Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Effect of premedication on lesion detection rate and visualization of the mucosa during upper gastrointestinal endoscopy: a multicenter large sample randomized controlled double-blind study.

BACKGROUND: Premedication in upper gastrointestinal endoscopy for higher lesions detection rate has not been well studied so far. This study aimed to confirm whether premedication could improve the detection rate of early cancer or precancerous lesions and mucosal visibility. METHOD: From July 2015 to December 2015, 7200 participants from 6 centers were screened by endoscopy with one of the 4 following premedications randomly: (1) water (group D); (2) pronase (group A); (3) simethicone (group B); (4) pronase and simethicone (group C). Early cancer and precancerous lesions detection rates were taken as the primary endpoints, and mucosal visibility was taken as the secondary endpoint. They were compared among four groups to determine different premedication effects in terms of different anatomical sites. Trial was registered at Chinese Clinical Trial Registry; the registration number is ChiCTR-IOR-17010985. RESULTS: The upper gastrointestinal overall precancerous lesion detection rates among four groups were 8.7, 8.4, 10.0, and 10.3%, the overall early cancer detection rates were 1.3, 1.4%, 1.5, and 1.6%, both without significant difference (p = 0.138 and 0.878). However, the visibility score distributions between control group (D) and premedication groups (A, B, and C) were all statistically significant, with all anatomical sites p values < 0.001. Subgroup analyses, from 2 centers without screening before, also showed significant difference in esophageal (3.9, 3.3, 4.5, and 8.4% with p = 0.004) and overall (7.0, 5.5, 7.3, and 12.0% with p = 0.004) precancerous lesion detection rate. CONCLUSIONS: Premedication with pronase and simethicone may not increase lesion detection rates but could significantly increase the upper gastrointestinal mucosal visibility.

Additive Effect of Pronase on the Eradication Rate of First-Line Therapy for Helicobacter pylori Infection.

BACKGROUND/AIMS: Helicobacter pylori colonizes on the apical surface of gastric surface mucosal cells and the surface mucous gel layer. Pronase is a premedication enzyme for endoscopy that can disrupt the gastric mucus layer. We evaluated the additive effects of pronase combined with standard triple therapy for H. pylori eradication. METHODS: This prospective, single-blinded, randomized, controlled study was conducted between June and October 2012. A total of 116 patients with H. pylori infection were enrolled in the study (n=112 patients, excluding four patients who failed to meet the inclusion criteria) and were assigned to receive either the standard triple therapy, which consists of a proton pump inhibitor with amoxicillin and clarithromycin twice a day for 7 days (PAC), or pronase (20,000 tyrosine units) combined with the standard triple therapy twice a day for 7 days (PACE). RESULTS: In the intention-to-treat analysis, the eradication rates of PAC versus PACE were 76.4% versus 56.1% (p=0.029). In the per-protocol analysis, the eradication rates were 87.5% versus 68.1% (p=0.027). There were no significant differences concerning adverse reactions between the two groups. CONCLUSIONS: According to the interim analysis of the trial, pronase does not have an additive effect on the eradication of H. pylori infection (ClinicalTrial.gov NCT01645761).

Effect of pronase premedication on narrow-band imaging endoscopy in patients with precancerous conditions of stomach.

BACKGROUND: Narrow-band imaging (NBI) endoscopy improves the detection of intestinal metaplasia. However, strategies to improve the visibility and diagnostic performance of NBI should be sought, as endoscopic views are often obscured by the presence of mucus. AIM: To compare the visibility and diagnostic performance of NBI endoscopy according to pronase premedication in patients with precancerous conditions of the stomach. METHODS: Consecutive outpatients with a previous diagnosis of precancerous condition of the stomach were invited to undergo a surveillance NBI endoscopy between June and December 2012. Enrolled subjects were randomly assigned to pronase or control groups before NBI endoscopy. The visibility score and diagnostic performance of NBI endoscopy were compared between the two groups. RESULTS: Patients' endoscopic and histopathological characteristics were similar between the two groups. Visibility score in the proximal part of the stomach and satisfaction score of the endoscopist were significantly higher in the pronase group than in the control group (p = 0.014 and p = 0.034, respectively). The diagnostic performance of NBI endoscopy to detect intestinal metaplasia was not different in either group (both p > 0.1). However, the negative predictive value of NBI endoscopy was much improved over that of white light endoscopy only in the pronase group (p = 0.013). CONCLUSION: Pronase premedication increased the visibility of the proximal part of the stomach and the satisfaction score during NBI endoscopy. Furthermore, negative predictive value of NBI endoscopy was much improved compared with that of white light endoscopy after pronase premedication.

