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991.
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Meriläinen S Mäkelä J Koivukangas V Jensen HA Rimpiläinen E Yannopoulos F Mäkelä T Alestalo K Vakkala M Koskenkari J Ohtonen P Koskela M Lehenkari P Karttunen T Juvonen T 《Hepato-gastroenterology》2012,59(114):599-606
Background/Aims: To examine whether intestinal bacterial translocation occurs early in acute mild and severe pancreatitis and whether the intestinal expression of tight junction proteins (claudins-2, -3, -4, -5, -7), apoptosis or proliferation would explain the possible translocation. Methodology: Fifteen pigs were randomized to controls (n=5) or to develop mild edematous pancreatitis (n=5, saline infusion to pancreatic duct) or severe necrotic pancreatitis (n=5, taurocholic acid infusion). Translocation was studied by measuring bacterial cultures from portal vein blood and mesenteric lymph nodes. Immunohistochemical expression of the tight junction proteins, apoptosis rate (TUNEL) and Ki-67 were analyzed quantitatively from the epithelium of the jejunum and colon. Results: There was no bacterial translocation during the 6 hours followup, nor changes in the expression of tight junction proteins claudins-2 and -5 in jejunum or colon. Saturation and proportional area of claudin-3 staining decreased in the colon, as did claudins-4 and -7 staining in the jejunum of the necrotic pancreatitis group. Increased apoptosis was found in all samples from controls and the edematous pancreatitis group but not in jejunum in the necrotic pancreatitis group. Ki-67 activity tended to increase in the upper half of the villus in edematous and necrotic pancreatitis. There were no changes in the basic histology. Conclusions: The major finding of this study was that bacterial translocation from the gut is not present at the beginning of acute pancreatitis. Tight junction proteins claudin-2 and -5 do not become altered in the early stages of pancreatitis. Claudin-3 decreases in the colon and claudins-4 and -7 in the jejunum in necrotic pancreatitis. Laparotomy itself causes increased apoptosis in the colon and the jejunum. 相似文献
994.
There is currently no structured system for nurses or allied health professionals to undertake further training to become a nurse specialist (NSp) or nurse practitioner (NP) in rheumatology on-site, while working in a district general hospital setting. These shortcomings have prompted us to develop a structured pathway that could be followed by staff nurses who wish to become NSp in rheumatology. The proposed pathway aims to assist the nurses or therapists (physiotherapists, psychologists, occupational therapist, podiatrists, etc.) to develop a sound knowledge based on the rationale, safety, and high quality clinical care when monitoring of patients taking disease-modifying anti-rheumatic drugs (DMARDs) to ensure they acquire skills enabling them to provide safe, evidence-based effective patient-centered care. Near the end of the pathway, the trainee would be expected to have an understanding of the particularities of chronic arthritis conditions as well as screening, assessment, and monitoring of patients receiving DMARDs and biological agents. Tests for competencies are included and certification may be considered. 相似文献
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Tostões RM Leite SB Serra M Jensen J Björquist P Carrondo MJ Brito C Alves PM 《Hepatology (Baltimore, Md.)》2012,55(4):1227-1236
Primary cultures of human hepatocyte spheroids are a promising in vitro model for long-term studies of hepatic metabolism and cytotoxicity. The lack of robust methodologies to culture cell spheroids, as well as a poor characterization of human hepatocyte spheroid architecture and liver-specific functionality, have hampered a widespread adoption of this three-dimensional culture format. In this work, an automated perfusion bioreactor was used to obtain and maintain human hepatocyte spheroids. These spheroids were cultured for 3-4 weeks in serum-free conditions, sustaining their phase I enzyme expression and permitting repeated induction during long culture times; rate of albumin and urea synthesis, as well as phase I and II drug-metabolizing enzyme gene expression and activity of spheroid hepatocyte cultures, presented reproducible profiles, despite basal interdonor variability (n = 3 donors). Immunofluorescence microscopy of human hepatocyte spheroids after 3-4 weeks of long-term culture confirmed the presence of the liver-specific markers, hepatocyte nuclear factor 4α, albumin, cytokeratin 18, and cytochrome P450 3A. Moreover, immunostaining of the atypical protein kinase C apical marker, as well as the excretion of a fluorescent dye, evidenced that these spheroids spontaneously assemble a functional bile canaliculi network, extending from the surface to the interior of the spheroids, after 3-4 weeks of culture. Conclusion: Perfusion bioreactor cultures of primary human hepatocyte spheroids maintain a liver-specific activity and architecture and are thus suitable for drug testing in a long-term, repeated-dose format. 相似文献
999.
Efficacy of ischemic preconditioning is decreased in animal models of type 2 diabetes mellitus while the responses in humans with diabetes are contradictory. It is unknown whether attenuation is related to decreased release of a mediating humoral cardioprotective factor or reduced ability to respond in the target tissue. The aim of the present study was to investigate the release and effect of a circulating cardioprotective factor in type 2 diabetes mellitus patients. Blood samples were drawn from nine non-diabetic subjects, eight diabetic patients without peripheral neuropathy, and eight diabetic patients with peripheral neuropathy before (control) and after a remote ischemic preconditioning (rIPC) stimulus. Blood samples were dialyzed against Krebs-Henseleit buffer and the cardioprotective effects of the dialysates were tested in rabbit hearts mounted on a Langendorff model and subjected to 30-min global ischemia and 120-min reperfusion. rIPC dialysate from non-diabetic and diabetic subjects without peripheral neuropathy reduced infarct size and improved hemodynamic recovery compared to control dialysate from non-diabetic and diabetic subjects. However, in the subgroup of diabetic patients with neuropathy the cardioprotective effect was attenuated. These findings indicate that the release mechanism involves neural pathways. 相似文献
1000.
Michelsen MM Støttrup NB Schmidt MR Løfgren B Jensen RV Tropak M St-Michel EJ Redington AN Bøtker HE 《Basic research in cardiology》2012,107(3):260-9
Exercise protects against myocardial ischemia-reperfusion (I-R) injury but the mechanism remains unclear. Protection can be transferred from a remotely preconditioned human donor to an isolated perfused rabbit heart using a dialysate of plasma. We hypothesized that physical exercise preconditioning also confers cardioprotection through a humorally mediated effector dependent on opioid receptor activation. Thirteen male volunteers performed vigorous exercise (four 2-minute bouts of high-intensity exercise) and 1 week later they underwent remote ischemic preconditioning (four cycles of 5 min upper limb ischemia and reperfusion). Dialysates were prepared from blood collected before (control) and after the two interventions. Isolated rabbit hearts were perfused with the dialysates without and with co-administration of naloxone (opioid receptor antagonist) prior to 40 min regional ischemia and 2 h reperfusion. Exercise and remote ischemic preconditioning (rIPC) reduced infarct size from 60 ± 5 to 35 ± 5 % and from 57 ± 7 to 27 ± 3 % of the area at risk, respectively (p < 0.05 and < 0.01). Furthermore, post-ischemic left ventricular developed pressure was improved compared with controls (p = 0.08 for exercise and p = 0.04 for rIPC). Co-perfusion with naloxone abrogated the protective effects of exercise and remote ischemic preconditioned dialysates. In conclusion, high-intensity exercise preconditioning elicits cardioprotection through a humorally mediated dependent on opioid receptor activation, similar to rIPC. 相似文献