Association Between Cerebral Microbleeds and Circulating Levels of Mid-Regional Pro-Adrenomedullin.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored. OBJECTIVE: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment. METHODS: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (< 0.65 nmol/L) or high (≥0.65 nmol/L). RESULTS: The mean MR-proADM level was 0.515±0.127 nmol/L. There were significant between-group differences in age, hypertension, and HbA1c levels (p < 0.05). In the high MR-proADM group, the MR-proADM level was associated with the identification of MBs on brain MR images and indications of mild cognitive impairment (MCI). In participants with ≥3 MBs and MCI, high MR-proADM levels remained a risk factor after multivariate adjustment (OR: 2.94; p < 0.05). CONCLUSION: High levels of MR-proADM may be a surrogate marker for the early detection of cognitive decline associated with the formation of cerebral MBs. This marker would be valuable during routine clinical examinations of geriatric patients.

Relationship between adiponectin multimer levels and subtypes of cerebral infarction.

AIM: Serum adiponectin levels are decreased in patients with cerebral infarction. Adiponectin in circulation exists in three isoforms: high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) adiponectin. We measured serum levels of total adiponectin and adiponectin multimers (HMW, MMW, and LMW) in patients with cerebral infarction and compared the serum levels of the three adiponectin multimers in stroke subtypes. We also evaluated the clinical value of adiponectin multimer levels as a biomarker for cerebral infarction. METHODS: We assessed a total of 132 patients with cerebral infarctions. The serum levels of total and adiponectin multimers were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The total and HMW adiponectin levels were significantly lower in atherothrombotic infarction (AI) than in cerebral embolism (CE) (total, p < 0.05; HMW, p < 0.05). In male patients, the MMW adiponectin level was significantly lower in the lacunar infarction (LI) group than in the AI group (p < 0.05). The LMW adiponectin level was significantly lower in the AI group than in the LI and CE groups (LI, p < 0.001; CE, p = 0.001). However, there were no significant differences in adiponectin multimer levels among the stroke subtypes in female subjects. Additionally, in female patients with AI and LI, the LMW adiponectin levels were negatively associated with C-reactive protein (CRP; AI, p < 0.05; LI, p < 0.05). CONCLUSION: These findings suggest that a decrease in adiponectin is associated with AI and that serum LMW adiponectin level represents a potential biomarker for AI.

Assessing the Relationship between Helicobacter pylori and Chronic Kidney Disease.

The relationship between Helicobacter pylori infection and/or gastric disorders and chronic kidney disease (CKD) has not been elucidated. We investigated the relationship between Helicobacter pylori and/or atrophic gastritis (AG) and chronic kidney disease. In total, 3560 participants (1127 men and 2433 women) were eligible for this cross-sectional study. We divided participants into four study groups: with/without Helicobacter pylori infection and with/without AG. The HP (+) AG (-) group demonstrated a significant association with CKD compared with the HP (-) AG (-) group (adjusted odds ratio, 1.443; 95% confidence interval, 1.047-1.989). In contrast, the HP (+) AG (+) group showed significantly lower adjusted odds of CKD than the HP (-) AG (-) group (adjusted odds ratio, 0.608; 95% confidence interval, 0.402-0.920). H. pylori infection without AG might be associated with CKD in these participants. Conversely, the HP (+) AG (+) group had lower odds of CKD. Uncovering an association between gastric and renal conditions could lead to development of new treatment strategies.

Evaluation of myostatin as a possible regulator and marker of skeletal muscle-cortical bone interaction in adults.

INTRODUCTION: Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Because circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in bone mass-skeletal muscle mass interactions. METHODS: The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. Cortical bone thickness and cancellous bone density were measured by ultrasonic bone densitometry in a health check-up survey. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle were then compared between the groups. RESULTS: The percentage of diabetic participants, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio (OR) of high myostatin levels in the LCT group compared with the NCT group was significant (OR 2.17) even after adjusting for related factors. Between the low cancellous bone density (LBD) and normal cancellous bone density (NBD) groups, significant differences were observed in the same items as between the LCT and NCT groups, but no significant differences were observed in skeletal muscle mass and blood myostatin levels. The myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. CONCLUSIONS: A decrease in cortical bone thickness was associated with a decrease in skeletal muscle mass accompanied by an increase in the blood myostatin level. Blood myostatin may regulate the bone-skeletal muscle relationship and serve as a surrogate marker of bone metabolism, potentially linking muscle mass to bone structure.

