High glucose impairs EDHF-mediated dilation of coronary arterioles via reduced cytochrome P450 activity

Endothelium-derived hyperpolarizing factor (EDHF) is an important vasodilator that regulates the vasomotor function. However, it remains unclear whether diabetes/hyperglycemia-induced vascular impairments extend to the EDHF. The present study aims to determine the effect of high glucose (HG) on EDHF-mediated arteriolar dilation and the underlying mechanism. Porcine coronary arterioles were isolated and pressurized for vasomotor study. Cultured porcine coronary artery endothelial cells (ECs) were used for molecular and biochemical analysis. Our results demonstrate that bradykinin (BK)-simulated arteriolar dilation is mediated by nitric oxide (NO) and EDHF pathways. Direct incubation of HG impaired vasodilation to BK but not to sodium nitroprusside (endothelium-independent vasodilator). In the presence of inhibitors of endothelial NO synthase (eNOS) and cyclooxygenase, the EDHF-mediated dilation was reduced by HG incubation. The inhibitory effect of HG was prevented by treating the vessels with superoxide scavenger Tempol. In cultured coronary endothelial cells, HG reduced endothelial epoxyeicosatrienoic acid (EET) production as well as cytochrome P450 epoxygenase (CYP) activity. Furthermore, the superoxide production was elevated in ECs after HG incubation. Pretreatment with Tempol before HG incubation prevented the increase of cellular superoxide and abolished the decrease of CYP activity. Collectively, our results suggest that, in addition to NO-mediated pathway, HG impairs the EET/EDHF-mediated vasodilation in coronary arterioles via the elevated level of superoxide leading to inhibition of CYP activity in coronary ECs.     

Impact of Acid Suppression on Upper Gastrointestinal pH and Motility

Background  

Proton pump inhibitors (PPIs), widely prescribed to patients with upper gastrointestinal symptoms, alter intragastric pH, and may affect upper gastrointestinal transit and motility parameters in addition to affecting the ability to determine Wireless Motility Capsule (WMC) gastric emptying time.     

Primary cutaneous diffuse large B cell lymphoma relapsed solely as a huge lung tumor mimicking a primary pulmonary lymphoma

Primary cutaneous large B cell lymphoma, leg type (PCLBCL-leg) has recently been identified and recognized as a specific entity. Patients with PCLBCL-leg have a higher relapse rate and a poorer prognosis than the other types of primary cutaneous B cell lymphomas, and disease relapse is confined to the skin in the majority of cases with rare exclusive extracutaneous progression. The late occurrence of lymphoma in patients with a prior history of lymphoma may represent a relapse/progression or a distinct tumor unrelated to the original one. The distinction is of important clinical and therapeutic implications. Here, we report the case of a 90-year-old lady with a history of PCLBCL-leg in complete remission after radiotherapy that developed a huge, solitary pulmonary lymphoma without lymphadenopathy 14 months later. The latter was initially considered as stage IE primary pulmonary lymphoma and was treated with combination chemotherapy resulting in complete remission. Retrospective pathologic review and B cell clonality study revealed that the pulmonary tumor was a diffuse large B cell lymphoma of the same clonal origin as the PCLBCL-leg. This case is unique in the exclusive pulmonary relapse and illustrates the importance of expert pathological review and molecular study in the management of lymphoma patients with unusual clinical features.     

Plasma Exchange Versus Double Filtration Plasmapheresis in the Treatment of Guillain‐Barré Syndrome

Abstract: Previous studies have shown that both plasma exchange (PE) and double filtration plasmapheresis (DFPP) are effective treatments in Guillain‐Barré syndrome (GBS). Whether PE and DFPP have similar effects in GBS is not clear. This report compares the therapeutic effectiveness of PE and DFPP in GBS patients treated in 3 major hospitals in northern Taiwan. A total of 102 patients were included in this survey, including 39 with PE (hereafter PE group) and 63 with DFPP (hereafter DFPP group). Both groups showed significant improvement of disability scores after treatment. However, time to onset of effect was shorter (5.6 ± 3.5 versus 7 ± 3.4 days, p < 0.05), and changes of disability scores were more prominent (1.3 ± 0.8 versus 0.8 ± 0.8, p < 0.05) in the PE group than the DFPP group. Mortality and outcome after 6 months were not different between the 2 groups. In conclusion, both PE and DFPP are effective treatments in GBS. PE was superior to DFPP in short‐term effectiveness. The long‐term effectiveness was not different.     

