Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes.

BACKGROUND/AIMS: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. METHODS: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. RESULTS: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the ß-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the ß-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05). CONCLUSION: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.

Effect of pitavastatin on erythrocyte membrane fatty acid content in patients with chronic kidney disease: two-arm parallel randomized controlled trial.

Background: Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment. Methods: A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively. Results: In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment. Conclusion: Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.

Indoxyl Sulfate Might Play a Role in Sarcopenia, While Myostatin Is an Indicator of Muscle Mass in Patients with Chronic Kidney Disease: Analysis from the RECOVERY Study.

Serum myostatin and indoxyl sulfate (IS) levels increase with kidney function decline and may function as uremic toxins in chronic kidney disease (CKD)-related sarcopenia. Herein, we analyzed the association between serum myostatin and IS levels and sarcopenia in patients with CKD, by performing a post hoc analysis of baseline data extracted from the RECOVERY study (clinicaltrials.gov: NCT03788252) of 150 patients with CKD. We stratified patients into two groups according to the median value of myostatin (cutoff 4.5 ng/mL) and IS levels (cutoff 0.365 mg/dL). The proportion of patients with sarcopenia was higher in those with high IS levels but lower in those with high myostatin levels. The skeletal muscle mass index (SMI) and handgrip strength (HGS) were significantly lower in patients with high IS levels but significantly higher in patients with high myostatin levels. IS levels showed a negative correlation with glomerular filtration rate (GFR), SMI, and HGS. However, myostatin levels were positively correlated with SMI and HGS, but not with GFR. Sarcopenia was independently associated with age and IS level after adjustment. Increased levels of serum total IS might play a role in sarcopenia, while increased levels of serum myostatin are associated with muscle mass in patients with CKD.

Primary bile acid activates Egr­1 expression through the MAPK signaling pathway in gastric cancer.

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI­N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids in vitro upregulated the expression of early growth response factor 1 (Egr­1) and the oncogenes including c­Jun, c­Myc and Snail, whereas a p42/44 MAPK inhibitor exposure reduced their expression. There was a significant difference in age and presence of atrophic gastritis with intestinal metaplasia in background mucosa between controls and patients with EGC. There were significant differences in the levels of unconjugated or conjugated primary bile acids between controls and EGC patients except lithocholic acid. After adjustment of age and presence of atrophic gastritis with intestinal metaplasia, the levels of cholic acid [adjusted odds ratio (aOR) 4.3; 95% confidence interval (CI): 1.2­16.2; P=0.029] and glycochenodeoxycholic acid [aOR 9.9; 95% CI: 1.3­75.3; P=0.027] were significantly higher in patients with EGC compared with controls. In conclusion, bile acids upregulate Egr­1 in gastric cancer cells via the MAPK signaling pathway, and higher gastric levels of primary bile acids are associated with EGC. Therefore, exposure of gastric cells to primary bile acids may play a role in gastric carcinogenesis.

Omega-3 fatty acid and menaquinone-7 combination are helpful for aortic calcification prevention, reducing osteoclast area of bone and Fox0 expression of muscle in uremic rats.

