Influence of ensitrelvir or nirmatrelvir/ritonavir on tacrolimus clearance in kidney transplant recipients: a single-center case series.

BACKGROUND: Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug-drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered. However, the influence of ESV on blood TAC levels has not yet been reported, and the management of TAC doses during the use of ESV remains unclear. CASE PRESENTATION: We experienced three kidney transplant recipients with COVID-19, whose blood trough levels of TAC increased by the concomitant use of NMV/RTV or ESV. In two patients administering NMV/RTV, blood trough levels of TAC increased more than tenfold after combination therapy, whereas in one patient administering ESV, TAC level increased approximately threefold. CONCLUSIONS: These cases suggest that TAC administration should be discontinued during NMV/RTV treatment to maintain blood TAC levels within the therapeutic range, and a reduced TAC dose is sufficient during ESV treatment.

Anatomically-Inspired Robotic Finger with SMA Tendon Actuation for Enhanced Biomimetic Functionality.

This research introduces an advanced robotic finger designed for future generalist robots, closely mimicking the natural structure of the human finger. The incorporation of rarely discussed anatomical structures, including tendon sheath, ligaments, and palmar plates, combined with the usage of anatomically proven 3D models of the finger, give rise to the highly accurate replication of human-like soft mechanical fingers. Benefiting from the accurate anatomy of muscle insertions with the utilization of Shape Memory Alloy (SMA) wires' muscle-like actuation properties, the bonding in-between the flexor tendons and extensor tendons allows for the realization of the central and lateral band of the finger anatomy. Evaluated using the computer vision method, the proposed robotic finger demonstrates a range of motion (ROM) equivalent to 113%, 87% and 88% of the human dynamic ROM for the DIP, PIP and MCP joints, respectively. The proposed finger possesses a soft nature when relaxed and becomes firm when activated, pioneering a new approach in biomimetic robot design and offering a unique contribution to the future of generalist humanoid robots.

Association between time in therapeutic range of tacrolimus blood concentration and acute rejection within the first three months after lung transplantation.

BACKGROUND: Tacrolimus is a key drug in immunosuppressive therapy following lung transplantation. The blood tacrolimus levels are likely to fluctuate in the early postoperative period, and failure to maintain the tacrolimus trough level in target ranges is a risk factor for rejection. However, there is little information about the relationship between the time in therapeutic range (TTR) of the tacrolimus trough level (tacrolimus TTR) and clinical outcomes. This study aimed to evaluate the association between tacrolimus TTR and acute rejection (AR) within the first three months after lung transplantation. METHODS: This was a retrospective study of patients who underwent lung transplantation at a single center. The target tacrolimus trough levels were 10-15 ng/mL, and tacrolimus TTR was calculated using the Rosendaal method. The cut-off value of the tacrolimus TTR was estimated by receiver operating characteristic analysis based on AR. RESULTS: The study included 90 patients. AR was observed in 26 patients. In this study, ''early-AR'' was defined as any AR within 2 weeks post-transplant (n = 22) and ''late-AR'' was defined as any AR after 1-month post-transplant (n = 4). For early AR, the relationship between tacrolimus TTR and the onset of AR was examined. There were no differences in the tacrolimus TTR between the early-AR group and non-AR group (35.7 ± 22.4 vs 31.5 ± 19.9%, P = 0.416). For late-AR, the relationship with tacrolimus TTR was examined every 10 d. The tacrolimus TTR during postoperative days (POD) 21-30 and POD 31-onset was significantly lower in the late-AR group than the no-AR group (50.0 ± 7.1 vs. 71.8 ± 18.0% and 37.0 ± 26.6 vs. 68.9 ± 31.5%, P < 0.05, respectively). The cutoff value of the tacrolimus TTR during POD 21-30 was estimated as 55.0%. CONCLUSIONS: Our findings suggest that a lower tacrolimus TTR is a predictor of late AR. A tacrolimus TTR of 55% or higher is necessary to reduce the risk of AR during this period after lung transplantation.

Newly-established in vitro inner BRB spheroids to elucidate retinal Ang2-linked substance transfer.

