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B Parodi

Publications and source records attributed to B Parodi.

At least 19 recordsLinked to original sources

Preparation and evaluation of a chitosan salt-poloxamer 407 based matrix for buccal drug delivery.

The aim of this work was to prepare and evaluate a matrix for buccal drug delivery composed of a chitosan salt and poloxamer 407. Different chitosan salts were formed by reacting chitosan with acetic, citric, and lactic acid. Various proportions of poloxamer 407 were added to the aqueous solution of chitosan salt, and the residue obtained by lyophilisation was compressed into discs, using a 30 kN compression force. An experimental design (3(2)) was used to study the influence of the type of chitosan salt and of the relative amount of poloxamer on drug release capacity, swelling, erosion, and mucoadhesiveness of matrices. The results showed that matrix properties depended significantly on both relative amount of poloxamer and chitosan salt type. The rank orders of chitosan salts for the four processes evaluated were as follows: drug release: chitosan acetate>chitosan citrate>chitosan lactate; swelling: chitosan lactate>chitosan acetate=chitosan citrate; erosion: chitosan citrate>chitosan lactate>chitosan acetate; mucoadhesion: chitosan lactate>chitosan acetate=chitosan citrate. Mucoadhesion was particularly favoured when poloxamer 407 was present at about 30% (w/w). The matrix composed of chitosan lactate and poloxamer 407 showed the best characteristics for buccal administration.

Administration, Buccal↗

Species identification and confirmation of human and animal cell lines: a PCR-based method.

Misidentification and cross-contamination of cell lines are major problems of cell cultures that can make scientific results and their reproducibility unreliable. This paper describes a PCR-based method for easily identifying or confirming the species of origin of cell lines by using a panel of oligonucleotides specific for the nine animal species most common in cell culture laboratories. A panel of 35 human and animal cell lines, whose species of origin were previously confirmed by isoenzyme assay, was studied with nine species-specific primer pairs that specifically anneal to DNA sequences codifying for human, cat, dog, mouse, rat, horse, rabbit, African Green monkey cytochrome c oxidase subunit I (cox I), and one primer pair specific for the cytochrome b gene of Chinese hamster. The amplified fragments were analyzed by electrophoresis in ethidium bromide-stained 2% agarose gels. The method is simple, rapid, highly sensitive, and useful for routinely monitoring the species identity of cell cultures.

Animals↗

Stability study of hard gelatin capsules containing retinoic acid.

Retinoic acid (RA) is employed in the therapeutic treatment of acute promyelocytic leukemia (APL). In this paper, the chemical stability and the most favorable storage conditions of RA in hard gelatin capsules containing alpha-lactose monohydrate, used in clinical experimentation, are reported. A secondary goal of this work was to show the usefulness of a robust regression technique, repeated median with replicates (RMWR) in a solid-state shelf life prediction by accelerated studies. The capsules were stored at room temperature and in the freezer. Their residual RA content was assayed for more than 3 years. RA chemical degradation was monitored by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) stability-indicating methods previously validated and able to detect various potential degradation products. Possible physical modifications were checked by dissolution tests and differential scanning calorimetry (DSC) of the content of the capsules. The shelf life was also predicted by an accelerated isothermal method to confirm room temperature results, and the activation energy estimated through this study was 12.5 +/- 1.1 kcal/mol (95% confidence interval). In the conditions of climatic zone II, the shelf life for the capsules stored at room temperature in light-resistant containers was equal to 678 days, while the capsules stored in the freezer retained the initial content of drug after 1289 days. From the results gathered in this study, the usefulness of RMWR for shelf life prediction in the presence of outliers is evident.

Calorimetry, Differential Scanning↗

Development and in vitro evaluation of buccoadhesive tablets using a new model substrate for bioadhesion measures: the eggshell membrane.

For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders. Metronidazole and benzydamine were used as model drugs. The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane). The use of the biological substrate seemed to supply more reliable data. All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems.

Administration, Oral↗

Study of the interaction of dithranol with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin in solution and in the solid state.

