Comparison of Two Types of 1-L Polyethylene Glycol-ascorbic Acid as Colonoscopic Bowel Preparation: A Prospective Randomized Study.

Background/Aims: Recently, 1-L polyethylene glycol-ascorbic acid (PEG-Asc) has been used to reduce the volume of preparation agents in colonoscopy. This clinical trial aimed to compare the efficacy and safety of two types of 1-L PEG-Asc (CleanViewAL® [Tae Joon Pharmaceutical Company, Seoul, Korea] and Plenvu® [Norgine, Harefield, United Kingdom]) in average-aged adults. Methods: This study was a prospective, randomized, non-inferiority, open-label, phase 4 clinical trial. The primary endpoint was the efficacy evaluated using the Boston bowel preparation scale (BBPS), and the secondary endpoint was clinical safety. Results: In total, 173 patients were assigned to either the CleanViewAL® (n=84) or Plenvu® (n=89) group. Overall cleansing successes of 97.6% (82/84) and 98.8% (88/89) were achieved in the CleanViewAL® group and in the Plenvu® group, respectively, showing that CleanViewAL® has similar bowel cleansing efficacy to Plenvu® (95% CI, -0.052 to 0.027; p=0.207). The total BBPS score was 8.67±1.00 and 8.70±0.76 in the CleanViewAL® group and Plenvu® group, respectively (p=0.869). The most common adverse symptom was nausea, and no adverse symptoms requiring hospitalization were reported in either group. There were no cases of critical hypernatremia and liver dysfunction exceeding the common terminology criteria for adverse events grade I. An overall satisfaction score (scale of 1 to 10) showed no difference between the two groups (p=0.289). However, the CleanViewAL® group showed a higher taste satisfaction score (scale of 1 to 5) than the Plenvu® group (CleanViewAL®: 2.90±0.91, Plenvu®: 2.60±0.86, p=0.028). Conclusions: Both types of 1-L PEG-Asc, CleanViewAL® and Plenvu®, are effective and safe bowel cleansing agents in average-aged adults. CleanViewAL® was preferred in terms of taste satisfaction.

[Usefulness of Stool Multiplex Polymerase Chain Reaction Assays in Patients with Acute Diarrhea].

Background/Aims: There is a recent increase in the use of stool multiplex PCR assay-based diagnostic tests in patients with acute diarrhea. We used multiplex PCR assays to analyze the distribution of diarrhea-causing bacteria and viruses, as well as the clinical features of patients with acute diarrhea. Methods: We retrospectively reviewed stool specimens of inpatients complaining of acute diarrhea from October 2018 to July 2020. The stool specimens had been tested for bacteria and viruses using multiplex PCR assays. Results: A total of 414 stool specimens from 346 patients were tested, and 152 pathogens were detected in 131 stool samples (131/414, 31.6%). Co-infection was detected in 20 patients (20/346, 5.8%). The common pathogens detected as causes of acute diarrhea, including co-infection, were Clostridium perfringens (34.9%), Clostridioides difficile (19.7%), and Campylobacter spp. (18.4%). The average age of patients with multiplex PCR-positive tests was lower than those with multiplex PCR-negative tests (p=0.001). In patients with suspected C. difficile infection (CDI), the RT-PCR for toxin gene assay was performed in 370 stool samples, 35 of which were positive (9.5%). Furthermore, 16 of the 35 samples were positive on the multiplex PCR assay (45.7%). Conclusions: The multiplex PCR assay revealed that C. perfringens was the most common diarrhea-causing pathogen. In addition, in patients with suspected CDI, the multiplex PCR assay alone was insufficiently sensitive to detect pathogens and a conventional CDI test was additionally required.

