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P Legrand

Publications and source records attributed to P Legrand.

At least 73 records · Page 4Linked to original sources
PubMed1994

Stearoyl-CoA desaturase activity in primary culture of chicken hepatocytes. Influence of insulin, glucocorticoid, fatty acids and cordycepin.

1. Stearoyl-CoA desaturase (delta 9-desaturase) activity was measured in chicken primary hepatocytes, as a function of time in culture. 2. When using fasted donor animals, the desaturase activity was low at the beginning of culture and then increased steadily to a maximum value between 30 and 70 hr of culture. When hepatocyte cultures were prepared from fed animals, enzyme activity was high at the beginning of culture and maintained thereafter at similar values to those obtained in cultured hepatocytes from fasted animals after 30 hr of culture. 3. Insulin significantly enhanced enzyme activity when added to the culture medium at a 10(-9) M concentration, and a small stimulating effect was also observed with 10(-6) M dexamethasone. 4. Linoleic acid (0.5 mM) added to the culture medium as albuminic complex partly inhibited delta 9-desaturase activity. 5. Cordycepin (3' deoxyadenosine) decreased enzyme activity when present at a 3 micrograms/ml concentration in the culture medium. 6. Taken together, the induction of enzyme activity in culture, its impairment by cordycepin and response to insulin and linoleic acid strongly suggest that synthesis and translation of the delta 9-desaturase mRNA occur in chicken hepatocytes in primary culture, and that this cellular model may be a useful tool for further studies on delta 9-desaturase regulatory mechanisms.

Animals↗
PubMed1994

Can topical and nonabsorbable antimicrobials prevent cross-transmission of resistant strains in ICUs?

Topical antimicrobials may complement traditional infection control measures and hasten the control of an outbreak. When a suitable nonabsorbable antimicrobial regimen can be found, its use during outbreaks caused by Enterobacteriaceae colonizing the digestive tract appears especially attractive, whether the infection occurs via primary endogenous colonization or exogenous colonization. In the latter circumstance, however, topical antimicrobials are not a substitute for isolation precautions and careful handwashing, which remain insufficiently adhered to in ICUs. Topical antimicrobials should be used as part of a global strategy in which isolation precautions remain of primary importance. It is likely, but unproven by well-designed studies, that nasal decontamination of patient carriers during outbreaks due to methicillin-resistant Staphylococcus aureus can be useful to control the outbreak. In this instance, however, skin and wound disinfection appears as an essential complementary measure, and careful attention should be given to extranasal sites of colonization with MRSA, where resistance to the topical agent can emerge. Whatever the circumstances and setting, prolonged use of topical antimicrobials during protracted outbreaks is less effective and carries a major risk of resistance to the topical agent(s) used against the outbreak strains. In such circumstances, careful microbiologic monitoring of colonization is mandatory.

Administration, Topical↗
PubMed1994

Characterization of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotypic and genotypic typing methods.

During a 13-month period, 31 patients hospitalized primarily in two intensive care units (ICUs) were either colonized or infected by imipenem-resistant Acinetobacter baumannii. Typing of the isolates by three methods (antibiotyping, biotyping, and pulsed-field gel electrophoresis) revealed that two distinct strains were involved in the first 9 cases of the outbreak and that one of these strains, which had acquired a higher level of imipenem resistance as well as resistance to all aminoglycosides, accounted for 21 of 22 cases in the second part of the outbreak. ICU environmental contamination was recognized as an important reservoir of this epidemic strain. The outbreak ceased only after the ICUs were closed for complete cleaning and disinfection.

Acinetobacter↗
PubMed1993

Liposomal amphotericin B bases of therapeutic index increase.

Liposomes represent for amphotericin B (AmB) a promising delivery system that may reduce the important toxicity of the drug. Liposomal AmB has a higher therapeutic index than AmB alone and allows to use larger doses. The mechanism of reduced toxicity may be related to a better targeting ability, a protective effect, and a selective transfer of liposomes. Anyway the liposomes intercalated AmB tends to be uptaken by organs that belong to the reticuloendothelial system, where fungi, the target cells, are localized.

