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Biomedical subjects

G Candiani

Publications and source records attributed to G Candiani.

13 recordsLinked to original sources

Synthesis and antibacterial activity of a series of basic amides of teicoplanin and deglucoteicoplanin with polyamines.

Basic carboxamides of teicoplanin A2 (CTA) and its aglycon (TD) are prepared by condensation of the 63-carboxyl function of these antibiotics with linear or branched polyamines. The antimicrobial activities of some of the resulting compounds were better than those of the unmodified antibiotics. The presence of more than one basic group in the amidic chain enhanced the in vitro activity of some TD-amides against Gram-negative bacteria; two of these derivatives were also effective in vivo against Escherichia coli septicemia in the mouse. Among the CTA derivatives, the amide with spermine showed some unexpected in vitro activity against Gram-negatives. Both CTA- and TD-amides with polyamines are very soluble in water over a wide range of pH and are very hydrophilic.

Amides

Antimicrobial activity of MDL 62,873, a semisynthetic derivative of teicoplanin, in vitro and in experimental infections.

MDL 62,873 is an amide derivative of teicoplanin A2-2. Like those of natural glycopeptides, its antibacterial activity is mediated by inhibition of cell wall peptidoglycan synthesis. Against streptococci and enterococci, the in vitro activity of MDL 62,873 was similar to that of teicoplanin and greater than that of vancomycin. Against staphylococci, it has activity similar to that of vancomycin, and it was significantly more active than teicoplanin against coagulase-negative isolates. Like teicoplanin and vancomycin, MDL 62,873 had slow but significant bactericidal activity (99 to 99.9% killing in 24 h) against staphylococci at concentrations near the MIC. In murine septicemia studies with Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, the 50% effective doses were lower than those of vancomycin. In staphylococcal endocarditis in rats, MDL 62,873 at 20 mg/kg of body weight and vancomycin at 40 mg/kg, both doses given intravenously twice daily, had similar efficacies in reducing the heart bacterial load. These results probably reflect the longer half-life of MDL 62,873, which has a pharmacokinetic profile in rats similar to that of teicoplanin.

Animals

[Clinical and parasitological observations on a case of disseminated furuncular myiasis caused by Cordylobia rodhaini in a man in Ethiopia].

A severe case of myiasis is reported in an Italian technician working in a forest yard in Illubabor (Ethiopia). The patient returned to Italy with fever, malaise and scattered skin lesions: these were papular at first, and later developed into furuncle-like, intensely burning boils which spread all over the body. Neutrophilic leukocytosis was present associated with increased IgA. From the lesions, 150 larvae were recovered and identified as Cordylobia rodhaini Gedoelst (Diptera, Calliphoridae), a myiasis agent adapted to various thin-skinned mammals in African forests, rarely observed in man. This is the first case recorded in Ethiopia and represents the most massive invasion by Cordylobia spp. published so far. The 3rd stage larva is described with some morphological details not reported by previous authors.

Animals

Definition of the transcription initiation site of human plasminogen gene in liver and non hepatic cell lines.

We have mapped the cap site of the human plasminogen mRNA by primer extension and PCR techniques and found that it is located at position -161 relative to the first ATG, 97 bases upstream to the 5' end of the previously isolated cDNA clone. Seven human hepatic and non hepatic cell lines and fresh liver cells were tested for human plasminogen mRNA expression: the liver and the liver derived HepG2 cell line represent the major site of plasminogen RNA synthesis while the other cell lines (Hep3B, HeLa, IMR, 293 CaCo and SW626) show much lower levels.

Base Sequence

Lecithin cholesterol acyl transferase deficiency: molecular analysis of a mutated allele.

The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.

Alleles

Activity of teicoplanin in localized experimental infections in rats.

We tested the ability of teicoplanin alone and in combination with rifampicin or gentamicin to cure experimental endocarditis and granuloma pouch infections in rats caused by Streptococcus faecalis, Str. sanguis, methicillin-sensitive and -resistant Staphylococcus aureus. Vancomycin and ampicillin were also tested. Teicoplanin was more active than vancomycin and ampicillin. Combinations of teicoplanin with rifampicin or gentamicin were significantly more effective than single drug therapy. These results suggest that teicoplanin could be an interesting alternative to vancomycin in the treatment of serious streptococcal and staphylococcal infections in man.

Animals

[Human pulmonary dirofilariasis. A third case in Italy].

A new case of Human Pulmonary Dirofilariasis, the third in Italy, is described. It occurred in August 1990 in a 66 years old man, living in San Donà di Piave (province of Venice). The pulmonary infarctual lesion caused few symptoms and was discovered by chance during a chest X-ray examination as a coin lesion and suspected to be of a neoplastic origin. The histological findings allowed the exact diagnosis, identifying the causal agent as Dirofilaria probably repens, a nematode common parasite of dogs in the Old World and recognised agent of over 90 human cases of Subcutaneous Dirofilariasis reported in Italy. The parasite was an immature male in advanced regressive conditions. It was inside the lumen of a small artery, surrounded by necrotic-phlogistic tissue with granulomatous giantcellular aspects of the foreign body type. Some questions are raised by the authors in relation to the presence of human cases by D. repens and not by D. immitis (dog heartworm) in areas of Italy where this last species is much more prevalent than the former in canine populations; to the fact that the 3 Italian pulmonary cases (which are the only ones reported in Europe) happened in the same restricted geographic area (Veneto and Emilia-Romagna regions); and finally to the fact that all the 3 cases occurred in elderly people.

Aged