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Biomedical subjects

M Mariani

Publications and source records attributed to M Mariani.

At least 181 records · Page 10Linked to original sources

[Effects of oxygen free radicals on the function of the cardiac sarcoplasmic reticulum].

Peroxidative stress, exerted by oxygen free radicals, seems to be an important mechanism of the ischemia-reperfusion myocardial damage. In the present study we evaluated the modifications of sarcoplasmic reticulum function subjected to peroxidation by ferric ions. A subcellular fraction enriched in sarcoplasmic reticulum was obtained from rabbit hearts by homogenization and differential centrifugations. Sarcoplasmic reticulum vesicles were peroxidated through incubation for 5 min at 37 degrees C in presence of ferric cloride (FeCl3) ranging in concentration between 0.3 and 0.9 mM. Peroxidation of sarcoplasmic reticulum vesicles determined a dose-dependent reduction of Ca-uptake (39.2 +/- 10.3, 36.5 +/- 9.9, 28.9 +/- 8.4 and 18.8 +/- 8.2 nmol/min/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; NS, p less than 0.05 and less than 0.01, respectively) which was paralleled by an increase in the production of malondialdehyde, an index of lipid peroxidation (1.0 +/- 1.0, 7.0 +/- 3.2, 14.1 +/- 3.9 and 27.0 +/- 4.7 nmol/mg in presence of 0, 0.3, 0.6 e 0.9 mM FeCl3; p less than 0.05, less than 0.01 and less than 0.01, respectively). Depression of Ca-uptake was not accounted for by modifications of Ca-ATPase activity or membrane aspecific permeability to Ca++ ions, since these parameters were not affected by exposure to 0.3-0.9 mM FeCl3. On the contrary, the responsiveness of Ca-release channels to the specific inhibitor ryanodine was greatly altered, even at lower FeCl3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of verapamil, gallopamil, diltiazem and nifedipine on sarcoplasmic reticulum function in rat heart.

We investigated the effect of the calcium antagonists verapamil, gallopamil, diltiazem and nifedipine on cardiac sarcoplasmic reticulum function. In a cell-free homogenate from rat hearts, oxalate-supported Ca uptake was stimulated by verapamil, gallopamil and diltiazem at concentrations in the order of 10 nM to 100 nM, while higher concentrations were ineffective. Nifedipine was also ineffective. Peak stimulation of Ca uptake averaged 15-20% of control. Ca uptake is the difference between active Ca transport by Ca-ATPase and passive efflux through sarcoplasmic reticulum channels. In the presence of 300 microM ryanodine, which blocks sarcoplasmic reticulum channels, Ca uptake increased by 50%, but no further stimulation was produced by the addition of any calcium antagonist, at concentrations ranging from 1 nM to 100 microM. In a fraction enriched in sarcoplasmic reticulum, no drug affected the activity of Ca-ATPase at concentrations able to stimulate Ca uptake. We conclude that low concentrations of verapamil, gallopamil and diltiazem reduce Ca efflux through the Ca channels of the sarcoplasmic reticulum. Such an action might contribute to the clinical effect of these drugs.

Animals↗

[An echographic study of left ventricular function in acute myocardial infarct undergoing thrombolysis].

To evaluate the changes of left ventricular diastolic and systolic function and the timing of these changes in the early stages of acute myocardial infarction, serial echocardiograms were performed in 10 male patients (mean age of 56 years) with acute myocardial infarction, undergoing reperfusion by thrombolysis (recombinant tissue plasminogen activator). Echocardiograms were performed before reperfusion and 3, 6, 12, 24, 48, 72 hours, 7 and 14 days after thrombolysis. Significant differences of heart rate, systolic and diastolic blood pressure, left ventricular end diastolic volume, end-systolic volume and ejection fraction were not found. The mean regional wall motion index improved from 1.02 +/- 0.50 to 0.89 +/- 0.51 (p less than 0.05) at 48 hours; to 0.79 +/- 0.46 (p less than 0.01) at 72 hours; to 0.69 +/- 0.43 (p less than 0.001) at 7 days and to 0.61 +/- 0.40 at 14 days (p less than 0.001). The deceleration time decreased from 223 +/- 33 to 169 +/- 30 ms (p less than 0.001) 24 hours after reperfusion without further improvement. E peak velocity and E/A ratio significantly increased at 72 hours, while A peak velocity was not statistically different. A slow and progressive recovery of left ventricular function occurred after thrombolysis in acute myocardial infarction. Left ventricular diastole improves earlier while regional systolic function improves slowly till the hospital discharge.

