays an important role in determining the individual sensitivity to the carcinogenic effects of chemicals.

Animals↗

Early assessment of coronary artery bypass graft patency by high-dose dipyridamole echocardiography.

To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiographic testing in the evaluation of coronary artery bypass graft patency early after surgery, 18 consecutive patients with angina underwent dipyridamole echocardiography and coronary angiography before and 7 to 10 days after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and 11 patients, respectively. A total of 53 bypass grafts were performed. Before bypass surgery 14 patients had a positive and 4 a negative test result. No complication occurred during the test performed early after surgery. Of the 14 patients with positive dipyridamole echocardiographic results before surgery, 10 had negative and 4 had positive results after surgery. All 4 patients had negative results before and after surgery. In the 4 patients with positive results after dipyridamole echocardiographic testing before and after bypass surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p = 0.3) after the procedure and wall motion score index at peak dipyridamole changed from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent as seen on angiography. Dipyridamole echocardiographic results were positive in 4 of 5 patients who had at least 1 obstructed graft or native vessel obstructed distal to bypass graft insertion. The remaining patient had diagnostic electrocardiographic changes during dipyridamole infusion without wall motion abnormalities. Dipyridamole echocardiographic results were negative in all 13 patients who had complete revascularization. In the 4 patients with positive test results, the procedure correctly identified the localization of the diseased bypass graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗

Relation between hyaluronan and sulphated glycosaminoglycan synthesis and degradation in cultured embryonic fibroblasts. Effect of concanavalin A and ammonium chloride administration.

In order to evaluate the relationship between glycosaminoglycan (GAG) synthesis and degradation, the effect of NH4Cl, which inhibits lysosomal degradation, on GAG production was analysed in vitro in concanavalin A (Con A) stimulated fibroblasts from 7 and 14-day-old chick embryos. 35SO4 incorporation into total proteoglycan (PG), 3H incorporation into individual GAG classes, beta-N-acetyl-D-glucosaminidase and beta-D-glucuronidase activity were determined. The results indicate a correlation between Con A and NH4Cl effects: NH4Cl induced a reduction principally in the GAG classes most stimulated by Con A. Thus HA and DS are much more stimulated by Con A and inhibited by NH4Cl than are CS and HS.

Acetylglucosaminidase↗

In vitro toxicity and metabolism of 2',3'-dideoxycytidine, an inhibitor of human immunodeficiency virus infectivity.

U937 human monoblastoid cell growth was inhibited in a concentration-dependent manner by 2',3'-dideoxycytidine (ddCyd) (an antiretroviral drug) up to 500 microM. Cell growth inhibition was associated with a pronounced increase in cell volume, however this was not due to cell ATP or NAD+ depletion that could effect osmotic balance or DNA repair. This ddCyd toxicity paralleled the accumulation of ddCyd into acid soluble material where 2',3'-dideoxycytidine-5'-triphosphate (ddCTP) was the predominant labelled nucleotide up to an extracellular ddCyd concentration of 150 microM. At higher ddCyd concentrations, the amount of 2',3'-dideoxycytidine-5'-diphosphate (ddCDP) became predominant over ddCTP. This increase of phosphorylated dideoxycytidine in U937 cells was also associated with an increased incorporation of the drug into cell DNA suggesting a possible toxicity mechanism. That ddCyd does indeed become cytotoxic to human cell by incorporation into DNA was shown by incubating human resting and stimulated lymphocytes with ddCyd. While the drug does not affect cell viability in resting cells it strongly affects cell proliferation upon phytohemagglutinin (PHA) addition.

Adenosine Triphosphate↗

DNA damage induced by 7,12-dimethylbenz[a]anthracene in the liver and the mammary gland of rats exposed to polycyclic aromatic hydrocarbon enzyme inducers during perinatal life.

The long-lasting modulating effect induced by the prenatal or neonatal exposure to phenobarbital (PB) and aroclor on the genotoxic activity of 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats was studied. The effect was measured as DNA damage evaluated in the liver and in the mammary gland of 55-day-old animals, 4 and 24 h after an i.g. injection of 80 mg/kg of DMBA. PB was given per os, i.g. or in drinking water to pregnant females and by i.g. only to neonates or in adult progeny. Aroclor was injected i.g. in prenatal and in neonatal life, and a second dose was given in adult life. Under these experimental conditions it was shown that DNA damage kinetics caused by DMBA are modulated by exposure to PB and, to a minor extent, by aroclor. The amount and persistence of DNA damage were highest when PB was administered to neonates. An average 2-fold increase in the elution constants (K) of DNA in the liver and the mammary gland was observed 4 h after DMBA treatment, as compared to uninduced animals. Repeated enzyme induction by PB seems to reduce DMBA genotoxicity, as shown by a decrease in DNA damage and persistence in the liver and mammary gland. The inducibility of the monooxygenase enzyme system in perinatal life favouring metabolic activation or inactivation of polycyclic aromatic hydrocarbons might be critical in determining individual susceptibility of adult progeny to chemical carcinogenesis by DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy.

