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S Serafini

Publications and source records attributed to S Serafini.

At least 37 records · Page 2Linked to original sources
PubMed1996

Engineering human interleukin-6 to obtain variants with strongly enhanced bioactivity.

Interleukin-6 (IL-6) triggers the formation of a high affinity receptor complex with the ligand binding subunit IL-6Ralpha and the signal transducing chain gp130. Since the intracytoplasmic region of the IL-6Ralpha does not contribute to signaling, soluble forms of the extracytoplasmic domain (sIL-6Ralpha), potentiate IL-6 bioactivity and induce a cytokine-responsive status in cells expressing gp130 only. This observation, together with the detection of high levels of circulating soluble human IL-6Ralpha (shIL-6Ralpha) in sera, suggests that the hIL-6-shIL-6Ralpha complex is an alternative form of the cytokine. Here we describe the generation of human IL-6 (hIL-6) variants with strongly enhanced shIL-6Ralpha binding activity and bioactivity. Homology modeling and site-directed mutagenesis of hIL-6 suggested that the binding interface for hIL-6Ralpha is constituted by the C-terminal portion of the D-helix and residues contained in the AB loop. Four libraries of hIL-6 mutants were generated by each time fully randomizing four different amino acids in the predicted AB loop. These libraries were displayed monovalently on filamentous phage surface and sorted separately for binding to immobilized shIL-6Ralpha. Mutants were selected which, when expressed as soluble proteins, showed a 10- to 40-fold improvement in shIL-6Ralpha binding; a further increase (up to 70-fold) was achieved by combining variants isolated from different libraries. Interestingly, high affinity hIL-6 variants show strongly enhanced bioactivity on cells expressing gp13O in the presence of shIL-6Ralpha at concentrations similar to those normally found in human sera.

Antigens, CD↗
PubMed1996

P-selectin and von Willebrand factor in bovine mesenteric lymphatics: an immunofluorescent study.

P-selectin (PADGEM, GMP-140, CD62) is an integral membrane protein specific to alpha granules of platelets and Weibel-Palade bodies of blood vascular endothelial cells. The presence in lymphatic endothelial cells of numerous Weibel-Palade bodies and their positivity to immunocytochemical reaction for von Willebrand factor have previously been characterized and described. Because von Willebrand factor and P-selectin codistribute in Weibel-Palade bodies of blood vascular endothelial cells we investigated the presence of both P-selectin and von Willebrand factor in lymphatic endothelium. Lymphatic vessels expressed positive reaction to immunocytochemical assay thereby demonstrating the presence of P-selectin in the endothelium. Distribution and intensity of the reaction were similar to those observed in bovine blood vascular endothelium.

Animals↗
PubMed1994

Elevated urinary excretion of endothelins in streptozotocin diabetic rats.

Endothelin-1,2 urinary excretion, has been determined in control and streptozotocin diabetic rats at different times after diabetes induction. Diabetic rats showed increased urinary excretion of endothelins as compared to control rats, already three days after diabetes induction and up to 20 weeks.

Animals↗
PubMed1994

[Surgical treatment of diverticular disease of the colon. Our experience in the last decade].

The authors analyse their personal experience of diverticular disease of the colon and, comparing it with that of other authors, draw attention to some fundamental data relating to the type of management chosen. Having underlined the high incidence of disease in relation changed living conditions, the authors point out that this pathology is becoming more frequent as a result of the increased average age and that subacute and acute clinical manifestations of the disease are also more common-place. Attention has often been drawn to the presence of non-evolved phlogistic symptoms which it is possible to treat medically thus enabling the operation to be postponed in some cases to a time which is more convenient for the patient, whereas in other cases it has resulted in the remission of symptoms. Surgical therapy need not be used in "silent" cases, but is obligatory in recurring or complicated forms. The authors also affirm that surgery is not burdened by particular postoperative complications which, if present, are linked essentially to peritonitis due to perforation or to other associated pathologies. The use of mechanical staplers has also restricted the number of derivative operations and those performed in several stages.

Adult↗
PubMed1993

Acetyl-L-carnitine effect on nerve conduction velocity in streptozotocin-diabetic rats.

Measurement of nerve conduction velocity (NCV) is a useful and sensitive tool for evaluating diabetes related neurological dysfunctions. The method used allows to monitor the parameter at different times in the same group of rats, so that it is possible to observe simultaneously the development of the damage in time, and to evaluate the improvement related to the treatment. The repeated oral treatment with acetyl-L-carnitine (ALC, CAS 5080-50-2) 250 mg/kg caused an improvement in NCV of the diabetic rats; the effect was higher when the treatment started early with respect to the diabetes induction. The improvement in NCV was constant in time and comparable from 2 to 6 weeks of the treatment. In conclusion, oral treatment with ALC was able to normalize the impairment of NCV in streptozotocin rats, the effect being constant in time from 2 to 6 weeks of treatment and up to 8 weeks after induction when administration started in early stage of diabetes (2-3 weeks after induction); however, at this time the NCV is already significantly decreased.

Acetylcarnitine↗
PubMed1992

Identification of the major degradation products of 4-methoxy-2-(3-phenyl-2-propynyl)phenol formed by exposure to air and light.

Exposure of 4-methoxy-2-(3-phenyl-2-propynyl)phenol (CO/1828) to air and light (accelerated by temperature) yields 1-(2-hydroxy-5- methoxyphenyl)-3-phenylpropynone as the major degradation product. With extraction, this product rapidly degrades to 5-methoxyaurone and 6-methoxyflavone. In addition, a mixture of dimeric and heterodimeric compounds that are not fully identified was observed. These results indicate the formation of a reactive ortho-quinone methide as an unstable intermediate. This hypothesis is supported by evidence that the aurone slowly isomerizes into the flavone in control samples. Identification of compounds was accomplished with mass spectrometry, nuclear magnetic resonance spectrometry, UV-high-performance liquid chromatography, and comparison with authentic samples.