Amphotericin B↗
PubMed1992

Effects of aggregation and solvent on the toxicity of amphotericin B to human erythrocytes.

In aqueous suspensions of amphotericin B (AmB), a polyene antibiotic and antifungal agent, three forms of AmB coexist: monomers, water-soluble oligomers, and non-water-soluble aggregates. The toxicity of the water-soluble self-associated form of AmB compared with that of the non-water-soluble self-associated form was tested by measuring induction of K+ leakage from human erythrocytes, using different suspensions containing the antibiotic and phosphate-buffered saline. These suspensions were obtained from various stock solutions of the antibiotic in dimethyl formamide or dimethyl sulfoxide. Their circular dichroism spectra around 340 nm, indicative of the degree of AmB self-association, were strongly dependent on the concentration of organic solvent in the suspensions. The nonsoluble self-associated form was separated from the water-soluble form by centrifugation. The nonsoluble form was favored by a high concentration of AmB of the stock solution. The kinetics of AmB-induced K+ leakage from human erythrocytes also appeared to be strongly dependent on the AmB concentration of the stock solution being much weaker with concentrated stock solutions. It was concluded that the only form of AmB toxic to human erythrocytes is the water-soluble self-associated form (in contrast with fungal cells on which the monomeric form is also active). This result may be important in the design of new less toxic AmB derivatives and in the understanding of the mechanism of action of liposomal AmB.

Amphotericin B↗
PubMed1992

Hepatic delta 9 desaturation and plasma VLDL level in genetically lean and fat chickens.

Plasma VLDL (very low density lipoprotein) content and composition have been investigated in chickens from two lines selected for high or low abdominal fat/live weight ratio, and related to the activity of hepatic delta 9 desaturase. The amounts of plasma VLDL and VLDL-triglycerides (VLDL-TG) were significantly higher in the fat line than in the lean one. Moreover, the chemical composition of VLDL was different between lines, since the greater content of TG in VLDL in the fat birds was associated with lower proportion of all other components. The fatty acid composition of VLDL-TG exhibited differences between lines: palmitoleic acid, which results from hepatic delta 9 desaturation, was in higher proportions in the fat line, whereas linoleic acid was more abundant in the lean one. The activity of liver delta 9 desaturase was significantly higher in the fat animals. A positive correlation between plasma VLDL-TG concentration and hepatic delta 9 desaturase activity in the fat line animals strongly suggests that availability of monoenoic fatty acids is involved in the control of VLDL assembly and secretion. That latter process may explain some of the differences in plasma lipids and in adiposity of the two lines of chickens.

Adipose Tissue↗
PubMed1991

Stearyl-CoA desaturase activity in cultured rat hepatocytes.

Stearyl-CoA desaturase activity was measured as a function of time in culture in rat primary hepatocytes up to 90 h of culture. A decrease to half of the original activity occurred within 40 h of culture. Activity remained constant thereafter. Stearyl-CoA desaturase activity increased with insulin molarity in the medium and remained constant as dexamethasone or triiodothyronine concentrations were increased in the medium. When fructose replaced glucose in the medium, the desaturase activity was enhanced. No stimulating effect of cholesterol on the enzyme activity was observed and no inhibiting effect of griseofulvin was shown. Finally, starvation (48 h) of the donor rat followed by 60% sucrose refeeding (48 h) did not enhance delta 9-desaturase activity in the cultured hepatocytes compared with ad libitum nutritional status.

Animals↗
PubMed1991

One-sided action of amphotericin B on cholesterol-containing membranes is determined by its self-association in the medium.

