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Biomedical subjects

E Lanza

Publications and source records attributed to E Lanza.

At least 19 recordsLinked to original sources
PubMed1992

K-opioid receptor changes in experimental models of cerebral ischaemia and atherosclerosis in the rabbit.

Thromboembolic phenomena and transient ischaemic attacks (TIA) are considered the basis of ischaemic pathologies. The aim of the present research is to investigate the involvement of k-opioid receptors in cerebral blood flow (CBF) impairment which results in experimental stroke or dietary atherosclerosis in rabbits. CBF measurement showed a significant decrease in rabbits submitted to embolization and/or atherosclerosis. Binding studies showed that massive cerebral ischaemia and atherosclerosis produced a significant increase in the number of k-opioid receptors (Bmax), without changing (KD) affinity values. In conclusion, the results obtained seem to indicate that the increase in k-opioid receptors might play a crucial role in a common cerebral biochemical mechanism both in ischaemic and atherosclerotic pathologies.

Animals↗
PubMed1992

Can bilingual two-year-olds code-switch?

Sociolinguists have investigated language mixing as code-switching in the speech of bilingual children three years old and older. Language mixing by bilingual two-year-olds, however, has generally been interpreted in the child language literature as a sign of the child's lack of language differentiation. The present study applies perspectives from sociolinguistics to investigate the language mixing of a bilingual two-year-old acquiring Norwegian and English simultaneously in Norway. Monthly recordings of the child's spontaneous speech in interactions with her parents were made from the age of 2;0 to 2;7. An investigation into the formal aspects of the child's mixing and the context of the mixing reveals that she does differentiate her language use in contextually sensitive ways, hence that she can code-switch. This investigation stresses the need to examine more carefully the roles of dominance and context in the language mixing of young bilingual children.

Attention↗
PubMed1992

[The effect of superoxide dismutase and catalase on the delayed toxicity of doxorubicin].

The production of oxygen-free radicals has been proposed as a determinant of the delayed toxicity of doxorubicin. The aim of the present investigation was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) and catalase (CAT) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD or CAT were administered intravenously at the dose of 10000 U/kg 2 min before and 30 min after each DXR administration. Cardiac toxicity was monitored by means of electrocardiography (QaT interval) and by light and electron microscopy evaluation of left ventricle fragments. DXR treated rats showed, in comparison with control animals, a decrease of body weight gain, a progressive and irreversible prolongation of QaT and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain and QaT prolongation. Moreover, morphologic lesions were significantly reduced in rats receiving DXR + SOD. On the contrary, CAT seems to be completely devoid of protective effect.

Animals↗
PubMed1991

Prevention of doxorubicin-induced cardiomyopathy by reduced glutathione.

The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v. at a weekly dose of 3 mg/kg for a total of 4 doses; 250 or 500 mg/kg of GSH was given i.v. 10 min before and 2 h after each DXR injection, resulting in a total weekly dose of 500 or 1000 mg/kg, respectively. The development of cardiotoxicity was monitored in vivo by means of electrocardiography (QaT duration), and was evaluated by measuring the contractile performance of isolated atria and by light and electron microscopy of left ventricular samples excised 5 weeks after the last DXR administration. DXR was found to impair body weight gain and to produce an irreversible and time-dependent prolongation of QaT, a decrease in myocardial contractility of isolated atria and typical morphologic alterations, including myocyte vacuolization and myofibrillar loss. Pretreatment with GSH at a dose of 500 mg/kg x 2, but not at 250 mg/kg x 2, partially prevented the impairment of body weight gain, QaT prolongation in ECG and the decrease in myocardial contractility of isolated atria induced by DXR. Alterations of the morphologic pattern were also significantly reduced in animals receiving the higher dose of GSH. Determinations of the cardiac non-protein sulfhydryl group content showed that GSH, at doses higher than or equal to 500 mg/kg, significantly increased this parameter, irrespective of the presence of DXR. In conclusion, the present data indirectly support the hypothesis that oxidative damage is involved in DXR cardiotoxicity and indicate that maintenance of the reduced thiol pool could be an important issue in myocardial protection.

Animals↗
PubMed1991

Effect of flunarizine on the delayed cardiotoxicity of doxorubicin in rats.

The calcium antagonist flunarizine (FLN) was tested for its ability to prevent doxorubicin (DXR)-induced cardiotoxicity in the rat. A cumulative dose of 9.0 mg/kg of DXR was administered i.v. over a period of 1 week. FLN (10 mg/kg/day i.p., 6 days/week) was administered according to two different time schedules, covering respectively the first and last 4 weeks after the beginning of DXR treatment. The two schedules were adopted to assess whether early and/or delayed DXR-induced cardiotoxic effects were affected by FLN. The development of cardiac toxicity was monitored by ECG recordings. The animals were sacrificed 8 weeks after the beginning of DXR treatment. The contractile performance of isolated atria and the morphological pattern of left ventricular fragments were subsequently evaluated. The early administration schedule of FLN was shown to be ineffective in preventing DXR-induced cardiotoxicity and in some cases was actually found to potentiate the effects of DXR. In contrast, the histological evaluation of ventricular preparations from rats treated with DXR and FLN according to the delayed time schedule showed a significant improvement with respect to hearts from animals treated with DXR alone. An inhibition of the delayed calcium overload occurring after DXR administration has been proposed as a possible mechanism for this protective action.

