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Biomedical subjects

A Pesce

Publications and source records attributed to A Pesce.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of indinavir and higher CD4+ T-cell count on viral load response after 6 months of highly active antiretroviral therapy.

This retrospective, unmasked chart review was undertaken to determine which HIV-infected patients receiving protease inhibitors (PIs) for the first time were most likely to experience a decrease in plasma viral load (PVL) and which factors were associated with a PVL < 500 copies/mL below the detectable limits after 6 months. A total of 308 patients aged > 15 years with a PVL > 500 copies/mL received therapy that included a PI in addition to other antiretroviral therapies (128 patients, saquinavir hard-gel capsule 600 mg TID; 107 patients, indinavir 800 mg TID; and 73 patients, ritonavir 600 mg BID). The choice of drug was at individual clinicians' discretion. Patients were followed for a median of 10 (range, 6 to 21) months. Of the 128 patients who received saquinavir, 45% were switched to another PI (33%, indinavir; 12%, ritonavir). Seventy percent of the 73 patients initially given ritonavir were switched (45%, indinavir; 25%, saquinavir), as were 23% of the 107 patients initially given indinavir (15%, saquinavir; 8%, ritonavir). A total of 34.1% (n = 105) of patients achieved a PVL < 500 copies/mL; in 51.6%, PVL decreased > 0.5 log copies/mL. In this subgroup, both treatment-naive patients and those who were receiving a new combination of antiretroviral therapy when they started PI treatment had a more pronounced decline in PVL (P < 0.001). After adjustment by logistic regression analysis for age, sex, mode of transmission, and duration of highly active antiretroviral therapy (HAART), CD4+ cell count and initial type of PI received were independently associated with PVL < 500 copies/mL. In the present study, the treatment success rate was low (34.1%) compared with rates observed in randomized, controlled trials. A higher CD4+ cell count and use of indinavir at the initiation of HAART are associated with a better viral load response.

Adult↗
PubMed1998

Structural, functional, and genetic characterization of Gastrophilus hemoglobin.

Hemoglobin of Gastrophilus intestinalis (Insecta, Diptera), was purified and characterized. At least two isoforms have been identified by isoelectrofocusing, mass spectrometry, and genomic Southern blotting. Functional studies show a high oxygen affinity due to a low ligand dissociation rate (koff = 2.4 s-1) and a relatively high autoxidation rate (t1/2 = 1.6/h). The globins were separated under denaturing conditions, and the sequence of Hb1 (Mr = 17,965 +/- 2) was determined at the protein and DNA level. The open reading frame codes for a polypeptide of 150 amino acids. Although the globin is distantly related to globins from other species, it has a low penalty score against globin templates. Freshly isolated hemoglobin was crystallized from polyethylene glycol. Crystals contain two hemoglobin molecules per asymmetric unit. Solution of the three-dimensional structure by molecular replacement could not be achieved, possibly due to the presence of three protein isoforms in the crystals. In order to determine its three-dimensional structure, G. intestinalis Hb1 was overexpressed in Escherichia coli, resulting in a fully functional molecule as confirmed by ligand binding affinity. The globin gene contains two introns at positions D7.0 and G7.0. The D7.0 intron is unprecedented, suggesting that globin gene evolution is much more complex than originally thought.

Amino Acid Sequence↗
PubMed1998

[Influence of HIV-related immunodeficiency on the histopathology of chronic hepatitis C].