The inducement of K+ permeability through membranes by the polyene antibiotic amphotericin B (AmB) has been analyzed as a measure of the antibiotic activity. Dose-response curves have been obtained with cholesterol- and ergosterol-containing egg yolk phosphatidylcholine large unilamellar vesicles (LUVs), human erythrocytes, and Saccharomyces cerevisiae cells. Conductance changes induced by AmB in sterol-containing planar bilayer membranes have also been studied. AmB self-association in aqueous buffer was determined by circular dichroism (CD) as a function of the antibiotic concentration. Electronic absorption and CD spectra of AmB were recorded in the presence of LUVs. For given AmB concentrations, the extent of permeability inducement is dependent on the lipid concentration. On the other hand, for cholesterol-containing LUVs or erythrocytes, a critical AmB concentration had to be reached before any permeability is observed. Independent of lipid concentration, this concentration was directly related to antibiotic self-association in the aqueous buffer. The same observation was made for erythrocytes and nystatin. The AmB absorption and CD spectra were totally different for ergosterol- and cholesterol-containing LUVs. Formation of single channels by one-sided addition of AmB could be observed only in ergosterol-containing membranes. These data lead us to propose that the permeability pathways induced by amphotericin B or nystatin, in ergosterol- and in cholesterol-containing membranes, are of different natures. In the latter case the antibiotics are only active, by single-sided addition, in the self-associated form. These findings offer important clues for the design of less toxic derivatives of AmB: they should have a low degree of self-association in water.

Absorption↗
PubMed1991

Diagnosis of nosocomial pneumonia in mechanically ventilated patients. Comparison of a plugged telescoping catheter with the protected specimen brush.

Protected samples of lower respiratory tract secretions processed by quantitative culture techniques are recommended to diagnose nosocomial bacterial pneumonia in intubated, mechanically ventilated patients. To evaluate the accuracy of a simple and inexpensive sampling device in this setting, we compared quantitative cultures of paired single-sheathed plugged telescoping catheter (PTC) and protected specimen brush (PSB) samples in 55 patients during 78 suspected episodes of nosocomial pneumonia. PTC and PSB samples were taken in randomized order, and patients were also randomized to have PTC samples taken "blindly" or via a fiberoptic bronchoscope. Fifteen PSB and 27 PTC samples were culture positive (greater than or equal to 10(3) cfu/ml). The two sampling procedures gave similar results in 58 (74%) episodes. A major discrepancy occurred in 20 episodes, including six false negatives of PSB in episodes of proved pneumonia, four possible false positives of PSB, and 10 possible false positives of PTC (three of which rapidly evolved towards overt pneumonia). The sensitivity and specificity of PTC were 100 and 82.2%, and those of PSB were 64.7 and 93.5%, respectively. Blinded or directed PTC samples had similar concordance with PSB samples taken via bronchoscopy. We conclude that PTC is at least as accurate as PSB in the bacteriologic diagnosis of nosocomial pneumonia in intubated patients, and that its use can result in substantial cost savings, especially when fiberoptic bronchoscopy is not otherwise indicated.

Bacterial Infections↗
PubMed1989

[Antibacterial effect of cefixime in the presence of the type of beta-lactamases produced by Enterobacteriaceae].

