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Biomedical subjects

G Pratesi

Publications and source records attributed to G Pratesi.

At least 109 records · Page 6Linked to original sources
PubMed1988

Improved bone morphology by normalizing serum magnesium in chronically hemodialyzed patients.

The dialysate magnesium concentration (dMg) was reduced from 1 to 0.5 mEq/l in a group of patients on chronic hemodialysis (RDT). Serum parameters and bone biopsy findings were evaluated before and after a 1-year period on the lower dMg. All patients were receiving only calcium carbonate before and during the study period. Serum magnesium (sMg) decreased significantly and fell in the normal range with low dMg, whereas the other serum parameters did not change significantly except serum phosphorous which increased, still remaining within the normal limits. Furthermore, a significant reduction of the osteomalacia pattern (evaluated by osteoid volume, osteoid surface and osteoid thickness index) was observed in all patients after 1 year on dMg of 0.5 mEq/l, whereas there was no significant variation in bone resorption patterns (resorption surface and osteoclasts). Therefore, normal sMg is recommended in RDT patients, by arranging their dMg according to individual need, in the hypothesis that high bone Mg content, attributed to hypermagnesemia, could interfere with the mineralization process.

Adult↗
PubMed1987

Increased therapeutic efficacy and reduced toxicity of doxorubicin linked to pyran copolymer via the side chain of the drug.

Doxorubicin was covalently linked to divinyl ether-maleic anhydride copolymer (pyran copolymer) in its polycarboxylate form via the methylketone side chain through a nucleophilic substitution reaction of the 14-bromo derivative of the drug. The drug conjugated to the synthetic polyanionic polymer was tested for antitumor activity in a range of experimental murine tumor systems. When administered ip to mice bearing ip implanted tumors (P388 leukemia or macrophage tumor J774), the polymer-linked drug was superior to free doxorubicin and daunorubicin in increasing the life span of treated animals. Treatment with the conjugate also resulted in an improvement in survival time of mice bearing ascitic M50 tumor, although the effects of a single dose of free drug, in the range of maximum tolerated doses, were marginal. When given iv, the conjugate was more effective than free drug against systemic Gross leukemia. The therapeutic advantage of the polymer-linked doxorubicin over free drug was more marked when a multiple treatment schedule was used. Studies in vitro showed that the drug following covalent fixation to the polymer had only marginally decreased cytotoxicity against HeLa and P388 cells when compared with that of free anthracycline. This effect paralleled the lack of reduction in in vivo potency. Moreover, the covalent linkage of the drug to synthetic polymer reduced drug toxicity. This effect was more marked with the ip route of administration than with the iv route.

Animals↗
PubMed1986

Growth characteristics of human colorectal and non-small cell lung tumors xenografted into nude mice: possible correlation with prognosis.

Specimens from human colorectal tumors and from non-small-cell lung tumors obtained at surgery were subcutaneously implanted as xenografts in athymic Swiss mice of both sexes to investigate to what extent the properties of the original tumors were maintained. A successful take was obtained in 5 of 9 colorectal tumor and 6 of 11 non-small-cell lung tumor xenografts. Moreover, 44% and 45% of the respective tumors could be established as tumor lines. Neither metastases nor local tumor invasion was observed in tumor-bearing mice. Seven of 9 serially transplantable tumors had a short latency period (14-30.5 days) when first xenografted. No significant changes in tumor histopathology were noted after growth into nude mice. Tumor take was partially related to clinical stage and prognosis of patients. In fact, 8 of 12 specimens from N0 patients failed to grow, whereas 7 of 8 tumors from patients with nodal invasion and/or metastasis grew in nude mice. Moreover, for the group of patients whose tumor was "take - ", the one-year survival was 85%, compared to 40% for the "take + " group (p less than 0.05).

Adult↗
PubMed1986

The optimal use of PAN membrane in RDT.