OBJECTIVE: There is substantial evidence demonstrating the aggravating effect of human immunodeficiency virus (HIV) infection on the progression of chronic hepatitis C virus (HCV) infection. There is however, little data on the affect of certain factors which could affect liver pathology findings in patients with concomitant HIV infection such as the duration of HIV infection or T-cell subpopulation counts. We examined pathology findings in patients with concomitant HIV and HCV infections to determine the impact of immunodepression. PATIENTS AND METHODS: We reviewed liver pathology data collected in patients with concomitant HIV and HCV infections grouping patients according to severity of the liver pathology: group 1 = cirrhosis or active hepatitis; group 2 = minimally active hepatitis or histologically normal liver. Transparietal liver biopsies were obtained for the work-up of viral hepatitis or because of long-term unexplained fever or suspected lymphoma. Epidemiological and biological data were obtained from medical files. The duration of the liver disease was estimated from the date of exposure to risk of immunodepression as determined by the peripheral CD4+ and CD8+ counts. All pathology specimens were read by two pathologists who established the Knodell score for each patient. RESULTS: Fifty patients were included: 23 were classed in group 1 and 28 in group 2. The Knodell score was significantly different between the two groups, 11 +/- 4 and 4 +/- 3 respectively (p < 0.0001). Disease duration was similar for the two groups: mean 8 years. Mean CD4+ count was significantly higher in group 1: 312/mm3 versus 110/mm3 for group 2 (p = 0.0057); as was the mean CD8+ count (758/mm3 versus 360/mm3, p = 0.0013). For the entire study population, there was a significantly negative correlation (p < 0.05) between the Knodell score and the CD4+ count (r = 0.31) and for the CD8+ count (r = 0.41). CONCLUSION: HCV-related liver pathology in patients co-infected with HIV depends on the level of immunodepression. CD8+ counts are better correlated with pathology findings than with CD4+ counts.

Adult↗
PubMed1998

On the coordination and oxidation states of the active-site copper ion in prokaryotic Cu,Zn superoxide dismutases.

The active-site copper ion of the prokaryotic Cu,Zn superoxide dismutase from P. leiognathi is found to undergo reversible reduction upon irradiation of the protein solution with a high-intensity X-ray beam from a third-generation synchrotron source. The same phenomenon is observed for the enzyme crystals, whose diffraction pattern has been obtained from synchrotron sources. In this case the active-site copper-ligand coordination bond lengths and in particular the Cu-NE2(His61) distance are consistent with a copper ion in the reduced state. These results are in line with previous studies on the eukaryotic Cu,Zn superoxide dismutases and suggest the conservation of an identical catalytic mechanism in both the prokaryotic and eukaryotic enzymes.

Animals↗
PubMed1998

[Lung cancer in patients infected with human immunodeficiency virus. Clinical course and therapeutic implications].

OBJECTIVES: HIV infection is associated with increased frequency of non-Hodgkin's lymphoma and Kaposi sarcoma. Like other malignancies, lung cancer has been described in HIV-infected patients although no evidence of a statistical correlation has been reported. PATIENTS AND METHODS: We performed a retrospective analysis of 15 HIV-infected patients with lung cancer. The patients were relatively younger (mean age 45 years) than is commonly found in lung cancer cohorts. RESULTS: The 15 patients had mild immunodepression (240 CD4+/mm3) and were in advanced clinical stage at diagnosis. Mean overall survival was 6 months and no clinical or biological prognostic factors were found. Death was usually due to infection, suggesting a synergetic effect between HIV and chemotherapy-induced immunodepression. CONCLUSION: We propose early antiretroviral therapy in cases of chemotherapy-treated HIV patients, even when commonly accepted immunological and/or clinical criteria are absent.

Adult↗
PubMed1998

Cross-enzyme inhibition by gabexate mesylate: formulation and reactivity study.

Gabexate mesylate (GM; commercialized under the brand name FOY) is a nonantigenic synthetic inhibitor of plasmatic and pancreatic serine proteinases that is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. The inhibitory effect of GM on nitric oxide synthase as well as serine proteinases and swine kidney copper amine oxidase, all acting on cationic substrates, has been investigated. On the basis of the available X-ray crystal structures of the enzymes considered, the possible binding mode(s) of GM has(have) been analyzed. The enzyme cross-inhibition by GM suggests that the use of this drug should be under careful control. With the aim to improve the scarce plasma stability of GM, the positively charged drug has been complexed to the surface of preformed anionic liposomes. The liposome-complexed GM half-life increases about five-fold, indicating the protective effect of liposomes on GM degradation. Moreover, the GM complexation with liposomes does not alter its inhibitory activity on NOS-I and porcine pancreatic trypsin.

Drug Carriers↗
PubMed1997

Unique structural features of the monomeric Cu,Zn superoxide dismutase from Escherichia coli, revealed by X-ray crystallography.