A Simple Method to Avoid Bile Duct Injury during Percutaneous Radiofrequency Ablation Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma represents a major global health burden. Its treatment is often complicated by the anatomical location of tumors, which can lead to adverse outcomes. Radiofrequency ablation has recently gained attention as a safe method for treating hepatocellular carcinoma, but only in tumors that are not adjacent to bile ducts. Here, we report a new method for cooling the bile duct during radiofrequency ablation therapy, in which the outer jacket of an elastor needle was fixed and flash-cooled with chilled saline. This method was applied in a patient with hepatocellular carcinoma tumors near the main bile duct. The patient underwent successful radiofrequency ablation with bile duct cooling. The advantages of this method include low medical cost, simpler securing of nonexpanded bile ducts, and simultaneous removal upon termination of the radiofrequency ablation therapy. Bile duct complications associated with radiofrequency ablation typically have delayed onset. Computed tomography examination 2 months after treatment showed no bile duct injury in this case.

A Case of Pathological Complete Response Following FOLFIRINOX Therapy for Pancreatic Adenocarcinoma with Synchronous Distant Lymph Node Metastases.

INTRODUCTION: We report a case of conversion surgery for pancreatic ductal adenocarcinoma (PDAC) with synchronous distant metastases showing pathological complete response (pCR) after FOLFIRINOX therapy. PRESENTATION OF CASE: A 46-year-old woman with obstructive jaundice was referred to our hospital. A CT scan revealed a hypo-vascular mass in the head of the pancreas with multiple para-aortic lymph nodes and a Virchow's node swollen. The serum CA 19-9 level was 71795.1 U/mL. The result of tumor biopsy from the biliary stenotic site was concordant with adenocarcinoma. She was diagnosed with PDAC with distant metastases. After 10 courses of FOLFIRINOX followed by 4 courses of FOLFIRI, a CT scan showed that distant lymph node swellings disappeared, and CA19-9 level became almost normal. She underwent pancreaticoduodenectomy with dissection of para-aortic lymph nodes 8 months after the initiation of chemotherapy. Pathologically, no evidence of residual adenocarcinoma was observed in neither pancreas nor lymph nodes. Adjuvant chemotherapy using S-1 was administered for 6 months, and no recurrence has been observed 4 years after surgery. BRCA1/2 mutations were not detected in patient's DNA. DISCUSSION: With the induction of intensive chemotherapies such as FOLFIRINOX, an increasing number of patients with synchronous distant metastases could become suitable candidates for surgery of the primary lesion because of the potential complete response of metastatic lesions. CONCLUSION: This case presented a rare occurrence of pCR in a patient with unresectable PDAC with distant metastases who received FOLFIRINOX. The feasibility and benefits of conversion surgery in such patients must be investigated in future trials.

Procedure of Direct Hepatic Artery Puncture for the Treatment of Hepatocellular Carcinoma: Two Case Reports.

Recently, treatment options for hepatocellular carcinoma (HCC) have expanded due to the development of the tyrosine kinase inhibitor ramucirumab and immune checkpoint inhibitors. Transcatheter arterial chemoembolization is the standard therapy for intermediate-stage HCC; however, in cases with anatomical problems, normal approaches are not possible. In such rare cases, direct hepatic puncture may be considered as an effective therapy and an indispensable treatment. We report our novel method of direct hepatic artery puncture in this case report. In 2011 and 2017, we reported 2 cases in the journal of the Japan Society of Hepatology in Japanese. This therapy is difficult and is associated with a high risk of complications; however, we succeeded in both cases in a similar way. We believe this method may provide an alternative treatment when standard treatment is not possible or when urgent therapy is required. In case 1, direct hepatic artery puncture was performed under ultrasonographic guidance, and we were able to control the disease with percutaneous lipiodol chemotherapy. Case 2 was an emergency case of ruptured HCC. Direct hepatic puncture successfully stopped tumor bleeding; furthermore, tumor necrosis also occurred, as seen on the enhanced computed tomography image. Our new method requires advanced puncture techniques and is not the treatment of choice if there are other safe alternatives available. However, it can be considered as an option if there are no other viable, effective treatments.

