The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis.Male Sprague-Dawley rats were given distilled drinking water containing 2.5% (wt/vol) synthetic DSS ad libitum. Bovine lactoferrin was given once daily through gavage, starting 3 days before beginning the DSS administration, until death. The whole colon was removed to be examined macroscopically and histologically. Myeloperoxidase activity, and pro-inflammatory and anti-inflammatory cytokines in the colonic tissue were also measured.Dextran sulfate sodium-induced colitis was attenuated by oral administration of lactoferrin in a dose-dependent manner, as reflected by improvement in clinical disease activity index, white blood cell count and hemoglobin concentration, macroscopic and histological scores, and myeloperoxidase activity. Reduced inflammation in response to lactoferrin was correlated with the significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and with significant reductions in the pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1beta, and interleukin-6.We concluded that oral administration of lactoferrin exerts a protective effect against the development of colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.
The purpose of the study reported in this article was to investigate effects of synthetic lipid A on the expression of adhesion molecule CD44 on bovine articular chondrocytes. Full-thickness bovine articular cartilage was dissected from the carpometacarpal joints of 24 cows. Cartilage pieces were enzymatically digested to liberate chondrocytes. The chondrocytes were incubated in the presence of synthetic lipid A in suspension culture. Cell characteristics and binding of monoclonal antihuman CD44 antibodies were assessed with a flow cytometer. The expression of CD44 mRNA in chondrocytes was detected by reverse transcription-polymerase chain reaction (RT-PCR) technique. PCR products were quantified with a charge-coupled device image sensor. The percentage of CD44-positive chondrocytes was 42.2% ± 12.0%, 51.7% ± 6.8%, and 51.1% ± 5.0%, in the presence of lipid A at 0.25 μg/ml, 2.5 μg/ml, and 25 μg/ml, respectively, whereas it was 39.2% ± 8.9% in the absence of lipid A. In flow cytometry, two subpopulations of chondrocytes were found in each of five separate experiments, one with smaller number of forward scatter (FS) and the other with larger number of FS. The percentage of CD44-positive cells was 24.8% ± 8.5% in the subpopulation with smaller number of FS and 31.9% ± 6.4% in the subpopulation with larger number of FS at time 24 h after incubation. The bacterial component, lipid A, upregulated expression of CD44 on articular chondrocytes.
Laparoscopic retro-muscular Rives-Stoppa (RS) ventral hernia repair using the enhanced-view totally extraperitoneal (eTEP) technique (eTEP-RS) is becoming common. Although self-fixating mesh is useful with good fixation, some surgeons think the fixating surface must be oriented towards the rectus abdominis muscle for safety reasons in eTEP-RS. Attaching the self-fixating mesh to the rectus abdominis, the ceiling of the operative field, is challenging and time-consuming.First, the self-fixating mesh is folded in half with the fixation surface facing outwards. Second, we create a partition sheet and insert the sheet between the two arms of the folded mesh. The folded mesh is then inserted intracorporeally. We can unfold the mesh easily from one-quarter width to half width on the rectus abdominis muscle because of the insertion of the partition sheet. Finally, the mesh is unfolded to full width, and the mesh placement is completed.The eTEP-RS is still a new procedure and has not yet been standardized. However, our technique will increase the use of self-fixating mesh and improve the outcomes of eTEP-RS.
Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis.The mRNA expression levels of iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with reflux esophagitis, using TaqMan PCR and reverse transcription PCR.The expression of iNOS mRNA in the esophageal mucosa increased parallel to the severity of the esophagitis. There were no significant differences between both eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter pylori infection did not affect the levels of mRNA expression.The accumulation of NO, produced by iNOS, was considered to be related to the exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO production may thus be of use in preventing development of esophageal mucosal injury in patients with reflux esophagitis.
