PubMed Health⌕ Search

Biomedical subjects

Chiara Casolari

Publications and source records attributed to Chiara Casolari.

6 recordsLinked to original sources

Antibacterial agent discovery using thymidylate synthase biolibrary screening.

Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H,3H-naphtho[1,2-c]furan-1-one (5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC=0.5-2.5 microg/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.

Animals↗

Case report: primary infection by human herpesvirus 6 variant a with the onset of myelitis.

A case of primary infection by human herpesvirus 6 (HHV-6) variant A in a 54-year-old woman, which occurred at the same time as the onset of encephalomyelitis, is reported. The correlation between the two events is discussed. It is speculated that, during the early phase of the infection, the HHV-6 spread to the central nervous system and triggered a pathogenic process that initially developed without symptoms. When the neurological disorders appeared, HHV-6 had already established a latent state: only the virus carried by infected blood cells was detected in the cerebrospinal fluid.

Cervical Vertebrae↗

A rare case of localized mucosal leishmaniasis due to Leishmania infantum in an immunocompetent Italian host.

The case of authoctonous isolated laryngeal leishmaniasis due to L. infantum in an italian immunocompetent host is reported. It is highlighed the need to consider mucosal leishmaniasis in the differential diagnosis of laryngeal tumors. Rapid nested-PCR technique and enzyme restriction analysis were useful for diagnosis and species identification directly from bioptic samples.

Animals↗

Interaction between saquinavir and antimycotic drugs on C. albicans and C. neoformans strains.

Candidiasis and cryptococcosis are the most common fungal diseases among patients suffering from HIV infection. In the present work we assess whether the combined therapies, proteinase inhibitors and antimycotic drugs, could modify the therapeutic effect of antimycotics. An in vitro study to evaluate the antifungal effect of saquinavir and antimycotic drugs combination on yeast growth was performed. Strains of C. albicans and C. neoformans from HIV-seropositive patients were used. Susceptibility tests of yeasts to amphotericin B, 5-fluorocytosine, miconazole and fluconazole, singly and in combination with saquinavir, were performed in two different media. In the combinations the antimycotic agents and saquinavir were tested at sub-inhibitory concentrations: 0.1-10 microg ml(-1) and 12.50 microg ml(-1), respectively. The fractionary inhibitory concentration (FIC) index was also calculated. The results show that the interaction between saquinavir and all the antimycotic drugs never resulted in antagonism. Fluconazole acts in more synergistic way, no matter which medium is used. The combined therapy miconazole/saquinavir results in synergism, especially in Sabouraud. The total absence of antagonism and the presence of synergism suggest that a combined therapy could be proposed in the treatment of HIV-seropositive patients to reduce side effects, thanks to the use of lower doses of antimycotic drugs.

Anti-Bacterial Agents↗

'In vitro' study of chemotherapeutic activity of sulphimidazole on some sensitive and metronidazole-resistant Trichomonas vaginalis strains.

Trichomonacidal treatment based on 5-nitroimidazoles is problematic both when Metronidazole, the drug of choice, is ineffective owing to the presence of resistant strains and when bacterial aerobic infections are present. Sulphimidazole (SIZ) possesses two distinct functional groups: one sulphonamide, the other 5-nitroimidazole. Since SIZ is active against aerobic and anaerobic bacteria, we set out to discover whether, in view of the presence of the 5-nitroimidazole group, it could also be effective against Trichomonas vaginalis. Twelve strains of T. vaginalis were cultured in Modified Thioglycate Medium in anaerobic conditions; subsequently, their growth was monitored in the presence of Metronidazole (MZ), SIZ, Sulphamethoxazole (SMX), Trimethoprim (TMP) and their associations. Eight strains proved to be sensitive to Metronidazole (minimum lethal concentration=0.5 microgml(-1)) and four to be resistant (minimum lethal concentration=40-60 microgml(-1)). SIZ was active against both the sensitive and the Metronidazole-resistant strains (minimum lethal concentrations=0.5-1 and 10 microgml(-1), respectively), thus showing that the chemotherapeutic activities of the two functional groups coexisting in SIZ remain unimpaired.

Animals↗