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Biomedical subjects

B Parodi

Publications and source records attributed to B Parodi.

At least 19 recordsLinked to original sources
PubMed1995

Cytotoxicity and cellular accumulation of a new cis-diammineplatinum (II) complex containing procaine in murine L1210 cells sensitive and resistant to cis-diamminedichloroplatinum (II).

The emergence of drug resistance during tumor chemotherapy is one of the main problems associated with cancer treatment, particularly with cisplatin (cis-DDP). In the hope of overcoming this problem, various cis-DDP-derived compounds have been synthesized, and their pharmacological activity was compared with that of cis-DDP. In this paper we report on studies on the cytotoxic activity induced by cis-diamminechloro-[2-(diethylamino)ethyl-4-aminobenzoate, N4]- chlorideplatinum(II) monohydrochloride monohydrate (DPR), a new complex of platinum containing procaine. All experiments were carried out on murine leukemic cells, which were either sensitive (L1210) or resistant (L1210/DDP) to cis-DDP. A tetrazolium dye (MTT) assay conducted 5 days after a 2-h exposure of cells to both drugs was utilized to determine the resistance factor (RF) of L1210/DDP cells as compared with the sensitive wild-type cells. Drug accumulation and efflux, together with the amount of platinum bound to DNA, were also investigated. The activity of DPR on sensitive cells was not significantly different from that of cis-DDP. Conversely, DPR was 4.3 times more effective than cis-DDP on resistant cells. A decreased drug accumulation is one of the mechanisms of resistance to cis-DDP of L1210/DDP cells. However, DPR accumulation was not significantly different in sensitive and resistant L1210 cells. Under culture conditions that yielded similar intracellular platinum concentrations, treatment with DPR produced significantly greater DNA platination than did treatment with cis-DDP in both cell lines. No difference in efflux was observed between L1210 and L1210/DDP cells exposed to either cis-DDP or DPR. Our results show that in parental cells, DPR is as potent as cis-DDP on a molar basis, and it is also minimally cross-resistant with cis-DDP in L1210/DDP cells. A direct implication of our results is that DPR could be useful in those human tumors showing a mechanism of resistance similar to that of L1210/DDP cells.

Animals↗
PubMed1994

Molecular Probe Data Base (MPDB).

This paper provides an update on the contents and structure, forms and mode of data distribution of the Molecular Probe Data Base (MPDB), a database that collects and provides on-line information on the sequence, target gene, applications and bibliographic references of synthetic oligonucleotides. The recent data extension and the new means of accessing the database are discussed.

Base Sequence↗
PubMed1993

Molecular Probe Data Base: a database on synthetic oligonucleotides.

The Molecular Probe Data Base (MPDB) was designed to collect and make information on synthetic oligonucleotides available on-line. This paper briefly describes its purpose, contents and structure, forms and mode of data distribution. Particular emphasis is given to recent data extension and system enhancements that have been carried out in order to simplify access to MPDB for unskilled users.

Base Sequence↗
PubMed1993

The cell line data base and the new catalogue: detailed information on 2650 human and animal cell lines.

The Cell Line Data Base (CLDB), set up within the Interlab Project, is a relational database containing data on 2650 human and animal cell lines which are available in labs and cell banks all over Europe. The second edition of the catalogue, directly generated from the database, has been produced, and will be published in the first months of 1993. Furthermore, the electronic catalogue is available for IBM-compatible personal computers and the version for MacIntosh is under preparation.

Animals↗
PubMed1993

Herbal mixtures with claimed slimming activity: determination by TLC and HPLC of illegally added drugs.

A method for the detection and quantitation of several undeclared drugs in herbal preparations with slimming activity is proposed. Samples containing various anorexics, hypoglycemics and antidepressants were prepared by addition of the drugs to a synthetic mixture containing the most commonly used plant powders for those preparations. Each sample was subjected to a treatment that permitted, after a simple ethanolic extraction, the identification of the drugs by TLC using three different solvent systems. A further purification of the ethanolic solution through a polyamide column allowed for quantitative analysis of the drugs by a RP-HPLC method. The analytical recovery was good (88-97%); the calibration curves were linear over a wide range of drug concentrations (30-500 micrograms/ml) (r > 0.9995); the precision was high (CV% = 0.4-2.8) as well as the accuracy (96-102%).

Appetite Depressants↗
PubMed1992

Molecular Probe Database: a database on synthetic oligonucleotides.

The Molecular Probe Data Base (MPDB) is designed to collect and make available on-line information on synthetic oligonucleotides. This paper briefly describes the purpose of MPDB, its content and structure, forms and mode of data distribution, and a series of additional services available to scientists using MPDB.