BACKGROUND: Osteopenia, sarcopenia, and vascular calcification (VC) are prevalent in patients with chronic kidney disease and often coexist. In the absence of proven therapies, it is necessary to develop therapeutic or preventive nutrients supplementation for osteopenia, sarcopenia, and VC. The present study investigated the effect of omega-3 fatty acid (FA) and menaquinone-7 (MK-7) on osteopenia, sarcopenia, and VC in adenine and low-protein diet-induced uremic rats. METHODS: Thirty-two male Sprague-Dawley rats were fed diets containing 0.75% adenine and 2.5% protein for three weeks. Rats were randomly divided into four groups that were fed diets containing 2.5% protein for four weeks: adenine control (0.9% saline), omega-3 FA (300 mg/kg/day), MK-7 (50 µg/kg/day), and omega-3 FA/MK-7. Von Kossa staining for aortic calcification assessment was performed. Osteoclast surface/bone surface ratio (OcS/BS) of bone and muscle fiber were analyzed using hematoxylin and eosin staining. Osteoprotegerin (OPG) immunohistochemical staining was done in the aorta and bone. Molecules related with sarcopenia were analyzed using western blotting. RESULTS: Compared to the normal control, OcS/BS and aortic calcification, and OPG staining in the aorta and bone were significantly increased in the adenine controls. OPG staining and aortic calcification progressed the least in the group supplemented with both omega-3 FA/MK-7. In the adenine controls, the regular arrangement of muscle fiber was severely disrupted, and inflammatory cell infiltration was more prominent. These findings were reduced after combined supplementation with omega-3 FA/MK-7. Furthermore, decreased mammalian target of rapamycin and increased Forkhead box protein 1 expression was significantly restored by combined supplementation. CONCLUSIONS: Combined nutrients supplementation with omega-3 FA and MK-7 may be helpful for aortic VC prevention, reducing osteoclast activation and improving sarcopenia-related molecules in adenine and low-protein diet induced uremic rats.

Potential Impact of the Involvement of Clinical Pharmacists in Antimicrobial Stewardship Programs on the Incidence of Antimicrobial-Related Adverse Events in Hospitalized Patients: A Multicenter Retrospective Study.

Although specialized pharmacists have been suggested to be essential members of antimicrobial stewardship programs (ASPs), not all hospitals in Korea operate ASPs with pharmacists involved. We aimed to evaluate the association of involvement of clinical pharmacists as team members of multidisciplinary ASPs with the incidence of antimicrobial-related adverse drug events (ADEs). Five tertiary teaching hospitals participated in this retrospective cohort study. At each participating hospital, we randomly selected 1000 participants among patients who had received systemic antimicrobial agents for more than one day during the first quarter of 2017. We investigated five categories of antimicrobial-related ADEs: allergic reactions, hematologic toxicity, nephrotoxicity, hepatotoxicity, and antimicrobial-related diarrhea. Multivariate logistic regression analysis was used to evaluate the potential impact of pharmacist involvement in ASPs on the incidence of ADEs. A total of 1195 antimicrobial-related ADEs occurred in 618 (12.4%) of the 4995 patients included in the analysis. The overall rate of ADE occurrence was 17.4 per 1000 patient days. Hospitals operating ASPs with pharmacists showed significantly lower AE incidence proportions than other hospitals (8.9% vs. 14.7%; p < 0.001). Multidisciplinary ASPs that included clinical pharmacists reduced the risk of antimicrobial-related ADEs by 38% (adjusted odds ratio 0.62; 95% confidence interval 0.50-0.77). Our results suggest that the active involvement of clinical pharmacists in multidisciplinary ASPs may contribute to reduce the incidence of antimicrobial-related ADEs in hospitalized patients.

Comparison of clinical outcome between incremental peritoneal dialysis and conventional peritoneal dialysis: a propensity score matching study.

BACKGROUND: Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not. METHODS: We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day. RESULTS: The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM. CONCLUSIONS: Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.

2-D08 treatment regulates C2C12 myoblast proliferation and differentiation via the Erk1/2 and proteasome signaling pathways.

SUMOylation is one of the post-translational modifications that involves the covalent attachment of the small ubiquitin-like modifier (SUMO) to the substrate. SUMOylation regulates multiple biological processes, including myoblast proliferation, differentiation, and apoptosis. 2-D08 is a synthetically available flavone, which acts as a potent cell-permeable SUMOylation inhibitor. Its mechanism of action involves preventing the transfer of SUMO from the E2 thioester to the substrate without influencing SUMO-activating enzyme E1 (SAE-1/2) or E2 Ubc9-SUMO thioester formation. However, both the effects and mechanisms of 2-D08 on C2C12 myoblast cells remain unclear. In the present study, we found that treatment with 2-D08 inhibits C2C12 cell proliferation and differentiation. We confirmed that 2-D08 significantly hampers the viability of C2C12 cells. Additionally, it inhibited myogenic differentiation, decreasing myosin heavy chain (MHC), MyoD, and myogenin expression. Furthermore, we confirmed that 2-D08-mediated anti-myogenic effects impair myoblast differentiation and myotube formation, reducing the number of MHC-positive C2C12 cells. In addition, we found that 2-D08 induces the activation of ErK1/2 and the degradation of MyoD and myogenin in C2C12 cells. Taken together, these results indicated that 2-D08 treatment results in the deregulated proliferation and differentiation of myoblasts. However, further research is needed to investigate the long-term effects of 2-D08 on skeletal muscles.

