The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Andrew L Chan - One of the best experts on this subject based on the ideXlab platform.
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the diagnosis and treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease and chronic bronchitis
Journal of the American Geriatrics Society, 2010Co-Authors: Timothy E Albertson, Samuel Louie, Andrew L ChanAbstract:The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, Pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.
Pm. Tulkens - One of the best experts on this subject based on the ideXlab platform.
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Accumulation and Oriented Transport of Ampicillin in Caco-2 Cells
2004Co-Authors: From Its Pivaloyloxymethylester Prodrug, Marie-paule Mingeot-leclercq, Hugues Chanteux, Françoise Van Bambeke, Pm. TulkensAbstract:Pivampicillin (PIVA), an acyloxymethylester of ampicillin, is thought to enhance the oral bioavailability of ampicillin because of its greater lipophilicity compared to that of ampicillin. The fate of PIVA in intestinal cells and the exact location of its conversion into ampicillin have, however, never been unambiguously established. Polarized Caco-2 cells have been used to examine the handling of PIVA and the release of ampicillin from PIVA by the intestinal epithelium. Experiments were limited to 3 h. Cells incubated with PIVA (apical pole) showed a fast accumulation of ampicillin and transport toward the basolateral medium, whereas PIVA itself was only poorly accumulated and transported. Cells incubated with free ampicillin accumulated and transported only minimal amounts of this drug. Release of ampicillin from cells incubated with PIVA was unaffected by PEPT1 and OCTN2 inhibitors but was sharply decreased after ATP depletion or addition of bis(4-nitrophenyl)-phosphate (BNPP; an esterase inhibitor). PIVA incubated with Caco-2 lysates released free ampicillin, and this release was inhibited by BNPP. Efflux studies showed that the ampicillin that accumulated in cells after incubation with PIVA was preferentially transported out of the cells through the basolateral pole. This efflux was decreased by multidrug resistance-associated protein (MRP) inhibitors (probenecid, MK-571) and by ATP depletion. A phthalimidomethylester of ampicillin that resists cellular esterases failed to cause any significant release (cell lysate) or transport (polarized Caco-2 cells) of ampicillin. These results show that when PIVA i
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Cell Handling, Membrane-Binding Properties, And Membrane-Penetration Modeling Approaches Of Pivampicillin And Phthalimidomethylampicillin, Two Basic Esters Of Ampicillin, In Comparison With Chloroquine And Azithromycin
2003Co-Authors: Chanteux H., Mingeot-leclercq Marie-paule, Brasseur Robert, Sonveaux E., Pm. TulkensAbstract:PURPOSE: The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin). METHODS: Cell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918). Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers. Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations. RESULTS: PIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4 degrees C as well as at 37 degrees C, saturation of uptake (apparent Kd 40 microM), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (Kd approx. 40 microM); and sharp increase in calculated free energy when forced in the hydrophobic domain. CONCLUSIONS: Although they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents. We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts.Peer reviewe
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DOI: 10.1093/jac/dkg431
2003Co-Authors: Hugues Chanteux, Marie-paule Mingeot-leclercq, E. Sonveaux, Françoise Van Bambeke, Pm. TulkensAbstract:Intracellular accumulation and activity of ampicillin used as free drug and as its phthalimidomethyl or pivaloyloxymethyl ester (Pivampicillin) against Listeria monocytogenes in J774 macrophage
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Cell Handling, Membrane-Binding Properties, and Membrane-Penetration Modeling Approaches of Pivampicillin and Phthalimidomethylampicillin, Two Basic Esters of Ampicillin, in Comparison with Chloroquine
2002Co-Authors: Hugues Chanteux, Marie-paule Mingeot-leclercq, Isabelle Paternotte, Robert Brasseur, E. Sonveaux, Pm. TulkensAbstract:Purpose. The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin). Methods. Cell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918). Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers. Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations. Results. PIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4°C as well as at 37°C, saturation of uptake (apparent K d 40 �M), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (K d approx. 40 �M); and sharp increase in calculated free energy when forced in the hydrophobic domain. Conclusions. Although they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents. We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts. KEY WORDS: Pivampicillin; phthalimidomethylampicillin; azithromycin; chloroquine; membrane binding
Timothy E Albertson - One of the best experts on this subject based on the ideXlab platform.
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the diagnosis and treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease and chronic bronchitis
Journal of the American Geriatrics Society, 2010Co-Authors: Timothy E Albertson, Samuel Louie, Andrew L ChanAbstract:The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, Pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.
Samuel Louie - One of the best experts on this subject based on the ideXlab platform.