Conjugation of angiopep-2 (Ang2) with drugs/compounds is known to increase plasma membrane permeability across endothelial barriers. The inner blood-retinal barrier (BRB) regulates retinal drug distribution and is formed by retinal capillary endothelial cells, supported by Müller cells and retinal pericytes. To elucidate the potential of Ang2 conjugation in promoting retinal drug distribution after peripheral administration across the inner BRB, an in vivo administration study and in vitro transport experiments using newly developed multicellular inner BRB spheroids were performed. After intravenous administration of Ang2-linked green fluorescence protein (GFP-Ang2) in mice, GFP-derived signals were observed in the neural retina. In contrast, GFP-derived signals were not observed after intravenous GFP administration, suggesting the promotion of the retinal distribution of substances by Ang2 conjugation. To overcome the limitations of in vitro studies using cells cultured on dishes, inner BRB spheroids were established using conditionally immortalized rat retinal capillary endothelial cells, Müller cells, and retinal pericytes. Immunocytochemistry of marker molecules suggests that the central part of the spheroids is occupied by Müller cells, and encapsulated by retinal pericytes and capillary endothelial cells. Studies on the expression and functions of tight junctions suggest that tight junctions are formed on the surface of the inner BRB spheroids by retinal capillary endothelial cells. The functional expression of drug transporters, such as P-glycoprotein, was observed in the spheroids, implying that the inner side of the spheroids reflects the retinal side of the inner BRB. In the inner BRB spheroids, energy-dependent accumulation of GFP-Ang2 and Ang2-linked 5(6)-carboxyfluorescein (FAM-Ang2) was observed. Moreover, an endocytic inhibition study revealed that clathrin-dependent endocytosis/transcytosis was involved in the transcellular transport of Ang2-conjugated drugs/compounds across the inner BRB. Consequently, it is suggested that the Ang2 linkage is useful for promoting retinal drug distribution via clathrin-dependent transcytosis at the inner BRB.

Assessment of Suvorexant and Eszopiclone as Alternatives to Benzodiazepines for Treating Insomnia in Patients With Major Depressive Disorder.

OBJECTIVES: We investigated the utility of switching from benzodiazepines to suvorexant or eszopiclone to manage benzodiazepine-unresponsive insomnia in patients with major depressive disorder (MDD) in a randomized, open-label study. METHODS: Patients with MDD who have insomnia symptoms (a score of >7 on the Insomnia Severity Index Japanese version [ISI-J]), who had received benzodiazepine treatment for more than 2 weeks (n = 18) were randomized to 4 weeks of suvorexant (20 or 15 mg/d) or eszopiclone (3 or 2 mg/d) treatment. The primary endpoint was an improvement in insomnia severity from baseline assessed by the ISI-J score at 2 and 4 weeks after switching from benzodiazepines. The secondary endpoints included changes in the scores of the Pittsburgh Sleep Quality Index Japanese version, the Beck Depression Inventory II, Generalized Anxiety Disorder 7, the digit span test, and the digit symbol substitution test from baseline. Adverse events were recorded throughout the study. RESULTS: Patients taking suvorexant or eszopiclone had improved ISI-J scores (-4.3 for suvorexant and -4.1 for eszopiclone at week 4; P = 0.04 for eszopiclone). Both drugs tended to improve the Beck Depression Inventory II and Generalized Anxiety Disorder 7 scores 2 and 4 weeks after switching. The Pittsburgh Sleep Quality Index Japanese version, digit symbol substitution test, and digit span test scores and the incidence of adverse events did not change from baseline. CONCLUSIONS: Switching to suvorexant or eszopiclone was well tolerated and improved the severity of benzodiazepine-unresponsive insomnia in MDD patients. Both drugs could be beneficial alternatives to benzodiazepines for treating insomnia in MDD patients.

Lubiprostone improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled 2-way crossover study.