Effect of pravastatin on erythrocyte membrane fatty acid contents in patients with chronic kidney disease.

BACKGROUND: Statin treatment has decreased the risk of cardiovascular events in patients with chronic kidney disease (CKD). Erythrocyte membrane oleic acid level is higher in patients with acute coronary syndrome. This study aimed to evaluate the effect of pravastatin on the erythrocyte membrane fatty acid (FA) contents in patients with CKD. METHODS: Sixty-two patients were enrolled from January 2017 to March 2019 (NCT02992548). Pravastatin was initially administered at a dose of 20 mg for 24 weeks. The pravastatin dose was increased to 40 mg after 12 weeks if it was necessary to control dyslipidemia. The primary outcome was change in erythrocyte membrane FA, including oleic acid, after pravastatin treatment for 24 weeks. RESULTS: Forty-five patients finished this study, and there was no adverse effect related to pravastatin. Compared with baseline, total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased after pravastatin treatment. Compared with baseline, saturated FA, oleic acid, and arachidonic acid levels were significantly increased and polyunsaturated FA and linoleic acid (LA) levels were significantly decreased after pravastatin treatment. There was also a decrease in eicosapentaenoic acid after pravastatin treatment in CKD patients with estimated glomerular filtration rate <60 mL/min/1.73 m2. CONCLUSION: Administration of pravastatin in patients with CKD leads to a decrease in FA known to be protective against the risk of CVD. Omega-3 FA or LA supplementation might be necessary to recover changes in erythrocyte membrane FA contents when pravastatin is used for treating dyslipidemia in patients with CKD.

Omega-3 Fatty Acids Upregulate SIRT1/3, Activate PGC-1α via Deacetylation, and Induce Nrf1 Production in 5/6 Nephrectomy Rat Model.

Mitochondrial dysfunction contributes to the pathogenesis of kidney injury related with cardiovascular disease. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protects renal tubular cells by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2). AMP-activated protein kinase (pAMPK)-mediated phosphorylation and sirtuin 1/3 (SIRT1/3)-mediated deacetylation are required for PGC-1α activation. In the present study, we aimed to investigate whether omega-3 fatty acids (FAs) regulate the expression of mediators of mitochondrial biogenesis in 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were assigned to the following groups: sham control, Nx, and Nx treated with omega-3 FA. The expression of PGC-1α, phosphorylated PGC-1α (pPGC-1α), acetylated PGC-1α, and factors related to mitochondrial biogenesis was examined through Western blot analysis. Compared to the control group, the expression of PGC-1α, pAMPK, SIRT1/3, Nrf1, mTOR, and Nrf2 was significantly downregulated, and that of Keap 1, acetylated PGC-1α, and FoxO1/3, was significantly upregulated in the Nx group. These changes in protein expression were rescued in the omega-3 FA group. However, the expression of pPGC-1α was similar among the three groups. Omega-3 FAs may involve mitochondrial biogenesis by upregulating Nrf1 and Nrf2. This protective mechanism might be attributed to the increased expression and deacetylation of PGC-1α, which was triggered by SIRT1/3.

Expression of Cyr61 is associated with clinical course in patients with Crohn's disease.

BACKGROUNDS: Cysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn's disease (CD). METHODS: Endoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients. RESULTS: The mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20-0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03). CONCLUSIONS: Cyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.

