Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-κB signaling pathway in rats with oxidative stress-induced pancreatic injury.

BACKGROUND: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain. PURPOSE: To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis. METHODS: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-κB pathway and fibrogenesis including NF-κB/p65, TNF-α, ICAM-1, α-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting. RESULTS: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-κB/p65, ICAM-1, and α-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse transcription polymerase chain reaction showed increased levels of NF-κB/p65, ICAM-1, TNF-α, α-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-κB/p65, ICAM-1, and α-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats. CONCLUSION: SF inhibits pancreatic inflammation and fibrogenesis via NF-κB signaling pathway.

Expression and significance of Musashi-1 in gastric cancer and precancerous lesions.

AIM: To investigate expression of stem cell marker Musashi-1 (Msi-1) in relationship to tumorigenesis and progression of intestinal-type gastric cancer (GC). METHODS: Endoscopic biopsy specimens and surgical specimens were obtained, including 54 cases of intestinal-type GC, 41 high-grade intraepithelial neoplasia, 57 low-grade intraepithelial neoplasia, 31 intestinal metaplasia, and 36 normal gastric mucosa. Specimens were fixed in 10% paraformaldehyde, conventionally dehydrated, embedded in paraffin, and sliced in 4-µm-thick serial sections. Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen (PCNA) expression. Correlation analysis was conducted between Msi-1 and PCNA expression. The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically. RESULTS: There were significant differences in Msi-1 and PCNA expression in different pathological tissues (χ² = 15.37, P < 0.01; χ² = 115.36, P < 0.01). Msi-1 and PCNA-positive cells were restricted to the isthmus of normal gastric glands. Expression levels of Msi-1 and PCNA in intestinal metaplasia were significantly higher than in normal mucosa (U = 392.0, P < 0.05; U = 40.50, P < 0.01), whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia. Msi-1 and PCNA expression in intestinal-type GC was higher than in high-grade intraepithelial neoplasia (U = 798.0, P < 0.05; U = 688.0, P < 0.01). There was a significantly positive correlation between Msi-1 and PCNA expression (r(s) = 0.20, P < 0.01). Msi-1 expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage (χ² = 12.62, P < 0.01; χ² = 11.24, P < 0.05), but not with depth of invasion and the presence of distant metastasis. CONCLUSION: Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.

Expression and significance of IGF-2, PCNA, MMP-7, and α-actin in gastric carcinoma with Lauren classification.

BACKGROUND/AIMS: By detecting the expression and distribution of insulin-like growth factor-2, proliferating cell nuclear antigen, and matrix metalloproteinase-7 in cancer cells and the expression of α-actin in interstitial myofibroblasts, we studied their differences and their relationship in intestinal type and diffuse type gastric cancer with Lauren classification. MATERIALS AND METHODS: Clinical and pathological data of 50 patients with gastric adenocarcinoma who underwent primary surgical resection between 2003 and 2008 in Qianfoshan Hospital were collected. The cancer was classified as intestinal or diffuse type with Lauren classification. Immunohistochemical technique was used to detect the protein expression of insulin-like growth factor-2, proliferating cell nuclear antigen, matrix metalloproteinase-7, and α-actin in both gastric cancer tissue and normal gastric mucosa. RESULTS: The expression of insulin-like growth factor-2, proliferating cell nuclear antigen, matrix metalloproteinase-7, and α-actin in the gastric tissue was significantly higher than in the normal gastric mucosa. Insulin-like growth factor-2 was mainly expressed in the nucleus in diffuse gastric cancer and in the cytoplasm in intestinal type. The expression of insulin-like growth factor-2 in the nucleus was correlated with depth of tumor invasion, lymph node metastasis and staging. Proliferating cell nuclear antigen and matrix metalloproteinase-7 showed higher expression in diffuse than in intestinal type gastric cancer. The overexpression of proliferating cell nuclear antigen was relevant to lymph node metastasis in gastric cancer. The overexpression of matrix metalloproteinase-7 was relevant to invasion, lymph node metastasis, distant metastasis, and staging in gastric cancer. There was no significant difference in α-actin expression between the intestinal type and diffuse type gastric cancer. The overexpression of α-actin was relevant to cancer invasion and lymph node metastasis. CONCLUSIONS: The expression patterns of insulin-like growth factor-2 and the expression intensity of proliferating cell nuclear antigen and matrix metalloproteinase-7 were significantly different between diffuse type and intestinal type gastric cancer cells, but the expression pattern and intensity of the interstitial myofibroblast marker showed no significant difference. The clinical pathology distinction between intestinal type and diffuse type gastric cancer may be due mainly to the change in the genetic structure and the phenotype of epithelial cells, and interstitial myofibroblasts and cancer cells jointly promote the invasion and metastasis of gastric cancer.