Amino Acid Sequence↗
PubMed1991

Somatostatin release from rat cerebral cortex synaptosomes.

Rat cerebral cortex synaptosomes were exposed in superfusion to various depolarizing stimuli and the release of somatostatin-like immunoreactivity (SRIF-LI) was measured by means of a radioimmunoassay procedure. High KCl (9-50 mM) concentration dependently evoked SRIF-LI release; the evoked overflow reached a plateau at 25 mM KCl and was completely abolished when Ca2+ ions were omitted from the superfusion medium, independently of the concentration of KCl used. The 15 mM K(+)-evoked release of SRIF-LI increased sharply as the Ca2+ concentration was raised to 0.8 mM, then leveled off and reached a plateau at 1.2 mM. The 15 mM K(+)-evoked overflow, but not the spontaneous outflow, was partially decreased (50%) by 1 microM tetrodotoxin. The presence in the superfusion fluid of a mixture of peptidase inhibitors did not improve the recovery of SRIF-LI both in the absence and in the presence of high K+. Exposure of synaptosomes to veratrine (1-50 microM) induced release of SRIF-LI in a concentration-dependent way. The effect of the alkaloid was strictly Ca2+ and tetrodotoxin sensitive. Replacement of extracellular Na+ by sucrose caused an acceleration of the spontaneous SRIF-LI outflow that was inversely correlated to the Na+ content in the superfusion medium. The release evoked by the sodium-deprived media did not exhibit any calcium dependence. HPLC analysis of the samples collected during superfusion showed that greater than 90% of the SRIF-LI released either during the spontaneous outflow or by 15 mM KCl was represented by SRIF-14 (SRIF-28(14-28]. These values reflected the ratio SRIF-14/SRIF-28 found in synaptosomes at the end of the experiments.

Animals↗
PubMed1991

Analysis and comparison of information and data recorded in carcinogenicity and genotoxicity databases.

The Interlab Project is a university-industry joint project recently funded by the Italian government as part of the improvement of the Italian research infrastructure; among its short-term goals are the implementation of data banks of biomedical interest and the spread of informatic tools for biomedical research. Results of both long-term assays of carcinogenicity in rodents and short-term in vitro and in vivo tests of genotoxicity are relevant for a wide body of users, ranging from carcinogenesis research laboratories to industries and governmental agencies. To evaluate the most appropriate ways of spreading information on these experiments, a detailed analysis on information recorded in available databases has been carried out. Furthermore, the contents of the most known databases have been compared, with respect to a specific compound, to evaluate both the overall reliability of these systems, compared to longer and more complex assessments carried out manually starting from bibliographic searches, and the level of concordance among them.

Academies and Institutes↗
PubMed1990

Polymorphism of the HLA-DP beta region detected by Southern blot hybridization.

A panel of homozygous cell lines, previously typed by primed lymphocyte test for their DPw specificity, have been studied by restriction fragment length polymorphism analysis, using a DP beta-specific probe. Highly stringent hybridization and washing conditions were used to prevent cross-hybridization with DR- and DQ-specific fragments. Three out of six enzymes employed allowed us to distinguish clustered or single DPw specificities, and by MspI digestion it was possible to detect different patterns within a single specificity such as DPw4. Some of the cell lines have been further studied with synthetic oligonucleotides derived from the polymorphic regions of the second exon of DP beta 1 gene, and, in general, a correlation with the primed lymphocyte test--defined specificities and restriction fragment length polymorphism was found. These data suggest a more extended complexity of the DP region, in addition to that defined as the DPw1-DPw6 segregant series.

Base Sequence↗
PubMed1987

Detection of HLA-DP serological allodeterminants by the use of radioiodinated DP molecules.

HLA class II molecules were partially purified from cells of an HLA deletion mutant cell line, LCL721.82, that lost DR and DQ expression but retained DPw2 specificity and labeled with radioactive 125I. The radioiodinated preparation bound to DP-specific monoclonal antibody B7/21 as well as rabbit anti-HLA class II antiserum. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the component involved in these bindings gave, unlike known HLA class II molecules, a sharp and dense band of approximately 60 kDa under nonreducing conditions and a single but diffuse band of approximately 30 kDa under reducing conditions. By screening 401 anti-HLA class II alloantisera, including those distributed in the 9th International Histocompatibility Workshop and also those locally available, eight were found to possess significant binding activity. Specificity analysis of these eight binding-positive antisera on a panel of DP-pretyped HLA homozygous typing cells revealed the presence of two clusters, one corresponding to an allodeterminant associated with DPw1, 2 and 3 and the other to that associated with DPw2 and 4. These two determinants were shown by the sequential binding test to reside on the B7/21-defined HLA class II molecules. Thus, two major conclusions were drawn: two distinct allodeterminants are carried by a single DP molecule; and these serologically detected DP allodeterminants are supertypic to cellularly defined DP allospecificities.

