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Biomedical subjects

F Piccinini

Publications and source records attributed to F Piccinini.

107 records · Page 6Linked to original sources

L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release.

OBJECTIVE: This study investigates the biochemical and cardiovascular effects of L-arginine administration in normotensive pregnant women and women with preeclampsia. METHODS: The study groups consisted of 12 women with uncomplicated pregnancies and 17 preeclamptic patients, four of whom were on antihypertensive treatment. In both groups, saline infusion was started, followed by 30 g L-arginine administration, and finally more saline. Blood pressure was recorded every 5 minutes and blood samples were collected for measurement of serum citrulline, arginine, and nitrite levels. Amino acid assays were done by using high-performance liquid chromatography with fluorometric detection. RESULTS: L-Arginine infusion was associated with a significant reduction of blood pressure in both groups, the decrease being greater in the women with preeclampsia. Baseline serum citrulline and arginine levels were not significantly different between the two groups. L-Citrulline levels were significantly increased during infusion of L-arginine, and the increase was significantly lower in the women with preeclampsia. Serum nitrite levels were increased only in controls and not in preeclampsia patients. The total citrulline production stimulated by L-arginine was related inversely to baseline blood pressure values and was unrelated to clinical parameters such as gestational age at delivery, birth weight, and Apgar score. CONCLUSIONS: L-Arginine load in pregnant women is associated with increased nitric oxide (NO) production and hypotension. Despite a reduced ability to produce NO, patients with preeclampsia may benefit from L-arginine supplementation. Overall, these findings partially support the hypothesis that preeclampsia is characterized by a dysfunction of the L-arginine-NO pathway.

Adult↗

Effect of trimetazidine on early and delayed doxorubicin myocardial toxicity.

The influence of the administration of trimetazidine on the myocardial toxicity induced by doxorubicin was studied on an in vivo model in the rat. Trimetazidine was chosen due to its ability to act as a scavenger of oxygen-derived free radicals, which have been implicated in both early and delayed cardiotoxic manifestations after doxorubicin treatment. In the present study, doxorubicin was administered as 4 weekly i.v. injections of 3 mg/kg. The cardiotoxic effects were evaluated by measuring predictive ECG parameters (QT and ST intervals) as well as the contractile performance of atria isolated from treated animals. Heart preparations were also examined by light microscopy. Trimetazidine, 2.5 mg/kg/day i.p. for 3 days before doxorubicin administration plus 2.5 mg/kg/day p.o. for 10 weeks, was unable to prevent the development of doxorubicin-induced long-term cardiotoxicity. However, a significant improvement of the early cardiotoxic signs was observed in trimetazidine-treated rats, as reported in previous investigations. The present findings suggest that different target structures may be involved in the early and delayed free radical-mediated effects of doxorubicin.

Animals↗

Trifluoperazine does not affect doxorubicin cardiotoxicity in the rat.

Sprague Dawley rats received doxorubicin (DXR) at a dose of 3 mg/kg i.v. every third day for a total of three administrations, according to an acute and delayed cardiotoxicity experimental model previously described. DXR was found to induce significant ECG alterations (Qat and Sat prolongation) and typical morphologic lesions in the left ventricle. Trifluoperazine (TFP), administered at the doses of 0.2 of 2 mg/kg i.p., 5 days a week for 4 weeks, starting 1 day before DXR, was ineffective in preventing the electrocardiographic and morphologic alterations induced by DXR.

Animals↗

The spin trap alpha-phenyl-tert-butyl nitrone protects against myelotoxicity and cardiotoxicity of adriamycin while preserving the cytotoxic activity.

The possibility of preventing the myelo- and cardiotoxicity of adriamycin (ADR), was explored in in vivo experiments in the rat. Assuming that free radicals play a key role in the ADR organotoxicity, a new anti-radical approach was set up by administering a spin trapping compound (PBN) which is taken up by the cells and specifically interacts with radicals. ADR was given i.v., 3 mg/kg every 3rd day for 3 times. PBN was continuously administered throughout the persistence time of ADR in myocardium (15 days). Serial ECG and leukocyte counting were performed during 10 weeks, then hearts were isolated and Langendorff-perfused; functional parameters (heart rate, contractility, coronary flow) were evaluated. PBN improved ECG and prevented the myelotoxicity, while functional parameters were not significantly different from those of control. Cytotoxicity was evaluated in vitro in 3 different human tumour cell lines; PBN did not modify the cytotoxicity of ADR, thus excluding a free radical involvement in this activity. The present results suggest that a proper administration schedule of spin traps might be a promising approach for improving the therapeutic index of ADR.

Animals↗

Analysis of calcium-dependent protein kinase-C isoenzymes in intrinsically resistant cloned lines of LoVo cells: reversal of resistance by kinase inhibitor 1-(5-isoquinolinylsulfonyl) 2-methylpiperazine.

In order to investigate the involvement of Protein Kinase C (PKC) in the signal transduction mechanisms related to intrinsic chemoresistance, two cellular clones were isolated from LoVo/WT colon adenocarcinoma cell line and their cytogenetic pattern was studied: LoVo C1.7 was intrinsically resistant to Doxorubicin while LoVo C1.5 showed the same resistance index as the mixed parental cell population. Two PKC isoforms, immunologically identified as beta and alpha PKC, were isolated from the cytosolic fraction of all cell types and one single peak of alpha PKC was obtained from the particulate fraction. Resistant LoVo C1.7 cells showed a significant increase of PKC activity; preincubation with H-7 induced PKC inhibition and reversal of drug resistance. These data suggest that in our cell system the identified calcium-dependent PKC subtypes can play a role in the mechanisms of intrinsic resistance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