Antimicrobial Activity of SCH 27899, Oligosaccharide Member of the Everninomycin Class with a Wide Gram-Positive Spectrum

The in vitro antimicrobial activity of SCH 27899 (everninomycin), a novel oligosaccharide compound of the everninomycin class, was compared with vancomycin, chloramphenicol, clinafloxacin, teicoplanin and doxycycline against 428 clinical strains of bacteria. Everninomycin base exhibited the greatest antimicrobial activity compared to other formulations against all strains tested (MIC₉₀: 0.25 μ/ml) followed by clinafloxacin and teicoplanin (MIC₉₀: 0.5 μg/ml), vancomycin (MIC₉₀: 2 μg/ml), and doxycycline (MIC₉₀: 16 μg/ml). Everninomycin demonstrated the best activity against Streptococcus spp. (serogroups A, B, C, F, G) and Streptococcus pneumoniae , and lower activity against coagulase-negative staphylococci (MIC₉₀: 0.5 μg/ml). All enterococci had an everninomycin MIC of 0.5 μg/ml or less. Everninomycin had no measurable antimicrobial activity against gram-negative aerobic organisms except Flavo-bacterium meningosepticum (MIC₅₀: 2 μg/ml). Some everninomycin activity was observed against Clostridium spp., Peptostreptococcus spp., and the Prevotella bivius-disiens group. Everninomycin showed excellent activity (MIC₉₀: 0.25 μg/ml) against the fluoroquinolone-resistant strains and all gram-positive strains resistant to vancomycin (MICs 4 μg/ml). The MBC/MIC ratios and killing curve data suggest that everninomycin is not uniformly or rapidly bactericidal. These in vitro data indicate that everninomycin could be useful against emerging gram-positive strains resistant to other contemporary antimicrobials.     

Pharmacokinetics of 18F-labeled trovafloxacin in normal and Escherichia coli-infected rats and rabbits studied with positron emission tomography

Objective: To measure tissue pharmacokinetics of trovafloxacin (CP 99,219) in normal and infected animals by both direct tissue radioactivity measurements and positron emission tomography (PET).
Method: Concentrations of [ ¹⁸ ]Ftrovafloxacin were measured in normal and infected rats ( n =6/group), at 10, 30, 60, and 120 min after injection, by radioactivity measurements. In normal rabbits ( n =4) and rabbits with Escherichia coli thigh infection ( n =4), tissue concentrations of drug were measured over 2 h with PET. After acquiring the final images, the rabbits were killed and tissue concentrations measured with PET were compared to the results of direct tissue radioactivity measurements.
Results: In both species, there was rapid distribution of [ ¹⁸ ]F trovafloxacin in most peripheral organs. Peak concentrations of more than five times the MIC₉₀ of most Enterobacteriaceae and anaerobes (>100-fold for most organisms) were achieved in all tissues and remained above this level for >2 h. Particularly high peak concentrations were achieved in the kidney (>75 μg/g), liver (>100 μg/g), blood (>40 μg/g), and lung (>10 μg/g). Even though the concentration of trovafloxacin in infected muscle was reduced ( p <0.01), the peak concentration was still >4 μg/g and tissue levels remained above 2 μg/g for more than 2 h. Due to the lower concentrations that were achieved in the brain (peak ˜5 μg/g), it is expected that trovafloxacin will have limited central nervous system toxicity.
Conclusions: PET with [¹⁸F] trovafloxacin is a useful technique for non-invasive measurements of tissue pharmacokinetics.     

In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey

We have evaluated the in vitro activities of seven fluoroquinolones against 69 strains of Brucella melitensis . According to their minimum inhibitory concentration for 90% growth (MIC₉₀) values, the most active agent was found to be sparfloxacin (MIC₉₀ 0.12 mg/L) followed by levofloxacin, ciprofloxacin, ofloxacin (MIC₉₀ 0.50 mg/L) and grepafloxacin (MIC₉₀ 1 mg/L), gemifloxacin (MIC₉₀ 2 mg/L) and gatifloxacin (MIC₉₀ 4 mg/L).     