Combined Treatment with Omega-3 Fatty Acid and Cholecalciferol Increases 1,25-Dihydroxyvitamin D Levels by Modulating Dysregulation of Vitamin D Metabolism in 5/6 Nephrectomy Rats.

The protein 1α-hydroxylase (CYP27B1) was expressed in liver and omega-3 fatty acid (FA) elevated 1,25-dihydroxyvitamin D [1,25(OH)2D] levels in dialysis patients. The aim of this study was to determine whether omega-3 FA and cholecalciferol have effects on vitamin D metabolism related to CYP27B1 and 24-hydroxylase (CYP24) activities in the kidney and liver of 5/6 nephrectomy (Nx) rats. Male Sprague-Dawley rats were divided into the following groups: sham control, 5/6 Nx, 5/6 Nx treated with cholecalciferol, 5/6 Nx treated with omega-3 FA, and 5/6 Nx treated with cholecalciferol/omega-3 FA. CYP27B1 and CYP24 expression were measured in the liver and kidney. Further, 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] levels were measured in serum. Among Nx groups, 1,25(OH)2D and 25(OH)D levels were lowest in the 5/6 Nx group. CYP24 expression was increased in the kidney of the 5/6 Nx rat model, which was found to be reversed by omega-3 FA or cholecalciferol/omega-3 FA supplementation. Decreased CYP27B1 expression was observed in the liver of the 5/6 Nx rats and its expression was recovered by supplementation with cholecalciferol/omega-3 FA. In conclusion, omega-3 FA and cholecalciferol may synergistically increase 1,25(OH)2D levels by inhibiting CYP24 expression in the kidney and liver and activating CYP27B1 expression in the liver of 5/6 Nx rats.

Serum myostatin levels are associated with abdominal aortic calcification in dialysis patients.

BACKGROUND: Serum myostatin levels are increased according to renal function decline and myostatin may be a main mediator of chronic kidney disease-related sarcopenia. A previous study reported that serum myostatin level was negatively associated with abdominal aortic calcification (AAC) in older males. The aim of this study was to assess the association between serum myostatin level and AAC among dialysis patients of both sexes. In addition, we analyzed the relationship between serum myostatin level, muscle mass, and bone mineral density (BMD). METHODS: In this cross-sectional study, we evaluated AAC in the lateral lumbar spine using plain radiography and BMD in 71 patients undergoing dialysis. We classified patients into two groups according to the median value of myostatin as follows: those with high myostatin levels (≥ 5.0 ng/mL) and those with low myostatin levels (< 5.0 ng/mL). RESULTS: The proportion of patients with an AAC score of five points or more was higher among those with low myostatin levels. Myostatin level was negatively associated with AAC scores on plain radiography and had a positive association with skeletal muscle mass and T-scores for BMD measured at the total hip and femur neck. Lower myostatin levels were independently associated with higher AAC scores following adjustment for age, sex, diabetes mellitus, dialysis vintage, dialysis modality, and osteoprotegerin level. CONCLUSION: Lower serum myostatin levels were associated with higher AAC scores, lower muscle mass, and lower BMD in dialysis patients. Further, prospective studies and those with larger cohorts are necessary to validate these findings.

Supplementary nutrients for prevention of vascular calcification in patients with chronic kidney disease.

Vascular calcification (VC) and malnutrition associated with cardiovascular disease are common in patients with chronic kidney disease (CKD) treated with dialysis. VC, which reflects vascular aging, and malnutrition are also encountered in the non-CKD elderly population. This similarity of clinical findings suggests that the progression of CKD is related to aging and the existence of a causal relationship between VC and malnutrition. To retard renal progression, a low- or very-low-protein diet is usually recommended for CKD patients. Dietary education may induce malnutrition and deficiency of important nutrients, such as vitamins K and D. Menaquinone-7, a type of vitamin K2, is under investigation for inhibiting VC in elderly patients without CKD, as well as for prevention of VC in patients with CKD. Nutritional vitamin D, such as cholecalciferol, may be considered to decrease the required dose of active vitamin D, which increases the risk of VC due to increased calcium and phosphate loads. Omega-3 fatty acids are important nutrients and their ability to inhibit VC needs to be evaluated in clinical trials. This review focuses on the ability of supplementary nutrients to prevent VC in patients with CKD, in whom dietary restriction is essential.