The susceptibility of isolates or Enterobacteriaceae to orally absorbed beta-lactams (amoxicillin, cephalexin, cefaclor, cefuroxime, and cefixime), was maximum for the iminomethoxy-aminothiazolyl-cephalosporin but variable according to bacterial species. For E. coli, P. mirabilis, Salmonella, Shigella, K. pneumoniae, K. oxytoca (group 1) MIC50 were congruent to 0.06 mg/l, and MIC90 congruent to 0.12 mg/l. Finally for C. freundii, E. aerogenes, E. cloacae, S. marcescens, M. morganii, MIC50 were higher, congruent to 1, and MIC90 16 mg/l. The slight increase reported between MIC50 ans MIC90 of cefixime against isolates belonging to group 1 was related to stability towards beta-lactamases (TEM, SHV) unlike groups 2 and 3, where the drug was less stable to chromosomal type 1 enzyme. The discovery of extended-spectrum beta-lactamases (ESB) (e.g. SHV-2, CTX-1 or TEM-3), mainly in K. pneumoniae, led to further investigations of the behavior of cefixime. The in vitro activity of cefixime (CFM), amoxicillin (AMX) combined or not with clavulanate (AMC, 2 mg/l), ticarcillin (TIC), cephalothin (CF), cefotaxime (CTX), ceftazidime (CAZ) and aztreonam (AZM) was determined by the agar dilution method (inoculum 10(5) cfu/ml) against clinical isolates: E. coli (26), K. pneumoniae (42), K. oxytoca (9), Salmonella (3) producing several types of beta-lactamases, chromosomal (cephalosoporinase, broad-spectrum) or plasmid-encoded (TEM-1, TEM-2, CTX-1, SHV-2, SHV-3, SHV-4). The geometric mean MIC values of AMX, AMC, TIC, CF, CTX, CAZ, AZM and CFM were as follows: greater than 480, 21.6, greater than 285, 45.6, 0.53, 1.12, 0.51, and 0.77 respectively. An MIC increase of oxyimino beta-lactams (CTX, CAZ, AZM, CFM) was observed against over-producing isolates of K. oxytoca and isolates producing ESB (CTX-1, SHV-2, SHV-3, SHV-4). The comparative behavior of cefixime was determined after transfer by conjugation to E. coli K-12. Sixty-one derivatives were constructed producing TEM-1, TEM-2, SHV-1, CTX-1, TEM-4, CAZ-2, SHV-2, SHV-3, SHV-4, the MICs of cefixime were stable against derivatives producing a penicillinase (TEM-1, TEM-2, SHV-1), but not against those producing an ESB. The MIC increases of undigestible beta-lactams ranged from 1 to 135 fold (CFM), 40 to 200 fold (CTX) 12 to 232 fold (CAZ), and 4 to 240 fold (AZM).

Anti-Bacterial Agents↗
PubMed1989

Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli. Study of an outbreak in an intensive care unit.

STUDY OBJECTIVE: To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates. DESIGN: A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3). SETTING: A medical intensive care unit of a tertiary care university hospital. PATIENTS: Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination). INTERVENTIONS: Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit. MEASUREMENTS AND MAIN RESULTS: Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3). CONCLUSIONS: Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.

Adult↗
PubMed1989

Detection of extended broad-spectrum beta-lactamases in Enterobacteriaceae in four French hospitals.

In 210 strains of Enterobacteriaceae which were isolated in four hospitals and which showed reduced susceptibility to cefotaxime, high synergy was demonstrated between amoxicillin (20 micrograms) + clavulanate (10 micrograms) and cefotaxime (30 micrograms) using a simple double-disk test. Isoelectric focusing on gel and specific iodometric detection using ceftriaxone identified four extended broad-spectrum beta-lactamases (isoelectric points 7.6, 6.3, 7.0 and 5.9) produced by the strains.

Amoxicillin↗
PubMed1988

Dissemination in five French hospitals of Klebsiella pneumoniae serotype K25 harbouring a new transferable enzymatic resistance to third generation cephalosporins and aztreonam.

A strain of Klebsiella pneumoniae K25 resistant to newer beta-lactam drugs was isolated in clusters in five hospitals in the Paris area. The MICs of ceftazidime and aztreonam (greater than or equal to 128 mg/l) were higher than that of cefotaxime (16 mg/l) for the strain but, when measured in the presence of clavulanic acid, they were less than or equal to 1 mg/l. The donor strains and derivatives produced a beta-lactamase with a pI of 7.75-7.8 and hydrolysing activity against a wide spectrum of beta-lactams similar to that of SHV-2 and SHV-3, but with significant hydrolysis of ceftazidime. This new enzyme could be designated SHV-4.

