Human prolactin-producing pituitary adenomas in three-dimensional culture.
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Adenoma↗
Biomedical subjects
J Duval
Publications and source records attributed to J Duval.
Effects of combinations of beta-lactams, daptomycin, gentamicin, and glycopeptides against glycopeptide-resistant enterococci.
Activities of combinations of beta-lactams, daptomycin, gentamicin, teicoplanin, and vancomycin against 11 clinical isolates of Enterococcus faecium highly resistant to glycopeptides, three plasmid-cured derivatives, eight E. faecalis and E. faecium transconjugants, and two susceptible recipient strains were tested. A marked synergy between penicillins or imipenem and glycopeptides against the glycopeptide-resistant strains but not against the glycopeptide-susceptible strains was observed by the double-disk agar diffusion assay. The synergy of combinations of amoxicillin, imipenem, penicillin G, or piperacillin with vancomycin or teicoplanin against resistant strains was confirmed by the checkerboard technique. The fractional inhibitory concentration indexes were generally below 0.25, except for one strain of E. faecium resistant to high levels of penicillin G. However, the combinations were not bactericidal as tested by time-killing experiments, and high concentrations (64 micrograms/ml) of amoxicillin, penicillin G, or piperacillin combined with 8 micrograms of vancomycin or teicoplanin per ml tended to be antagonistic. Addition of 4 micrograms of gentamicin per ml to these combinations enhanced their bactericidal effect, but they occasionally remained slightly less effective than beta-lactams associated with gentamicin. The combination of 10 micrograms of daptomycin per ml with gentamicin was bactericidal after 6 h against 11 glycopeptide-resistant strains.
Anti-Bacterial Agents↗
Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium.
Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.
Animals↗
Differential expression of secretogranin II and chromogranin A genes in the female rat pituitary through sexual maturation and estrous cycle.
Secretogranin II (SgII) is a protein of pituitary secretory granules released by LHRH-stimulated gonadotrope cells. Estrogens and androgens are modulators of SgII release. Experiments were performed to determine the regulation of expression of the SgII gene in the female rat pituitary, during sexual maturation and according to the estrous cycle. Age- and cycle-related changes in SgII mRNA content were estimated through cytoplasmic slot blot; SgII content was determined by western blotting; maturation of the protein was controlled through [35S]sulfate labeling. Variations in chromogranin A (CgA), another protein of secretory granules, were analyzed in the same experimental conditions to assess the specificity of SgII regulation. The pituitary SgII concentration increased between days 7 and 21 (2.2-fold) and then declined to the initial 7-day-old value. Simultaneously, the CgA concentration went through a maximum between days 14 and 21 and then strongly dropped to barely detectable levels in the adult pituitary. The SgII mRNA concentration followed roughly the same pattern as the protein. Moreover, the sulfation level remained constant between days 14 and 60. These results demonstrated a regulatory mechanism operating, during sexual maturation, on the SgII gene and not on the protein processing or on storage/release steps. In the 4-day cycling females, the pituitary SgII mRNA and protein contents were the lowest during estrus. They then increased to their highest values in diestrus II. Moreover, the sulfation level of SgII was significantly higher during estrus than during any other stage. Due to its low content level, variations in pituitary CgA could not be demonstrated during the cycle.
Aging↗
Estradiol negatively regulates secretogranin II and chromogranin A messenger ribonucleic acid levels in the female rat pituitary but not in the adrenal.