In order to compare the efficiency of PAN (Biospal 3000S) for small molecules, Cr, BUN, UA and Pi clearances were determined during hemodiafiltration with both pre and postdilution fluid (PreHDF, PostHDF) and during biofiltration in 3 regular dialysis treatment patients. The highest clearances were obtained during PostHDF. Therefore, since the small molecules are still considered the most important toxins in chronic renal failure, these findings indicate that optimal use of PAN is with PostHDF, in which high diffusion and convection are combined, in order to obtain best dialytic efficiency.

Acrylic Resins↗
PubMed1985

Prevention of cyclophosphamide-induced urotoxicity by reduced glutathione and its effect on acute toxicity and antitumor activity of the alkylating agent.

The effect of reduced glutathione on acute lethal toxicity and urotoxicity induced by cyclophosphamide was studied on both mice and rats. The results of this investigation indicate that reduced glutathione is an effective protective agent against bladder damage from treatment with the alkylating agent. The timing of glutathione administration (IV) with respect to cyclophosphamide treatment influenced the uroprotective efficacy of the thiol compound. A schedule-dependent protective effect of glutathione against acute lethal toxicity of the antitumor drug was also observed. This partial protection was accompanied by a reduction in body weight loss following cyclophosphamide treatment. The therapeutic activity of cyclophosphamide on two experimental tumor systems (L1210 and Gross leukemia) was not impaired by combined treatment with glutathione, even at a relatively high dose of glutathione compared with cyclophosphamide.

Animals↗
PubMed1985

Poly-L-aspartic acid as a carrier for doxorubicin: a comparative in vivo study of free and polymer-bound drug.

The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.

Animals↗
PubMed1985

NMU-1, a new transplantable mouse lung tumor: biological and chemosensitivity properties in vivo.

NMU-1 is a lung adenocarcinoma induced by N-nitroso-N-methyl-urea in a BALB/c Lac Dp mouse and maintained in vivo by sc passages of tumor fragments. No spontaneous regressions have been observed. After sc implantation, NMU-1 metastasizes to the lung as shown by a bioassay. Seven established antitumoral drugs were used to evaluate the chemosensitivity of this neoplasm. Mitomycin, cyclophosphamide, and cisplatin statistically affected tumor growth, as evaluated by three end points (ie, tumor weight, increase in lifespan, and tumor growth delay). 5-FU, doxorubicin, and vincristine showed significant activity on two end points. Carmustine did not affect any end points.

Adenocarcinoma↗
PubMed1985

Effects of high CaCO3 supplements on serum calcium and phosphorus in patients on regular hemodialysis treatment.

The effect of high doses of CaCO3 on serum phosphorus and calcium (sPi,sCa) and the changes in serum aluminum (sAl) induced by Al(OH)3 interruption were investigated in patients on regular hemodialysis treatment. Some patients were administered Al(OH)3 and CaCO3, others only the former or the latter and others nothing. Al(OH)3 was stopped in all but one in whom it was only reduced, and CaCO3 was started or increased in all patients. A better control of sPi and serum Ca-Pi product was observed during high Ca supplementation, despite Al(OH)3 discontinuation, and was associated with a significant decrease of sAl. As expected, taking into account the dialysate Ca level of 4 mEq/l, a significant hypercalcemia occurred in some patients, especially in those who had a normal predialytic sPi without Al(OH)3 supplementation. Therefore, lowering the dialysate Ca concentration according to individual need and increasing interdialytic oral Ca supplements can be recommended with the dual purpose of keeping a positive Ca balance and correcting hyperphosphatemia.

Adult↗
PubMed1984

The antitumoral activity of 4'-deoxydoxorubicin compared to doxorubicin and 5-fluorouracil on methylazoxymethanol acetate-induced colon tumors in CF1 mice.