Solid pseudopapillary neoplasm of the pancreas showing marked distal atrophy: A case report.

INTRODUCTION: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm, affecting primarily young females. Because SPNs are of low-malignancy, they rarely obstruct the main pancreatic duct (MPD) and cause atrophy of the distal pancreas even if their tumor sizes are large. PRESENTATION OF CASE: A 35-year-old female was referred to our hospital due to pancreatic tumor. Imaging findings showed the presence of well-defined round tumor in the body of the pancreas with 25-mm in diameter. The pancreas parenchyma distal to the tumor was markedly atrophic, and MPD dilatation was not observed. The lesion was diagnosed as SPN by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), and central pancreatectomy was performed. Intraoperative frozen section of the distal atrophic pancreas showed no evidence of acinar cells, indicating exocrine dysfunction. Therefore, we closed distal pancreas stump instead of reconstruction. In the distal atrophic parenchyma, scattered foci of islets of Langerhans and the vestige of dilated MPD were observed. She has shown neither endocrine nor exocrine insufficiency after surgery. DISCUSSION: SPNs are usually found without atrophic change of distal pancreas. To the best of our knowledge, this is the first report of SPN in which exocrine dysfunction of atrophic pancreas was demonstrated pathologically and central pancreatectomy without anastomosis of distal pancreas was chosen for the surgical treatment. CONCLUSION: We reported a very rare case of SPN with marked distal parenchymal atrophy. We successfully performed central pancreatectomy without reconstruction.

Inhibitory Effects of Sodium Alginate on Hepatic Steatosis in Mice Induced by a Methionine- and Choline-deficient Diet.

Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH). The mice (n = 31) were divided into three groups (mice fed with regular chow, MCD diet, and MCD diet premixed with 5% SA) for 4 and 8 weeks. The MCD diet increased lipid accumulation and inflammation in the liver, the NAFLD Activity Score and hepatic mRNA expression of tumor necrosis factor- and collagen 11, and induced macrophage infiltration. Villus shortening, disruption of zonula occludens-1 localization and depletion of mucus production were observed in the small intestine of the MCD-group mice. SA administration improved lipid accumulation and inflammation in the liver, and impaired barrier function in the small intestine. Collectively, these results suggest that SA is useful for NASH treatment because it can prevent hepatic inflammation and fatty degeneration by maintaining intestinal barrier function.

CD44v-dependent upregulation of xCT is involved in the acquisition of cisplatin-resistance in human lung cancer A549 cells.

Cisplatin (CDDP) is widely used as an anti-cancer platinum agent but its therapeutic efficacy is limited by acquired drug resistance. To develop a new therapeutic strategy that could overcome this resistance, it is important to characterize CDDP-resistant cancer cells. Here we established human lung cancer A549 cell-derived low- and high-grade CDDP-resistant sublines, termed ACR4 and ACR20 cells, by stepwise increasing CDDP concentrations up to 4 and 20 µM, respectively. ACR4 and ACR20 cells showed 6- and 16-fold higher resistance to CDDP than A549 cells, respectively. Cell migration, invasion, and sphere formation were significantly decreased, whereas expression of the stem cell marker CD44v was increased in order of A549, ACR4, and ACR20 cells. The expression of the cystine-glutamate transporter xCT, which is encoded by SLC7A11, was upregulated because of the increased cell surface expression of CD44v in ACR20 cells. Treatment with the xCT inhibitor salazosulfapyridine and knockdown of SLC7A11 mRNA by a specific siRNA significantly improved sensitivity to CDDP in A549, ACR4, and ACR20 cells. Thus, our results suggest that CD44v overexpression is not involved in cancer stem cell properties but increases xCT expression, which leads to the acquisition of CDDP-resistance. This mechanism may contribute to the development of a new therapeutic strategy that can overcome resistance.