Animals↗
PubMed1991

Ischemic cerebral pathologies and K opioid receptors in rabbits.

Recently it has been suggested that endogenous k-opioid receptors may have a physiopathological role in ischemia induced neurodegeneration. The aim of this research is to show that in experimental thromboembolic (obtained mechanically using microspheres injected in the carotid) and atherosclerotic pathologies (obtained through a special diet) there is a common mechanism which involves mediation by dynorphine and the receptor compartment considered. The results, obtained using receptor binding techniques, showed a statistically significant increase in the number of k-opioid receptors (Bmax) without variations in the affinity (Kd) for the 3H dynorphine. We can therefore support the hypothesis that these changes in the modulation of the dynorphinergenic system may be part of a mechanism causing early cerebrovascular damage which results from embolic insults and is a consequence of such metabolic risk factors as are activated by atherogenesis.

Animals↗
PubMed1991

[The prevention of the myocardial toxicity of doxorubicin with superoxide dismutase].

The production of oxygen free radicals during anthracycline therapy has been proposed as a determinant of the toxicity of anthracyclines. Oxygen radical generation might specifically affect the myocardium because of the low antioxidant defense systems in cardiac tissue. The aim of the present investigations was to evaluate the potential cardioprotective effect of superoxide dismutase (SOD) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a rat model. Female Sprague Dawley rats received 3 mg/kg of DXR intravenously weekly for 4 weeks. SOD was administered intravenously at the dose of 10,000 U/Kg one minute before and 30 minutes after each DXR administration. Cardiac toxicity was monitored in vivo by means of electrocardiography (QaT interval), by determining the contractile properties of isolated atria, and by light and electron microscopy evaluation of left ventricle fragments excised 5 weeks after the last DXR administration. The degree of morphologic lesions was quantitated according to the score system proposed by E. Billingham. DXR treated rats showed, in comparison with control animals treated with saline a decrease of body weight gain, a progressive and irreversible prolongation of QaT, decrease of contractility of isolated atria, and significant morphologic lesions consisting in myocyte vacuolization and myofibrillar loss. SOD significantly prevented the impairment of body weight gain, QaT prolongation and the impairment of myocardial contractility. Moreover morphologic lesions were significantly reduced in rats receiving DXR + SOD. The present data indicate that SOD could represent an important issue in myocardial protection against DXR cardiotoxicity.

Animals↗
PubMed1991

Dietary fiber and cancer prevention.

A large body of literature suggests that eating a variety of foods containing high fiber has a protective effect against colon cancer. Evidence also indicates that a high fiber-containing diet may be protective against breast, ovary, endometrial, and gastrointestinal cancer. The focus of this review is the epidemiologic data for an inverse association between a high-fiber diet and risk for the previously mentioned cancers. Epidemiologic studies are categorized as international, within country, metabolic, time trend, case control, and cohort. Since 1980, 32 studies have assessed the role of fiber-containing foods in relation to colon cancer. Among these studies, 25 showed an inverse association. Of the seven case-control studies, which evaluated the relationship between the fiber-rich diet and breast cancer, six demonstrated an inverse association. For cancers of the esophagus, mouth, pharynx, stomach, rectum, endometrium, and ovary, there are only a limited number of studies, most showing a protective effect from eating a diet high in fiber-containing foods. The epidemiologic studies reviewed previously focus on dietary patterns in which fiber-rich foods usually occur as a complex mixture with other foods and food components, thus making it difficult to assess at this time if the protection is clearly from fiber per se or some other dietary component, such as low fat. For cancer prevention, the emphasis for dietary recommendation should be on a dietary pattern rather than on an isolated dietary fiber supplement.

Animals↗
PubMed1990

Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence.

Whether colon cancer risk can be modified by a diet rich in vegetables, grains, and fruit, and, if so, whether the protective factor is dietary fiber or other biologically active components correlated with a high-fiber diet are questions of active research interest. Because studies on diet are susceptible to bias from a number of sources, in this review we evaluated the adequacy of study methodology as well as study results to clarify how much protection, if any, is conferred by a high-fiber diet. The review consisted of an aggregate assessment of the strength of evidence from 37 observational epidemiologic studies as well as meta-analyses of data from 16 of the 23 case-control studies. Both types of analyses revealed that the majority of studies gave support for a protective effect associated with fiber-rich diets; an estimated combined odds ratio (OR) of 0.57 (95% confidence interval = 0.50, 0.64) was obtained when the highest and lowest quantiles of intake were compared. Risk estimates based on vegetable consumption (OR = 0.48) were only slightly more convincing than those based on an estimate of fiber intake (OR = 0.58), but the data do not permit discrimination between effects due to fiber and nonfiber effects due to vegetables.