BACKGROUND AND STUDY AIMS: Lubiprostone has been reported to be an anti-constipation drug. The aim of the study was to investigate the usefulness of lubiprostone both for bowel preparation and as a propulsive agent in small bowel endoscopy. PATIENTS AND METHODS: This was a double-blind, placebo-controlled, 2-way crossover study of subjects who volunteered to undergo capsule endoscopy (CE). A total of 20 subjects (16 male and 4 female volunteers) were randomly assigned to receive a 24-µg tablet of lubiprostone 120 minutes prior to capsule ingestion for CE (L regimen), or a placebo tablet 120 minutes prior to capsule ingestion for CE (P regimen). Main outcome was gastric transit time (GTT) and small-bowel transit time (SBTT). Secondary outcome was adequacy of small-bowel cleansing and the fluid score in the small bowel. The quality of the capsule endoscopic images and fluid in the small bowel were assessed on 5-point scale. RESULTS: The capsule passed into the small bowel in all cases. Median GTT was 57.3 (3 - 221) minutes for the P regimen and 61.3 (10 - 218) minutes for the L regimen ( P  = 0.836). Median SBTT was 245.0 (164 - 353) minutes for the P regimen and 228.05 (116 - 502) minutes for the L regimen ( P  = 0.501). The image quality score in the small bowel was 3.05 ±â€Š1.08 for the P regimen and 3.80 ±â€Š0.49 for the L regimen ( P  < 0.001). The fluid score in the small bowel was 2.04 ±â€Š1.58 for the P regimen and 2.72 ±â€Š1.43 for the L regimen ( P  < 0.001). There was a significant difference between the 2 regimens with regard to image quality. The fluid score was more plentiful for the L regimen than for the P regimen. There were no cases of capsule retention or serious adverse events in this study. CONCLUSION: Our study showed that use of lubiprostone prior to CE significantly improved visualization of the small bowel during CE as a result of inducing fluid secretion into the small bowel.

Intraspecific variation among Tetranychid mites for ability to detoxify and to induce plant defenses.

Two genotypes coexist among Kanzawa spider mites, one of which causes red scars and the other of which causes white scars on leaves, and they elicit different defense responses in host plants. Based on RNA-Seq analysis, we revealed here that the expression levels of genes involved in the detoxification system were higher in Red strains than White strains. The corresponding enzyme activities as well as performances for acaricide resistance and host adaptation toward Laminaceae were also higher in Red strains than White strains, indicating that Red strains were superior in trait(s) of the detox system. In subsequent generations of strains that had survived exposure to fenpyroximate, both strains showed similar resistance to this acaricide, as well as similar detoxification activities. The endogenous levels of salicylic acid and jasmonic acid were increased similarly in bean leaves damaged by original Red strains and their subsequent generations that inherited high detox activity. Jasmonic acid levels were increased in leaves damaged by original White strains, but not by their subsequent generations that inherited high detox activity. Together, these data suggest the existence of intraspecific variation - at least within White strains - with respect to their capacity to withstand acaricides and host plant defenses.

Is a fecal occult blood test a useful tool for judging whether to perform capsule endoscopy in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy?

BACKGROUND: Aspirin use is reportedly not to be associated with fecal immunochemical occult blood test (FIT) false-positive results for the detection of colorectal cancer. The need for additional small bowel exploration in FIT-positive, low-dose aspirin users with a negative colonoscopy is controversial. The aim of this study was to assess the ability of FIT to judge whether capsule endoscopy (CE) should be performed in low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy findings by comparing FIT results with CE findings. METHODS: A total of 264 consecutive low-dose aspirin users with negative colonoscopy and esophagogastroduodenoscopy who were scheduled to undergo CE at five hospitals in Japan were enrolled. Patients had been offered FIT prior to the CE. The association between the FIT results and the CE findings was then assessed. RESULTS: One hundred and fifty-seven patients were included in the final analysis. Eighty-four patients (53.5 %) had positive FIT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of positive FIT results for small bowel ulcers were 0.56, 0.47, 0.30, and 0.73, respectively. Furthermore, the NPV of positive FIT results for severe small bowel injury (Lewis score ≥790) was markedly high (0.90). When the analysis was performed only in low-dose aspirin users with anemia, the sensitivity of the positive FIT results was notably improved (0.72). CONCLUSIONS: Small bowel evaluation using CE is not recommended for FIT-negative, low-dose aspirin users. However, small bowel evaluation using CE should be considered in both FIT-positive and anemic low-dose aspirin users.

Can magnifying endoscopy with narrow-band imaging discriminate between carcinomas and low grade adenomas in gastric superficial elevated lesions?