In Japan, the transhiatal approach, including lower mediastinal lymph node dissection, is widely performed for Siewert type II esophagogastric junction adenocarcinoma. This procedure is generally performed in a magnified view using laparoscopy or a robotic system, therefore, the microanatomy of the lower mediastinum is important. However, mediastinal microanatomy is still unclear and classification of lower mediastinal lymph nodes is not currently based on fascia or other microanatomical structures.To clarify the fascia and layer structures of the lower mediastinum and classify the lower mediastinal tissue.We dissected the esophagus and surrounding organs en-bloc from seven cadavers fixed in 10% formalin. Organs and tissues were then cut at the level of the lower thoracic esophagus, embedded in paraffin, and serially sectioned. Tissue sections were stained with Hematoxylin-Eosin (all cadavers) and immunostained for the lymphatic endothelial marker D2-40 (three cadavers). We observed the periesophageal fasciae and layers, and defined lymph node boundaries based on the fasciae. Lymphatic vessels around the esophagus were observed on immunostained tissue sections.We identified two fasciae, A and B. We then classified lower mediastinal tissue into three areas, paraesophageal, paraaortic, and intermediate, using these fasciae as boundaries. Lymph nodes were found to be present and were counted in each area. The dorsal part of the intermediate area was thicker on the caudal side than on the cranial side in all cadavers. On the dorsal side, no blood vessels penetrated the fasciae in six of the seven cadavers, whereas the proper esophageal artery penetrated fascia B in one cadaver. D2-40 immunostaining showed lymphatic vessel connections between the paraesophageal and intermediate areas on the lateral and ventral sides of the esophagus, but no lymphatic connection between areas on the dorsal side of the esophagus.Histological studies identified two fasciae surrounding the esophagus in the lower mediastinum and the layers separated by these fasciae were used to classify the lower mediastinal tissues.
In 55 gastrointestinal cancer patients the mean change ratios for platelets were, respectively, 1.22 +/- 0.75 and 0.67 +/- 0.45, in the romurtide administration (30 cases) and non-administration (25 cases) groups, [statistically significant difference (p < 0.005)]. The number of cases in each group with a decrease in platelet count was 13 (43%) and 20 (80%) with and without romurtide, respectively. The difference was statistically significant, (p < 0.01). In addition, the number of cases with a marked decrease ( < 6 x 10(4)/mm3) in platelet count was 2 (7%) and 7 (28%) with and without romurtide, respectively, reaching statistical significance (p < 0.05). For patients treated with a bolus administration of 450 mg/m2 carboplatin (27 cases), the mean change ratios for leukocytes and platelets in the romurtide administration group (13 cases) were 1.10 +/- 0.52 and 1.23 +/- 0.59, respectively. Meanwhile, in the romurtide non-administration group the mean change ratios for leukocytes and platelets were, respectively, 0.74 +/- 0.27 and 0.74 +/- 0.42, a statistically significant reduction (p < 0.05) compared with the romurtide administration group. The number of cases with an increase in the number of lymphocytes after i.v. administration was significantly more than that observed after s.c. administration (p < 0.01). These results indicate that romurtide has a restorative effect on thrombocytopenia similar to that displayed for leukocytopenia when given as concomitant therapy with anticancer drugs and/or irradiation in patients undergoing intensive treatment for gastrointestinal cancer.
A 67-year-old woman underwent laparoscopy-assisted left hemicolectomy for early descending colon cancer(pTis, pN0, cH0, cM0, Stage 0).Her postoperative course was uneventful, without fever and/or tenderness at the anastomotic site.A month following discharge from the hospital, enhanced computed tomography revealed a liver abscess measuring 80mm in diameter at the lateral segment and a left adrenal abscess measuring 30mm in diameter.Although some free air and fluid collection was noted near the anastomotic site, there was no tenderness, and a gastrografin enema did not reveal leakage and/or pooling of the contrast agent near the anastomotic site.We administered antibiotics and performed percutaneous transhepatic abscess drainage following which imaging revealed shrinkage of her liver and adrenal abscesses and lowering of fever.However, enhanced computed tomography, performed a month later, revealed recurrence of the liver abscess, for which we performed a hepatic lateral segmentectomy.After undergoing the hepatectomy, she has shown no recurrence of the liver and adrenal abscesses.Several cases of liver abscess have been reported in association with colorectal cancer; however, an adrenal abscess occurring in association with colorectal cancer has not yet been reported.This case reveals that a minor leak could be associated with a liver and adrenal abscess.