Association between α-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI.

BACKGROUND: The anti-aging protein, α-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α-Klotho in the brain has not been sufficiently investigated. OBJECTIVE: Here, we investigated the association between α-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). METHODS: Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α-Klotho level were retrospectively investigated. RESULTS: The α-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the α-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low α-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. CONCLUSION: A reduced blood α-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α-Klotho level may serve as a useful clinical index of vascular cognitive impairment.

Japanese female Kendo practitioners are associated with high radial bone mineral density.

Osteopenia is a condition in which bone mineral density (BMD) is lower than normal. Exercise increases BMD in both the young and adults. This study aimed to compare the radial apparent BMD (aBMD) in Japanese females who are Kendo practitioners (KPs) and those with no regular exercise habits (no-REH). The analysis participants consisted of 45 KPs (mean age: 49.4 years old) and 110 no-REH (mean age: 48.8 years old). Radial aBMD was measured using an ultrasonic bone densitometry system. Radial aBMD in KPs was 196.1 ± 33.9 mg/cm3, and was 182.9 ± 45.3 mg/cm3 in no-REH participants. KPs had significantly higher BMD than no-REH participants. In KPs, left radial aBMD was 196.1 ± 33.9 mg/cm3, and right radial aBMD was 184.5 ± 37.7 mg/cm3. The left radius was also significantly higher than the right radius with respect to aBMD in KPs. After adjusting for age, body mass index, menstrual status, parous women and frequency of milk and dairy intake, the odds ratio (OR) of osteopenia associated with no-REH was 6.58 (95% confidence interval (CI): 1.72-25.1) and the prevalence ratio (PR) of osteopenia associated with no-REH was 4.12 (95% CI: 1.23-13.7). Therefore, the Kendo practice may have a protective efficacy for osteopenia in women.

Association between Mid-Regional Proadrenomedullin Levels and Progression of Deep White Matter Lesions in the Brain Accompanying Cognitive Decline.

BACKGROUND: Adrenomedullin (ADM) is a vasoreactive physiological peptide with anti-inflammatory effects and vasodilative and immunomodulatory actions that is widely distributed throughout the vascular system of the brain. OBJECTIVE: To investigate mid-regional proADM (MR-proADM), a stable fragment of the ADM precursor, and cerebral deep white matter lesions (DWMLs) in association with cognitive decline. METHODS: The study participants were 288 patients (194 men, 94 women) who gave consent to participate in a 5-year longitudinal survey on arteriosclerosis from 2008 to 2013. The Fazekas classification system (Grade [G] 0 [normal] to G3 [severe]) was used for the evaluation of DWMLs on brain magnetic resonance imaging (MRI). In addition, all participants were asked to undergo cognitive function tests regarding word/letter fluency, the results of which were assessed for correlations with MR-proADM levels. RESULTS: MR-proADM levels significantly increased with DWML grade progression. The odds ratio for high MR-proADM levels was 3.08 (95% confidence interval: 1.49-5.17) in the groups graded G3 on brain MRI, suggesting that a high level of MR-proADM is an independent risk factor for DWMLs. A significant inverse correlation was observed between MR-proADM levels and cognitive test scores. MR-proADM levels were significantly increased in the G3 group in 2013 compared with 2008. CONCLUSION: MR-proADM levels were significantly different between the DWML groups and inversely correlated with cognitive function test scores, suggesting that high MR-proADM levels and DWMLs are associated with cognitive decline. Therefore, the MR-proADM level may be an effective candidate as a potential diagnostic surrogate marker of cognitive decline.

Association between loss of bone mass due to short sleep and leptin-sympathetic nervous system activity.