Omega-3 fatty acid decreases oleic acid by decreasing SCD-1 expression in the liver and kidney of a cyclosporine-induced nephropathy rat model.

AIM: Stearoyl-CoA desaturase (SCD)-1 and elongase-6 (Elovl-6) are associated with fatty acid (FA) synthesis. We evaluated the effect of omega-3 FA on erythrocyte membrane FA contents through SCD-1 and Elovl-6 expression in the liver and kidney of a cyclosporine (CsA)-induced rat model. METHODS: Male Sprague Dawley rats were divided into control, CsA, and CsA treated with omega-3 FA groups. We measured SCD-1 and Elovl-6 expression levels via western blot and immunohistochemistry analysis. RESULTS: Erythrocyte membrane oleic acid content was lower in the CsA with omega-3 FA group compared to the CsA group. Compared to the control group, CsA-induced rats showed elevated SCD-1 expression in the kidney and liver, which omega-3 FA treatment reversed. Elovl-6 expression was increased in the liver, but decreased in the kidney in CsA group compared to control, which omega-3 FA treatment also reversed. CONCLUSIONS: Omega-3 FA supplementation decreased erythrocyte membrane oleic acid content by modulating SCD-1 and Elovl-6 expression in the kidney and liver of CsA-induced rats.

Lower expression of endogenous intestinal alkaline phosphatase may predict worse prognosis in patients with Crohn's disease.

BACKGROUNDS: Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn's disease (CD). METHODS: A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. RESULTS: Median age of patients was 22.5 years (range, 15-49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months-54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). CONCLUSION: Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

Impact of Blood or Erythrocyte Membrane Fatty Acids for Disease Risk Prediction: Focusing on Cardiovascular Disease and Chronic Kidney Disease.

Fatty acids (FAs) are essential nutrients and main constituents of cell membranes that are involved in the signaling pathway and associated with health conditions. We investigated if blood or erythrocyte membrane FAs can predict the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and related complications. Omega-3 (n-3) FAs are important predictors for metabolic syndrome, diabetes, CVD, and CKD risks, and the n-3 index is also a good biomarker for sudden cardiac death in coronary artery disease. Linoleic acid, which is one of the major n-6 FAs reflecting recent dietary FA intake, may predict CVD risk and mortality in the general population and patients with CKD. Monounsaturated FAs (MUFAs) are also related to diabetes or diabetic nephropathy. Oleic acid, a major MUFA, is an emerging marker that is related to acute coronary syndrome, low glomerular filtration rate, and vascular calcification in patients with CKD, and can be modified by n-3 FA supplementation. Saturated FAs, trans-FAs, and FA desaturation/elongation are associated with CVD risk; however, few studies have been conducted on patients with CKD. In summary, blood or erythrocyte membrane FA measurements are important for CVD and CKD risk prediction and management. Further studies are needed to elucidate the FAs for their risk predictions.

Early technical complications and long-term survival of urgent peritoneal dialysis according to break-in periods.

