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Biomedical subjects

S Bonora

Publications and source records attributed to S Bonora.

At least 19 recordsLinked to original sources
PubMed2007

Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected with HIV/hepatitis C virus.

OBJECTIVES: To evaluate the early anti-HIV activity of pegylated interferon (PEG-IFN) alfa-2a and ribavirin in HIV/hepatitis C virus (HCV) co-infected patients not receiving antiretroviral therapy. PATIENTS AND METHODS: In 19 patients with baseline plasma HIV load (HIV-RNA) >1000 copies/mL treated with PEG-IFN alfa-2a and ribavirin, HIV-RNA and T-cell subsets were measured at baseline and 2, 4 and 12 weeks after initiation of anti-HCV therapy. RESULTS: We observed a significant HIV-RNA decrease (>1 log(10) copies/mL) through week 12 of anti-HCV treatment. The magnitude of HIV-RNA decline was associated with baseline HIV-RNA, CD4 count and PEG-IFN weight-adjusted dose. CONCLUSIONS: A significant early anti-HIV activity of PEG-IFN alfa-2a was observed. Such an effect warrants further clinical evaluation in the management of co-infected patients.

Adult↗
PubMed2006

Gratings in a conical diffraction mounting for an extreme-ultraviolet time-delay-compensated monochromator.

The conical diffraction mounting in which the direction of incident light belongs to a plane parallel to the direction of the grooves has the unique property of maintaining high diffraction efficiency, even in the extreme-ultraviolet (EUV) region. This property is useful for designing high-throughput time-delay-compensated monochromators for the spectral selection of ultrashort EUV pulses as the high-order harmonics generated by the interaction between an ultrashort laser pulse and a gas jet. The time compensation allows one to exploit the femtosecond scale duration of the harmonics both to have high intensity and to reach an unprecedented temporal resolution for pump and probe experiments. Because two gratings have to be used for time compensation, the high diffraction efficiency becomes an essential requirement, which can be fulfilled by the conical diffraction mounting. Measurements recently accomplished at the Bending Magnet for Emission Absorption and Reflectivity (BEAR) beam line (ELETTRA Synchrotron, Trieste, Italy) for three gratings in the 10-90 nm region are reported here that show a peak efficiency of as much as 0.7 in the first order. A model computing the electromagnetic propagation and the grating efficiency, implemented and tested with the experimental data, permits the study and design of rather complex systems operating in the conical mounting. Basic physical principles and mathematical aspects of the model are discussed here.

Journal Article↗
PubMed2006

Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).

A panel of leading Italian specialists in infectious diseases, virologists and immunologists met in Rome in 2005 to review critical data and discuss recommendations for each of the key questions in antiretroviral therapy today: When to start treatment? How to start? When to switch? What to switch to? Whether to stop or not to stop treatment, and how? The method of a nominal group meeting was used and recommendations were graded for their strength and quality using a system based on the one adopted by the Infectious Diseases Society of America. Main conclusions are summarized and critically discussed in this consensus statement, as well as some of the most recent data supporting these recommendations are provided.

Anti-HIV Agents↗
PubMed2006

Penetration of didanosine in semen of HIV-1-infected men.

OBJECTIVES: The disposition of antiretroviral agents into genital tissue and fluids is one of the factors implicated in the control of viral replication within the male genital tract and should be an objective of highly active antiretroviral therapy. We have investigated didanosine penetration in seminal plasma of 16 HIV-infected patients. PATIENTS AND METHODS: A total of 16 patients on didanosine (200 mg every 12 h or 400 mg once daily) participated in the pharmacokinetic study. After the didanosine morning dose, peripheral blood plasma and semen plasma were collected within the intervals 0-4, 4-8 and 8-12 h in the twice-daily regimen and 0-4, 4-12 and 12-24 h in the once-daily regimen. RESULTS: Within each sampling time interval didanosine concentrations in seminal plasma were higher than in blood. The interquartile range of concentrations in seminal plasma was 292-1217 ng/mL, compared with 50-150 ng/mL in blood plasma. Didanosine could be detected in 14 of the 16 semen samples analysed and in 8 of the 16 blood samples. CONCLUSIONS: We have demonstrated that didanosine penetrates into the seminal plasma in higher concentrations than in blood plasma.