Estradiol (E2) effects on the pituitary and adrenal secretogranin II (SgII) and chromogranin A (CgA) proteins and mRNA levels were analyzed in the adult female rat. Animals were ovariectomized or sham-operated for 2 weeks and then daily injected with various doses of 17 beta-E2 (from 5-100 micrograms) for the following week. SgII and CgA levels were determined by Western blot analysis using two specific antisera. Messenger RNA (mRNA) levels were measured by RNA slot blot analysis using specific cDNA probes. Simultaneously, pituitary LH content and gonadotropin subunit (LH beta, FSH beta, alpha) mRNAs were quantified. Ovariectomy promoted a significant increase in pituitary SgII and CgA proteins (2-fold vs. sham-operated animals, P less than 0.01) and a concomitant rise in their mRNA levels (2.5-fold and 4.5-fold for SgII mRNA and CgA mRNA, respectively, P less than 0.01). In the same animals LH beta, FSH beta, and alpha-subunit mRNA levels increased by 20-, 12-, and 6-fold, respectively. Estrogen replacement resulted in a parallel decrease of CgA and LH beta mRNA to the control values, starting from the lowest steroid dose (5 micrograms). The SgII mRNA decrease was initiated only with a higher concentration of E2 (10 micrograms), as was that of alpha-subunit mRNA; yet, the SgII mRNA level remained significantly higher than in the control pituitary, even with the highest steroid dose (P less than 0.05) at variance with the alpha-mRNA level. Concerning protein concentration, the postcastration increase in CgA was fully reverted with 10 micrograms E2 while that of SgII remained unaffected, as was the pituitary LH content. In the adrenal gland, neither the ovariectomy nor the E2 therapy altered significantly the SgII or CgA protein and mRNA concentrations. We conclude that, in rats, 1) ovarian factors regulate the pituitary SgII and CgA protein and mRNA steady-state levels while such factors are inefficient in the adrenal gland, 2) CgA and LH beta mRNAs exhibit the same sensitivity to E2 while SgII and alpha-subunit mRNAs appear less sensitive, and 3) SgII and LH pituitary contents present a similar pattern of variations when the estrogenic status of the animal is modified.
Adrenal Glands↗
[Conn's adenoma in pregnancy].
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Adenoma↗
[In vitro activity of imipenem against hospital bacteria].
Imipenem proved highly active against Enterobacteriaceae: the different bacterial groups exhibited similar mode MICs (0.12 to 0.25 micrograms/ml), except for Serratia (0.25-0.5 micrograms/ml), Proteus mirabilis (0.5 micrograms/ml), indole-positive Proteus (2 micrograms/ml) and Providencia (1 mu/ml). The MICs of cefotaxime-resistant strains (cephalosporinase hyperproducing or very broad spectrum betalactamase producing) were within the susceptibility range. Imipenem also exhibited satisfactory activity against Pseudomonas aeruginosa (mode MIC 1-2 micrograms/ml), although resistant strains by decrease of permeability were observed, and against Acinetobacter (mode MIC 0.25-0.5 micrograms/ml). The MICs ranged from 0.03 to 4 micrograms/ml (mode MIC 0.5) for Haemophilus and from 0.25 to 1 micrograms/ml for Neisseria gonorrhoeae, regardless of the betalactamase producing status. The MICs for N. meningitidis were less than 0.06 micrograms/ml. Methicillin-susceptible staphylococci had low MICs ranging from 0.008 to 0.5 micrograms/ml (mode MIC 0.016). The MICs for methicillin-resistant strains varied widely from 0.016 to 64 micrograms/ml and were higher after incubation at 30 degrees C. Streptococci and pneumococci were highly susceptible (usually 0.008 to 0.03 micrograms/ml). The MICs for enterococci varied from 0.12 to 32 micrograms/ml (mode MIC 1-2). With the exception of Clostridium difficile, anaerobic bacteria were inhibited by concentrations lower than 1 (mode MIC 0.06 for C. Perfringens and 0.03 for Bacteroides fragilis).
Acinetobacter↗
Combretodendron Africanum bark extract as an antifertility agent. I: Estrogenic effects in vivo and LH release by cultured gonadotrope cells.
