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Biomedical subjects

R Serafini

Publications and source records attributed to R Serafini.

43 records · Page 3Linked to original sources

High dose chemotherapy with cisplatin, VP16 and carboplatin with stem cell support in patients with advanced ovarian cancer.

Authors treated 4 patients suffering from advanced ovarian cancer with high-dose chemotherapy and autologous peripheral blood stem cell (APBSC) or autologous bone marrow stem cell (ABM) as hematopoietic support. In three patients were collected peripheral blood stem cells using a fully automated blood cell separator during hematopoietic recovery following aplasia induced by non-intensive chemotherapy (cisplatin 200 mg/m2 and cyclophosphamide 1,500 mg/m2). Hemopoietic reconstitution of the four patients submitted to APBSC or ABM support after high-dose chemotherapy (cisplatin 100 mg/m2, VP16 650 mg/m2 and carboplatin 1,800 mg/m2) showed the low hematological toxicity of our treatment with APBSC support. Moreover, the drug combination of cisplatin and cyclophosphamide has clinical activity in ovarian cancer and it is an optimal association to mobilize and harvest large number of PBSC.

Adult↗

A comparison between two different procedures for bone marrow processing: a semiautomated procedure vs manual starch sedimentation.

After high-dose chemotherapy, autologous cryopreserved bone marrow infusion is employed to restore rapidly the compromised hematopoietic function. An efficient bone marrow processing reduces the infusion toxicity produced by hemolized red cells, granulocytes and platelets clumping and DMSO amount; moreover it increases freezing efficacy, a critical step in autologous bone marrow grafting techniques. Gravity sedimentation technique with 6% hydroxyethyl-starch (HES) or a semiautomated procedure using a blood cell processor were used in our center to manipulate ex-vivo the collected bone marrow. In our experience we compared these two different procedure and we evaluated their efficiency.

Antineoplastic Combined Chemotherapy Protocols↗

Autologous bone marrow processing for autotransplantation using an automated cell processor and a semiautomated procedure.

Twenty bone marrow aspirates harvested for autotransplantation from 20 patients suffering from several oncohematological diseases were processed using the automated Du Pont SteriCell processor. In 15 bone marrow harvests, the interface buffy coat cells were collected using the SteriCell processor in manual mode with a semiautomated procedure. The procedure yielded an average red cell removal of 84% and an average mononuclear cell (MNC) recovery of 86%. Cloning efficiencies of hematopoietic progenitor cells (CFU-GM and BFU-e) did not differ between processed and recovered MNCs. Four cryopreserved bone marrow buffy coats were thawed and reinfused into four patients who had undergone high dose chemotherapy. Stable engraftment was observed in all cases. In five bone marrow harvests, the SteriCell automated density gradient MNC isolation procedure was performed after buffy coat collection. The whole two-step procedure allowed an average MNC recovery of 69%. CFU-GM and BFU-e assays did not show a significant difference in cloning efficiency between processed and recovered bone marrow MNCs. We conclude that the SteriCell processor offers rapid, safe and feasible procedures for the semiautomated processing of human bone marrow for transplantation. The clinical efficacy of density gradient separated bone marrow employing the automated step and the opportunity to use fully automated processing must be investigated.

Adult↗

Autoradiographical analysis of excitatory amino acid binding sites in rat hippocampus during the development of hippocampal kindling.

Binding sites for excitatory amino acids have been determined by autoradiographical procedures in the rat hippocampus and striatum during hippocampal kindling. The binding sites measured were the N-methyl-D-aspartate (NMDA)-sensitive sites for L-[3H]glutamate and [3H]MK-801 sites (transmitter recognition site and ion channel of the NMDA receptor, respectively), [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) sites (quisqualate receptor), [3H]kainate sites (kainate receptor) and NMDA-insensitive sites for L-[3H]glutamate. In general, little change was apparent in the hippocampus or striatum for any of these binding sites when assessed 48 h after attaining stages 1/2, 3 or 5 of kindling. These results suggest that hippocampal kindling does not bring about a change in the excitatory amino acid receptor binding sites examined, and that the appearance of an NMDA receptor-mediated component to synaptic responses in the hippocampus produced by kindling, cannot be explained on this basis.