The first three-dimensional structure of a functional monomeric Cu, Zn superoxide dismutase (from Escherichia coli, E_SOD) is reported at 2.0 A resolution (R-factor=16.8%). Compared to the homologous eukaryotic enzymes, E_SOD displays a perturbed antiparallel beta-barrel structure. The most striking structural features observed include extended amino acid insertions in the surface 1, 2-loop and S-S subloop, modification of the disulfide bridge connection, and loss of functional electrostatic residues, suggesting a modified control of substrate steering toward the catalytic center. The active site Cu2+ displays a distorted coordination sphere due to an unusually long bond to the metal-bridging residue His61. Inspection of the crystal packing does not show regions of extended contact indicative of a dimeric assembly. The molecular surface region involved in subunit dimerization in eukaryotic superoxide dismutases is structurally altered in E_SOD and displays a net polar nature.

Amino Acid Sequence↗
PubMed1997

Trends in the activity of macrolide and beta-lactam antibiotics and resistance development. Alexander Project Group.

The Alexander Project is an ongoing international multicenter study monitoring trends in the antimicrobial susceptibilities of community-acquired lower respiratory tract (LRT) pathogens. In 1995, 4011 isolates were collected. The incidence of beta-lactamase-positive Haemophilus influenzae was 28.4% in the United States and 15.4% in Europe, and the incidence of beta-lactamase-positive Moraxella catarrhalis has risen to > 90% in Europe and the United States. The incidence of penicillin-resistant Streptococcus pneumoniae is higher in Europe (24.9%) than the Unites States (12.3%). For the majority of centers, there is a marked association between penicillin and macrolide resistance in S. pneumoniae with erythromycin, azithromycin and clarithromycin exhibiting MIC90s of > or = 32 mg/l against penicillin-resistant strains. For Toulouse and Genoa, at least, the high levels of macrolide resistance may be attributable to high macrolide usage. Ceftriaxone and amoxycillin/clavulanate are the most potent agents for empirical therapy, with MIC90s of < or = 2 mg/l against all three principal pathogens. The majority of oral agents studied are active against > 90% H. influenzae and M. catarrhalis and > 80% S. pneumoniae on breakpoint criteria. However, on the basis of the time above MIC criteria for the beta-lactam and macrolide agents tested, only amoxycillin/clavulanate and the parenteral agent ceftriaxone can be recommended for empirical therapy of LRT infections caused by these pathogens.

Anti-Bacterial Agents↗
PubMed1996

Human alpha-thrombin inhibition by the active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester: a comparative kinetic and X-ray crystallographic study.

Kinetics for the hydrolysis of the chromogenic active site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp) catalyzed by bovine beta-trypsin, bovine alpha-thrombin, human alpha-thrombin, human Lys77-plasmin, human urinary kallikrein, the M(r) 33,000 and M(r) 54,000 species of human urokinase, as well as by porcine pancreatic beta-kallikrein-A and B have been obtained between pH 6.0 and 8.0, at 21.0 degrees C. Moreover, the three dimensional structure of the human alpha-thrombin-(hirugen).Dmc-azaLys acyl.enzyme complex has been analyzed and refined by X-ray crystallography at 2.0 A resolution (R-factor = 0.168). As observed for bovine beta-trypsin, the acylating inhibitor molecule is covalently bound to the Ser195 catalytic residue, filling the human alpha-thrombin S1 primary specificity subsite with its lysyl side-group. However, the carbonyl group of the scissile human alpha-thrombin.Dmc-azaLys acyl bond does not occupy properly the oxyanion binding hole. At variance from the bovine beta-trypsin.Dmc-azaLys acyl.enzyme structure, a second, not covalently bound, inhibitor molecule, partly shielded by the 60-insertion loop of human alpha-thrombin, is contacting the enzyme "aryl-binding site".

Animals↗
PubMed1996

Crystallization and preliminary X-ray analysis of the monomeric Cu,Zn superoxide dismutase from Escherichia coli.