[The effects of pronase on drugs concentrations for treatment of Helicobacter pylori infection in gastric tissue].

OBJECTIVE: To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. METHODS: C57BL/6 mice were randomly divided into experimental group (n = 70) and control group (n = 70). Amoxicillin (28.6 mg/kg), metronidazole (22.5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in-time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa (hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5AC (Western blot) were detected at 120 min and 360 min after administration. RESULTS: The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P < 0.05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control (P < 0.05). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28 ± 0.18 vs 0.14 ± 0.14, P > 0.05; 0.43 ± 0.20 vs 0.28 ± 0.18, P > 0.05). The expressions of mucin 5AC in experimental group were lower than those of control (0.036 ± 0.006 vs 0.197 ± 0.058; P < 0.05; 0.039 ± 0.008 vs 0.208 ± 0.072, P < 0.05). CONCLUSIONS: Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time.

Additive effect of pronase on the efficacy of eradication therapy against Helicobacter pylori.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes not only the surface of the surface mucous cells but also the surface mucous gel layer (SMGL). Thus, we examined the possible value of pronase, a mucolytic agent, as a potential eradication therapy. MATERIALS AND METHODS: One hundred and thirty-five patients were randomly assigned to two treatment groups. Sixty-eight patients received 30 mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole thrice daily for 2 weeks (LAM group), while the other 67 patients received the same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily for 2 weeks (LAMP group). Eradication was assessed 4-6 weeks after treatment by immunohistochemical tests and cultures. We also determined the in vitro activity of pronase against H. pylori, and evaluated the synergistic effects between pronase and the other three drugs. To investigate the effect of pronase on the structure of the SMGL, surgically removed stomachs obtained from patients who had taken pronase were examined histopathologically. RESULTS: The cure rates for H. pylori infection in the LAMP group were significantly higher than those in the LAM group (intention to treat analysis: 94.0 vs. 76.5%, p =.0041). Pronase exhibited no antibacterial activity against H. pylori., and no in vitro synergistic effects were observed. In the patients who took pronase before surgery, the SMGL was thinner than in the patients who did not take pronase, and the structure of the SMGL was markedly disrupted. CONCLUSIONS: Pronase has an additive effect in curing H. pylori infection. Pronase has no apparent in vitro activity against H. pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL.

A comparison of four different techniques of assisted hatching.

BACKGROUND: Assisted hatching (AH) has been proposed as a means to increase the implantation rate in patients with poor prognosis for pregnancy. The procedure appears to be effective when used selectively. Several different methods for AH have been introduced over the years but comparative studies are lacking. The aim of the current study was to compare retrospectively the efficacy of AH performed with four different methods in patients undergoing IVF or ICSI. METHODS: AH was performed prior to day 3 embryo transfer in 794 IVF/ICSI cycles. Indications for AH were females aged >35 years and/or elevated follicular phase FSH levels, previous failed IVF/ICSI cycles, poor embryo quality, and thick zona pellucida (>15 microm). Assignment to one of the four methods of AH was according to the availability of the particular method during the study period. The study was not randomized. RESULTS: Partial zona dissection was used in 239, acid Tyrode in 191, diode laser in 219 and pronase thinning of the zona pellucida in 145. Mean female age, mean number of previous failed IVF/ICSI cycles, number of oocytes retrieved, fertilization and cleavage rates, good quality embryos and zona thickness on day 3 did not differ between groups. Mean number of embryos transferred, implantation rate, clinical pregnancy rate, and abortion rates were likewise similar. CONCLUSIONS: Selective AH using four different methods yields similar implantation and pregnancy rates.

Improved flow cytometric detection of HLA alloantibodies using pronase: potential implications in renal transplantation.