Aged↗

Characterization by somatic cell genetics of a monoclonal antibody to the MDR1 gene product (P-glycoprotein): determination of P-glycoprotein expression in multi-drug-resistant KB and CEM cell variants.

We isolated an IgG2a murine monoclonal antibody (MAb) termed MAb57, specifically reactive with multi-drug-resistant (MDR) human cells. Its specificity toward the MDRI gene product (P-glycoprotein) has been demonstrated by the concordant segregation of the MAb57 epitope with the MDRI gene in interspecific mouse x human cell hybrids, and the reactivity of several different MDRI gene-expressing cells with MAb57, particularly insect cells acutely infected with a baculovirus encoding the MDRI gene. MAb57 can be used to detect, by flow cytometry, variations in the relative drug-resistance levels of several MDR KB and CEM cell variants. This immunological probe has also proven useful in selectively destroying MDR target cells in an antibody-dependent cell-mediated (ADCC) assay system as well as in detecting P-glycoprotein expression in normal and malignant tissues and cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

In vivo and in vitro studies on modulation of the pineal endocrine function by L-acetyl-carnitine in the rat.

Male Sprague-Dawley rats injected (i.p.) at 1500h with L-acetyl-carnitine in doses of 10, 30 or 90 mg/kg exhibited a notable increase in their pineal and serum melatonin content 1 hr later. Likewise, L-acetyl-carnitine administered in the same dose range induced a significant increase of pineal and serum melatonin content in rats treated at 0100h, following exposure of 30 min to bright white light to suppress endogenous melatonin. Under in vitro experimental conditions, however, 60 min of coincubation of isolated rat pineal glands with L-acetyl-carnitine (10(-5) M) did not result in an elevation in melatonin accumulated in the incubation medium. These results demonstrate that, in vivo, L-acetyl-carnitine can exert a modulatory action on synthesis and release of melatonin, possibly by modifying noradrenergic transmission and signal transduction in the pineal gland.

Acetylcarnitine↗

Preclinical pharmacokinetics and localization studies of the radioiodinated anti-ovarian carcinoma MAb MOv18.

The in vivo behavior of the monoclonal antibody (MAb) MOv18, with a restricted specificity for human ovarian carcinoma was analyzed on normal and tumor-bearing animals. The pharmacokinetics of the iodine-labeled MAb carried out in BALB/c mice fits an open two-compartment model. The t1/2 alpha was found not to be influenced by the different iodine isotopes used (125I vs 131I) and by the time between labeling procedures and administration. The t1/2 beta were found to be longer after i.p. than i.v. administration and influenced by the time lapse between preparation and administration. A radiolocalization study was carried out in CD1 nu/nu mice bearing i.p. xenotransplant of the human ovarian carcinoma cell line IGROV1. Tumor/non tumor ratios were higher when the time between administration and sacrifice was short and, for 131I-MOv18, with a short interval between labeling and injection. Even if longer half lives were obtained using 125I-MOv18 and i.p. administration a fairly rapid decrease in the values of the percentage of the injected dose per gram of tumor during the time was noted. These data indicate that this MAb could be considered a good candidate for radiotherapeutic approaches.

Animals↗

Monoclonal antibodies to a soluble metallic radioisotope chelator: development and characterization.

Monoclonal antibodies (MAbs) have been prepared with specificity for diethylenetriaminopentaacetic acid (DTPA) used to chelate metal radioisotopes to immunoglobulins for radioimmunoimaging and radioimmunotherapy. The use of fusion partners of lymph node-derived B cells resulted more frequently in the isolation of IgG secreting hybridomas than with splenocytes. All MAbs have been selected for simultaneous recognition of chelated and unchelated DTPA, and have been characterized in their biochemical, physico-chemical and immunochemical features. In view of the potential use in development of bifunctional MAb, these novel MAbs were also proven to lack detectable cross-reactivity with normal human tissues.

Animals↗

Evaluation of pulmonary vascular pressures in cardiac patients: the role of the chest roentgenogram.

In 77 patients (34 with left heart valvulopathy, 17 with dilated cardiomyopathy, and 26 with chronic coronary artery disease) pulmonary vascular pressures were estimated from the chest film by means of a new scoring system. Standard chest x-ray films taken immediately before diagnostic right and left cardiac catheterization were analyzed independently by three readers without knowledge of the hemodynamic findings. The radiographic signs were subdivided into three groups as follows, and to each one a score derived from a retrospective statistical analysis was attributed: (A) signs of interstitial edema, (B) patterns of pulmonary blood flow distribution, and (C) alterations in the pulmonary arteries. The sum of the scores of groups A and B x-ray findings correlated well with pulmonary wedge pressure, and the sum of the scores of groups A, B, and C correlated more strongly with the mean pulmonary artery pressure. These results confirm that it is possible, in patients with chronic heart disease, to assess accurately the pulmonary artery and wedge pressures by means of the noninvasive and easily performed chest roentgenogram.