The suitability of carcinogen-induced colon tumors in mice for chemotherapy investigations and the potential antitumoral activity of a new anthracycline, 4'-deoxydoxorubicin (4' deoDX ) were evaluated. The latter was compared with 5-fluorouracil (5-FU) and doxorubicin (DX) either alone or in combination. CF1 mice were given 10 weekly subcutaneous injections of methylazoxymethyl acetate (MAM) and killed between 16 and 39 weeks after delivery of the first carcinogen treatment. The number and size of macroscopic tumors was observed; only 6% of mice showed no tumor development (19 of 327). Statistically significant reduction of tumor size occurred at a tolerated dose of 5-FU given as six intravenous injections (46 mg/kg) (P less than 0.05). With 4' deoDX a significant decrease in tumor number was observed using four weekly injections of 2.7 mg/kg (P less than 0.05) or six weekly injections of 5 mg/kg (P less than 0.05). Given in combination, 4' deoDX (3.3 mg/kg) and 5-FU (23 mg/kg) demonstrated a statistically significant reduction of the tumor number as compared with the untreated controls (P less than 0.025). Moreover, this reduction was greater than the observed response with any dose levels of the single compound thus demonstrating a potentiation of activity. These results indicate that MAM-induced colonic tumors are an appropriate model for the assessment of chemotherapeutic drugs. Moreover, 4' deoDX showed antitumoral activity comparable with 5-FU indicating this new anthracycline may be a useful candidate either alone or combined with 5-FU for clinical trials against colon cancer.

Animals↗
PubMed1983

Synthesis, biological and biochemical properties of new anthracyclines modified in the aminosugar moiety.

New 4'-C-methyl analogues of daunorubicin, synthesized by the coupling reaction of daunomycinone with 1-chloroderivatives of protected 4-C-methyldaunosamine analogues, were chemically transformed to the corresponding doxorubicin analogues. Their cytotoxic effect against HeLa cells, ability to bind to DNA, and in vivo toxicity and antitumor activity were compared with those of daunorubicin, doxorubicin, and their 4'-O-methyl analogues. The cytotoxic effect of the new anthracyclines could be correlated with their ability to bind to DNA and with their toxicity in experimental animals; however, the antitumor effectiveness did not seem to be related to these parameters. In general all the compounds retained a remarkable antitumor activity at their optimal doses. The most active compound against P388 leukemia was 4'-O-methyldoxorubicin, which was also more active than doxorubicin against L1210 leukemia.

Animals↗
PubMed1983

Antitumor activity in mice of 4'-deoxydoxorubicin in comparison with doxorubicin.

4'-Deoxydoxorubicin has been compared with doxorubicin as regards potency, antitumor activity and toxicity in tumored and non-tumored mice treated i.v. according to different schedules. 4'-Deoxydoxorubicin was 1.5-3 times more toxic and more potent than doxorubicin. At equitoxic doses, 4'-deoxydoxorubicin was: as active as doxorubicin against Gross leukemia, mammary carcinoma and MS-2 sarcoma; slightly less active than doxorubicin against B16 melanoma; more active than doxorubicin against colon 38 adenocarcinoma. The best schedule of administration of 4'-deoxydoxorubicin in mice was the weekly treatment. The strong effectiveness against colon 38 adenocarcinoma makes 4'-deoxydoxorubicin a particularly interesting new anthracycline derivative that deserves clinical trials.

Animals↗
PubMed1982

New anthracycline glycosides: 4-O-demethyl-11-deoxydoxorubicin and analogues from Streptomyces peucetius var. aureus.

The new anthracyclines 4-O-demethyl-11-deoxydoxorubicin, 4-O-demethyl-11-deoxydaunorubicin along with its 13-dihydro and 13-deoxo analogues are the main components of the anthracycline complex produced by cultures of Streptomyces peucetius var. aureus. They were isolated by solvent partition, separated by column chromatography and characterized by chemical and physical methods. Among these new anthracyclines, displaying antibacterial and cytotoxic activity "in vitro", 4-O-demethyl-11-deoxydoxorubicin and the corresponding daunorubicin analogue were also active against experimental tumors.

Animals↗