Aztreonam↗
PubMed1988

[Activity of 9 beta-lactam antibiotics combined with clavulanic acid or sulbactam against the strains of broad-spectrum beta-lactamase (CTX-1) producing Enterobacteriaceae isolated at the Henri Mondor Hospital].

Minimal inhibitory concentrations (MICs) of seven cephalosporins: cefotaxime (CTX), ceftriaxone (CRO), ceftazidime (CAZ), latamoxef (MOX), cefoxitin (FOX), cefotetan (CTT) and CM 40876 (CM), of aztreonam (ATM) and imipenem (IPM) were evaluated by agar dilution with and without 5 mg/l of clavulanic acid (AC) or sulbactam (SB) for 28 strains isolated in 1986 (15 K. pneumoniae, 3. K. oxytoca, 4 E. coli, 4 E. cloacae, 1 E. aerogenes and 1 C. freundii). Comparatively to MICs of sensitive strains and to those of cured variants, MICs of these strains were very increased for CTX, CRO, ATM (mode MIC: 1 mg/l), and CAZ (2); weakly increased for MOX and CTT (0.25), and identical for IMP (0.12-0.25), CM (0.06) and FOX (2-4), except for Enterobacter and Citrobacter (64). Association with AC or SB did not modify MICs of FOX, CM and IMP. For the other antibiotics, MICs were reduced by addition of AC: Klebsiella: 5 log2 for CTX and CRO, 4 for CAZ and ATM, 2 for MOX and CTT; E. coli: 4 log2 for CTX and ATM, 3 for CRO and CAZ, 1 for MOX and CTT; Enterobacter and Citrobacter 2 log2 for CTX, CRO, CAZ and ATM, 1 for MOX and CTT. With SB, decrease of MICs was two to for fold lesser than with AC. AC, and less efficiently SB, restored activity of CTX, CRO, CAZ and ATM on CTX-1 producing Enterobacteriaceae, particularly Klebsiella and E. coli. It was the same for MOX and CTT, weakly affected by this resistance. AC and SB had not effect on FOX, CM and IPM which remained active on these strains.

Anti-Bacterial Agents↗
PubMed1987

Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae.

Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated urinary tract infection, but failed in major infections at other sites. 1-5 mg/l of the beta-lactamase inhibitors clavulanic acid or sulbactam restored normal activity to cefotaxime against the multiresistant strains. Resistance to third-generation cephalosporins was mediated by a new broad-spectrum enzyme of isoelectric point 6.3. Resistance to beta-lactams and aminoglycosides was transferable to Escherichia coli. The emergence of transferable enzymatic resistance to newer beta-lactams in K pneumoniae strains indicates a major risk of spread of such resistance to otherwise sensitive strains.

Amikacin↗
PubMed1987

Lipid biosynthesis and deposition in genetically lean and fat chickens. Comparative in vivo studies with 14C acetate.

Following intravenous administration of 14C-acetate to genetically lean or fat chickens, the radioactivity in their liver, plasma, striated muscle and abdominal adipose tissue lipids and that in the breathed out CO2 were studied in function of time. As compared to the lean ones, the fat chickens showed a higher labelling of their triglyceride fatty acids in the plasma and adipose tissue, but not in the liver. Thus a higher rate of triglyceride secretion from the liver would be responsible for the higher abdominal fat weight in the fat line chickens.

Acetates↗
PubMed1987

Hepatic lipogenesis in genetically lean and fat chickens. In vitro studies.

1. Acetyl-coenzyme A carboxylase, malic enzyme, glucose 6-phosphate dehydrogenase and delta 9-desaturase activity was measured in liver extracts from 5- to 11-week-old genetically lean or fat chickens. 2. A significant difference between the two lines of chickens was shown as concerns desaturating activity only, which was 45% higher in the fat animals than in the lean ones. 3. This result is consistent with the hypothesis of a higher rate of lipoprotein processing and secretion in the liver of the fat line chickens.

Acetyl-CoA Carboxylase↗