Antibodies, Monoclonal↗
PubMed1986

Reaction of N,N-disubstituted alpha-aminomethyleneketones with tosyl isocyanate. Synthesis of amino-disubstituted 2-acyl-3-amino-N-tosylpropenamides, N,N-(3-amino-1-alkyl-2-propenylidene) and N,N-[2-(aminomethylene)cyclohexylidene]tosylamides.

The reaction of N,N-disubstituted open-chain and cyclohexane alpha-aminomethyleneketones (I) and (II) with p-toluenesulfonyl (tosyl) isocyanate gave amino-disubstituted 2-acyl-3-amino-N-tosylpropenamides (III) and/or N,N-(3-amino-1-alkyl-2-propenylidene) and N,N-[2-(aminomethylene)-cyclohexylidene] tosylamides (IV) and (V), the final product being related to the carbon and nitrogen substituents of the enaminone. The evaluation of the hypoglycemic activity concerning some of the above compounds gave no interesting results.

Amides↗
PubMed1984

The same human alloreactive T cell clone can help both B lymphocytes and specific cytotoxic precursors.

Human alloreactive proliferating T cell clones have been compared for their capacity to provide help for B cell activation and the generation of a specific cytotoxic response. The results demonstrate that, when triggered by the relevant alloantigen, the same T cell clone can induce a strong polyclonal B cell activation and serve as the only source of helper cells for the generation of a specific cytotoxic response by any source of CTL precursors against any stimulator cell present in culture.

B-Lymphocytes↗
PubMed1984

In vitro stimulation of IgE production at a single precursor level by human alloreactive T helper clones.

Human alloreactive proliferating T cell clones were isolated by a combination of allogeneic stimulation and interleukin 2-dependent growth. When cultured with B cells and macrophages bearing the appropriate alloantigens, the helper clones induced the production of high levels of IgE, while in the absence of the appropriate stimulation B cells produced undetectable IgE levels. Allogeneic peripheral blood T cells did not provide any help, but rather suppressed the IgE production induced by the alloreactive clones. The development of culture conditions where the help provided by specific T cell clones is non-limiting and suppressor-cytotoxic T cells are absent allowed the set up of limiting dilution experiments to determine the frequency of the B cells activated to high rate IgE production. One in 2,200-6,000 B cells in the peripheral blood of normal donors was activated to produce measurable amounts of IgE. This experimental system will allow the clonal analysis of the IgE antibody repertoire, in different physiological and pathological conditions.

B-Lymphocytes↗
PubMed1983

Activation of human B lymphocytes: frequency of antigen-specific B cells triggered by alloreactive or by antigen-specific T cell clones.

Human T cell clones specific for tetanus toxoid (TT) or for alloantigens were isolated and expanded in culture using antigen stimulation and soluble growth factors. When stimulated by the specific antigen, the clones were able to proliferate in the absence of exogenous growth factors and to provide help to B cells. The alloreactive and TT-specific clones were compared for their capacity to help an anti-TT as well as a polyclonal antibody response. The frequency of the B cells activated to the production of specific antibody was determined by limiting dilution analysis in cultures containing limiting numbers of responding B cells and optimal numbers of cloned T helper cells. In these conditions a single activated b cell was able to produce about 10 ng of antibody. TT-specific clones, in the presence of low TT concentrations, selectively induced a number of TT-specific B cells to produce IgG antibody in the absence of a detectable polyclonal B cell activation. On the other hand the alloreactive clones activated higher numbers of TT-specific B cells as a part of a strong polyspecific B cell activation. In this case the antibody production did not require the presence of TT in culture; furthermore cells producing antibodies of unrelated specificities were also activated in allostimulated cultures. IgG anti-TT were produced only by immune donors, while IgM anti-TT were produced by immune and nonimmune donors, providing the B cells were activated by alloreactive clones. These data demonstrate that human memory B cells can be triggered by both antigen-specific and alloreactive T cells to antibody production. The alloreactive clones can therefore be used to analyze at the clonal level the repertoire of a pool of B cells that contain most, if not all, the memory antibody specificities.

Antibody Formation↗
PubMedDate not supplied

Synthesis and antitumor activity of a new cis-diammineplatinum (II) complex containing procaine hydrochloride.