BACKGROUND: Flow cytomeric crossmatch (FCXM) has grown in popularity and has become the "standard of practice" in many programs. Although FCXM is the most sensitive method for detecting alloantibody, the B cell FCXM has been problematic. Difficulties with the B cell FCXMs have been centered around high nonspecific fluorescence background owing to Fc-receptors present on the B cells and autoantibodies. To improve the specificity and sensitivity of the B cell FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from lymphocytes before their use in FCXM. METHODS: Lymphocytes isolated from peripheral blood, spleen, or lymph nodes were treated with pronase and then used in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated and untreated cells were performed. Testing used serial dilutions of HLA allosera (22 class I and 6 class II), with the titer of each antibody at one dilution past the titer at which the complement-mediated cytotoxicity anti-human globulin crossmatch became negative. RESULTS: After pronase treatment, the actual channel values of the negative control in both T cell and B cell FCXMs declined from 78+/-10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase treatment resulted in improved sensitivity of the T and B cell FCXM in detecting class I antibody by 20% and 80%, respectively. In no instance was a false-positive reaction observed. In this study, pronase treatment improved the specificity of B cell FCXM for detecting class II antibodies from 75% to 100% (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the basis of these observations we re-evaluated three primary transplant recipients who lost their allografts because of accelerated rejection. One of the patients was transplanted across negative T and B cell FCXM, whereas the other two patients were transplanted across a positive T cell, but negative B cell, FCXM. After pronase treatment, T and B cell FCXMs of each patient became strongly positive, and donor-specific anti-HLA class I antibody was identi. fied in each case. CONCLUSION: Utilization of pronase-treated lymphocytes improves both the sensitivity and specificity of the FCXM.

Randomized comparison of 1-hour topical method vs. amoxycillin plus omeprazole for eradication of Helicobacter pylori in duodenal ulcer patients.

BACKGROUND: A novel 1-h topical method eradicated Helicobacter pylori in 96% of dyspeptic patients. The eradication rate of amoxycillin/omeprazole therapy varies from 0 to 93%. AIM: To compare both methods in patients with endoscopically proven duodenal ulcer. METHODS: Eighty patients (59 males, 21 females; median age 43 years) were randomized into two therapeutic groups. The first group (group A) was treated with a 6-week course of ranitidine 300 mg/day, then omeprazole 20 mg b.d. with pronase 36000 units/day for 2 days, followed by 1-h topical therapy with a solution of bismuth, metronidazole, amoxycillin and pronase. The second group (group B) consisted of patients treated with omeprazole 20 mg b.d. and amoxycillin 2 g/day for 2 weeks, followed by a 4-week course of ranitidine 300 mg/day. Eradication of H. pylori was assessed by urease test, histology, a polymerase chain reaction and a 13C-urea breath test, all of which were performed 4 weeks after discontinuation of the antibacterial treatment. RESULTS: Eradication rates in groups A and B were 2.5% and 35% in an intention-to-treat analysis, respectively. Side-effects were encountered in 40.5% and 12.5% of subjects in groups A and B, respectively. Treatment tolerance was rated as poor by 54% of patients in group A and 2.5% of patients in group B. CONCLUSIONS: Both treatment regimens, the 1-h topical method and amoxycillin with omeprazole, have low eradication rates in patients with duodenal ulcer. In addition, the topical treatment is characterized by a high rate of side-effects and poor tolerance. Based on the results of our study, neither method can be recommended for eradication of H. pylori in patients with duodenal ulcer.

Chemical treatment of cavity walls following manual excavation of carious dentin.

PURPOSE: To improve the conditioning of cavity walls resulting from minimal mechanical preparation of carious lesions, such as is done in modified Class II tunnel preparations. MATERIALS AND METHODS: Proximal carious lesions in premolars and molars were excavated manually and the cavity walls studied using a stereomicroscope and by scanning electron microscopy (SEM) following treatment with either polyacrylic acid, sodium hypochlorite, the enzyme preparation Pronase, or sequential combinations of the agents. Polyacrylic acid (10%) was used according to the manufacturer's instructions, while concentrated sodium hypochlorite (5.25%) was applied with either intermittent scrubbing or with ultrasonic energy for 5-10 minutes, or the cavity wall was incubated with the agent at +/- 37 degrees C for periods up to 24 hours. Incubation with the proteolytic enzyme preparation Pronase was carried out at 37 degrees C for a period up to 48 hours. RESULTS: Manual excavation did not remove all carious dentin, neither did treatment with polyacrylic acid. Scrubbing or sonication with ample amounts of sodium hypochlorite, followed by treatment with polyacrylic acid, or prolonged incubation with sodium hypochlorite, removed most of the remaining carious dentin. However, the "cleanest" surfaces were obtained after 48 hours of incubation with Pronase. Spots of thicker, soft layers of decayed dentin that were left intentionally at some locations could be disintegrated only by the Pronase treatment. It was concluded that treatment with sodium hypochlorite and polyacrylic acid in tandem, or with Pronase may represent potential supplements to conventional cavity cleaning that deserve further investigation. In the clinic more efficient cavity cleaning may improve the bonding ability and thus reduce the risk of marginal ridge fracture in teeth with Class II tunnel restorations.