Evaluation of nutritional status using bioelectrical impedance analysis in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Nutritional status influences quality of life among patients with inflammatory bowel disease (IBD), although there is no clear method to evaluate nutritional status in this setting. Therefore, this study examined whether bioelectrical impedance analysis (BIA) could be used to evaluate the nutritional status of patients with IBD. METHODS: We retrospectively analyzed data from 139 Korean patients with IBD who were treated between November 2018 and November 2019. Patients were categorized as having active or inactive IBD based on the Harvey-Bradshaw index (a score of ≥5 indicates active Crohn's disease) and the partial Mayo scoring index (a score of ≥2 indicates active ulcerative colitis). BIA results and serum nutritional markers were analyzed according to disease activity. RESULTS: The mean patient age was 45.11±17.71 years. The study included 47 patients with ulcerative colitis and 92 patients with Crohn's disease. Relative to the group with active disease (n=72), the group with inactive disease (n=67) had significantly higher values for hemoglobin (P<0.001), total protein (P<0.001), and albumin (P<0.001). Furthermore, the group with inactive disease had higher BIA values for body moisture (P=0.047), muscle mass (P=0.046), skeletal muscle mass (P=0.042), body mass index (P=0.027), and mineral content (P=0.034). Moreover, the serum nutritional markers were positively correlated with the BIA results. CONCLUSIONS: Nutritional markers evaluated using BIA were correlated with serum nutritional markers and inversely correlated with disease activity. Therefore, we suggest that BIA may be a useful tool that can help existing nutritional tests monitor the nutritional status of IBD patients.

Successful Medical Treatment for Peritonitis Resulting from a Large Pyogenic Liver Abscess Rupture.

The rupture of a pyogenic liver abscess (PLA) with peritonitis is a rare occurrence but a surgical emergency with a high mortality rate in the case of gas-forming PLA. Rare cases of ruptured PLA that recovered completely with only medical treatment have been reported. This paper reports a case of a large PLA rupture with peritonitis. In this case, surgical intervention was too risky because of the patient's age and poor general condition. The patient recovered fully with appropriate antibiotic therapy and sufficient percutaneous drainage. Therefore, medical treatment may be considered an alternative option in cases of a ruptured large PLA with peritonitis if surgical intervention is too risky.

Variation in the rate of well-controlled status of chronic disease by income level in Korea: 2010 to 2015.

Although it is known that the prevalence rates of chronic diseases depend on income level, annual changes of the control rate have not been evaluated. In this cross-sectional study, we analyzed the variation in rate of well-controlled status of chronic diseases based on the annual income level using data from national nutrition surveys conducted between 2010 and 2015.Prevalence and controlled rate of hypertension, diabetes mellitus, and chronic kidney disease were analyzed in relation to annual income levels, using data from the Korea National Health and Nutrition Examination Survey (KNHANES), obtained from 2010 to 2015. We also analyzed the incidence of use of necessary medical care services and the reasons cited for not using these services.The data of 28,759 persons were analyzed. The average age increased, and sex ratio remained unchanged over the study period. Although the prevalence rates of diabetes increased, that of increased glycated hemoglobin gradually decreased. A significant change has been shown recently on the prevalence rates of hypertension patients. The prevalence rates of chronic kidney disease stayed unchanged during the course of the study period. The incidence of controlled chronic disease status increased with the income level, and over time during the study, in the case of diabetes and chronic kidney disease. However, while controlled hypertension status rate increased from year to year, there was no trend of increase with increased income level. The incidence of participants not using hospital services declined with increasing income level, but the rate of economic causes being cited as reasons for not using hospital services increased over time and showed no change among income levels. Results of regression analysis of prevalence rates of chronic diseases by income level showed that lower income groups tended to have higher odds ratios for chronic diseases.Our results suggest that the incidence rate of well-controlled chronic disease status remains low in lower income groups. These results imply that financial status may play an important role in the management of chronic diseases.

Lysophosphatidic acid activates ß-catenin/T cell factor signaling, which contributes to the suppression of apoptosis in H19-7 cells.