Background and study aims: The aim of this study was to investigate the capability of magnifying endoscopy with narrow-band imaging (ME-NBI) to discriminate between early carcinomas (EC) and low grade adenomas (LGA) in gastric superficial elevated epithelial neoplasias. Patients and methods: We investigated 100 consecutive cases of gastric superficial elevated epithelial neoplasias that were removed using endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification; category 4 (mucosal high grade neoplasia) and category 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, whereas category 3 (mucosal low grade neoplasia) lesions were diagnosed as LGA. The associations between the postoperative pathological diagnoses and the ME-NBI findings were analyzed, and included the shape, specification, and area of irregularity in the microvascular architecture (MV) and the microsurface structure (MS). Results: Seventy-nine EC and 21 LGA cases diagnosed postoperatively were evaluated retrospectively. The lesion size (median; range (mm)) was significantly larger in the EC group (14; 2 - 95) compared to the LGA group (5; 2 - 16) (P < 0.001). Wavy forms in the MV shapes (P = 0.031), extension in the MV specifications (P = 0.035), and area with MV irregularity (P = 0.001) were found to be statistically significant predictive findings for EC. Villous forms in the MS shapes (P = 0.026), enlargement in the MS specifications (P = 0.044), and area with MS irregularity (P = 0.021) were also found to be statistically significant predictive findings for EC. The rates of preoperative sensitivity, specificity, and diagnostic accuracy of ME-NBI for discriminating EC were 86.1 %, 38.9 %, and 75 %, respectively. Conclusions: The present study suggests that ME-NBI is useful for the differential diagnosis of EC and LGA in gastric superficial elevated epithelial neoplasias. STUDY REGISTRATION: UMIN000012925.

Combination treatment with fingolimod and a pathogenic antigen prevents relapse of glucose-6-phosphate isomerase peptide-induced arthritis.

INTRODUCTION: Combination treatment with fingolimod (FTY720) plus pathogenic antigen is thought to prevent glucose-6-phosphate isomerase (GPI)325-339-induced arthritis progression by effective induction of immune tolerance. Here, we examined the efficacy of this combination treatment on remission maintenance. METHODS: GPI325-339-induced arthritis mice were treated for 5 days with FTY720 (1.0 mg/kg, p.o.) alone, GPI325-339 (10 µg/mouse, i.v.) alone, or with the FTY720 plus GPI325-339 combination. In some experiments, mice were resensitized with GPI325-339. RESULTS: Following resensitization with GPI325-339, combination-treated mice exhibited neither severe relapse nor elevated lymphocyte infiltration in joints. Neither anti-human nor mouse GPI325-339 antibody levels were correlated with clinical symptoms. This suggests that combination treatment prevents relapse following resensitization via regulation of pathogenic antigen-specific T cells. The proportion of regulatory T (Treg) cells in inguinal lymph nodes was increased post treatment in the FTY720 alone and FTY720 plus GPI325-339 groups. In contrast, the proportion of glucocorticoid-induced tumor necrosis factor receptor-family-related gene/protein (GITR)(+) non-Treg cells was increased only in combination-treated mice. Furthermore, GITR(+) non-Treg cells, which were induced by the combination treatment in vivo, possess suppressive activity and high ability to produce interleukin (IL)-10. CONCLUSION: GITR(+) non-Treg cells might play a key role in relapse prevention following resensitization. Thus, this combination treatment might establish immune tolerance by induction of GITR(+) non-Treg cells.

Diagnostic test accuracy of glutamate dehydrogenase for Clostridium difficile: Systematic review and meta-analysis.

We performed this systematic review and meta-analysis to assess the diagnostic accuracy of detecting glutamate dehydrogenase (GDH) for Clostridium difficile infection (CDI) based on the hierarchical model. Two investigators electrically searched four databases. Reference tests were stool cell cytotoxicity neutralization assay (CCNA) and stool toxigenic culture (TC). To assess the overall accuracy, we calculated the diagnostic odds ratio (DOR) using a DerSimonian-Laird random-model and area the under hierarchical summary receiver operating characteristics (AUC) using Holling's proportional hazard models. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. According to 42 reports consisting of 3055 reference positive comparisons, and 26188 reference negative comparisons, the DOR was 115 (95%CI: 77-172, I(2) = 12.0%) and the AUC was 0.970 (95%CI: 0.958-0.982). The summary estimate of sensitivity and specificity were 0.911 (95%CI: 0.871-0.940) and 0.912 (95%CI: 0.892-0.928). The positive and negative likelihood ratios were 10.4 (95%CI 8.4-12.7) and 0.098 (95%CI 0.066-0.142), respectively. Detecting GDH for the diagnosis of CDI had both high sensitivity and specificity. Considering its low cost and prevalence, it is appropriate for a screening test for CDI.

Evaluation of endoscopic findings for discriminating between early carcinomas and low-grade adenomas in superficial elevated gastric lesions.