An aqueous extract from the stem bark of Combretodendron africanum was prepared to investigate its potency as a regulator of fertility. The intraperitoneal LD50 in mice was 95.2 +/- 4.3 mg/kg. Daily i.p. injections of 50 mg/kg promoted a significant increase in the uterine weight of 25 day-old female rats while pituitary weight remained unaffected. Similar injections for 21 days to mature females blocked the estrous cycle in the luteal phase with a mean length of efficiency of 15 days and decreased plasma LH and FSH levels. Regular cycles were restored 10 days following the last injection. C. africanum extract was shown to compete with estradiol and with progesterone on uterine receptors. Consequently, it is thought to contain substances exhibiting estrogenic (and possibly anti-estrogenic) potency. The effects of the extract on LHRH-induced release were investigated on cultured pituitary cells. Although gonadotropin release was amplified, the extract itself appeared as to be a potent secretagogue not requiring LHRH receptors. It follows that the active molecules contained in C. africanum extracts may be different from classical steroid estrogens.
Animals↗
Inhibitory effects of saponins from Tetrapleura tetraptera on the LH released by cultured rat pituitary cells.
Ethanolic extracts from stem bark of Tetrapleura tetraptera exerted an inhibitory effect on the luteinizing hormone (LH) released by cultured rat pituitary cells. These extracts contained triterpenic saponins, tannins, and flavonoids as estimated through phytochemical screening. Saponins were extracted. They apparently inhibited the luteinizing hormone-releasing hormone (LHRH)-induced LH release, the inhibition level being dose-dependent. Yet, the intracellular LH content remained constant whatever the saponin concentration, which demonstrated a lack of effect on the true release process. Accordingly, an interaction between saponins and LH released into the medium was demonstrated, which led to a decrease in the amount of immunoassayable hormone. This decrease was both time- and dose-dependent. It occurred even in the presence of serum in the medium, which suggests that the inactivation process may occur in vivo. Taken together, these results could explain the anti-gonadotrope properties of T. tetraptera extracts that are used as natural contraceptives in Ivory Coast pharmacopoeia.
Animals↗
Phenotypic and genotypic heterogeneity of glycopeptide resistance determinants in gram-positive bacteria.
Gram-positive glycopeptide-resistant bacteria isolated in various hospitals in Europe and in the United States between 1986 and 1988 were collected. Three resistance phenotypes could be distinguished. Thirty-one enterococci were highly resistant to vancomycin and teicoplanin. Resistance was transferable to other enterococci by conjugation for 16 of the 22 isolates that were tested. Homology was detected by hybridization between a probe specific for the vanA gene, which encodes an inducible high-level glycopeptide resistance protein in Enterococcus faecium BM4147, and DNA of the 31 clinical isolates and the 16 corresponding transconjugants. This indicates that a single class of resistance determinants accounts for high-level glycopeptide resistance in enterococci. The strains differed in their biotypes and resistance phenotypes and harbored resistance plasmids of various sizes, suggesting that spread of this resistance phenotype is due to dissemination of a gene rather than of a bacterial clone or of a single plasmid. Four enterococcal isolates were resistant to low levels of vancomycin and susceptible to teicoplanin. Twenty-three coagulase-negative staphylococcal isolates were resistant to teicoplanin and susceptible to vancomycin. These two groups of strains did not hybridize with the vanA probe and did not transfer resistance at a detectable frequency. The vanA gene was not detected in the glycopeptide-producing strains of Amycolatopsis orientalis (vancomycin) and Actinoplanes teichomyceticus (teicoplanin) or in various gram-positive bacteria intrinsically resistant to glycopeptides.
Anti-Bacterial Agents↗
[A double-blind placebo-controlled study of a 2 percent foaming lotion of ketoconazole in a single application in the treatment of pityriasis versicolor].