Alterations in cerebral potentials evoked by rectal distention and drinking ice water in patients with irritable bowel syndrome.

AIM: Visceral hypersensitivity has been found to be present in irritable bowel syndrome (IBS). The current study sought to study visceral afferent hypersensitivity in IBS patients and obtain further objective evidence of alterations in intestinal afferent pathways in IBS patients by cerebral evoked potentials (CEP). METHOD: We studied 30 female IBS patients and 12 female healthy subjects. Rectal perception thresholds to balloon distention were measured and CEP was recorded in response to rhythmic rectal distention (two distention series, each of 100 repetitions at a frequency of 1 Hz) at the volume of perception thresholds. All subjects were then asked to drink 220 mL 4 degrees C ice water and the above steps were repeated 20 min later. RESULTS: Rectal distention led to recognizable and reproducible CEP. Compared to healthy subjects, IBS patients demonstrated significantly shorter N1, P1 and N2 latencies (P < 0.05). After drinking ice water, IBS patients exhibited further shortened N1, P1 and N2 latencies (P < 0.05), but drinking did not alter the latencies of healthy controls and the amplitudes of both IBS patients and healthy controls. CONCLUSION: The shorter latency of cerebral potentials evoked by rectal distention and ice water stimulation in IBS patients provided further objective evidence for defective visceral afferent transmission in IBS patients.

Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome.

BACKGROUND: Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). This study sought to investigate rectal sensitivity and abdominal symptoms in IBS patients before and after 220 ml cold water intake. METHODS: A total of 60 IBS patients and 18 healthy controls participated in this study. Both the perception thresholds and defecation thresholds to rectal balloon distension were measured. Then, all subjects were asked to drink 220 ml 37 degrees C warm water or 4 degrees C cold water, and these steps were repeated 20 min later. Symptoms including abdominal pain/discomfort, bloating, and diarrhea were recorded during the study. RESULTS: Compared with the controls, the thresholds of initial sensation to rectal balloon distention in IBS patients were significantly lower while the defecation thresholds were higher in constipation-predominant IBS patients. After drinking cold water, the perception thresholds in IBS patients and the defecation thresholds in diarrhea-predominant IBS patients were further decreased. However, warm water intake did not change the perception thresholds significantly in either IBS patients or controls. A negative linear correlation was found between the symptoms and the visceral perception thresholds in diarrhea-predominant IBS patients who showed significant symptoms after cold water intake. CONCLUSION: The results indicated that cold water intake leads to lowered visceral perception thresholds in IBS patients that were inversely relevant to the abdominal symptoms in symptomatic diarrhea-predominant IBS patients. The alteration of rectal sensitivity and abdominal symptoms following cold water stimulation provided further objective evidence for visceral hypersensitivity in IBS patients.

[Study on early fibrinolytic therapy to avoid acute myocardial infarction].

OBJECTIVE: To investigate the frequency of aborted AMI and clinical characteristics of the patients received prompt fibrinolytic therapy. METHODS: 1120 patients with AMI were divided into two groups, true AMI group and aborted AMI group. Aborted AMI was defined as maximal creatine kinase-MB < or = 2 x upper limit of normal coupled with the presence of resolution of chest pain and 50% of ST-segment deviation within 2 hours after onset of therapy. We compared some characteristic of two groups such as the fibrinolytic time after symptom onset and the frequency of aborted AMI. RESULTS: The reopening ratio of infarct was 80.5%. 7.1% of the patients escaped myocardial necrosis. Aborted AMI was highest frequency within the first hour (22.0%) than other time groups (P < 0.01); There were no significant differences in the frequency of Aborted AMI in UK group, SK group and rt-PA group (7.0%, 6.7%, 7.1%, P > 0.05); The rate of Killip III/IV, major arrhythmias, angina pectoris and mortality at 30 day in aborted AMI patients compared with those who had true AMI was 3.9% versus 17.1%, 18.0% versus 30.0%, 1.3% versus 8.0%, 0 versus 6.0%, respectively (P < 0.01). CONCLUSION: Prompt fibrinolytic therapy improved the likelihood of aborted AMI and clinical outcomes. The frequency of aborted AMI has no relationship with fibrinolytic drug, but closely related to the starting time of treatment from symptom onset.