Nodular scleroderma: focally increased tenascin expression differing from that in the surrounding scleroderma skin.

Nodular scleroderma is a rare variant of the disease, whose pathogenesis is uncertain. Tenascin is a recently cloned extracellular matrix protein which is thought to be a marker for tissue remodelling. To further investigate the pathogenesis of nodular scleroderma, we have followed up a case of this disease and studied tenascin expression in the nodular lesions and surrounding progressive systemic sclerosis skin. Previously, we demonstrated a long-lasting intermediate level of dermal tenascin expression in progressive systemic sclerosis; morphea and hypertrophic scar lesions showed strong but short-lived tenascin expression. In our current patient, high levels of tenascin were found in the nodules, which rapidly resolved. Thus, the time course of the clinical and histopathological findings together with the tenascin expression were more suggestive of hypertrophic scar than progressive systemic sclerosis. These findings imply that nodular scleroderma has a supplementary pathogenesis, such as itching, in addition to the proceeding systemic sclerosis.

A 1-h topical therapy for the treatment of Helicobacter pylori infection.

OBJECTIVE: A novel topical therapeutic methodology for the treatment of Helicobacter pylori infection was developed and studied in 25 patients with H. pylori to evaluate safety and efficacy. METHODS: The patients had been given lansoprazole (30 mg, hs) orally and pronase (18,000 tyrosine units, b.i.d.) for the 2 days before topical therapy. One hundred milliliters of solution with 80 ml of 7% sodium bicarbonate and 20 ml of contrast medium meglumine sodium amidotrizoate containing bismuth subnitrate (1 g), amoxicillin (2 g), metronidazole (1 g), and pronase (36,000 tyrosine units) were instilled into the stomach through a nasally introduced 16-Fr intestinal tube with a balloon at its radiopaque tip, which was inflated with approximately 25 ml of air and lodged postbulbarly at the superior duodenal angle under fluoroscopy, thus preventing leakage of the solution distally into the jejunum. The solution was kept in the stomach for 1 h, and the patient's position was changed every 15 min from the sitting to the supine, prone, and right lateral position to expose the entire gastric mucosa. The solution was suctioned at the end of the procedure. RESULTS: H. pylori infection was successfully cured in 24 (96%) patients, confirmed 4 wk after the therapeutic procedure by negative smear, culture, and histology of the antral and corpus biopsy specimens. No side effects were observed except for loose stools in one case. CONCLUSION: This 1-h topical therapy is a safe, effective, and well tolerated procedure for the treatment of H. pylori infection. With further improvements and modifications of the method itself, as well as of the drug regimens, this method may become a highly efficient modality for anti-H. pylori therapy.

[Therapeutic effect of a pharmacologic combination of choleretics and digestive enzymes in exocrine pancreatic insufficiency]. / Sull'effetto terapeutico di una associazione farmacologica a base di coleretici ed enzimi digestivi nell'insufficienza pancreatica esocrina

Phosphorylcholine and homocysteine have an important choleretic action and also potentiate exocrine pancreatic secretion by way of stimulation and a more effective preparation of the substrate against attack by lipolytic enzymes. The protection offered by pancreatic enzymes in the correction of the digestive insufficiency in the endoluminal stage is also known. An analysis was therefore made of the action of an association of phosphorylcholine homocysteine and digestive enzymes in cases of exocrine pancreatic insufficiency and primary or secondary malabsorption. This action was evaluated on the basis of the reduction of elimination of steatorrhoea. For this purpose, faecal lipids were determined with the method proposed by van de Kramer et al. The most significant results were obtained in cases where digestive insufficiency was most marked, where correction of the pancreatic enzyme deficiency and improved biliary function were particularly required.