Susceptibility testing by E-test and agar dilution of 30 strains of Legionella spp. isolated in Portugal

Objective: To evaluate the activity of erythromycin, roxithromycin, ciprofloxacin, doxycycline, sulfamethoxazole trimethoprim and rifampin against 32 strains of Legionella spp. under different testing conditions.
Method: Minimum inhibitory concentrations (MICs) were determined by the E-test (Ab Biodisk, Solna, Sweden) and agar dilution reference technique (National Committee for Clinical Laboratory Standards (NCCLS), 1990) on two different media, buffered charcoal yeast extract agar (BCYE-α) and buffered yeast extract agar (BYE-α), under 48- and 72-h incubation, without CO₂.
Results: All the antimicrobial agents were inhibited by BCYE-α agar. The MIC₉₀ values on BYE-α were lower than those on BCYE-α but the variation factor was not the same: ciprofloxacin and rifampin, followed by erythromycin, suffered the greatest inhibition by the charcoal in the culture medium. Except for ciprofloxacin and rifampin, the 72-h MIC₉₀ readings were always higher than the 48-h results whenever the agar dilution method was used. The E-test results showed slight variations with some, but not all, antibiotics. The most active agents against the 32 Legionella strains tested were rifampin and ciprofloxacin.
Conclusions: BCYE-α is not suitable for susceptibility testing of Legionella spp. The E-test method on BYE-α agar with 48-h incubation is recommended.     

Comparative activity of linezolid against staphylococci and enterococci isolated in Italy

The activity of linezolid, a new oxazolidinone, was tested against 862 Gram-positive cocci isolated in Italy and compared with the activities of 12 antibiotics. Overall, MIC₉₀s for linezolid (2–4 mg/L) indicated an in vitro activity comparable to that of vancomycin in methicillin-resistant Staphylococcus aureus (4 mg/L), S. epidermidis (2 mg/L) and methicillin-susceptible strains. Enterococcus faecalis strains were susceptible to linezolid (MIC₉₀ 2–4 mg/L), glycopeptides and β -lactams. In E. faecium , only glycopeptides (MIC₉₀ 2 mg/L) and linezolid (MIC₉₀ 2 mg/L) were active. Linezolid was the only drug active against two strains of Enterococcus showing a VanA phenotype. Owing to its antibacterial profile, linezolid represents a promising drug for the treatment of Gram-positive infections.     

In vitro activity of tigecycline and occurrence of tetracycline resistance determinants in isolates from patients enrolled in phase 3 clinical trials for community-acquired pneumonia

The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC₉₀ 0.06 mg/L), Staphylococcus aureus (MIC₉₀ 0.25 mg/L), Haemophilus influenzae (MIC₉₀ 0.5 mg/L) and Klebsiella pneumoniae (MIC₉₀ 1 mg/L). Twelve isolates of S. pneumoniae expressing tet (M) and two isolates of K. pneumoniae producing extended-spectrum β-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.     

Antimicrobial susceptibility of 840 clinical isolates of Haemophilus influenzae collected in four European countries in 2000–2001

In 2000–2001, 840 clinical isolates of Haemophilus influenzae were collected from laboratories in France, Germany, Italy and Spain (210 isolates/country). β -Lactamase production among the isolates varied considerably by country, ranging from 8.1% in Germany to 34.8% in France. H. influenzae from patients ≤4 years old showed the highest prevalence of β -lactamase production (23.2%), compared with isolates from patients aged 5–17 years (17.8%) and ≥18 years (16.5%). All isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin and levofloxacin; 99.6% and 98.9% of isolates were susceptible to azithromycin and cefuroxime, respectively. Among the macrolides tested, azithromycin (MIC₉₀, 2 mg/L) was eight-fold more potent than clarithromycin (MIC₉₀, 16 mg/L) and roxithromycin (MIC₉₀, 16 mg/L). Despite variations in β -lactamase production between different countries, > 99% of all isolates were susceptible to amoxicillin–clavulanate, ciprofloxacin, levofloxacin, and azithromycin.     

European survey of glycopeptide susceptibility in Staphylococcus spp.

Objectives: To reassess the relative potencies of teicoplanin and vancomycin following several years of clinical usage.
Methods: The glycopeptide susceptibilities of clinical isolates of staphylococci collected from 70 hospitals in 1995 were determined using NCCLS (National Committee for Clinical Laboratory Standards) methods.
Results: In total, 2885 isolates of Staphylococcus aureus and 1480 isolates of coagulase-negative staphylococci were collected. S. aureus was significantly less susceptible to vancomycin (MIC₅₀ 1 mg/L) than teicoplanin (MIC₅₀ 0.5 mg/L), but the reverse was the case for S. haemolyticus and S. epidermidis . No S. aureus isolate was resistant (≥32 mg/L) to either glycopeptide, but nine isolates of coagulase-negative staphylococci had an MIC of teicoplanin of 32 mg/L. Respiratory isolates of S. aureus were less susceptible to glycopeptides than those from other sites. Staphylococci from Belgium and Italy were less susceptible to teicoplanin than isolates from other countries.
Conclusions: This European survey shows that in 10 years of clinical use there have been no major changes in the susceptibility of staphylococci to the glycopeptides.     

Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms

NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance ( mef and/or erm ) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8–64 compared to 1–32 (levofloxacin), 0.5 ≥ 32 (sparfloxacin) and 0.125–4 (moxifloxacin). Telithromycin MIC₅₀ and MIC₉₀ values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.     

Central 5-HT7 receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats

5-Hydroxytryptamine (5-HT; serotonin)-containing neurones contribute to reflex activation of parasympathetic outflow in a number of species, but the 5-HT receptors mediating these effects have yet to be fully determined. The present experiments demonstrate that central 5-HT₇ receptors are involved in the vagal bradycardia evoked during the cardiopulmonary reflex, baroreflexes and the chemoreflex, as well as other autonomic changes caused by these reflexes. The experiments examined the effects of the selective 5-HT₇ receptor antagonists SB-269970 and SB-656104 on these reflexes. For the cardiopulmonary reflex, when compared to time-matched vehicle control experiments, intracisternal application of SB-269970 (30–300 μg kg⁻¹, i.c. ) dose-dependently attenuated the evoked bradycardia. At the highest dose, SB-269970 also attenuated the reflex hypotension and sympathoinhibition. The structurally different 5-HT₇ receptor antagonist SB-656104 (100 μg kg⁻¹, i.c. ) similarly attenuated the reflex bradycardia and hypotension. SB-269970 (100 μg kg⁻¹, i.c. ) also attenuated the bradycardias evoked by electrical stimulation of aortic nerve afferents and the baroreflex evoked by the pressor response to phenylephrine (3–25 μg kg⁻¹, i.v. ). The gain of the baroreflex was also significantly attenuated (0.15 ± 0.06 versus 0.34 ± 0.06 ms mmHg⁻¹). Finally, SB-269970 (100 μg kg⁻¹, i.c. ) significantly attenuated both the bradycardia and sympathoexcitation evoked by the chemoreflex. These data indicate that central 5-HT₇ receptors play an important facilitatory role in the reflex activation of vagal outflow to the heart.     

In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe

Objective   To assess the activities of levofloxacin and the comparator agents erythromycin, clarithromycin, azithromycin and doxycycline against atypical respiratory pathogens.
Methods   One hundred and forty-six Legionella pneumophila , 41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured from various culture collections in North America and Europe and tested for susceptibility to the above agents by broth microdilution. The isolates came primarily from clinical sources and were collected from patients between 1995 and 1999.
Results   Against L. pneumophila , levofloxacin was the most active agent, with an MIC₉₀ of 0.03 mg/L, twofold more active than clarithromycin (0.06 mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64-fold more active than doxycycline. Against M. pneumoniae , azithromycin (MIC₉₀ ≤ 0.0005 mg/L) was the most active agent. However, two isolates of M. pneumoniae , one from the USA and one from Finland, were macrolide resistant (MIC ≥ 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any antimicrobial agent tested. Against C. pneumoniae , clarithromycin was the most active agent, with an MIC range of ≤0.008–0.03 mg/L.
Conclusions   Levofloxacin had comparable activity to the other agents tested against the atypical respiratory pathogens, confirming its potential as an alternative for empirical therapy of community-acquired pneumonia.     

Lack of antimicrobial activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique

Objective   To elucidate the potential antimicrobial activity of sodium heparin in the treatment of catheter-infection using the antibiotic-lock technique.
Methods   We performed in vitro studies of the antibiotic susceptibility, stability and synergy of sodium heparin, vancomycin and ciprofloxacin. Efficacy studies were performed in a new animal model of Staphylococcus aureus catheter-related infection in which infection was produced via the endoluminal route. White New Zealand rabbits were surgically implanted with a sylastic catheter into the inferior cava vein. Immediately afterwards, infection was induced by filling and locking the catheters with 0.7 mL of broth culture containing 10⁸ colony-forming units of S. aureus . Eighteen hours later the antibiotic-lock technique was started. Treatment groups were: control without treatment, sodium heparin at 2500 IU/mL, vancomycin at 2500 mg/L, ciprofloxacin at 1000 mg/L, vancomycin plus heparin and ciprofloxacin plus heparin.
Results   Sodium heparin showed an MIC₉₀ higher than 6000 UI/mL against S. aureus causing catheter infection. Studies of antimicrobial synergy by the time-kill method between vancomycin and ciprofloxacin at MIC with sodium heparin at 2500 IU/mL showed no interactions. Vancomycin (2000 µg/mL) and ciprofloxacin (1000 µg/mL) in a solution containing sodium heparin (2500 IU/mL) were stable at 37 °C for a 72-h period. Two sets of in vivo experiments were carried out using differents strains of S. aureus . In both cases, sodium heparin showed no therapeutic efficacy when compared to control group and did not increase the antibiotic efficacy when used in combination with vancomycin or ciprofloxacin.
Conclusion   Sodium heparin lacked antibacterial activity against S. aureus causing catheter-related infections.     