Lysophosphatidic acid (LPA) is a lipid growth factor that regulates diverse cell functions, including cell proliferation, survival and apoptosis. LPA has been demonstrated to be involved in the regulation of cortical neurogenesis by increasing the survival of neural precursors. Previously, we reported that LPA stimulated the inactivation of glycogen synthase kinase 3 (GSK3) via the G protein-coupled LPA1 and LPA2 receptors, by which apoptosis is suppressed in H19-7 cells [an embryonic hippocampal progenitor cell (HPC) line]. Increasing numbers of studies have demonstrated that certain G protein-coupled receptors activate ß-catenin/T cell factor (TCF) signaling independently of Wnt, which is involved in cell fate determination, cell proliferation and cell survival. To determine whether LPA activates ß-catenin-mediated transcriptional activation pathways and whether ß-catenin/TCF signaling is involved in neurogenesis by controlling the survival of neural precursors, ß-catenin/TCF signaling cascades induced by LPA were investigated in the HPCs. Activation of ß-catenin/TCF signaling was determined by the nuclear translocation of ß-catenin and the transcriptional activation of a TCF reporter gene. The activation of ß-catenin/TCF signaling was blocked by pertussis toxin (PTX) and a protein kinase C (PKC) inhibitor. The expression of a constitutively active mutated form of GSK3ß activated ß-catenin/TCF signaling to comparable levels to those induced by LPA, and protected against apoptosis in differentiating H19-7 cells. These results showed that LPA activates ß-catenin/TCF signaling in a PTX- and PKC-dependent manner, which contributes to LPA-induced cell survival in the HPCs. Activation of ß-catenin/TCF signaling by LPA may be involved in neurogenesis by controlling the survival of neural precursors.

Human group V secretory phospholipase A2 is associated with lipid rafts and internalized in a flotillin­dependent pathway.

The mechanisms of secretory phospholipase A2 (sPLA2) action are not understood clearly. Previously, it was suggested that sPLA2s are internalized into cells for the targeting of sPLA2 to intracellular action sites. However, the mechanisms for sPLA2 internalization remain to be identified. The present study demonstrated for the first time that human group V sPLA2 (hVPLA2) is associated with lipid rafts and is internalized in a flotillin­dependent pathway. The lipid raft association was probed by cholesterol­sensitive enrichment of hVPLA2 in low­density fractions and co­patching of ganglioside GM1 rafts through cross­linking of hVPLA2 in HEK293 and CHO cells. The hVPLA2 associated with lipid rafts was shown to be internalized into HEK293 cells at a relatively rapid rate (t1/2 =16 min) and this internalization was inhibited by the knockdown of flotillin­1, but not by chlorpromazine, an inhibitor of clathrin­mediated endocytosis. Moreover, internalized hVPLA2 was shown to be colocalized extensively with flotillin­1 in a punctate structure, but not caveolin­1. These data revealed that the internalization of hVPLA2 is mediated by flotillin­1. Attenuation of arachidonic acid release from plasma membrane through the association of hVPLA2 with lipid rafts suggested that this association with lipid rafts may be important in protecting mammalian cells from excessive degradation of plasma membrane and trafficking hVPLA2 into intracellular targets.

Antiproliferative and cytotoxic effects of resveratrol in mitochondria-mediated apoptosis in rat b103 neuroblastoma cells.