BACKGROUND/AIMS: This study aimed to determine the useful endoscopic findings in a differential diagnosis between early carcinomas (EC) and low-grade adenomas (LGA) in superficial elevated gastric epithelial neoplasia during conventional endoscopy with white-light imaging (C-WLI). MATERIALS AND METHODS: We investigated 270 consecutive cases of superficial elevated gastric epithelial neoplasias, which were removed by endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification: category 4 (mucosal high-grade neoplasia) or 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, while category 3 (mucosal low-grade neoplasia) lesions were diagnosed as LGA. The association between the postoperative pathological diagnoses (EC or LGA) and the following endoscopic findings: localized site, lesion size, color (reddish or whitish), shape (smooth, petal, or irregular), and presences of depression, erosion, ulceration, or nodularity on the surface, were evaluated. RESULTS: Of 270 epithelial neoplasias, 222 (58 LGA and 164 EC) were retrospectively evaluated. Multiple logistic regression analysis revealed that the lesion size [odds ratio (OR), 1.216; p<0.001) and reddish color (OR, 5.274; p<0.001) were independent findings for EC. CONCLUSION: The lesion size and reddish color were useful optical findings for discriminating between EC and LGA.

Feasibility of deep sedation with a combination of propofol and dexmedetomidine hydrochloride for esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: The aim of the present study was to evaluate the efficacy and safety of sedation with a combination of propofol (PF) and dexmedetomidine (DEX) compared with sedation with benzodiazepines in esophageal endoscopic submucosal dissection (ESD). METHODS: We retrospectively reviewed clinical data for 40 consecutive patients who had undergone esophageal ESD at the Yokohama City University Hospital between July 2012 and August 2014. Of these patients, 20 were sedated with benzodiazepines (conventional group) and another 20 patients were sedated with a combination of PF and DEX (combination group). Parameters for efficacy and safety of sedation were evaluated by comparisons between the two groups. RESULTS: Median procedural times in the combination group were shorter than those in the conventional group (61 min vs. 89 min, P = 0.03), and the percentage of patients who showed restlessness in the combination group was significantly lower than that in the conventional group (25% vs. 65%, P = 0.025). Incidences of hypotension and bradycardia in the combination group were higher than those in the conventional group (60% vs. 15%, P = 0.008, and 60% vs. 15%, P = 0.008, respectively). CONCLUSION: This retrospective study suggests that a combination of PF and DEX may provide stable deep sedation with less body movement than benzodiazepines during esophageal ESD.

Clinical value of capsule endoscopy for detecting small bowel lesions in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: To evaluate the clinical value of capsule endoscopy (CE) in patients with intestinal Behçet's disease (BD). METHODS: The present study was a case-control pilot study conducted in intestinal BD patients and healthy volunteers. A total of 19 patients with intestinal BD (intestinal BD group) and 19 healthy volunteers (control group) matched for age and sex were enrolled. Frequency, number of small bowel lesions per subject, and Lewis score were comparatively evaluated between the two groups. RESULTS: Of the 19 patients with intestinal BD, 18 (94.7%) had reddened lesions, 15 (78.9%) had erosions, and nine (47.4%) had ulcers. There were significant differences in the frequency of reddened lesions (P < 0.0001), erosions (P < 0.0001) and ulcers (P = 0.0011) between the two groups. The difference in the number of small bowel lesions between the two groups was also statistically significant. The median Lewis score in the intestinal BD group was significantly higher than that in the control group (intestinal BD group 237 (0-768) vs. control group 8 (0-135); P < 0.0001). Analysis according to the location in the small bowel revealed that the frequency of ulcers tended to increase towards the distal intestine. CONCLUSION: This is the first CE study conducted to examine small bowel involvement in intestinal BD patients. Our results suggest that CE evaluation is necessary, in addition to colonoscopy, in all intestinal BD patients.

Visual distraction alone for the improvement of colonoscopy-related pain and satisfaction.