BACKGROUND: Sleep has been reported to be an important factor in bone metabolism, and sympathetic nervous system activity has been reported to regulate bone metabolism. In this study, we evaluated the association between sleep, sympathetic nervous system activity, and bone mass. METHODS: The study subjects were 221 individuals (108 males; 113 females; mean age: 55.1±7.0years) divided into two groups: those who slept for less than 6h a day (short sleep [SS] group), and those who slept 6h or longer (normal sleep [NS] group). The groups were compared with regard to lifestyle, cortical bone thickness, cancellous bone density, bone metabolism markers, blood leptin levels, and sympathetic nervous system activity as evaluated by heart rate variability analysis. RESULTS: Significant differences were observed between the two groups in cortical bone thickness, blood TRACP-5b, and leptin levels. The L/H ratio (an index of sympathetic nervous system activity) was higher in the SS group than in the NS group. Significant negative correlations were observed between cortical bone thickness and both the L/H ratio and leptin levels, and a significant positive correlation was observed between the L/H ratio and leptin levels. CONCLUSIONS: Short sleep was associated with a decline in cortical bone thickness due to the promotion of bone resorption and sympathetic nervous system hyperactivity in the middle-aged group. Leptin levels and cortical bone thickness were found to be closely related, suggesting that cortical bone mass may be regulated via interaction with the leptin-sympathetic nervous system.

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study.

BACKGROUND: Recent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD. METHODS: A total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD. RESULTS: Among CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710-13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010-0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein). CONCLUSIONS: The current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.

Radiofrequency Ablation Guided by Contrast-Enhanced Sonography versus B-Mode Sonography for Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization.

PURPOSE: Contrast-enhanced sonography increases negative enhancement in the Kupffer phase after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). We compared contrast-enhanced sonography with B-mode sonography for guidance of radiofrequency ablation (RFA) of HCC after TACE. METHODS: After TACE was performed, 18 nodules in 12 patients were treated by B-mode sonography guided RFA, while 22 nodules in 18 patients were treated by contrast-enhanced sonography-guided RFA. RESULTS: The success rate of initial RFA was 83.3% (15/18 nodules) in the B-mode sonography group. On the other hand, the success rate was 100% (22/22 nodules) in the contrast-enhanced sonography group and the difference was significant (p = 0.046). CONCLUSION: These findings suggest that RFA guided by Kupffer phase contrast-enhanced sonography after TACE is a promising therapeutic option for curing HCC.

Down-regulation of hepatic CYP3A1 expression in a rat model of indomethacin-induced small intestinal ulcers.

The liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti-inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established. This study examined the expressional changes of cytochrome P450 (CYP) in the liver using an indomethacin-induced small intestinal ulcer rat model and in cultured cells. After the administration of indomethacin to rats, ulcers were observed in the small intestine and expression of CYP3A1, the major isoform of hepatic CYP, was significantly down-regulated in the liver, accompanied by increased expression of inducible nitric oxide synthase, tumor necrosis factor α, interleukin (IL)-1ß and IL-6, in the small intestine and the liver. The indomethacin-induced small intestinal ulceration, the increase in inflammatory mediators in the small intestine and the liver, and the down-regulation of CYP3A1 expression in the liver were inhibited by co-administration of ampicillin, an antibacterial agent. In the human hepatic HepG2 cell line, IL-1ß, IL-6 and NOC-18, an NO donor, caused down-regulation of CYP3A4, the major isoform of human CYP3A. Thus, this study suggests that after indomethacin treatment small intestinal ulcers cause the down-regulation of CYP3A1 in the rat liver through an increase in ulcer-derived inflammatory mediators. Copyright © 2016 John Wiley & Sons, Ltd.

Preventative Effects of Sodium Alginate on Indomethacin-induced Small-intestinal Injury in Mice.