Adult↗
PubMed2006

Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation.

The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C(trough)) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C(trough) of 5293 ng/mL and RTV C(trough) of 186 ng/mL. Forty-eight hours after initiation of HAART, C(trough) of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C(trough) of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C(trough) of CsA was around 600 ng/mL and C(trough) of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity.

Adult↗
PubMed2006

[Clinical pharmacology of nucleoside and nucleotide reverse transcriptase inhibitors].

Options for antiretroviral therapy in patients infected with HIV continue to expand as new drugs are integrated into treatment regimens. Nucleoside/nucleotide reverse transcriptase inhibitors (Nt/NRTIs) remain the backbone of highly active antiretroviral therapy (HAART). Although this is the oldest class of antiretrovirals, pharmacokinetic and pharmacodynamic properties have been less studied as compare to protease inhibotors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). The aim of this article is to review the current status of clinical pharmacology onf Nt/NRTIs, highlighting the issues with clinical interest. Therefore, implications of intracellular pharmacokinetics on dosing schedule, potential for drug-drug interaction and pharmacodynamics is discussed.

Anti-HIV Agents↗
PubMed2005

Nevirapine plasma exposure affects both durability of viral suppression and selection of nevirapine primary resistance mutations in a clinical setting.

The relationship between nevirapine plasma concentrations and the durability of both viral suppression (VS) and selection of nevirapine primary resistance mutations (PRMs) was evaluated. A nevirapine trough concentration (Ctrough) of >4,300 ng/ml was found to predict longer VS. Patients with nevirapine Ctrough s ranging from 3,100 to 4,300 ng/ml had higher probabilities of developing PRMs than those with nevirapine Ctrough s below and above this concentration interval.

Adult↗
PubMed2004

Clinical pharmacology of antiretroviral therapy.

Antiretroviral therapy represents by all means a new branch of anti-infective chemotherapy, and in order to describe the mode of action of antiretrovirals, a series of inferences from anti-bacterial chemotherapy were made. The currently available antiretroviral agents can be classified as time-dependent drugs, and therefore the key pharmacokinetic parameter adopted in their clinical-pharmacological assessment is the concentration at the end of the dosing interval (Ctrough). By focusing on this parameter, the application of Therapeutic Drug Monitoring (TDM) allows for the successful individual tailoring of the drug dosage in some clinical circumstances, such as treatment of drug-resistant infections, drug-drug interactions and side effects. While this procedure has now been sufficiently standardized for protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), no clinical applications are yet recognized for nucleoside/nucleotide reverse transcriptase inhibitors (N/NtRTIs) and fusion inhibitors. The main unfavourable peculiarity of HIV infection, such as the need for lifelong treatment, is one of the reasons why increasing attention is being paid to pharmacological aspects of antiretroviral therapy. Issues like treatment potency, maintenance over time of the immunovirological benefit and long-term side effects require intensive pharmacological investigation in order to obtain the information on which basing the most convenient strategy to be adopted for the therapeutical management of this condition.

Anti-HIV Agents↗
PubMed2003

Raman and IR study on copper binding of histamine.

A comparative Raman and FTIR study of histamine (Hm), a small hormone present in a wide selection of living organisms, and its complexes with copper(II) at different pH values was carried out. Both the Raman and IR spectra present some marker bands useful for the identification of the structure of the species predominating in the Cu(II) aqueous and alcoholic systems. In particular, Raman spectroscopy appears to be a useful tool for analyzing the tautomeric equilibrium of the imidazole ring of Hm, because some bands (i.e., nuC(4)dbond;C(5)) appear at different wavenumbers, depending on whether the imidazole moiety is in the N(tau)-H (tautomer I) or N(pi)-H (tautomer II) protonated form. In aqueous solutions the manner in which Hm binds to Cu(II) depends on the pH. At basic pH the most relevant species formed are a dimer, [Cu(2)L(2)H(-2)](2+), and a monomeric complex, [CuL](2-) or [CuL(2)](+). On the contrary, by decreasing the pH, Hm acts as a mono- or bidentate ligand, giving rise to two types of monomeric complexes, [CuLH](2-) and [CuL](2-) or [CuL(2)](+). With respect to the Cu(II)-Hm alcoholic system, both the aminic group and the imidazole ring (tautomer I) take part in the Cu(II) coordination, leading to the formation of the [CuL](2-) or [CuL(2)](+) monomeric complex.

