Associations between clinical features and therapy with macrophage subpopulations and T cells in inflammatory lesions in the aorta from patients with Takayasu arteritis.

Takayasu arteritis (TAK) is a large-vessel granulomatous vasculitis; the inflammatory infiltration in arteries comprises macrophages, multi-nucleated giant cells, CD4+ and CD8+ T cells, γδ T cells, natural killer (NK) cells and neutrophils. However, it is unknown which subtype of macrophages predominates. This study aims to evaluate macrophages subpopulations in the aorta in TAK. Immunohistochemistry was performed in the aorta from TAK patients (n = 22), patients with atherosclerotic disease (n = 9) and heart transplant donors (n = 8) using the markers CD68, CD86, CD206, CD3, CD20 and CD56. Active disease was observed in 54·5% of patients and active histological lesions were found in 40·9%. TAK patients presented atherosclerotic lesions in 27·3% of cases. The frequency of macrophages, M1 macrophages, T, B and NK cells was higher in the aorta from TAK and atherosclerotic patients compared to heart transplant donors. In TAK, macrophages and T cells were the most abundant cells in the aorta, and the expression of CD206 was higher than CD86 (P = 0·0007). No associations were found between the expression of cell markers and active disease or with atherosclerotic lesions. In TAK patients, histological disease activity led to higher T cell counts than chronic fibrotic lesions (P = 0.030), whereas prednisone use was associated with lower T cell counts (P = 0·035). In conclusion, M1 macrophages were more frequent in TAK and atherosclerotic patients compared to heart transplant donors, while M2 macrophages dominated M1 macrophages in TAK. T cells were associated with histological disease activity and with prednisone use in TAK.

Early and late postoperative inflammatory and collagen deposition responses in three different meshes: an experimental study in rats.

PURPOSE: Although meshes reduce abdominal hernia recurrence, they increase the risk of inflammatory complications. This study aimed to compare the early and late postoperative inflammation and collagen deposition responses induced by three meshes. METHODS: Rats were allocated into three groups. In group I, a polypropylene (PP) mesh was implanted in the abdominal wall. In groups II and III, PP + polyglactin (PP + PG) and PP + titanium (PP + TI) meshes were employed, respectively. On the seventh (7th) postoperative day, collagen deposition and inflammation were evaluated, and immunohistochemistry was performed on abdominal wall biopsies. These data were compared with those obtained on the fortieth (40th) postoperative day in a previous study. RESULTS: The early inflammatory responses were the same in all groups. With time, it decreased in group I (p = 0.047) and increased in group II (p = 0.003). Group I exhibited early elevated VEGF (p < 0.001), COX2 (p < 0.001), and collagen (p = 0.023) levels, and group II exhibited the most severe inflammatory tissue response. On the 40th postoperative day, the VEGF (p < 0.001) and collagen (p < 0.005) were reduced as compared with the 7th postoperative day in all groups. CONCLUSIONS: Belatedly, the inflammatory reaction decreased in PP mesh group and increased in PP + PG mesh group. The PP mesh induced early great elevations in VEGF, COX2 and collagen levels, whereas the PP + PG mesh caused severe tissue inflammation with small elevation in these levels. PP + TI mesh induced inflammatory response levels between the others. In conclusion, the inflammatory response depends on the mesh density and also the mesh material with clinical implications.

Experimental study comparing meshes made of polypropylene, polypropylene + polyglactin and polypropylene + titanium: inflammatory cytokines, histological changes and morphometric analysis of collagen.

PURPOSE: Incisional hernia occurs in approximately 11% of all laparotomies. Changes in collagen have been closely implicated in its pathogenesis. The high recurrence rate (45-54%) after primary suture has stimulated the development of meshes. Currently, meshes are the biomaterials implant group most used in medicine. This study aims to compare the serum and tissue inflammatory responses and collagen deposition caused by meshes made of polypropylene, polypropylene + polyglactin and polypropylene + titanium. METHODS: Thirty Wistar rats were divided into three groups. In group I, a high-density polypropylene mesh was positioned on the abdominal wall. In groups II and III, low-density meshes were used in associations with polyglactin and titanium, respectively. Immediately before the operation and on the first, third and fortieth postoperative days, pro-inflammatory cytokines were assayed. On the 40th postoperative day, the region of the inserted prosthesis was biopsied. The tissue inflammatory reaction was evaluated using a scale for objective scoring. For collagen, picrosirius was used with data reading using the Image Tool computer software. RESULTS: Cytokines: there were no statistically significant differences between the groups. HISTOLOGY: on the 40th postoperative day in group I, there were fewer inflammatory tissue response and greater collagen deposition (P < 0.01). In group II, there were greater inflammatory tissue response and less collagen deposition (P < 0.01). Group III presented intermediate values between groups I and II. CONCLUSIONS: There were no significant differences in cytokine levels between the groups in the present study. In the animals with the polypropylene + polyglactin mesh implant there was the most intense inflammatory process with lower tissue maturation and collagen deposition on the 40th postoperative day. The polypropylene mesh presented a less severe late inflammatory process, with greater tissue maturation and collagen deposition. The polypropylene + titanium mesh presented intermediate values between the others.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1 percent). Histological examination revealed fundic type epithelium in 58.3 percent of cases, H. pylori was present in 50 percent and chronic inflammation in 66.7 percent. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7 percent of cases and Barrett's esophagus in 90 percent of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa.

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis.

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.

Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29 percent of the cases and in inflammatory cells in 43 percent. COX-2 positivity in epithelial and inflammatory cells was found in 69 percent of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.