Recent advances in diagnostic technologies have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious mucosal injury in the upper and lower gastrointestinal tract (including the small intestine). A drug to treat NSAID-induced small-intestinal injury (SII) is lacking. Sodium alginate is a soluble dietary fiber extracted from brown seaweed and its solution has been used as a hemostatic agent to treat gastrointestinal bleeding due to gastric ulcers. Whether sodium alginate has therapeutic effects on NSAID-induced SII and its mechanism of action are not known. Here, we investigated if administration of two forms (high-molecular-weight (HMW) and low-molecular-weight (LMW)) of sodium alginate could ameliorate indomethacin-induced SII. Pretreatment with HMW sodium alginate or LMW sodium alginate before indomethacin administration improved ulceration and the resultant intestinal shortening was associated with reduced histological severity of mucosal injury and ameliorated mRNA expression of inflammation-related molecules in the small intestine. We found that mRNAs of secretory Muc2 and membrane-associated Muc1, Muc3 and Muc4 were expressed in the small intestine. mRNA expression of Muc1-4 was increased in indomethacin-induced SII, and these increases were prevented by sodium alginate. Thus, administration of sodium alginate could be a therapeutic approach to prevent indomethacin-induced SII.

CD62-mediated activation of platelets in cerebral white matter lesions in patients with cognitive decline.

BACKGROUND: Vascular dementia is related to intracranial arteriosclerosis associated with deep white matter lesions (DWMLs). DWMLs have been linked to thrombogenesis due to sustained platelet activation; therefore, an accurate hematological marker is needed. This study was done to evaluate the usefulness of a new method to examine the function of activated platelets in order to assess DWMLs associated with cognitive decline. METHODS: A total of 143 individuals (70.4 ± 6.1 years old) who underwent hospital-based health screening using head MRI were evaluated. DWLs were evaluated on T2-weighted and FLAIR images by semi-quantitatively grading them from Grade 0 (none) to Grade 3 (severe) using the Fazekas classification. Cognitive function was evaluated using the MMSE and the word fluency test. Platelet activation was assessed using fluorescence-labeled anti-human platelet monoclonal antibodies and semi-quantitatively determining PAC-1- and CD62P-positive rates by flow cytometry. RESULTS: Significant increases in hypertension and CD62P levels were observed with increasing DWML grade (2.6% in Group 0, 3.1% in Group 1, 4.1% in Group 2, and 5.0% in Group 3). CD62P levels were defined as elevated when they were above the mean+2SD of the Grade 0 group, and the odds ratio of the Grade 2+3 group was 3.03. A significant negative correlation was observed between CD62P levels and word fluency tests or the MMSE score. CONCLUSION: Elevations in CD62P levels, which reflect platelet function activation, were associated with white matter lesions accompanied by a decline in cognitive function. CD62P levels may be useful as a sensitive clinical marker for the early detection of DWMLs with cognitive decline.

Self-expanding metallic stent improves histopathologic edema compared with transanal drainage tube for malignant colorectal obstruction.

AIMS: To compare the usefulness of the self-expanding metallic stent (SEMS) with that of the transanal drainage tube (TDT) and emergency surgery after failure of decompression (ESFD) in patients with malignant colonic obstruction (MCO), and to evaluate post-decompression histopathologic changes. METHODS: From January 2010 to June 2015, 39 patients with MCO received SEMS, TDT, and ESFD. We evaluated the outcomes including success rates of placement, clinical outcomes after decompression, and histopathologic findings of the resected specimens. RESULTS: Technical success rates were 100% for SEMS and 78.9% for TDT. Clinical success rates were 100% for SEMS and 80.0% for TDT. Postoperative ileus was significantly less frequent after SEMS than after TDT (p = 0.014). Histopathologic edema grade was significantly lower for SEMS than for TDT and ESFD (p < 0.0001). There was no significant difference between edema grade and duration of decompression in the TDT group (p = 0.629), while all patients with SEMS were classified in a low edema grade (grade 0-2). The rate of stoma creation was significantly higher in patients with a high edema grade (grade 3) than in those with a low edema grade (grade 0-2) (p = 0.003). There was no microscopic perforation in any group. CONCLUSION: Significantly greater resolution of histopathologic edema was achieved after placement of SEMS than after placement of TDT. These findings provide an indication of favorable clinical outcomes of SEMS in comparison with TDT and ESFD. This article is protected by copyright. All rights reserved.