Resveratrol, a natural compound, has been shown to possess anti-cancer, anti-aging, anti-inflammatory, anti-microbial, and neuroprotective activities. In this study, we examined the antiproliferative and cytotoxicity properties of resveratrol in Rat B103 neuroblastoma cells; although it's molecular mechanisms for the biological effects are not fully defined. Here, we examined the cellular cytotoxicity of resveratrol by cell viability assay, antiproliferation by BrdU assay, DNA fragmentation by DNA ladder assay, activation of caspases and Bcl-2 family proteins were detected by western blot analyses. The results of our investigation suggest that resveratrol increased cellular cytotoxicity of Rat B103 neuroblastoma cells in a dose-and time-dependent manner with IC(50) of 17.86 µM at 48 h. On the other hand, incubation of neuroblastoma cells with resveratrol resulted in S-phase cell cycle arrests which dose-dependently and significantly reduced BrdU positive cells through the downregulation of cyclin D1 protein. In addition, resveratrol dose-dependently and significantly downregulated the expression of anti-apoptotic protein includes Bcl-2, Bcl-xL and Mcl-1 and also activates cleavage caspase-9 and-3 via the downregulation of procaspase-9 and -3 in a dose-dependent manner which indicates that involvement of intrinsic mitochondria-mediated apoptotic pathway. In conclusion, resveratrol increases cellular cytotoxicity and inhibits the proliferation of B103 neuroblastoma cells by inducing mitochondria-mediated intrinsic caspase dependent pathway which suggests this natural compound could be used as therapeutic purposes for neuroblastoma malignancies.

Lysophosphatidic acid induces neurite retraction in differentiated neuroblastoma cells via GSK-3ß activation.

Lysophosphatidic acid (LPA) is a lipid growth factor that exerts diverse biological effects, including rapid neurite retraction and cell migration. Alterations in cell morphology, including neurite retraction, in neurodegenerative disorders such as Alzheimer's disease involve hyperphosphorylation of the cytoskeletal protein tau. Since LPA has been shown to induce neurite retraction in various cultured neural cells and the detailed underlying molecular mechanisms have not yet been elucidated, we investigated whether LPA induced neurite retraction through taumediated signaling pathways in differentiated neuroblastoma cells. When Neuro2a cells differentiated with retinoic acid (RA) were exposed to LPA, cells exhibited neurite retraction in a time-dependent manner. The retraction of neurites was accompanied by the phosphorylation of tau. The LPA-induced neurite retraction and tau phosphorylation in differentiated Neuro2a cells were significantly abolished by the glycogen synthase kinase-3ß (GSK-3ß) inhibitor lithium chloride. Interestingly, the LPA-stimulated tau phosphorylation and neurite retraction were markedly prevented by the administration of H89, an inhibitor of both cyclic-AMP dependent protein kinase (PKA) and cyclic-AMP response element-binding protein (CREB). Transfection of the dominant-negative CREBs, K-CREB and A-CREB, failed to prevent LPA-induced tau phosphorylation and neurite retraction in differentiated Neuro2a cells. Taken together, these results suggest that GSK-3ß and PKA, rather than CREB, play important roles in tau phosphorylation and neurite retraction in LPA-stimulated differentiated Neuro2a cells.

Lysophosphatidylcholine-induced apoptosis in H19-7 hippocampal progenitor cells is enhanced by the upregulation of Fas Ligand.

Lysophospholipids regulate a wide array of biological processes including apoptosis and neutrophil migration. Fas/Apo-1 and its ligand (FasL) participate in neuronal cell apoptosis causing various neurological diseases. Here, we use hippocampal neuroprogenitor cells to investigate how lysophosphatidylcholine (LPC) induces apoptosis in H19-7 hippocampal progenitor cells via Fas/Fas ligand-mediated apoptotic signaling pathway. Exposed cells with LPC presented on apoptotic morphology, positive TUNEL staining, and DNA fragmentation. We found that the expression of FasL was increased after LPC treatment. Furthermore, LPC-induced H19-7 cell apoptosis was decreased by agonistic anti-FasL antibody. In addition to promotion of caspase cascade activity by LPC, the administration of the caspase inhibitor, DEVD-fmk, prevented H19-7 cell apoptosis. LPC also increased the activation of nuclear factor-kappaB (NF-kappaB), which in turn, significantly increased FasL mRNA level. The increase in FasL mRNA level by NF-kappaB transfection was significantly decreased in the presence of IkappaB-SR, a super-repressor of IkappaB. Taken together, these results demonstrate that LPC has the ability to induce apoptosis in H19-7 cells through the upregulation of FasL expression via NF-kappaB activation.