AIM: To evaluate the effect of a relaxing visual distraction alone on patient pain, anxiety, and satisfaction during colonoscopy. METHODS: This study was designed as an endoscopist-blinded randomized controlled trial with 60 consecutively enrolled patients who underwent elective colonoscopy at Yokohama City University Hospital, Japan. Patients were randomly assigned to two groups: group 1 watched a silent movie using a head-mounted display, while group 2 only wore the display. All of the colonoscopies were performed without sedation. We examined pain, anxiety, and the satisfaction of patients before and after the procedure using questionnaires that included the Visual Analog Scale. Patients were also asked whether they would be willing to use the same method for a repeat procedure. RESULTS: A total of 60 patients were allocated to two groups. Two patients assigned to group 1 and one patient assigned to group 2 were excluded after the randomization. Twenty-eight patients in group 1 and 29 patients in group 2 were entered into the final analysis. The groups were similar in terms of gender, age, history of prior colonoscopy, and pre-procedural anxiety score. The two groups were comparable in terms of the cecal insertion rate, the time to reach the cecum, the time needed for the total procedure, and vital signs. The median anxiety score during the colonoscopy did not differ significantly between the two groups (median scores, 20 vs 24). The median pain score during the procedure was lower in group 1, but the difference was not significant (median scores, 24.5 vs 42). The patients in group 1 reported significantly higher median post-procedural satisfaction levels, compared with the patients in group 2 (median scores, 89 vs 72, P = 0.04). Nearly three-quarters of the patients in group 1 wished to use the same method for repeat procedures, and the difference in rates between the two groups was statistically significant (75.0% vs 48.3%, P = 0.04). Patients with greater levels of anxiety before the procedure tended to feel a painful sensation. Among patients with a pre-procedural anxiety score of 50 or higher, the anxiety score during the procedure was significantly lower in the group that received the visual distraction (median scores, 20 vs 68, P = 0.05); the pain score during the colonoscopy was also lower (median scores, 23 vs 57, P = 0.04). No adverse effects arising from the visual distraction were recognized. CONCLUSION: Visual distraction alone improves satisfaction in patients undergoing colonoscopy and decreases anxiety and pain during the procedure among patients with a high pre-procedural anxiety score.

Early effects of oral administration of esomeprazole and omeprazole on the intragastric pH.

BACKGROUND/AIMS: The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral dose of a proton pump inhibitor, esomeprazole 20 mg and omeprazole 20 mg. METHODOLOGY: A total of 14 Helicobacter pylori-negative male subjects participated in this study. Intragastric pH was monitored continuously for 6 hours after a single oral dose of omeprazole 20 mg and a single oral dose of esomeprazole 20 mg. Each administration was separated by a 7-day washout period. RESULTS: During the 6-hour study period, the average pH after administration of esomeprazole was higher than that after the administration of omeprazole. Also during the 6-hour study period, each of pH > 2, 3, 3.5, 4, and 5 was maintained for a longer duration after administration of esomeprazole 20 mg than after administration of omeprazole 20 mg (median: 75.4% vs. 53.8%, p = 0.0138; 52.1% vs. 33.4%, p = 0.0188; 45.8% vs. 28.2%, p = 0.0262; 42.5% vs. 20.7%, p = 0.0414; 35.8% vs. 11.6%, p = 0.0262; respectively). CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, single oral administration of esomeprazole 20 mg increased the intragastric pH more rapidly than single oral administration of omeprazole 20 mg.

Low-dose ramosetron accelerates gastric emptying in the early phase: A crossover study in healthy volunteers using a continuous real-time 13C breath test (BreathID System).

BACKGROUND/AIMS: The aim of this study was to determine the correlation between low-dose ramosetron pre-treatment and gastric emptying using a novel, non-invasive technique for measuring gastric emptying, namely, the continuous real-time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). MATERIALS AND METHODS: Twelve healthy male volunteers participated in this randomized two-way crossover study. The subjects fasted overnight and were randomly assigned to receive the test meal (200 kcal per 200 mL) after an hour pre-treatment with 5 µg ramosetron or the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal with the 13C-acetic acid breath test performed continuously using the BreathID system. Using Oridion Research Software (ß version), T 1/2, T lag, GEC and the regression-estimated constants (ß and κ) were calculated. The differences in the parameters measured at two time-points were analyzed using Wilcoxon's signed-rank test. RESULTS: There was a significant difference in the calculated parameter ß. No significant differences in the calculated parameters T 1/2, T lag, GEC or κ were observed between the test meal with ramosetron group and the test meal alone group. CONCLUSION: This study showed that ramosetron pre-treatment enhances the early gastric emptying of liquid nutrients.

Association between factors associated with colorectal cancer and rectal aberrant crypt foci in humans.