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the diagnosis and treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease and chronic bronchitis
Journal of the American Geriatrics Society, 2010Co-Authors: Timothy E Albertson, Samuel Louie, Andrew L ChanAbstract:The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components--emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more-common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less-common nonenteric, gram-negative organisms including Pseudomonas aeruginosa, gram-positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk-stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk-stratification approach for elderly patients, first-line antibiotics (e.g., amoxicillin, ampicillin, Pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more-limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second-line antibiotics (e.g., amoxicillin/clavulanic acid, second- or third-generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.
Sb Lee - One of the best experts on this subject based on the ideXlab platform.
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Effect of organic solvents on penicillin acylase-catalyzed reactions: Interaction of organic solvents with enzymes
'Elsevier BV', 2019Co-Authors: Mg Kim, Sb LeeAbstract:The effects of various organic solvents on penicillin acylase-catalyzed synthesis of p-lactam antibiotics (Pivampicillin and ampicillin) have been investigated in water-solvent mixtures. The rates of penicillin acylase-catalyzed reactions were found to be significantly reduced by the presence of a small amount of organic solvent. In particular, the rate of enzyme catalysis was extremely low in the presence of ring-structured solvents and acids while enzyme activities were fully restored after removing the solvents. This indicates that interactions between the solvents and the enzyme are specific and reversible. To correlate the inhibitory effects of organic solvents with solvent properties the influence of solvent hydrophobicities and solvent activity on the rate of Pivampicillin synthesis was examined. The reaction rate was found to decrease with increasing solvent hydrophobicities, and a better correlation was observed between the reaction rate and solvent activity. The effects of ionic strength on the synthesis of Pivampicillin and ampicillin were also examined. The ionic strength dependence indicates that electrostatic interactions are involved in the binding of ionic compounds to the enzyme. On the basis of the active site structure of penicillin acylase, a possible mechanism for molecular interactions between the enzyme and organic solvents is suggested.X1146sciescopu
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Penicillin acylase-catalyzed synthesis of Pivampicillin: Effect of reaction variables and organic cosolvents
'Elsevier BV', 2019Co-Authors: Mg Kim, Sb LeeAbstract:Enzymatic synthesis of Pivampicillin (PVM) from D-alpha-phenylglycine methyl ester (PGM) and pivaloyloxymethyl 6-aminopenicillanic acid (POM-6-APA) was investigated using an immobilized Escherichia coli penicillin acylase. The effects of reaction variables such as enzyme concentration, pH, temperature, and molar ratio of the substrates on PVM synthesis were investigated, The time-course profiles of the PVM synthesis reaction followed a typical pattern of the kinetically-controlled synthesis of beta-lactam antibiotics: the concentration of PVM reached a maximum and then decreased gradually. By lowering the reaction temperature, the maximum yield was enhanced significantly. This was mainly attributed to the suppressed hydrolysis of PVM and PGM at low temperatures. A higher yield of PVM was also attained with increasing the molar ratio of PGM to POM-6-APA. When the molar ratio of PGM to POM-6-APA was 10, the maximum yield of 61.8% was obtained at 4 degrees C. The addition of organic cosolvents, on the other hand, showed no improvement in the PVM synthesis yields due to inhibitory effect of the solvent; both synthetic and hydrolytic activities of penicillin acylase were reduced by organic solvents. The degree of inhibition was found to be more profound in the presence of less polar solvents.X1132sciescopu
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Penicillin acylase-catalyzed synthesis of beta-lactam antibiotics in water-methanol mixtures: Effect of cosolvent content and chemical nature of substrate on reaction rates and yields
'Elsevier BV', 2019Co-Authors: Mg Kim, Sb LeeAbstract:The synthesis of four beta-lactam antibiotics (penicillin G, pivaloyloxymethyl ester of penicillin G, ampicillin and Pivampicillin) catalyzed by Escherichia coli penicillin acylase has been investigated in water-methanol mixtures, The enzyme reactions were either thermodynamically or kinetically controlled at the same conditions using phenylacetic acid and D-alpha-phenylglycine methyl ester as acyl donors and 6-aminopenicillanic acid and pivaloyloxymethyl 6-aminopenicillanic acid as acyl accepters. It has been found that the influences of the cosolvent content on the reaction rates and synthetic yields are significantly different depending on the substrates used in the experiments. On the other hand, within certain ranges of the methanol content (up to ca. 40% (v/v)) the residual activities of the enzymes in water-methanol mixtures were only slightly lower than those in aqueous media. To analyze the factors that determine the reaction rate in water-cosolvent mixtures, the effect of methanol on the apparent pK values of the substrates has been investigated, and a mathematical model has been developed on the basis of the assumption that the enzyme binds non-ionized substrates. Model simulation results indicate that the solvent effect on reaction rates is mainly attributed to the kinetic effects of changes in apparent pK values.X1150sciescopu