Amino Acids↗

Kinetics of MK-801 and its effect on quinolinic acid-induced seizures and neurotoxicity in rats.

MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate], a noncompetitive antagonist of the N-methyl-D-aspartate-type of excitatory aminoacid receptors, was measured in plasma and brain tissues after i.p. administration to rats by using a novel high-performance liquid chromatography assay. The drug reached maximal concentrations in plasma and brain within 10 to 30 min of injection (2 mg/kg) with an elimination half-life of 1.9 and 2.05 hr, respectively. Mean ratio of brain area concentration-time curve to plasma area concentration time curve was 12.5, referring to total plasma concentrations. MK-801 distributed almost equally between plasma and red cells (mean blood-to-plasma ratio averaged 1.2 +/- 0.2 when calculated 30 and 180 min from drug administration). Plasma and brain concentrations of MK-801 rose almost linearly from 0.5 to 4 mg/kg 30 min after injection and the brain-to-plasma ratio (12.9 +/- 2.8) was constant in the dose range studied. The distribution of the drug in various brain regions 30 and 180 min after 2 mg/kg i.p. showed no preferential concentration or retention in any of the areas studied. The anticonvulsant effect of MK-801 was evaluated against limbic seizures (measured by EEG) induced by intrahippocampal injection of 120 nmol of quinolinic acid, an agonist of the N-methyl-D-aspartate-type receptors, in freely moving rats. At 0.25 and 0.5 mg/kg, MK-801 significantly lowered by 71 to 77% the number of seizures and by 80% the total time spent in seizures (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epileptogenic activity of two peptides derived from diazepam binding inhibitor after intrahippocampal injection in rats.

Peptides DBI 42-50 (DRPGLLDLK) and DBI 43-50 (RPGLLDLK) are synthetic fragments of an 18 amino acid peptide called octadecaneuropeptide (QATVGDVNTDRPGLLDLK), a brain derivative of diazepam-binding inhibitor (DBI). The two peptides were unilaterally injected into the dorsal hippocampus (granule cells of dentate gyrus) of freely moving adult rats. The electroencephalographic (EEG) pattern was continuously recorded from bilateral hippocampal and cortical electrodes, and the animals' behavior was observed throughout the experiment. A dose of 100 nmol peptide 42-50 was required to reliably cause EEG alterations (seizures and spiking). EEG changes, defined as seizures, were characterized by discrete repetitive periods of high-frequency and/or multispike complexes and/or high-voltage synchronized spike or wave activity. EEG seizures were often associated with a frozen appearance of the animal and "wet dog shakes." Tonic-clonic convulsions were not observed. EEG seizures induced by peptide 42-50 were prevented by 90 mg/kg PK 11195, a selective antagonist of a novel GABAA receptor-linked subtype of a benzodiazepine (BDZ) receptor, but were unaffected by flumazenil, an agonist of the "central" type of BDZ receptor and by D(-)2-amino-7-phosphonoheptanoic acid, a selective antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptors. Light microscopy showed no neuropathological changes in the injected hippocampus. The data show that these DBI-derived peptide fragments induce a typical pattern of limbic seizures in rats. DBI and/or its natural processing products may play a role in the pathophysiology of epilepsy.

Amino Acids↗

A preliminary survey of Italian experience on bone marrow harvesting, processing and manipulation. The Italian Cooperative Study Group on Cell Manipulation in Hematology.

The following report describes the initial stage of the activity of the Italian Cooperative Study group on cellular manipulation in hematology consisting of a retrospective evaluation of data regarding bone marrow (BM) harvesting processing, and proceedings from 20 Italian Centers. Two thousand, three hundred and eighty-four BM have considered: 1073 were performed for autografts and 1311 for allografts. A cohort of adverse effects in marrow harvesting were reported by 7 Centers out of 20, including one death caused by tracheomalacia during the anesthesia. Twelve Centers used blood separators as a mean for marrow processing. Eight Centers used the RBC removal technique in major donor/recipient AB0 incompatibility. Ficol-Hipaque gradient was employed in 7 Centers. T-depletion were accomplished with monoclonal antibodies in 7 Centers and elutriation in two Centers. Fifteen Centers provided to purge the residual tumour cells with chemicals (11), immunological (4) and chemo-physical means (1).

Bone Marrow Transplantation↗