A double-blind, placebo-controlled therapeutic trial of ketoconazole presented as a foam and applied only once was carried out on 61 patients by a group of 15 private dermatologists practising in the Paris region. All patients had tinea versicolor clinically diagnosed, then confirmed by a positive patch test, as assessed by a single mycologist. The main criterion of therapeutic effectiveness was negativation of the patch test 30 days after a single topical application of the ketoconazole foam. On day 30, the test was negative in 22 of the 28 patients in the ketoconazole group and in 5 of the 29 patients in the placebo (i.e. excipient) group (p less than 10(-5). Clinical and mycological cure was observed in only 11 of the 28 patients treated with the active substance, but among the 11 patients who still showed skin lesions despite a negative mycological examination 10 had achromic lesions which could be regarded as residual. This clearly indicates that the only criterion that can be used in a therapeutic trial on tinea versicolor is the mycological result. The active substance and the excipient were well tolerated; two patients in the ketoconazole group reported tingling of the skin at the site of application. We conclude that a single application of ketoconazole foam in effective and well tolerated in tinea versicolor. The single application technique unquestionably has advantages over repeated applications and should result in better patient's compliance and greater effectiveness in the long term.
Administration, Cutaneous↗
[Antibacterial activity of norfloxacin, ofloxacin and ciprofloxacin according to resistance phenotypes to nalidixic acid and pefloxacin].
In vitro antibacterial activity of 5 quinolones: nalidixic acid (NAL), pefloxacin (PEF), norfloxacin (NOR), ofloxacin (OFL) and ciprofloxacin (CIP) was evaluated by agar diffusion (disks Diagnostics Pasteur) for 1,253 bacterial strains (767 Enterobacteriaceae: E 164 P. aeruginosa: PA, 90 A. baumannii: AB and 232 S. aureus: SA) isolated during the last three months of 1988. Strains were ranged in susceptible (S) intermediate (I) and resistant (R) according to recommendations of Comité Français de l'Antibiogramme; in addition, activity of NOR, OFL and CIP was precised according to susceptibility to NAL and PEF. Frequencies of strains R + I observed for NAL, PEF, NOR, OFL and CIP were (%): E: 14.4; 13.4; 7.3; 7.6; 2.4 - PA: 100; 68.5; 18.4; 36.8; 8.9 - AB: 78.9; 57.8; 75.5; 54.4; 50 - SA: 100; 27.5; 28.9; 28.5; 28.7. For E and AB, analysis according to resistance phenotypes to NAL and PEF showed reduction of activity of NOR, OFL and CIP, on strains RI and particularly RR by comparison with strains SS and RS. Activity of PEF, NOR, OFL and CIP is similar on PA, belonging to RS and RR phenotypes. On RI strains, only CIP showed activity practically identical to that on RS strains. For SA, NOR, OFL and CIP were inactive on PEF R strains. Analysis of populations of strains according to resistance phenotypes to NAL and PEF permitted to show reduction of activity of other compounds on strains with an acquired resistance character to quinolones; currently, only test of PEF is presently sufficient for susceptibility testing of other fluoroquinolones (NOR, OFL and CIP) on E, AB and SA; however for PA, test of CIP is also necessary.
Ciprofloxacin↗
[Antibacterial effect of cefixime].
Cefixime (CFM) is a new hemi-synthetic orally active cephalosporin which exhibits a particular affinity for PBPs 3, 1a, 1bs. Its penetration through the Gram negative bacilli outer membrane is similar to that of third generation cephalosporins. The MICs were assessed by the agar dilution method against 2,489 bacterial strains collected in 10 hospitals. Against Enterobacteriaceae, MICs50 and 90 are respectively (mg/l): naturally non beta-lactamase-producing species: E. coli and Shigella: 0.25-0.5, Salmonella: 0.06 - 0.25, P. mirabilis: 0.008 - 0.0.32; chromosomal penicillinase producing species: Klebsiella: 0.06 - 2; chromosomal cephalosporinase producing species: E. cloacae and C. freundii: 1 - greater than 128, S. marcescens: 0.25 - 16, Proteus indole: + 0.06 - 4, P. stuartii: 0.032 - 0.5. CFM activity is not altered in strains producing an acquired penicillinase. On the other hand, CFM appears to be inactive against cephalosporinase hyperproducing mutants and its activity is variably decreased against expanded spectrum beta-lactamase producing strains. CFM is inactive against P. aeruginosa (MIC50 and 90: 64 - 128) and against A. baumannii (16 - 128). Haemophilus and gonococci, beta-lactamase producing or not, as well as meningococci, are highly susceptible to CFM (MIC 0.008 - 0.12). B. catarrhalis is usually inhibited by 0.03 to 0.5. CFM is moderately active against meticillin-sensitive staphylococci (MIC50 and 90: 1-64), and inactive against meticillin-resistant strains. Enterococci are usually resistant, whereas streptococci and pneumococci are inhibited by low concentrations: 0.08 to 1. CFM is a bactericidal antibiotic, as shown by MBC and killing curves determination. These antibacterial properties relate CFM to the third generation cephalosporins and position the compound in an excellent place among the orally active cephalosporins.