Blood Pressure↗

[The evaluation of the cardiotoxicity of 4'-epidoxorubicin at high doses].

Twenty-eight patients with small cell lung cancer were treated with high dose 4'-epidoxorubicin (EDX). Fifteen patients underwent EDX monotherapy (cumulative dose: 800 mg/m2) while 13 were treated with EDX (cumulative dose: 660 mg/m2) associated with cyclophosphamide, etoposide and cisplatin. A 2D-echo was performed in basal condition, after the third and sixth dose and 2 months after the end of the therapy. In the patients without cardiovascular disease (n = 19) left ventricular end-diastolic volume (EDV), end systolic volume (ESV) and ejection fraction (EF) were unchanged. The patients with coronary artery disease (n = 5) showed a statistically significant decrease in EF with an increase of ESV. All patients with systemic hypertension (n = 4) showed a significant reduction of EF and a significant increase of ESV and EDV.

Aged↗

Retrovirus-derived shuttle vectors in the generation of murine bispecific MoAbs to be used in ex vivo and in vivo immunotherapy.

Mouse monoclonal antibodies specific for CD3, FcR and a melanoma associated antigen have been produced. Drug resistence of such hibrydomas has been obtained tranfecting them with plasmids containing genes conferring specific resistence. Retrovirus derived shuttle vectors with high transfection efficiency have been used for transfection. Hybrydomas were than fused and bispecific antibody producing cells selected. Purification was performed by HPLC. Such bispecific antibodies can be used in ex vivo and in vivo immunotherapy.

Animals↗

Polyamines reduce heart injury caused by doxorubicin.

Isolated rat heart was perfused with 18 microM doxorubicin in the recirculating buffer. This treatment resulted in progressive contractile impairment. Aortic flow and minute work (i.e the product of cardiac output and peak systolic pressure) were reduced up to 20 and 29% of basal values, respectively. These parameters were partially restored in hearts perfused with 400 microM spermine, a naturally occurring polyamine, and 18 microM doxorubicin in the recirculating buffer. The results suggest the need for an investigation of the possible antagonistic role of polyamines against anthracycline cardiotoxicity.

Animals↗

[The echocardiographic evaluation of valve prostheses].

Transthoracic and transesophageal echocardiography were used to demonstrate prosthetic valve dysfunction in 134 patients with cardiac prosthetic valves in aortic, mitral and tricuspid position. Transthoracic echocardiography showed a high accuracy in the diagnosis of prosthetic valve dysfunction, especially in aortic position or when a stenosis was present. Transesophageal echocardiography allowed to verify the etiology and site of dysfunction and to show even minor leaks. Sixty-six patients underwent reoperation while 68 underwent a clinical and echocardiographic follow-up because only mild symptoms were present. Thus echocardiography represents the technique of choice in the follow-up of patients with prosthetic valves and it is able to help in decision making. However, cardiac catheterization is mandatory if a disagreement between clinical and echocardiographic data is present or when coronary artery disease is suspected or present.

Adult↗

[Coronary disease in patients operated on for valvulopathy].

In order to evaluate the influence of a significant coronary artery disease in patients with valvular heart disease or with prosthetic valves, we reviewed literature and our own experience. The incidence of coronary artery disease in valvulopathies has been diffusely studied and reported and, in a consecutive series of our hemodynamic studies, resulted 11%. The influence of a coronary artery disease on early and late results of a surgical procedure is different whether the coronary artery disease is operated or not. In particular, the combined surgery shows a higher early mortality, but a much better long-term prognosis. In addition, sometimes surgery introduces rare causes of coronary artery disease. Finally, it seems that coronary artery disease arises very rarely in patients undergone valvular surgery or, at least, patients rarely complain anginal symptoms in the post-surgical follow-up. In our experience on 529 patients only 6 complained typical angina and only 2 showed a coronary artery disease not present at the time of operation.

Aortic Valve↗

[Osteotomy in the prosthetic substitution of severe axial deviation of the knee].

Arthroplasty can be a successful treatment for arthritis even in cases of severe axial deviation of the knee. Since significant bone loss is often present in these cases, the technique and extent of the resection is very important. In this paper we review our series and compare it with solutions proposed by other authors, focusing our attention on the techniques of resection and replacement of lost bone employed in order to achieve optimal axial alignment and anchoring of the prosthetic components.

Aged↗

Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population.

We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.

Animals↗