The Cu,Zn superoxide dismutase (Cu,Zn SOD) originally isolated from the periplasmic space of Escherichia coli has been cloned and overexpressed in the E. coli strain BMH 71/18. The protein has been purified as a single component of 17,000 Da, corresponding to one subunit of the common dimeric eukaryotic Cu,Zn SODs. Large crystals of the purified protein have been grown in the presence of polyethylene glycol 4,000 at pH 8.5; the crystals belong to the monoclinic space group P2(1), with unit cell constants a = 33.1 A, b = 52.6 A, c = 43.3 A, beta = 111.4 degrees. One SOD subunit is contained in the asymmetric unit, yielding a Vm value of 2.1 A3/Da; the crystals diffract X-rays beyond 2.0 A resolution.

Amino Acid Sequence↗
PubMed1996

[Hemostasis anomalies and human immunodeficiency virus infection].

Because hemostasis disorder in HIV infected patients are frequent and have clinical effects, they have aroused the interest of internal medicine. Such anomalies are not yet clearly defined and include various parameters. Thrombocytopenia which is the most widespread and the best documented manifestation, whether of peripheral origin by immunological platelet destruction or of central origin by a shortage in platelet production, responds well to medical treatment, especially to zidovudine. The circulating anti-coagulants frequently observed in HIV infected patients, whether anti-phospholipid antibodies or anti-cardiolipines are mostly asymptomatic. Other coagulation disorders (affection of the inhibitory system or fibrinolysis) are rarely observed and generally have no clinical incidence. Apart from thrombocytopenias and thrombotic thrombocytopenic purpura the incidence of clinical signs (thrombotic or hemorrhagic accidents) in HIV infected patients is not higher than in an HIV-free population and respond to the same treatment.

Blood Coagulation Disorders↗
PubMed1996

Susceptibility of respiratory strains of Staphylococcus aureus to fifteen antibiotics: results of a collaborative surveillance study (1992-1993). The Alexander Project Collaborative Group.

As part of the Alexander Project during 1992 and 1993, 690 Staphylococcus aureus strains isolated from community-acquired lower respiratory tract infections by clinical microbiology centres located in Europe and the USA were analysed by a co-ordinating laboratory that determined minimal inhibitory concentrations of 15 antimicrobial agents using a standardised microdilution technique. The prevalence of penicillin-susceptible microorganisms in this collection of pathogens was significantly higher in Europe (21.2%) than it was in the USA (12.1%). Most isolates (72.5%), however, were strains that had acquired the ability to synthesise a beta-lactamase but which were sensitive to methicillin. The incidence of methicillin-resistance (9.1% overall) was highly variable depending on geographic location and year of isolation. Analysis of MIC50, MIC90, MIC range and modal MIC of the 15 antibiotics assayed disclosed no major differences between the data sets obtained during the 2-year survey. Except for methicillin-resistant S. aureus, the activity of all the beta-lactams tested, with the exclusion of penicillin, amoxycillin and cefixime (that were completely inactive), was satisfactory. The effect of beta-lactamase synthesis was inhibited by the combination of amoxycillin with clavulanate, and by cefuroxime and ceftriaxone. Cefaclor was slightly less effective. Erythromycin, clarithromycin and azithromycin showed identical cross-resistance rates (around 10%). Resistance to the macrolides was more frequent in the USA than in Europe and was the sole trait found to increase during the survey. Doxycycline, chloramphenicol, co-trimoxazole and the two fluoroquinolones tested (ofloxacin and ciprofloxacin) were remarkably effective (resistance lower than 1%). Only doxycycline and, to a lesser extent, co-trimoxazole were partially active against methicillin-resistant strains.

Anti-Bacterial Agents↗
PubMed1995

Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels.