Cefixime↗
[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↗
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↗
Transferable vancomycin and teicoplanin resistance in Enterococcus faecium.
Enterococcus faecium BM4165 and BM4178, isolated from immunocompromised patients, one treated with vancomycin, were inducibly resistant to high levels of the glycopeptide antibiotics vancomycin and teicoplanin but susceptible to the new lipopeptide daptomycin (LY146032). Strain BM4165 was also resistant to macrolidelincosamide-streptogramin B-type (MLS) antibiotics. The genes conferring resistance to glycopeptides and to MLS antibiotics in strain BM4165 were carried on plasmids pIP819 and pIP821, respectively; pIP819 also carried genes that encoded resistance to MLS antibiotics. The two plasmids, which were distinct although related, were self-transferable to other E. faecium strains. Plasmid pIP819 could also conjugate to E. faecalis, Streptococcus sanguis, S. pyogenes, S. lactis, and Listeria monocytogenes, in which it conferred inducible glycopeptide resistance, but not to S. aureus. Glycopeptide-inactivating activity was not detected, and the biochemical mechanism of resistance remains unknown. Based on this first report of transferable resistance to glycopeptides, we anticipate dissemination of resistance to these antibiotics in gram-positive cocci and bacilli in which it can be phenotypically expressed.
Adult↗
[In vitro antibacterial activity of a new fluoroquinolone, fleroxacin as a function of the sensitivity or resistance to nalidixic acid and to pefloxacin].
Minimal inhibitory concentrations (MIC) of fleroxacin (FLE) were evaluated by agar dilution for 375 bacterial strains. For Enterobacteriaceae, MIC of FLE were (microgram/ml): nalidixic acid (NAL), susceptible (S), pefloxacin (PEF), susceptible (S) strains: 0.032 to 0.5; NAL, resistant (R), PEF S: 0.25 to 1; NAL R, PEF R: 1 to 32; NAL R, PEF R strains were particularly observed among Serratia marcescens and Providencia stuartii, Pseudomonas aeruginosa was less susceptible to FLE (MIC 1 to 4), as to PEF; two PEF R strains were inhibited by 32 micrograms/ml of FLE. FLE was active on A. baumannii PEF S strains (0.5), but this activity was reduced on PEF R strains (2 to 64). H. influenzae and N. meningitidis (0.03 to 0.06), N. gonorrhoeae (0.016 to 0.03) and L. pneumophila (0.03 to 0.25) were very susceptible to FLE. MIC of FLE on S. aureus were 0.25 to 1 for PEF S strains and greater than or equal to 16 for PEF R strains, also resistant to methicillin. Enterococci, Streptococci and Pneumococci were less susceptible to FLE (2 to 8). C. perfringens (0.5 to 1) appeared susceptible to FLE whereas B. fragilis was inhibited by higher concentrations (4 to 8). So, antibacterial properties of FLE are very similar to that of PEF; PEF R strains appear generally resistant to FLE.
Anti-Infective Agents↗
[Early postoperative enteral feeding using the jejunostomy catheter].
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Adult↗