BACKGROUND: We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS: Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS: DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention.

Coronary Angiography↗

[Electrocardiographic monitoring of myocardial ischemia during coronary angioplasty correlated with results of the procedure].

In 24 patients 2 leads Holter monitoring was performed during percutaneous transluminal coronary angioplasty (PTCA) of left anterior descending (17 patients), right coronary artery (6 patients), left circumflex (1 patient). In 20 patients (83%) significant ST segment deviations were recorded in the lead CM2 or RV. The following characteristics of ST segment deviation were analyzed during 7 +/- 3 successive occlusions: time to onset, maximal ST shift, slope to development, time to onset and slope of ST segment normalization. In 17 patients with successful PTCA the slope of ST segment normalization increased progressively from the first to the third-fifth inflation and then was constant. The improvement in ST segment normalization velocity was correlated (p less than 0.01) with the reduction of the diameter and with improvement of sectional area of the dilated vessel. The maximal ST segment normalization slope was correlated (p less than 0.01) with the diameter and the area of the residual stenosis. Continuous electrocardiographic recording, during PTCA, for evaluation of ST segment normalization velocity is a promising approach for monitoring the immediate result of coronary angioplasty.

Adult↗

[A computerized method for studying contractility of isolated cardiac myocytes].

In recent years methods for the isolation of cardiac myocytes have gained increasing interest. Single cardiac cells represent an effective model for the study of cardiac contractility thanks to their features of simplified preparation. This improves the understanding of cardiac contractile properties and the effects of cardio-active substances. Moreover, it has been demonstrated that the isolation procedure does not alter the basic characteristics of the original tissue. The contractility indices in multicellular models are derived from the direct measurement of mechanical parameters (pressure and tension). These are difficult to perform in the case of isolated cardiac myocytes for which optical techniques of measurement proved particularly suitable. A system based on the video motion detector technique has been used to measure the extent of shortening. The cell is observed using a video camera connected with a phase contrast microscope. The video dimension analyser receives the cell image from the video camera and its output is a voltage proportional to the cell length. This signal is sent to a personal computer for acquisition and analysis. The signal is then digitalized by an analog to digital conversion board and subsequently elaborated to calculate the contraction parameters. Then these values are visualized on the computer screen, printed and stored with other pertinent information typed by the user. The result is the creation of a data file, available for further processing.

Animals↗

Histopathology of specialized and ordinary myocardium and nerves in chronic Chagas disease, with a morphometric study of inflammation and fibrosis.

Chagas disease, in the chronic phase, is known to be characterized by cardiac failure, and/or arrhythmias. To assess the involvement of the conduction system and of the working myocardium, morphometric and immunohistochemistry studies have been carried out on 4 autoptic hearts of chronic chagasic myocardiopathy. The characterization of interstitial infiltrates was performed by lymphocyte immunophenotyping with immunocytochemical techniques. These infiltrates were more prominent in the working myocardium and in the left branch of the His bundle. The infiltrates consisted of about 50% of macrophages and 50% of T-lymphocytes. Mast cells would not play a role in the chronic stages of the disease. Eosinophils were present in no more than the 5% of the inflammation. The fibrosis, especially of the conducting system seems to be facilitated by an impaired lymphatic outflow, whereas the evidence of neuroganglionic involvement was variable.

Cardiomegaly↗

[Angina due to anatomical anomalies and to functional changes in the epicardial coronary vessels].

Myocardial ischemia with normal coronary arteries can be due to anatomic or functional reasons. The more severe congenital coronary anomalies in the adulthood are the origin of the left main of the left coronary artery from the right aortic sinus, with a course between the aorta and the pulmonary trunk, and the origin of the left main from the pulmonary trunk. Both these anomalies can cause sudden death, usually associated with physical exertion. The coronary vasomotion of epicardial vessels depends on the interaction of several neurohumoral substances. We report the hemodynamic, angiographic and stress test data of 30 patients affected by chest pain, with myocardial ischemia and normal coronary arteries. In 8 patients the response of epicardial coronary arteries to intracoronary infusion of acetylcholine was evaluated.

Acetylcholine↗