AIM: To define the evolution of ischemic lesions with 7T magnetic resonance imaging (7T-MRI) in an animal model of acute colonic ischemia. METHODS: Adult Sprague-Dawley rats were divided into two groups. Group I u...AIM: To define the evolution of ischemic lesions with 7T magnetic resonance imaging (7T-MRI) in an animal model of acute colonic ischemia. METHODS: Adult Sprague-Dawley rats were divided into two groups. Group I underwent inferior mesenteric artery (IMA) ligation followed by macroscopic observa- tions and histological analysis. In group H, 7T-MRI was performed before and after IMA ligation and followed by histological analysis. RESULTS: Morphological alterations started to develop 1 h after IMA ligation, when pale areas became evident in the splenic flexure mesentery and progressively wors-ened up to 8 h thereafter, when the mesentery was less pale, and the splenic flexure loop appeared very dark. The 7T-MRI results reflected these alterations, showing a hyperintense signal in both the intraperitoneal space and the colonic loop wall 1 h after IMA ligation; the lat- ter progressively increased to demonstrate a reduction in the colonic loop lumen at 6 h. Eight hours after IMA ligation, MRI showed a persistent colonic mural hyper- intensity associated with a reduction in peritoneal free fluid. The 7T-MRI findings were correlated with histolog- ical alterations, varying from an attenuated epithelium with glandular apex lesions at 1 h to coagulative necro- sis and loss of the surface epithelium detected 8 h after IMA ligation. CONCLUSION: MRI may be used as a substitute for invasive procedures in diagnosing and grading acute ischemic colitis, allowing for the early identification of pathological findings.展开更多
AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to ...AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.展开更多
One of biggest recent achievements of neurobiology is the study on neurotrophic factors. The neurotrophins are exciting examples of these factors. They belong to a family of proteins consisting of nerve growth fac-tor...One of biggest recent achievements of neurobiology is the study on neurotrophic factors. The neurotrophins are exciting examples of these factors. They belong to a family of proteins consisting of nerve growth fac-tor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, NT-6, and NT-7. Today, NGF and BDNF are well recognized to mediate a diz-zying number of trophobiological effects, ranging from neurotrophic through immunotrophic and epitheliotro-phic to metabotrophic effects. These are implicated in the pathogenesis of various diseases. In the same vein, recent studies in adipobiology reveal that this tissue is the body’s largest endocrine and paracrine organ producing multiple signaling proteins collectively termed adipokines, with NGF and BDNF being also produced from adipose tissue. Altogether, neurobio-logy and adipobiology contribute to the improvement of our knowledge on diseases beyond obesity such as cardiometabolic (atherosclerosis, type 2 diabetes, and metabolic syndrome) and neuropsychiatric (e.g. , Alzheimer’s disease and depression) diseases. The present review updates evidence for (1) neurotrophic and metabotrophic potentials of NGF and BDNF linking the pathogenesis of these diseases, and (2) NGF- and BDNF-mediated effects in ampakines, NMDA receptor antagonists, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and purinergic P2X3 recep-tor up-regulation. This may help to construct a novel paradigm in the feld of translational pharmacology of neuro-metabotrophins, particularly NGF and BDNF.展开更多
AIM: TO investigate colonic endocrine cells in lympho- cytic colitis (LC) patients. METHODS: Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 yea...AIM: TO investigate colonic endocrine cells in lympho- cytic colitis (LC) patients. METHODS: Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 years (range 19-84 years). Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleed- ing was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years (range 18-67 years). Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for se- rotonin, peptide YY (PYY), pancreatic polypeptide (PP) enteroglucagon and somatostatin cells. The cell densi- ties were quantified by computerised image analysis using Olympus software. RESULTS: The colon of both the patient and the control subjects were macroscopically normal. Histo- pathological examination of colon biopsies from con- trols revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC: an increase in intraepithelial lymphocytes (〉 20 lymphocytes/100 epithelial cells) and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreac- tive cells were primarily located in the upper part of the crypts of Lieberk0hn. These cells were basket- or flask-shaped. There was no statistically significant dif- ference between the right and left colon in controls with regards to the densities of serotonin- and PYY- immunoreactive cells (P = 0.9 and 0.1, respectively). Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6±2.6 (P = 0.008). In the left colon, the corresponding figures were 28.5± 1.9 and 42.4± 2.9, respectively (P = 0.009). PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 (P = 0.00006). In the left colon, PYY cell density in controls was 6.6± 1.2 and in LC patients 53.3 ± 4.6 (P = 0.00007). CONCLUSION: The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be sec- ondary.展开更多
文摘AIM: To define the evolution of ischemic lesions with 7T magnetic resonance imaging (7T-MRI) in an animal model of acute colonic ischemia. METHODS: Adult Sprague-Dawley rats were divided into two groups. Group I underwent inferior mesenteric artery (IMA) ligation followed by macroscopic observa- tions and histological analysis. In group H, 7T-MRI was performed before and after IMA ligation and followed by histological analysis. RESULTS: Morphological alterations started to develop 1 h after IMA ligation, when pale areas became evident in the splenic flexure mesentery and progressively wors-ened up to 8 h thereafter, when the mesentery was less pale, and the splenic flexure loop appeared very dark. The 7T-MRI results reflected these alterations, showing a hyperintense signal in both the intraperitoneal space and the colonic loop wall 1 h after IMA ligation; the lat- ter progressively increased to demonstrate a reduction in the colonic loop lumen at 6 h. Eight hours after IMA ligation, MRI showed a persistent colonic mural hyper- intensity associated with a reduction in peritoneal free fluid. The 7T-MRI findings were correlated with histolog- ical alterations, varying from an attenuated epithelium with glandular apex lesions at 1 h to coagulative necro- sis and loss of the surface epithelium detected 8 h after IMA ligation. CONCLUSION: MRI may be used as a substitute for invasive procedures in diagnosing and grading acute ischemic colitis, allowing for the early identification of pathological findings.