Removal of a mis-swallowed long spoon via gastrotomy--a case report

Foreign body ingestions are a frequent occurrence, a common presentation at emergency departments, but long, pointed-end metallic spoon swallowing is an uncommon occurrence. Unlike most cases of foreign-body ingestion, there have been no cases of spontaneous passage reported. Consequently, prompt removal is recommended before complications develop. We report a case of accidental ingestion of a long, pointed metallic spoon which failed to pass through the gastrointestinal tract and be excreted. This patient was managed successfully with gastrotomy to remove the object. We recommend this approach for the removal of long pointed foreign bodies to avoid complications developing.     

运动性心律失常

运动性心律失常是指发生于机体剧烈运动期间或之后的心律失常。临床表现不一,从心悸、头晕、晕厥、心绞痛、急性心肌梗死和充血性心力衰竭,甚至到心脏性猝死。运动性心律失常可见于心肌缺血,如患有动脉粥样硬化性心脏病以及患有原发性或继发性心肌病的患者。然而,也可能发生在似乎健康的个体。在后一组人群中,运动性心律失常可以是良性的,但也可以是获得性(如药物诱发)或先天性(如先天性长QT综合征或致心律失常性右室发育不良)心电活动或结构的异常而呈恶性。这种潜在病理生理学机制的复杂性,使运动性心律失常的诊断和治疗成为临床医学上的…     

Neurotransmitter and neuromodulator genes associated with a history of depressive symptoms in individuals with alcohol dependence

Background: Depressive symptoms are common among individuals with alcohol use disorders and impact treatment outcome. Substantial overlap exists among the neurobiological systems proposed in the pathophysiology of depressive and alcohol use disorders; however, specific genetic effects contributing to risk for depressive comorbidity remain poorly understood. Methods: This study examines the association of depressive symptom scores for lifetime depression (the sum of DSM‐IV major depression co‐endorsed criteria for lifetime depression) with markers in 120 candidate genes in 554 alcohol‐dependent individuals. The candidate genes code for molecules involved in dopamine, serotonin, glutamate, gamma‐aminobutyric acid (GABA), and opioid neurotransmission, cell signaling, pharmacokinetics, stress biology, and behavioral control. Analyses were conducted at the single marker level with experimentwise permutation to control for multiple testing. Results: Results revealed nominal associations for markers in 20 genes. Following experimentwise permutation, markers in the corticotropin‐releasing hormone‐binding protein (CRHBP) the μ‐opioid receptor (OPRM1) and the β1 subunit of GABA A (GABA_A) receptors (GABRB1) met or exceeded the significance threshold. None of the markers associated with depressive symptom scores were significantly associated with alcohol dependence symptom scores. Conclusion: These findings suggest potential risk genes for depressive symptoms in alcohol‐dependent individuals.     

Tumor suppressor death-associated protein kinase is required for full IL-1β production

Interleukin-1β (IL-1β) is critical for inflammation and control of infection. The production of IL-1β depends on expression of pro-IL-1β and inflammasome component induced by inflammatory stimuli, followed by assembly of inflammasome to generate caspase-1 for cleavage of pro-IL-1β. Here we show that tumor suppressor death-associated protein kinase (DAPK) deficiency impaired IL-1β production in macrophages. Generation of tumor necrosis factor-α in macrophages, in contrast, was not affected by DAPK knockout. Two tiers of defects in IL-1β generation were found in DAPK-deficient macrophages: decreased pro-IL-1β induction by some stimuli and reduced caspase-1 activation by all inflammatory stimuli examined. With a normal NLRP3 induction in DAPK-deficient macrophages, the diminished caspase-1 generation is attributed to impaired inflammasome assembly. There is a direct binding of DAPK to NLRP3, suggesting an involvement of DAPK in inflammasome formation. We further illustrated that the formation of NLRP3 inflammasome in situ induced by inflammatory signals was impaired by DAPK deficiency. Taken together, our results identify DAPK as a molecule required for full production of IL-1β and functional assembly of the NLRP3 inflammasome. In addition, DAPK knockout reduced uric acid crystal-triggered peritonitis, suggesting that DAPK may serve as a target in the treatment of IL-1β-associated autoinflammatory diseases.     

