RESUMEN
Daikenchuto (DKT) has been widely used for the treatment of postsurgical ileus in Japan. However, its effect on postsurgical adhesion formation has been obscure. In this study, the effect of DKT on postsurgical adhesion formation induced by cecum cauterization or cecum abrasion in mice was investigated. First, the expression of adhesion-related molecules in damaged ceca was investigated by quantitative (q)RT-PCR. During 24 h after surgery, mRNA expressions of interferon-γ (IFN-γ), plasminogen activator inhibitor-1 (PAI-1), interleukin-17 (IL-17), and Substance P (SP) in cauterized ceca and those of PAI-1 and IL-17 in abraded ceca were significantly up-regulated. Next, the effect of DKT on adhesion formation macroscopically evaluated with adhesion scoring standards. DKT (22.5-67.5 mg/d) was administered orally for 7 d during the perioperative period, and DKT did not reduce adhesion scores in either the cauterization model (control : DKT 67.5 mg/d, 4.8 ± 0.2 : 4.8 ± 0.2) or in the abrasion model (control : DKT 67.5 mg/d, 4.9 ± 0.1 : 4.5 ± 0.3). Histologically, collagen deposition and leukocyte accumulation were found at the adhesion areas of control mice in both models, and DKT supplementation did not alleviate them. Last, effect of DKT on expression of proadhesion moleculs was evaluated. DKT also failed to down-regulate mRNA expression levels of them in damaged ceca of both models. In conclusion, PAI-1 and IL-17 may be key molecules of postsurgical adhesion formation. Collagen deposition and leukocytes accumulation are histological characteristic feature of post-surgical adhesion formation. DKT may not have any preventive effect on postsurgical adhesion formation in mice.
Asunto(s)
Ciego/efectos de los fármacos , Ciego/cirugía , Extractos Vegetales/farmacología , Adherencias Tisulares/tratamiento farmacológico , Animales , Cauterización/métodos , Ciego/metabolismo , Ciego/patología , Colágeno/metabolismo , Femenino , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Ratones , Ratones Endogámicos BALB C , Panax , Serpina E2/metabolismo , Sustancia P/metabolismo , Zanthoxylum , ZingiberaceaeRESUMEN
Cancer-associated fibroblasts (CAFs) are an important constituent of the cancer stroma. In intrahepatic cholangiocarcinoma (ICC), the features of CAFs at the primary site and in the metastatic lymph nodes (Met-LNs) and their origin have been unclear. In the present study, we characterized CAFs at the primary site (n = 42) and in the Met-LNs (n = 10) of human ICC by immunohistochemistry using potential molecular markers of CAFs, portal fibroblasts (PFs), hepatic stellate cells (HSCs), and bone marrow-derived fibrocytes (BMDFs). At the primary site, the stroma was strongly positive for α-smooth muscle actin (α-SMA; marker for CAFs), platelet-derived growth factor receptor-ß (PDGFR-ß) (common marker for HSCs and PFs), fibulin-2, and thymus cell antigen-1 (Thy-1; PF marker), whereas immunoreactivity for fascin (HSC marker) was scarce. Most of the α-SMA-positive cells were found to express PDGFR-ß, Thy-1, and fibulin-2 by double immunostaining. A small population of BMDF marker-positive (α-SMA+CD45+CD34+) cells was found by triple immunostaining. In the micro-Met-LNs, α-SMA-positive cells were absent in cancer aggregates of the LN sinus, whereas they were present in the invasion area of cancer cells from the LN sinus to the LN parenchyma. In the macro-Met-LNs, there were abundant α-SMA-positive cells that were also positive for PDGFR-ß and Thy-1 but negative for fibulin-2 and fascin. Thus, regarding the expression of molecular markers, CAFs at the primary site of ICC are similar to PFs and different from those of HSCs or CAFs in the Met-LNs. CAFs at the primary sites and in the Met-LN are thought to be derived from PFs/BMDFs and resident cells of LNs, respectively.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Fibroblastos Asociados al Cáncer/patología , Colangiocarcinoma/patología , Metástasis Linfática/patología , Fibroblastos/patología , Células Estrelladas Hepáticas/patología , Humanos , InmunohistoquímicaRESUMEN
A 66-year old man, who had been diagnosed with dilated cardiomyopathy and felt a progressive shortness of breath and fatigability, was admitted to hospital. Computed tomography showed a thickening of the aortic wall from the aortic arch to the aortic bifurcation, as well as mild pleural and pericardial effusion. Intravenous pyelography showed severe ureteral stenosis, along with hydronephrosis, of the left side. There was a marked increase in C-reactive protein and the erythrocyte sedimentation rate, but the serology for connective tissue disease and perinuclear antineutrophil cytoplasmic antibodies was negative. Retroperitoneal fibrosis (RPF) with intrathoracic extension was diagnosed. After confirming the absence of malignant disease, an oral predonisolone treatment of 30 mg/day was started, and this ameliorated the ureteral obstruction, aortic wall thickening and pericardial effusion. The patient had been taking 300 mg of loxoprofen sodium for headaches every day for 16 years. The relationship between loxoprofen, cardiomyopathy and RPF remains unclear. There is a possibility of RPF in the patients with a thickening of thoracic aortic wall, as in this case.