基金Supported by National Health and Medical Research Council, Australia
文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.
文摘One of biggest recent achievements of neurobiology is the study on neurotrophic factors. The neurotrophins are exciting examples of these factors. They belong to a family of proteins consisting of nerve growth fac-tor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, NT-6, and NT-7. Today, NGF and BDNF are well recognized to mediate a diz-zying number of trophobiological effects, ranging from neurotrophic through immunotrophic and epitheliotro-phic to metabotrophic effects. These are implicated in the pathogenesis of various diseases. In the same vein, recent studies in adipobiology reveal that this tissue is the body’s largest endocrine and paracrine organ producing multiple signaling proteins collectively termed adipokines, with NGF and BDNF being also produced from adipose tissue. Altogether, neurobio-logy and adipobiology contribute to the improvement of our knowledge on diseases beyond obesity such as cardiometabolic (atherosclerosis, type 2 diabetes, and metabolic syndrome) and neuropsychiatric (e.g. , Alzheimer’s disease and depression) diseases. The present review updates evidence for (1) neurotrophic and metabotrophic potentials of NGF and BDNF linking the pathogenesis of these diseases, and (2) NGF- and BDNF-mediated effects in ampakines, NMDA receptor antagonists, antidepressants, selective deacetylase inhibitors, statins, peroxisome proliferator-activated receptor gamma agonists, and purinergic P2X3 recep-tor up-regulation. This may help to construct a novel paradigm in the feld of translational pharmacology of neuro-metabotrophins, particularly NGF and BDNF.
文摘AIM: TO investigate colonic endocrine cells in lympho- cytic colitis (LC) patients. METHODS: Fifty-seven patients with LC were in- cluded. These patients were 41 females and 16 males, with an average age of 49 years (range 19-84 years). Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls. These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries, where the source of bleed- ing was identified as haemorrhoids or angiodysplasia. They were 19 females and 8 males with an average age of 49 years (range 18-67 years). Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. Biopsies were fixed in 4% buffered paraformaldehyde, embedded in paraffin and cut into 5 μm-thick sections. The sections immunostained by the avidin-biotin-complex method for se- rotonin, peptide YY (PYY), pancreatic polypeptide (PP) enteroglucagon and somatostatin cells. The cell densi- ties were quantified by computerised image analysis using Olympus software. RESULTS: The colon of both the patient and the control subjects were macroscopically normal. Histo- pathological examination of colon biopsies from con- trols revealed normal histology. All patients fulfilled the diagnosis criteria required for of LC: an increase in intraepithelial lymphocytes (〉 20 lymphocytes/100 epithelial cells) and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution. In the colon of both patients and control subjects, serotonin-, PYY-, PP-, enteroglucagon- and somatostatin-immunoreac- tive cells were primarily located in the upper part of the crypts of Lieberk0hn. These cells were basket- or flask-shaped. There was no statistically significant dif- ference between the right and left colon in controls with regards to the densities of serotonin- and PYY- immunoreactive cells (P = 0.9 and 0.1, respectively). Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6±2.6 (P = 0.008). In the left colon, the corresponding figures were 28.5± 1.9 and 42.4± 2.9, respectively (P = 0.009). PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4 (P = 0.00006). In the left colon, PYY cell density in controls was 6.6± 1.2 and in LC patients 53.3 ± 4.6 (P = 0.00007). CONCLUSION: The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells, and that of PYY density might be sec- ondary.