Administration, Topical↗
PubMed1992

Metabolism of (-)-6(S)-hydroxy-4(R)-(1-hydroxy-1-methylethyl)-1- cyclohexene-1-ethanol in rat and dog.

1. The metabolism of a new mucoactive drug, chemically (-)-6(S)-hydroxy-4(R)- (1-hydroxy-1-methylethyl)-1-cyclohexene-1-ethanol (CO/1408), has been studied in rat and dog after a single oral dose; eight metabolites were identified. 2. Oxidation of the primary and secondary alcohol groups, hydroxylation in allylic positions and conjugation with glucuronic acid occurred in both species. Products of oxidation on the double bond have not been identified. 3. Using reversed-phase h.p.l.c. and beta-cyclodextrin in the eluent it was found that the glucuronide metabolites varied with species and with the biological fluid examined.

Animals↗
PubMed1989

[Stapler reconstruction after total gastrectomy contrasted with manual anastomosis].

A personal series (1985-1987) of 22 cases of total gastrectomy for cancer is analysed, a comparison being made between 11 cases treated with manual anastomosis and 11 reconstructed using a stapler. The advantages and disadvantages of the various techniques are examined and although no substantial difference is noted between the two reconstructive modalities, at least as regards morbidity and mortality, stress is laid on the unquestionable advantages of mechanical staplers. These are essentially speed of execution, suture perfection and excellent long-term results.

Esophagoplasty↗
PubMed1986

Biotransformation of trans-sobrerol. III. Metabolites of 8-hydroxycarvotanacetone in the rat.

The metabolism of 8-hydroxycarvotanacetone (HCA), a major metabolite of trans-sobrerol, was studied in female rats after a single oral dose. The metabolic pathways include hydroxylation, reduction to cis- and trans-sobrerol, glucuronylation and Michael addition with glutathione giving rise to mercapturic acids which then undergo reduction. Biological reduction appears to occur more readily for the alicyclic-saturated ketones (Michael adducts) than for the alpha, beta unsaturated ketones (HCA and hydroxylated metabolites). This is in agreement with the chemical reactivity of the compounds.

Animals↗
PubMed1985

Further studies of trans-sobrerol metabolism: rat, dog and human urine.

The urinary metabolites of d, l-trans-sobrerol were investigated after oral administration to rats, dogs and humans. Structural analysis of the urinary metabolites indicates that allylic hydroxylation, oxidation and glucuronylation are the common interspecies modes of trans-sobrerol biotransformation. Comparison of the findings of trans-sobrerol with previous investigations of cyclic monoterpenes shows similarities in their metabolism in vivo, including the resistance to oxidation of the cyclic trisubstituted double bond.

Adult↗
PubMed1984

[Pathogenicity of various species of Candida in an experimental murine system].

The systemic infection induced by Candida albicans, Candida krusei and Candida viswanathii was studied in an experimental murine system. Candida albicans is able to kill outbred CD1 mice within a few days and at a very low concentration; C. krusei is not pathogenic not even when inoculated at a higher concentration; C. viswanathii is able to kill animals only a a higher concentration. The different resistances do not seem to be under genic control, in as much as the different strains of mice used (hybrid CD2F1 and B6C3HF1, inbred Balb/c) show the same degree of resistance as the CD1 mice to the three species of Candida. The colony forming units (CFU) in the kidneys of CD1 mice inoculated intravenously with 10(5) cells of the three species of Candida, collected at various intervals showed a good correlation with the median survival times: a rapid moltiplication of the C. albicans is evident in the kidneys of the animals 24 hours after the inoculation, while the C. krusei and the C. viswanathii do not moltiply.

Animals↗
PubMed1984

[Pathogenicity of various species of Candida in mice immunodepressed with cyclophosphamide].

The resistance of outbred CD1 mice immunodepressed with cyclophosphamide to the systemic infection induced by the three species of Candida: C. albicans, C. krusei and C. viswanathii was studied. The administration of cyclophosphamide, three days before the challange of the Candida species causes a degree of immunodepression in relation to the dose of drug: decrease of leucocytes of the peripheral blood and decrease of the weight and of the cellularity of the spleens. The CD1 mice were immunodepressed with cyclophosphamide (150mg/Kg) three days before the intravenous challange with graded doses of cells of the three species of Candida. They are much more susceptible, compared to normal mice, to the systemic infection induced by C. albicans and also by C. viswanathii but in this case only when inoculated at the highest concentration. They are resistant, like normal mice, towards the C. krusei even in the case in which the degree of immunodepression of the animal is furtherly increased (with stronger doses of the drug). The number of colony forming units (CFU) from the kidneys of the immunodepressed mice with cyclophosphamide correlates the median survival times.

Animals↗
PubMed1983

The metabolism of trans-sobrerol in the rat.

The biotransformation of trans-sobrerol, a potent mucofluidifying agent, has been investigated in rat urine, bile and faeces after single p.o. and i.v. administration. The identification of the isolated metabolites was carried out by g.l.c.-mass spectrometry, n.m.r. and i.r. spectroscopy. The metabolic pathways involve oxidation of the allylic C (sp3) atoms, and mono-beta-glucuronylation of the secondary or tertiary alcoholic group. The mono-beta-glucuronides of sobrerol excreted in bile undergo enterohepatic circulation.

Administration, Oral↗