Cefdinir is one of the few oral third generation cephalosporins that shows useful activity against nosocomial Gram-positive pathogens. For this reason the anti-staphylococcal potency of the new drug, alone or in combination with other drugs was further characterized. Against penicillin-resistant, oxacillin-susceptible Staphylococcus isolates, cefdinir demonstrated useful in-vitro activity. MIC90 values (in mg/L) were 0.25 for Staphylococcus aureus (30 strains), 0.06 for Staphylococcus epidermidis (24), 0.125 for Staphylococcus hominis (10), 0.5 for both Staphylococcus xylosus (15) and Staphylococcus capitis (11) and 4 for Staphylococcus saprophyticus (10), while Staphylococcus haemolyticus (12) was less susceptible with a MIC90 value of 32. Cefdinir activity was not adversely affected by several variables such as pH, inoculum size or the presence of serum or urine. The new cephem induced a PAE on all isolates studied: with S. aureus the extent of regrowth suppression ranged from 0.8 to 1 h, and with the other species from 0.5 (S. epidermidis) to 4.1 h (S. haemolyticus). Development of resistant strains was rare. At the highest level used (10 x MIC) mutants arose with a frequency of 6 x 10(-8) with S. haemolyticus and 2 x 10(-9) with S. epidermidis. The absence of a paradoxical effect of increasing concentrations of cefdinir on its bactericidal activity was confirmed up to a value of 500-fold the MICs. When cefdinir activity was assessed in association with ciprofloxacin, netilmicin, clarithromycin, fosfomycin, rifampicin, teicoplanin and vancomycin using the chequerboard and time-kill techniques, indifference predominated with all strains and in all combinations. Synergism was detected only in 11 out of a total of 175 tests performed by the chequerboard method. Using the time-kill technique cefdinir reacted synergically in 25 of 126 tests. Antagonism was never observed. S. aureus exposed to sub-inhibitory concentrations of cefdinir failed to grow on mannitol-salt agar and to produce haemolysins, but retained coagulase activity. Penicillinase production was also lost in about 17% of the survivors. Hydrophobicity changes were detected in all species tested with the exception of S. saprophyticus.

Anti-Bacterial Agents↗
PubMed1995

Susceptibility of Streptococcus pneumoniae strains isolated in Italy to penicillin and ten other antibiotics.

The susceptibility of 312 Streptococcus pneumoniae strains isolated during 1993 in Italy has been studied. Overall resistance to penicillin, erythromycin and co-trimoxazole was 5.5, 6 and 18% respectively. The penicillin resistant isolates (nine displaying low- and eight high-level resistance) were further tested against cefotaxime, ceftriaxone, cefepime, cefodizime, ceftazidime, imipenem, meropenem and rifampicin. The low-level penicillin resistant strains were inhibited by all these drugs. Among the eight high-level penicillin resistant pneumococci, four were resistant to one or more cephalosporins. Imipenem and rifampicin remained effective against all isolates. In comparison with other European Mediterranean countries, penicillin resistance is a minor threat at present in Italy.

Anti-Bacterial Agents↗
PubMed1995

[In vitro antibacterial activity of meropenem, a new carbapenem: European data].

Meropenem is a new DHP-I stable carbapenem with a very promising microbiological, pharmacokinetic and clinical profile. The antibacterial activity of this new agent has been assessed in vitro against 8741 aerobic and 854 anaerobic strains reflecting current incidence and epidemiology in Italy, France, Germany, Spain, Switzerland and United Kingdom. Comparator agents were imipenem, ceftriaxone, vancomycin, ciprofloxacin gentamicin and amikacin. The results of this study show that meropenem has a spectrum of antibacterial activity which embraces the vast majority of clinically significant Gram-positive and Gram-negative aerobes and anaerobes. This is due in part to excellent stability to chromosomal or plasmid mediated beta-lactamases including those which hydrolyse current cephalosporins. Data from the Italian study identified meropenem as the most potent agent against all Enterobacteriaceae, with the exception of Proteus species with were most susceptible to ciprofloxacin. Moreover, meropenem was 10 times more active than the other drugs against Haemophilus and Neisseria and was active against all the anaerobic strains. Conversely, staphylococci and enterococci were more susceptible to imipenem. Overall, these European data showed that meropenem was the most powerful drug against Enterobacteriaceae and it also was the most effective drug tested against the Italian and French Pseudomonas aeruginosa strains. Meropenem was less effective than imipenem or vancomycin against Enterococcus stains but had similar activity to imipen against anaerobes. Based on this microbiological profile, the use of meropenem is appropriate in the empirical treatment of serious infections, including those caused by multiple pathogens.

Anti-Bacterial Agents↗