The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMBCyD) has been investigated in aqueous solution containing isoascorbic acid (0.2% w/v) as antioxidant and in the solid state. The interaction in the solid state was studied by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a dissolution-rate method. The extent of complexation between the two substances was poor, as indicated by the low value of the slope of the linear part of the solubility curve. A phase diagram was constructed by measuring the thermal behaviour of various re-solidified physical mixtures of dithranol and of TMBCyD previously subjected to heating until melting of the TMBCyD. The loss of dithranol, owing to sublimation and degradation caused by the thermal treatment used, was less than 10%. In keeping with XPD and IR data, the phase diagram indicated that a complex was formed containing 13.7% dithranol (molar ratio 1:1) which had a congruent melting point at 164 degrees C. The drug dissolution rate from the 1:1 complex was measurable, unlike that of the corresponding physical mixture, and was significantly increased when the complex was dispersed in the glassy matrix of TMBCyD, as it was in re-solidified mixtures containing 2-7% dithranol. The results show that the solubility of dithranol is increased significantly as a consequence of its interaction with TMBCyD, despite the low extent of complexation between the two substances.

Administration, Topical↗

Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.

The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.

Animals↗

Median-based robust regression methods in prediction of drug stability.

The classical isothermal approach for the prediction of drug stability exploits least squares regression. In this paper the use of some robust regression techniques to estimate the rate constants at different temperatures has been evaluated. These techniques are able to give accurate estimates when data are contaminated by the presence of outliers. The successful application of two robust methods, single median and repeated median, to real stability data from the literature is shown. Moreover, the authors have modified the original methods in order to apply them to data sets with replicates, typical of stability studies. The performances of the modified techniques have been investigated with simulated data sets containing outliers and with real data. They appear suitable for preliminary stability studies, especially on solid dosage forms. For a quick implementation of these methods, macroprograms written for a widely used spreadsheet are reported.

Computer Simulation↗

[Surgical implications of familial polyposis coli].

Surgical treatment of familial congenital polyposis (FCP) is deemed necessary as soon as diagnosis is obtained. The goals of any surgical procedure must be: removal of all adenomatous tissue, reliable prophylaxis of cancer, good quality of life. Among the different procedures (proctocolectomy with ileostomy, total colectomy with ileo-rectal anastomosis and postoperative endoscopic surveillance, ileo-rectal pull-through) we consider Soave ileo-endorectal pull-through as the treatment of choice. Between 1974 and 1993, 14 patients, 12 to 40 years old, underwent an ileo-endorectal pull-through (in 4 cases as secondary procedure after ileo-rectal anastomosis performed elsewhere). We had only two major complications, ileal perforation in one case and breakdown of ileo-rectal anastomosis in another case that needed permanent ileostomy. Continence is good in all patients (safe for the one with ileostomy) with an average of three bowel movements per day. Prophylaxis of cancer must be considered complete and permanent without need of surveillance.

Adenomatous Polyposis Coli↗

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↗

Reliability of short-term esophageal pH monitoring versus 24-hour study.

The child's discomfort and the cost of overnight hospitalization are clear disadvantages of prolonged esophageal pH monitoring. The aim of this study was to verify the reliability of short recording versus 24-h testing in a pediatric series with symptoms suggestive of gastroesophageal reflux (GER) disease. A 24-h pH monitoring performed on 160 patients with either gastroenterological symptoms (n = 61), respiratory problems (n = 58), or emesis plus respiratory problems (n = 41) was reviewed. Regardless of clinical presentation, children were also classified according to age: < 12 months (n = 39), 12-71 months (n = 81), and 72-168 months (n = 40). A diurnal fraction of 6 h, including at least 2 h after a meal, was compared to the entire 24-h recording in all groups with respect to the reflux index (RI) (sum of the periods with pH < 3.9 expressed as percentage of time) and reflux/h. RIs of > 10% were considered positive in patients < 1 year of age, whereas RIs of > 5% were considered positive in other age groups. Negative predictive values of the short recording RI ranged from 71 to 90%. Positive predictive values ranged from 50 to 83%; it was unreliable for children < 12 mos (50%) and patients with emesis plus respiratory problems (64%), who were, significantly, the youngest. Reflux/h values were not in agreement for the same groups. Absence of agreement was found if the absolute value of RI was considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