Case-Control Studies↗
PubMed1990

The effects of RU-38486 on cervical ripening. Clinical studies.

One hundred eighty pregnant patients, 17 to 39 years old (mean (+)/- SEM: 25.1 (+)/- 0.39), with an amenorrhea of 7 to 12 weeks (mean (+)/- SEM: 9.4 (+)/- 0.10), and requesting a therapeutic abortion, were selected according to general good health and gave their informed consent to the study. Mifepristone (RU-486; Roussel UCLAF, Paris, France) an antiprogestin steroid, was administered at random in doses of 0, 50, 100, 200, 400, or 600 mg. Clinical evaluations and measurements of cervical dilatation were done before the study and repeated at 24 hours after administration of Mifepristone and at 48 hours, at which time the aspiration was performed. Significant increases in cervical dilatation were observed at 48 hours with all doses of Mifepristone above 50 mg. The increases were significantly greater in patients with a gestational age greater than 10 weeks than in those less than 10 weeks' gestational age. Parity had no influence on cervical dilatation at 48 hours. Bleeding was observed significantly more often with 100 to 600 mg doses of Mifepristone than with 0 to 50 mg. No influence of gestational age or parity on bleeding could be detected. Abdominal cramps were reported more frequently with 200, 400, and 600 mg of Mifepristone at 48 hours and their occurrence appeared to parallel cervical dilatation.

Abortion, Induced↗
PubMed1990

Effect of ICRF-187 pretreatment against doxorubicin-induced delayed cardiotoxicity in the rat.

Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF-187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cells.

Animals↗
PubMed1990

Kappa-opioid receptor changes and neurophysiological alterations during cerebral ischemia in rabbits.

Endogenous opioids have been shown to produce beneficial effects in experimental stroke. To evaluate both neurophysiological and biochemical parameters, we induced massive cerebral ischemia in 11 rabbits according to the method standardized in our laboratory, using microspheres injected through the internal carotid artery. Binding studies were performed in the 11 embolized, in nine control, and in five sham-operated rabbits using the appropriate concentration of [3H]dynorphin A (1-8). Neurophysiological parameters were evaluated under baseline conditions and 1 hour after embolization, surgical preparation, or sham operation in 17 rabbits. Comparison of visual readings of the electroencephalograms and analyses of the quantified electroencephalograms under baseline conditions and after embolization indicated a marked and statistically significant (p less than 0.01) increase in bilateral delta activity; histologic examination confirmed bilateral brain edema. Binding studies on kappa-opioid receptors indicate that 1 hour after embolization there were significantly more (28%) kappa-opioid receptors (Bmax) in six embolized rabbits than in five sham-operated animals. No significant changes were observed in the affinity parameters, particularly in the dissociation constant (Kd). Our results indicate a role for endogenous dynorphin peptides in the pathogenesis of stroke.

Animals↗
PubMed1990

Effect of glutathione and N-acetylcysteine on in vitro and in vivo cardiac toxicity of doxorubicin.

The effects of two sulfhydryl compounds, glutathione (GSH) and N-acetylcysteine (NAC), on the cardiotoxicity of doxorubicin (DXR) were tested on in vitro and in vivo models. DXR was administered to rats as 4 weekly i.v. doses of 3 mg/kg. GSH (1.5 mmoles/kg), given i.v. 10 min before and 1 hr after DXR, was found to prevent the development of the delayed cardiotoxic effects of DXR, as assessed by electrocardiographic and mechanical parameters, as well as by histological examination of left ventricular preparations. In contrast, equimolar oral doses of NAC (1 hr before and 2 hrs after DXR) were found to be ineffective. Both GSH and NAC prevented the negative inotropic effect produced by DXR on isolated rat atria. A good correlation exists between the cardioprotective effects of the two agents and their ability to enhance the non-protein sulfhydryl group content of the myocardium. Differences observed in vivo between GSH and NAC might be accounted for by pharmacokinetic factors.

Acetylcysteine↗
PubMed1989

The rat model in the comparative evaluation of anthracyclines cardiotoxicity.

In the present investigation, the cardiotoxic effects of three anthracycline analogs (doxorubicin, 4'-epi-doxorubicin and 4'-deoxy-doxorubicin) were compared. For this purpose, 9.0 mg/kg of doxorubicin, divided into three closely spaced subdoses, were injected intravenously in rats. The two derivatives were administered according to the same time schedule and their doses were chosen on the basis of the clinically adopted ratio, doxorubicin: 4'-epidoxorubicin: 4'-deoxy-doxorubicin = 1:1:0.5. The degree of cardiomyopathy induced by the three anthracyclines was evaluated by ECG changes and morphological alterations. Doxorubicin was found to produce a significant degree of cardiotoxicity, thus confirming the validity of the experimental model adopted. Both 4'-substituted derivatives proved to be less cardiotoxic than the parent compound, although not completely devoid of this side effect.

Animals↗