Aberrant crypt foci (ACF) are regarded as potential biomarkers for colorectal cancer (CRC), and have been used as such in recent early-phase chemoprevention trials. However, the associations between the presence of ACF and other factors associated with the development of CRC, such as lifestyle factors, medication use and comorbid medical conditions, remain unknown. Thus, the present retrospective, large, cross-sectional study was conducted to evaluate the potential usefulness of ACF as a surrogate biomarker of CRC. Total colonoscopy was performed and the number of rectal ACF was counted in a total of 902 subjects. A retrospective review of the medical records of the study subjects was performed, and the factors associated with the increased prevalence of ACF was investigated using univariate and multivariate logistic regression analyses. The analysis results identified older age [odds ratio (OR), 9.24; 95% confidence interval (CI), 4.80-17.8; P<0.01], smoking habit (OR, 1.78; 95% CI, 1.20-2.63; P<0.01) and use of insulin (OR, 9.97; 95% CI, 1.28-77.5; P=0.03) as significant independent risk factors associated with the increased prevalence of ACF, regardless of the presence/absence of colon tumors. In addition, it was revealed that the prevalence and number of ACF, and the Ki-67 labeling indices of the colonic epithelial cells were significantly higher in diabetic patients receiving insulin therapy than in those not receiving insulin therapy (P<0.01, P=0.03 and P=0.01, respectively). In conclusion, the potential usefulness of ACF as a surrogate biomarker of CRC was confirmed, although useful data could not be obtained on candidate chemopreventive agents. These results indicated that insulin can enhance colonic epithelial proliferative activity and induce the formation of ACF, thereby possibly triggering CRC development.

Small bowel injury in low-dose aspirin users.

The use of low-dose aspirin (LDA) is well known to be associated with an increased risk of serious upper gastrointestinal complications, such as peptic ulceration and bleeding. Until recently, attention was mainly focused on aspirin-induced damage of the stomach and duodenum. However, recently, there has been growing interest among gastroenterologists on the adverse effects of aspirin on the small bowel, especially as new endoscopic techniques, such as capsule endoscopy (CE) and balloon-assisted endoscopy, have become available for the evaluation of small bowel lesions. Preliminary CE studies conducted in healthy subjects have shown that short-term administration of LDA can induce mild mucosal inflammation of the small bowel. Furthermore, chronic use of LDA results in a variety of lesions in the small bowel, including multiple petechiae, loss of villi, erosions, and round, irregular, or punched-out ulcers. Some patients develop circumferential ulcers with stricture. In addition, to reduce the incidence of gastrointestinal lesions in LDA users, it is important for clinicians to confirm the differences in the gastrointestinal toxicity between different types of aspirin formulations in clinical use. Some studies suggest that enteric-coated aspirin may be more injurious to the small bowel mucosa than buffered aspirin. The ideal treatment for small bowel injury in patients taking LDA would be withdrawal of aspirin, however, LDA is used as an antiplatelet agent in the majority of patients, and its withdrawal could increase the risk of cardiovascular/cerebrovascular morbidity and mortality. Thus, novel means for the treatment of aspirin-induced enteropathy are urgently needed.

Effects of ramosetron oral disintegrating tablets on gastric emptying: crossover study using the 13C-acetic acid breath test.

BACKGROUND/AIMS: Ramosetron is a new selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist that reportedly has more potent antiemetic effects than other 5-HT3 receptor antagonists. The aim of this study was to determine the effect of ramosetron pretreatment on gastric emptying using the 13C-acetic acid breath test. METHODOLOGY: Ten healthy male and female volunteers participated in this randomized, twoway crossover study. After they had fasted overnight, the subjects were randomly assigned to receive 0.1 mg ramosetron 1 hour before ingestion of a test meal (200 kcal per 200 mL, containing 100 mg 13C acetate) or to receive the test meal alone. Under both conditions, breath samples were collected for 150 min following ingestion of the meal. Statistical comparison of the parameters between the two test conditions was performed. RESULTS: No significant differences in the calculated parameters, including T 1/2, T lag, GEC or ß and κ, were observed between the two test conditions. CONCLUSIONS: The present study revealed that 0.1 mg ramosetron had no significant effect on the rate of gastric emptying. Thus, our results suggest that ramosetron can be administered safely, without gastrointestinal adverse effects, even to terminal cancer patients with delayed or accelerated gastric emptying abnormality.