BACKGROUND: Guidelines recommend a break-in period of 2 weeks before starting peritoneal dialysis (PD), but PD within 14 days is also an acceptable and safe alternative to hemodialysis (HD) in patients with an urgent need. However, the effect of the break-in period within 48 hours or later had not been evaluated for early technical complications, long-term maintenance, and survival in patients starting urgent PD. METHODS: Of 360 patients with a surgically inserted PD catheter, we evaluated 190 patients who needed urgent PD and 29 patients who received conventional PD at a single center between January 2007 and December 2014 in this retrospective observational study. Enrolled patients were divided according to break-in period of <48 hours (P1) or 2-13 days (P2) before starting urgent PD. The primary endpoint was incidence of early technical complications and secondary endpoints included long-term PD maintenance, and patient survival. RESULTS: PD was started in 103 patients (54.2%) within 48 hours and in 87 patients (45.8%) within 2 to 13 days. The incidence of early technical complication was significantly higher in P1 group (28.2%) than in P2 group (10.3%) (P = 0.002). The need for a repositioning procedure was significantly greater in P1 group (14.6%) than in P2 group (3.4%) (P = 0.009). However, we observed no significant differences between the two groups with respect to the prevalence of catheter dysfunction requiring change to HD within 6 months or incidence of peritonitis or exit-site infection. There was no significant difference in PD maintenance and patient survival according to the break-in period between P1 and P2 as well as against the control group. CONCLUSION: Urgent PD was associated with a low incidence of early technical complications if start was avoided within 48 hours after catheter insertion, and long-term PD maintenance was independent of the break-in period.

Effect of Omega-3 Fatty Acid on STAMP2 Expression in the Heart and Kidney of 5/6 Nephrectomy Rat Model.

Six transmembrane protein of prostate 2 (STAMP2) is a critical modulator of inflammation and metabolism in adipose tissue. There are no data on the expression of STAMP2 in chronic kidney disease, which is an inflammatory disease related to metabolic disorders. This study aimed to investigate STAMP2 expression in the kidney and heart in 5/6 nephrectomy (Nx) rats, and the effect of omega-3 fatty acid (FA) on STAMP2 expression. Male Sprague Dawley rats were divided into three groups: sham control (0.9% saline), 5/6 Nx (0.9% saline), and 5/6 Nx treated with omega-3 FA (300 mg per kg per day by gastric gavage). The expression of STAMP2 in the kidney and heart were examined by western blotting. Serum creatinine levels were higher in 5/6 Nx rats than in controls. Compared with sham controls, the expression of IκB, NF-κB, NOX4, SREBP-1, and LXR were upregulated and STAMP2 and phosphorylated-AMPK expression were downregulated in the kidney and heart of 5/6 Nx rats. Omega-3 FA supplementation prevented these changes in biomarkers related to inflammation and metabolic lipid disorders. Omega 3-FA supplementation induced the upregulation of STAMP2 protein in 5/6 Nx rats, which was associated with an attenuation of inflammation- and metabolic disease-related markers.

Key lime (Citrus aurantifolia) inhibits the growth of triple drug resistant Helicobacter pylori.

BACKGROUND: Eradication rate for Helicobacter pylori (H. pylori) has decreased due to antibiotic resistance. Therefore, new strategies are needed to enhance H. pylori eradication, especially for H. pylori with high antibiotic resistance. The objective of this study was to evaluate anti-H. pylori activities of constituents from key lime (Citrus aurantifolia) and their possible inhibitory effects on urease activity of H. pylori. METHODS: Helicobacter pylori strain ATCC 43526 and triple drug resistant (TDR) H. pylori strains were used in this study. Urease activities of H. pylori strains were measured by ammonia colorimetrical quantification using ELISA reader. Minimum inhibitory concentrations were determined by agar dilution method for antibiotics and by modified media dilution method for each constituent of Citrus aurantifolia (C. aurantifolia). RESULTS: Citrus aurantifolia extract decreased the number of colonies of H. pylori strain ATCC 43526 and TDR H. pylori stains. An increasing concentration of C. aurantifolia extract attenuated urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains. Among constituents of C. aurantifolia, citral and 4-hexen-3-one were found to be able to inhibit the growth of H. pylori strain ATCC 43526 and TDR H. pylori strains. Furthermore, citral and 4-hexen-3-one inhibited urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains in a dose-dependent manner. CONCLUSION: Citrus aurantifolia has antimicrobial effect on TDR H. pylori strains, suggesting that C. aurantifolia might have therapeutic potential to control antibiotic-resistant H. pylori strains that cause eradication failure using other antibiotics.