Biomedical subjects
Publications and source records attributed to A Guarnieri.
The synthesis, diastereomeric separation, assignment to erythro- and threo-configuration by 1HNMR, and optical resolution of 3-(p-trifluoromethyl-phenyl)- and (p-thioanisyl)-2-biphenylyl-3-hydroxypropionic acids are described. The enantiomers were submitted to a preliminary assay to determine antiinflammatory activity.
As fluorenyl rigid analogues of previous biphenylyl alcanoic acids with very interesting antiinflammatory activity, the 3-(m-tolyl and m-anisyl)-3-hydroxy-3-(2-fluorenyl)-propionic acids have been prepared by means of the Reformatsky reaction and following hydrolysis of the obtained ethyl esters. The preliminary antiinflammatory assay showed that the structural modification inactivates the compounds.
Personal experience in the treatment of 60 cases of cancer of the large bowel with left hemicolon and rectal localisation is reported. 20 manual double layer anastomoses (group I), 20 single layer (group II) and with mechanical stapler (EEA stapler) (group III) were carried out in consecutive series. The results are reported in terms of early local and general complications: specifically 13 cases of anastomotic dehiscence of which 69.2% were observed in group I, 15.4% in group II and 15.4% in group III. Total postoperative mortality was 5%, average hospitalisation was as follows: 19 days group I, 14 days group II, 17 days group III. The value of single layer anastomoses, which is comparable to results with the stapler whose use is essential in cases of real manual technical difficulty, is stressed.
The optically active diastereometric erythro- and threo-3-thienyl-analogues 6a-d of 3-aryl-2-biphenylyl-3-hydroxy-propionic acids have been prepared. Some stereoisomers of 3-(3-thienyl)derivative 6b showed inhibition around 40% in the carrageenan-induced rat paw edema test.
Twenty-nine advanced breast cancer patients, considered unable to tolerate conventional cytotoxic chemotherapy, were treated with a weekly schedule of epirubicin (15 mg/m2 i.v.). All patients were fully evaluable. A remission of 34.5% was observed (2 CR; 8 PR), with a median duration of response of 9 months (range, 3-24 months). Side effects were mild, and on the whole the toxicity was negligible. This regimen showed a favorable therapeutic ratio in our series and seems active and well tolerated even in elderly and/or poor performance status patients.
Two cases of unresectable retroperitoneal malignant fibrous histiocytoma (MFH) achieving a prolonged complete remission by a combination of chemotherapy (adriamycin plus cyclophosphamide) and abdominal irradiation are reported. Although an optimal treatment policy for such cases has not been established, on the basis of data currently available, chemotherapy regimens including anthracyclines seem the most reliable therapeutic approach in unresectable and/or metastatic MFH.
A modified technique of sphincteroplasty with the use of a specially prepared cannula can exclude the pancreatic duct from the operative field by covering it with the posterior wall of the cannula. The use of the cannula can avoid some of the technical difficulties that may be encountered with operations involving the papilla of Vater. Our experience with 51 patients has been presented.
As a part of wider research project on chiral anti-inflammatory arylacanoic acids, the 3-(o- and m-)-(methyl and methoxy)-phenyl-2-biphenylyl-3-hydroxypropionic acids 3a-d were synthesized and resolved in their optically active erythro and threo stereomers, which were submitted to the carrageenan induced rat paw edema test. With respect to the p-isomers, only the threo p-methoxy substitution enhances the anti-inflammatory activity. Some conclusions on structure-activity relationship are discussed.
The authors synthesized the title compounds as analogues of previously prepared potential antiphlogistic agents. Starting from appropriate carbonyl compound and alpha-metallated phenylacetic acid the diastereomeric racemate pairs were obtained; they were separated, attributed to erythro/threo-configuration by NMR and finally resolved. The potassium salts of the enantiomers were tested for analgesic and antiinflammatory activity, as well as for acute toxicity. Their action in the carrageenan test has been found to be stereoselective, but relatively poor or of briefly lastening.
The optically active stereomers of some 3-(fluoro-, chloro-, bromophenyl)-2-biphenylyl-3-hydroxypropionic acids were prepared and tested for antiinflammatory activity. Surprisingly, the four bromo-isomers were the most active ones, particularly in the threo configuration.
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A brief analysis of the acid-base equilibria in pure organic solvents and/or in their aqueous mixtures is reported with the aim of determining dissociation constants of acidic drugs that are sparingly soluble in water. Among aqueous organic mixtures, aqueous Me2SO (80% w/w) presents properties particularly suitable for acid-base studies, and thermodynamically meaningful acidity constants can be obtained by a potentiometric technique, provided that the glass electrode is properly calibrated. Thermodynamic acidity constants of more than 100 acids have been potentiometrically determined at 25 degrees C in this mixed solvent, and the selected series of acids has been divided into four classes according to the nature of the acidic group (COOH, OH, SH) and the structure of the acid (aliphatic, aromatic, heterocyclic). A linear relationship between the experimental pKa values in water and pKa values in aqueous Me2SO (80% w/w) has been found within the single classes and a group of equations has been derived (the asterisk denotes pKa values in which infinite dilution in the mixed solvent is taken as a standard state). For the carboxylic acid class, the following "common" equation has been found: pKa(H2O) = -0.80 + 0.67 pKa (Me2SO; 80% w/w). As an application, pKa values in water are reported for a representative number of sparingly soluble acids. These values have been calculated by means of the "common" equation, using pKa values experimentally determined in aqueous Me2SO (80% w/w). The calculated values are in good agreement with those expected from the acid structures.
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A combined modality therapy (irradiation plus low-dose Adriamycin and Cyclophosphamide) was delivered to 41 patient affected by extensive bone diffusion from breast carcinoma. A 36% (15/41) objective response rate was obtained, no change was also detectable in 36%, while progressive disease in 28% (11/41). A subjective response was achieved in 37/41 patients, i.e. 90%. The Authors remark the difficulties in evaluating the objective response of metastatic bone to therapy and confirm the keystone role of radiation therapy in the palliative treatment of breast cancer skeletal diffusion.
As part of a wider research project on structure-activity relationships of chiral arylalkanoic acids, stereomeric aryl- biphenylyl-hydroxypropionic acids 3a-d have been prepared and their antiinflammatory activity evaluated. Diastereomeric racemic erythro- and threo-acids have been synthesized by reaction of alpha-lithiated biphenylyl-acetic acid salts with the appropriate aldehyde. They were separated, and after attribution of their relative configuration by 1H-NMR analysis, resolved. The antiinflammatory activities of the enantiomeric potassium salts were determined by the carrageenan test.