Antimicrobial susceptibilities of clinical isolates of Haemophilus influenzae and Moraxella catarrhalis collected during 1999–2000 from 13 countries

Objective   To determine antimicrobial activity against Haemophilus influenzae and Moraxella catarrhalis .
Methods   A central laboratory performed NCCLS susceptibility testing for all isolates and β -lactamase and capsular serotype determinations for H. influenzae .
Results   A total of 2712 H. influenzae and 1079 M. catarrhalis were collected . H. influenzae susceptibilities were >90% for amoxicillin/clavulanate, cefaclor, loracarbef, cefprozil, cefuroxime, ciprofloxacin, azithromycin and clarithromycin and were <80% for trimethoprim/sulfamethoxazole and ampicillin. 19.3% were β -lactamase positive. The most common serotype was type-b (5.6%); 86.1% were nontypeable. M. catarrhalis had MIC₉₀ within therapeutic range for all antimicrobials except ampicillin.
Conclusion   The conclusion of the study is that antimicrobials, except ampicillin and trimethoprim/sulfamethoxazole, remain good empiric choices against H. influenzae and M. catarrhalis .     

Cyclic AMP-dependent Cl− secretion induced by thromboxane A2 in isolated human colon

Increased release of thromboxane A₂ (TXA₂) has been shown to be involved in inflammatory bowel diseases. In the present study, we have investigated the effect of a stable TXA₂ analogue (STA₂) on the electrical parameters in isolated human colonic mucosa. In the human mucosa set between Ussing chambers, STA₂ stimulated Cl⁻ secretion in a concentration-dependent manner with an EC₅₀ of 0.06 μ m . The STA₂-induced Cl⁻ secretion was significantly inhibited by ONO-3708 (10 μ m ), a specific TXA₂ receptor antagonist. The effect of STA₂ (0.3 μ m ) was independent of the colonic segment from which the tissue was obtained, from caecum to rectum. Chromanol 293B, an inhibitor of the cAMP-dependent KvLQT1 channel, attenuated the STA₂-induced Cl⁻ secretion in the human colonic mucosa (IC₅₀ value 1.18 μ m ). We found that KvLQT1 mRNA and protein were expressed in all the tested segments of the human colon. The STA₂-induced Cl⁻ secretion was significantly inhibited by 8-bromo-2'-monobutyryladenosine-3',5'-cyclic monophosphorothioate (50 μ m ), a membrane-permeant cAMP antagonist. STA₂ (0.3 μ m ) significantly increased the intracellular cAMP levels and the short-circuit current via TXA₂ receptor in a human colonic cell line. These results suggest that the TXA₂-induced Cl⁻ secretion in the colon is mediated via the cAMP pathway in addition to the Ca²⁺–calmodulin pathway which was previously reported.     

Trends in quinolone susceptibility of Enterobacteriaceae among inpatients of a large university hospital: 1992–98

Objectives   To assess trends in quinolone susceptibility of Enterobacteriaceae isolated in a large university hospital.
Methods   Between 1992 and 1998, bacterial isolates were collected each year during a 3-month period to evaluate annual changes in susceptibility. In addition, the activities of fluoroquinolones (pefloxacin, norfloxacin, ofloxacin, ciprofloxacin) against nalidixic acid-resistant strains were determined by disk diffusion and MIC methodologies during the first and last year of the study.
Results   The susceptibility of Enterobacteriaceae to nalidixic acid was unchanged between 1992 and 1998 (86% versus 85%). However, at the species level, the susceptibility rates to nalidixic acid decreased for Escherichia coli from 92% to 89%, and for Enterobacter cloacae from 87% to 82%. In contrast, there was a 10% increase in the nalidixic acid susceptibility rates for Klebsiella pneumoniae (74% versus 83%), which was thought to be due to the control of the spread of epidemic extended-spectrum β -lactamase (ESBL)-producing strains. The overall susceptibility of the Enterobacteriaceae to the fluoroquinolones remained high during the study period, greater than 90% in the case of ciprofloxacin. However, nalidixic acid-resistant Escherichia coli showed decreased susceptibility to ciprofloxacin between 1992 and 1998, as reflected by a decrease in median zone diameter (26 mm to 19 mm), an increase in MIC₅₀ (0.25 mg/L to 1 mg/L) and a shift in MIC distribution (unimodal in 1992 to bimodal in 1998). This has resulted in the reduced susceptibility of Escherichia coli to fluoroquinolones between 1992 and 1998 (pefloxacin, 95–90%; ciprofloxacin, 99–95%).
Conclusions   The susceptibility of Escherichia coli to quinolones has decreased, and the level of susceptibility of the resistant strains has increased over the 7-year study period.     

Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study

Background:  Indacaterol is a novel, once-daily β₂-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation.
Objective:  A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol.
Methods:  A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 μg via multi-dose dry-powder inhaler (MDDPI; Certihaler^™), indacaterol 400 μg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored.
Results:  All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV₁) from 22 to 24 h postdose ( P  ≤ 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 μg via MDDPI and 400 μg via SDDPI, respectively. All doses increased mean FEV₁ ( P  < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders.
Conclusion:  Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 μg appears the optimum dose, offering the best efficacy/safety balance.     

The effect of carbon dioxide on susceptibility testing of azithromycin, clarithromycin and roxithromycin against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes by broth microdilution and the Etest: Artemis Project—first-phase study

Objective: To evaluate the effect of carbon dioxide on the susceptibility testing, using broth microdilution and the Etest (AB Biodisk, Solna, Sweden), of azithromycin, clarithromycin and roxithromycin against Streptococcus pneumoniae and Streptococcus pyogenes .
Methods: Fresh clinical isolates collected from 36 hospital laboratories in 12 countries were evaluated using the Etest in the presence of carbon dioxide. The isolates were retested under ambient conditions (absence of carbon dioxide) using broth microdilution and/or the Etest.
Results: Carbon dioxide falsely elevated azithromycin, clarithromycin and roxithromycin MIC₉₀S for S. pneumoniae , determined by the Etest, approximately 12-fold. Also, the azithromycin MIC₉₀ for S. pyogenes was increased fourfold; the effect was less marked for clarithromycin and roxithromycin. When isolates were retested in the absence of carbon dioxide, using the Etest or microdilution, susceptibilities to azithroymycin were comparable to those to clarithromycin ( S. pneumoniae , 93.4% versus 91.3%; S. pyogenes , 96.4% versus 95.8%). Both organisms were less susceptible to roxithromycin ( S. pneumoniae , 71.3%; S. pyogenes , 85.7%). An internal standard control, consisting of 50 isolates each of S. pneumoniae, S. pyogenes and Haemophilus influenzae , confirmed that azithromycin susceptibility testing resulted in falsely elevated MICs.
Conclusions: Carbon dioxide falsely elevated azithromycin MICs for S. pneumoniae and S. pyogenes , with an apparent reduction in susceptibility. When the in vitro activity of azithromycin and other macrolides against S. pneumoniae and S. pyogenes is being evaluated, awareness of the pH effect is essential.     

Increased Expression of Glutathione by Estradiol, Tumor Necrosis Factor-Alpha, and Interleukin 1-Beta in Endometrial Stromal Cells

Problem  The intracellular antioxidant system, based on glutathione (GSH), plays a key role in endometrial detoxification reactions and has been proposed to be involved in the pathogenesis endometriosis. This study was designed to evaluate whether estradiol (E₂) and proinflammatory cytokines have any effects on expression of glutathione in endometrial stromal cells (ESCs).
Method of study  Glutathione levels were measured utilizing high-performance liquid chromatography following in vitro culture and treatment of ESCs with estradiol, tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β).
Results  The GSH level in E₂ (10⁻⁸  m ) treatment group was significantly higher than in the control group at 48 h ( P  < 0.05). In vitro treatment of ESCs with TNF-α 10 ng/mL as well as E₂ (10⁻⁸  m ) plus TNF-α 10 ng/mL for 48 hr also led to a significant increase in GSH level ( P  < 0.05; P  < 0.05, respectively). Both IL-1β 10 ng/mL and E₂ (10⁻⁸  m ) plus IL-1β 10 ng/mL for 48 hr increased GSH level significantly ( P  < 0.05; P  < 0.05, respectively) as well.
Conclusions  These findings might suggest that increased production of estradiol and proinflammatory cytokines in the peritoneal cavity possibly leads to the establishment of endometriosis through increased level of GSH.