Copper↗
PubMed2001

Identification of 54 mycobacterial species by PCR-restriction fragment length polymorphism analysis of the hsp65 gene.

A total of 121 reference and clinical strains of both slowly and rapidly growing mycobacteria belonging to 54 species were studied for restriction fragment length polymorphism of a PCR-amplified 439-bp segment of the gene encoding the 65-kDa heat shock protein. Restriction digests were separated by 10% polyacrylamide gel electrophoresis (PAGE). By including a size standard in each sample, the restriction fragment profile was calculated using a computer-aided comparison program. An algorithm describing these 54 species (including 22 species not previously described) is proposed. We found that this assay based on 10% PAGE provided a more precise estimate than that based on agarose gel electrophoresis of the real size of restriction fragments as deduced from the sequence analysis and allowed identification of mycobacteria whose PCR-restriction fragment length polymorphism analysis patterns were unequivocally identified by fragments shorter than 60 bp.

Algorithms↗
PubMed2000

Raman and IR spectroscopic investigation of zinc(II)-carnosine complexes.

The zinc(II)-L-carnosine system was investigated at different pH and metal/ligand ratios by Raman and IR spectroscopy. The Raman and IR spectra present some marker bands useful to identify the sites involved in metal chelation at a specific pH value. In particular, the neutral imidazole group gives rise to some Raman bands, such as the nu C(4)===C(5) band, that change in wave number, depending on whether the imidazole ring takes the tautomeric form I or II. Even if tautomer I is predominant in the free ligand, metal coordination can upset tautomeric preference and N(tau)- and N(pi)-ligated complexes can be identified. Although weak compared to those of aromatic residues, these Raman marker bands may be useful in analyzing metal-histidine interaction in peptides and proteins. On the basis of the vibrational results, conclusions can be drawn on the species existing in the system. Depending on the available nitrogen atoms, various complexes can be formed and the prevalent form of the species depends mainly on the pH. At basic pH carnosine gives rise to two different neutral complexes: a water-insoluble polymeric species, [ZnH(-1)L](0)(n), and a dimer, [Zn(2)H(-2)L(2)](0). The first is predominant and involves the tautomeric I form of the imidazole ring in metal chelation; the second contains tautomer II and increases its percentage by going from a 2 to 0.25 metal/ligand ratio. Conversely, the dimeric species dominates at pH 7, whereas two charged species, [ZnHL](2+) and [ZnL](+), are formed under slightly acidic conditions. In the [ZnHL](2+) complex the imidazole ring takes part in the Zn(II) coordination in the tautomeric I form, whereas in [ZnL](+) the ring is protonated and not bound to the Zn(II) ion. In addition, the curve fitting analysis of the 1700-1530 cm(-1) Raman region was helpful in indicating the predominant species at each pH.

Anti-Ulcer Agents↗
PubMed2000

Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid.

The concentrations of meropenem were measured in plasma, bronchoalveolar lavage (BAL) and epithelial lining fluid (ELF) 0.5-8 h after the administration of a single 1 g iv dose of meropenem. Thirty-five patients undergoing bronchoscopy were studied. Mean concentrations in plasma, BAL and ELF, respectively, measured by high performance liquid chromatography, were as follows: 0.5 h: 25. 96, 0.14, 5.04 mg/L; 1 h: 14.98, 0.09, 7.07 mg/L; 2 h: 12.01, 0.06, 3.86 mg/L; 4 h: 2.51, 0.04, 2.20 mg/L; 6 h: 0.57, 0, 0.59 mg/L; 8 h: 0.29, 0, 0 mg/L. Throughout the 2 h following infusion, concentrations in ELF exceeded the MIC90 for all nosocomial and community-acquired respiratory pathogens, including Pseudomonas aeruginosa (3.05 mg/L), Haemophilus influenzae (0.16 mg/L) and penicillin-resistant Streptococcus pneumoniae (0.86 mg/L). These results support the clinical efficacy of meropenem in the treatment of a wide range of pulmonary infections.

Adult↗