Endoscopic flushing with pronase improves the quantity and quality of gastric biopsy: a prospective study.

BACKGROUND AND STUDY AIMS: Pronase, a proteolytic enzyme, is known to improve mucosal visibility during esophagogastroduodenoscopy (EGD), but little is known about its effects on gastric biopsy. This study assessed whether endoscopic flushing with pronase improves the quality of gastric biopsy. PATIENTS AND METHODS: Consecutive patients who underwent EGD were randomly assigned to either the control group or the pronase group in a prospective setting. The first biopsy of the identified lesion was performed during endoscopy. Endoscopic flushing with either 50 mL of water and dimethylpolysiloxane (DMPS; control group) or 50 mL of water, pronase, sodium bicarbonate, and DMPS (pronase group) was then applied to the lesion. After 5 minutes, the second biopsy was performed 2 - 3 mm away from the first biopsy site. The thickness of mucus, depth of the specimen, overall diagnostic adequacy, anatomical orientation, and crush artifact were measured to assess the quality of the biopsy. RESULTS: Of the 208 patients, 10 were not analyzed due to the absence of an identifiable lesion. Compared with the control group, the pronase group showed significantly decreased thickness of mucus (P < 0.001), increased depth of biopsy (P < 0.001), improved anatomical orientation (P = 0.010), and improved overall diagnostic assessment (P = 0.011) in the second biopsied specimen following endoscopic flushing. The crush artifact and hemorrhage did not differ between the groups. CONCLUSIONS: Endoscopic flushing with pronase not only improved the depth of biopsy but also the anatomical orientation and overall diagnostic adequacy. Pronase can be recommended for flushing during EGD to improve the quantity and quality of biopsy.

Assessing bolus retention in achalasia using high-resolution manometry with impedance: a comparator study with timed barium esophagram.

OBJECTIVES: The aim of this study was to assess whether high-resolution impedance manometry (HRIM) could be used to assess bolus retention similar to the timed barium esophagram (TBE). METHODS: Twenty achalasia patients (10 males, aged 21-79 years) were prospectively evaluated with HRIM and TBE to determine the correlation between barium column height and the impedance bolus height (IBH). The TBE protocol used a 200-ml barium challenge and the HRIM protocol used a 200-ml saline challenge protocol. Both protocols were performed in an upright position and the heights of the barium and impedance columns were measured at 1 and 5 min. Analysis of IBH was performed with a topographic technique and a spatial impedance variation plot. RESULTS: There was no significant difference between the median IBH and barium column at 1 min (IBH: 12.0 cm (interquartile range (IQR), 8.0-18.0); TBE: 12.0 cm (IQR, 7.0-19.0); P=0.90) or at 5 min (IBH: 11.0 cm (IQR, 1.0-17.0); TBE: 9.0 cm (IQR, 4.0-12.0); P=0.47). In addition, the correlation between the two measurements at 1 and 5 min was 0.60 and 0.86, respectively. Using a barium column or impedance height of >5.0 as a definition of bolus retention was associated with 75% concordance at 1 min and 95% concordance at 5 min. CONCLUSIONS: There was excellent agreement between TBE and high-resolution impedance manometry (HRIM) for assessing bolus retention at 5 min. Thus, HRM with impedance may be used as a single test to assess bolus retention and motor function in the management of achalasia.

Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-up.

Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC(0-t)) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/f(u)) (L/h) and log species body weight (W) (kg) [CL (or CL/f(u)) = 3.29 (34.0) W(0.723 (0.789))] and log V(ss) (or V(ss)/f(u)) (L) and log W (kg) [V(ss) (or V(ss)/f(u)) = 0.340 (3.52) W(0.882 (0.948))]. Interspecies scale-up of plasma concentration-time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration-time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies.

Time-dependent effects of Klebsiella pneumoniae endotoxin on the telithromycin pharmacokinetics in rats; restoration of the parameters in 96-hour KPLPS rats to the control levels.

OBJECTIVES: It has been reported that telithromycin is primarily metabolized via hepatic CYP3A4 and 3A1/2 in humans and rats, respectively, and that the protein expression of hepatic CYP3A subfamily significantly decreased (59.1% decrease) in 24-h KPLPS rats (lipopolysaccharide derived from Klebsiella pneumoniae; the protein expression was measured 24h after KPLPS administration) compared with that in control rats, but restored to that in control rats in 96-h KPLPS rats. METHODS: The pharmacokinetic parameters of telithromycin were compared after intravenous and oral administration at a dose of 50mg/kg to control, 24-h KPLPS, and 96-h KPLPS rats. RESULTS: After both intravenous and oral administration of telithromycin to 24-h KPLPS rats, the AUC of telithromycin became significantly greater (68.2% and 88.7% increase for intravenous and oral administration, respectively) and this could have been due to the significantly slower CL(NR) (45.7% decrease). Because telithromycin is a low hepatic extraction ratio drug, the slower CL(NR) could have been due to the decreased protein expression of the hepatic CYP3A subfamily compared with that in control rats, and was supported by the significantly slower in vitro CL(int) in hepatic microsomes (13.1% decrease). However, in 96-h KPLPS rats, the pharmacokinetic parameters of telithromycin restored fully to those in control rats due to restoration of the protein expression of the hepatic CYP3A subfamily to that in control rats. The protein expression of the intestinal CYP3A subfamily was comparable among three groups of rats. CONCLUSIONS: These findings indicate the existence of the time-dependent effects of KPLPS on the pharmacokinetics of telithromycin in rats.

Effects of Escherichia coli lipopolysaccharide on telithromycin pharmacokinetics in rats: inhibition of metabolism via CYP3A.

It has been reported that telithromycin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP) 3A1/2 in rats and that the expression of hepatic and intestinal CYP3A decreases in rats pretreated with Escherichia coli lipopolysaccharide (ECLPS rats; an animal model of inflammation). Thus, it is possible that the area under the plasma concentration-time curve from 0 h to infinity (AUC 0-infinity) of intravenous and oral telithromycin is greater for ECLPS rats than for the controls. To assess this, the pharmacokinetic parameters of telithromycin were compared after intravenous and oral administration (50 mg/kg). After intravenous administration of telithromycin, the AUC 0-infinity was significantly greater (by 83.4%) in ECLPS rats due to a significantly lower nonrenal clearance (by 44.5%) than in the controls. This may have been due to a significantly decreased hepatic metabolism of telithromycin in ECLPS rats. After oral administration of telithromycin, the AUC 0-infinity in ECLPS rats was also significantly greater (by 140%) than in the controls and the increase was considerably greater than the 83.4% increase after intravenous administration. This could have been due to a decrease in intestinal metabolism in addition to a decreased hepatic metabolism of telithromycin in ECLPS rats.