A better method for confirming <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in Mongolian gerbils

Background. Our aim was to evaluate the accuracy of the stool antigen test and the optimal time point for detecting Helicobacter pylori infection in a Mongolian gerbil model. Methods. We inoculated 8-week-old Mongolian gerbils with H. pylori (Vac A (+)/CagA(+)). The gerbil-infected model was developed as follows: H. pylori was put into broth (about 10⁹ CFU/ml), and 50 gerbils were then fed with 1 ml intragastrically twice within a 3-day interval. Another ten gerbils were fed broth only. Twenty-six weeks after the inoculation, the gerbils were killed. The gastric mucosa was sampled for a series of examinations including culture, histology, rapid urease test, and polymerase chain reaction. Stool samples for a stool antigen test, H. pylori-specific stool antigen assay (HpSA), were collected during weeks 4, 6, 8, 12, and 26 after inoculation. Of the 50 gerbils inoculated with H. pylori, the inoculation was successful in 88%. Severe active gastritis, ulceration, and intestinal metaplasia were obvious. Results. The HpSA test results were sensitivity, 88.6%; specificity, 100%; positive predictive value (PPV), 100%; negative predictive value (NPV), 54.5%, and accuracy, 90%. The HpSA test began to be more sensitive and accurate (P < 0.05) beginning during week 6 after inoculation. We also found that H. pylori could be detected earlier and more easily in the group with high H. pylori density. Conclusions. HpSA seems to be suitable for confirming colonization of gerbils with H. pylori. The optimal testing time point is around 6 weeks after inoculation. This test is a good choice for long-term observation of H. pylori infection in Mongolian gerbils.     

Acquirement and disappearance of HBsAg and anti‐HCV in an aged population: a follow‐up study in an endemic township

Background: HBsAg and anti‐hepatitis C virus (anti‐HCV) are stable markers and widely used. The seroconversion and seroclearance of HBsAg and anti‐HCV are important for disease control and prognosis of diseases. Aims: To investigate acquirement and disappearance of HBsAg and anti‐HCV in an endemic area. Methods: Seven years after a community screening, 1002 of 2909 residents of Tzukuan Township were recruited. HBsAg, anti‐HCV and alanine transaminase (ALT) were checked in all who participated and hepatitis B virus (HBV) DNA, anti‐HBs, anti‐HBc, HCV RNA, anti‐HDV and upper abdominal ultrasonography were studied in different groups. Results: There were 461 male and 541 female residents with a mean age of 66.7±8.6 years. No new HBsAg carrier was noted and the HBsAg clearance rate was 1.58% per year. One of the 17 cases with HBsAg clearance had positive HBV DNA, three had ALT elevation, two had cirrhosis and seven had anti‐HBs seroconversion. Quantitative of HBsAg and HBV DNA were concordant and 78.1% subjects had low levels of titration. Anti‐HBc alone contributed to 32.1% and was prominent in old age and the anti‐HCV‐positive group. The anti‐HCV seroconversion rate was only 0.74% per year and household transmission was the only risk factor. Only 37.5% of cases with anti‐HCV seroconversion had HCV viraemia and the anti‐HCV seroreversion rate was 0.63% per year. The anti‐HDV seroconversion rate was 0.72% per year and no subject showed anti‐HDV clearance. Conclusions: Much higher rates of HBsAg seroclearance, anti‐HCV seroreversion and anti‐HBc alone were noted in this endemic area and no subject showed anti‐HDV clearance.