This paper refers to some of the chemical and biological properties of a new platinum (II) complex where the aromatic amino group of procaine is involved in the coordination with platinum and whose structure was defined by UV, IR, 1H-NMR, and elemental analysis. This new cationic platinum-triamine complex (DPR) displays excellent solubility (> 50 mg/ml) and stability in water. DPR has significant in vitro cytotoxicity against murine P388 leukemic cell line, human K562 erythroleukemic cell line and human Jurkat T cell line. The in vitro cytotoxic effects of DPR on P388 and Jurkat leukemic cells were comparable to those of cis-diamminedichloroplatinum (II) (DDP), while its activity on K562 cells was significantly better than that of DDP [IC50 = 1.07 +/- 0.36 (SD) microM vs 2.62 +/- 0.23 (SD) microM, P < 0.01]. The in vitro Pt accumulation rate for P388 cells was twice as rapid after DPR than after DDP exposure, while no difference in cellular platinum efflux was observed. The antitumor activity of DPR was tested in vivo against P388 leukemic cells in BDF1 mice and gave a % ILS value (75%) similar to that of the maximum tolerated dose (MTD) of DDP (8 mg/Kg). A comparative study of plasma urea nitrogen (PUN) levels and kidney morphological analysis in tumor-bearing mice receiving the LD50 dose of both drugs (39.3 mg/Kg and 16.5 mg/Kg for DPR and DDP, respectively), showed DPR to be less nephrotoxic than DDP. These results indicate that this new cationic platinum-triamine complex containing primary amine ligand is surprisingly active both in vitro and in vivo. In summary, the good characteristics of DPR in terms of high solubility, encouraging anticancer activity and absence of nephrotoxic effects make DPR a promising new platinum anticancer agent for preclinical development.

Animals↗
PubMedDate not supplied

Effect of normal saline on cisplatin pharmacokinetics and antitumor activity in mice bearing P388 leukemia.

The effect of normal saline (NS) on the antitumor activity, toxicity and pharmacokinetic of cisplatin (DDP) was investigated in BDF1 mice bearing P388 leukemia. Tumor-bearing mice received 8 or 16 mg/Kg of DDP dissolved in NS or distilled water (DW) intraperitoneally. Control animals were treated with DW or NS alone. The administration of 8 mg/Kg of DDP+NS produced a significantly better survival (P less than 0.05) compared to that observed in mice receiving DDP+DW. The proportion of long-term survivors was 3.5 times higher in the DDP+NS group (39%) compared to the DDP+DW group (11%). The administration of 16 mg/kg DDP+DW was highly toxic, resulting in early deaths (MST = 5 days) and no long-term survivors. NS protected from DDP toxicity without further improving the survival achieved following the injection of 8 mg/kg DDP+NS. Investigation of platinum pharmacokinetics showed that NS significantly decreases both plasma and tissue concentrations of total platinum, mainly through a decrease in the amount of platinum bound to high molecular weight plasma proteins. HPLC studies indicated that mice receiving 8 mg/kg DDP+NS or DDP+DW fail to show clear differences both in the total ultrafilterable platinum and unchanged DDP in plasma ultrafiltrate. Conversely, mice treated with DDP+NS had higher concentrations of platinum-species in plasma ultrafiltrate than mice receiving DDP+DW. These latter results, together with the observation that NS decreases the amount of platinum bound to plasma proteins, suggest that the effect of NS does not solely depend in vivo on the ability of the chloride ion concentration to stabilize the DDP molecule and suppress the formation of DDP metabolites, but also on its ability to prevent DDP toxicity by reducing the protein binding of DDP aquated products.

Animals↗
PubMedDate not supplied

Serum, urine and peritoneal fluid levels of 5-FU following intraperitoneal administration.

Seven patients with advanced colon cancer, refractory to conventional chemotherapy, and malignant disease confined to the intra-abdominal space received a total of 24 consecutive courses of ip 5-Fluorouracil (5-FU). 5-FU 1000 mg was administered in 2 L of warm (37 degrees C) dialysate daily for five consecutive days every 28 days. 5-FU concentrations in serum, peritoneal fluid and urine were measured by high pressure liquid chromatography (HPLC). The mean disappearance half-life of 5-FU from the peritoneal fluid was 1.6 hours with a mean permeability area product (PA) of 22.4 ml/min. The mean peritoneal AUC was 450 +/- 165 times greater than the mean serum AUC. Ip 5-FU treatment is well tolerated, can be safely administered on an outpatient basis and produces a significant pharmacological advantage over conventional routes of administration.

Adult↗