Mitochondria DNA 4977 bp common deletion in peripheral whole blood from healthy donors.

To investigate the distribution of mitochondria DNA 4 977 bp deletion, a common deletion (CD), in normal populations of Chinese, human peripheral blood samples from sixty healthy donors were collected, and levels of the CD in genomic DNA from the samples were detected using real-time PCR. The results showed that the CD was found in 27 health donors, with its positive rate being 45% (27/60). The CD ratio was between 0 and 0.00308%, and not affected by age and gender in sixty healthy donors. Our studies indicate that the CD ratio is low, and do not show the age-dependent accumulation and any gender difference in peripheral whole blood from the normal Chinese population.

[Characteristic analysis of plasma lipid metabolism level in patients with colorectal adenoma].

OBJECTIVE: To evaluate the relationship between serum lipid level and colorectal adenoma. METHODS: A review analysis was carried out of the patients who underwent colonoscopy in Peking University Third Hospital from May 2009 to February 2010. Subjects with history of colorectal adenocarcinoma before colorectal surgery or of medication which had influenced the serum lipid level were excluded. Adenoma group included the patients who had colorectal adenoma which was evidenced by pathology. The patients with no adenoma were ascribed to control group. The serum total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol levels of the two groups were analyzed. The relation between serum lipid level and location of colorectal adenoma was also summarized. RESULTS: A total of 227 patients were included for final analysis, of whom 124 were in adenoma group (77 males and 47 females; mean age: 56.5±10.7 years )and 103 in control group(53 males and 50 females; mean age: 56.8±13.6 years). Serum triglyceride level in adenoma group [(1.83±1.04) mmol/L] was significantly higher than that of control group[(1.54±0.86) mmol/L(P=0.022)] and HDL-C level in adenoma group[(1.05±0.32) mmol / L] was significantly lower than that of control group [(1.26±0.46) mmol/L(P=0.000)]. In adenoma group, 73 cases were with HDL-C decreased, which was significantly higher than that of control group (44 cases, P=0.015). In addition, higher incidence of proximal colonic adenomas was observed in elevated triglycerides group and low HDL-C group (39.8%, 37.4%), compared with control group (25.5%), but there was no statistical difference between the two groups(P=0.358). CONCLUSION: The findings of this study suggest that dyslipidemia may affect the incidence of colorectal adenoma, particularly hypertriglyceridemia and low HDL-C levels. In addition, higher triglyceride and lower HDL-C levels seem to be related to higher incidence of proximal colonic adenomas.

[Role of peroxisome proliferators-activated receptor-gamma in the chemical prevention therapy of sulindac for precancerous lesions of rats].

OBJECTIVE: To understand whether peroxisome proliferators-activated receptor-gamma (PPAR-gamma) plays an important role in the chemopreventive effect of sulindac on precancerous lesions (aberrant crypt foci, ACF) of rats. METHODS: Male Sprague-Dawley rats were used in this study and raised in Special Pathogen Free room. Sulindac was the main research object. Carcinogenic agent, 1, 2-dimethylhydrazine (DMH), was used to induce colonic precancerous lesions. Pioglitazone was chosen as agonist of PPAR-gamma and GW9662 used as a specific complete antagonist of PPAR-gamma. ACFs were induced according to the protocol certified in prior experiments. There were 7 groups, named as Negative control group, DMH group, Sulindac group, Sulindac+GW9662 group, Pioglitazone group, Pioglitazone+GW9662 group and GW9662 group. The experiment period was 12 weeks. At the end of the experiment, all rats were sacrificed by euthanasia. Half of the colon including the rectum was taken and immersed in formalin at 4 degrees Celsius overnight, and then recorded the number and size of ACF with the help of anatomic microscope stained by methylene blue. RESULTS: (1) Sulindac and agonist of PPAR-gamma could significantly inhibit DMH-induced ACFs of rats from 137.8+/-59.4 to 73.9+/-32.1 and 96.4+/-32.6 with a decrease of 45.7% (P<0.01) and 30.0%(P<0.05) compared with DMH group. Antagonist of PPAR-gamma could counteract the chemopreventive effect of sulindac with an increase from 73.9+/-32.1 to 106.3+/-33.9; (2) The expression of PPAR-gamma in colorectal mucosa increased significantly during the DMH induction period compared with negative control group, the relative values of gray were 0.304+/-0.288 and 2.292+/-1.380 (P<0.01), sulindac and pioglitazone could decrease the expression of PPAR-gamma remarkably compared with DMH group, the relative values of gray were 1.023+/-1.115 and 0.352+/-0.187 (P<0.01), and the application of GW9662, antagonist of PPAR-gamma could promote the expression of PPAR-gamma in some degree, and the relative values of gray were 1.279+/-0.303 and 0.998+/-0.295 (P>0.05). CONCLUSION: The expression of PPAR-gamma had risen in DMH-induced ACFs of rats significantly. Sulindac and agonist of PPAR-Gamma (pioglitazone) could inhibit the formation of ACF, and followed by a decrease of PPAR-gamma. Antagonist of PPAR-gamma could interfere with the effect of sulindac. PPAR-gamma might play an important role in the chemopreventive effect of sulindac on colorectal pre-cancerous lesions of rats and activation of PPAR-gamma pathway could inhibit the initiation and evolvement of ACF induced by DMH.

[Mechanism of exacerbation of colonic damage in experimental colitis treated with celecoxib].

OBJECTIVE: To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid (TNBS) treated with celecoxib (a selective COX-2 inhibitor). METHODS: The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 g/L) in a vehicle of 50% ethanol (0.25 mL) of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib (1.25 mg/kg, Group 1) and distilled water (1 mL/0.3 kg, Group 2) respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment (d 7) were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry. RESULTS: The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 (8.5+/-2.5) was significantly reduced, as compared with Group 2 (13.5+/-1.9, P<0.05). The levels of COX-2 protein expression was decreased significantly in Group 1 (3.7 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 10(-2), P<0.05). The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 (30%) was decreased as compared with Group 2 (90%, P<0.05). No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4. CONCLUSION: Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But the application of celecoxib resulted in exacerbation of colonic damage. These adverse events are probably relevant to the suppression of COX-2 expression in the neural cells of the myenteric plexus, leading to decrease of intestinal contractivity and peristalsis, enteroparalysis, megacolon and death of the rat.

[Effect of peroxisome proliferators-activated receptor-gamma in the mechanisms of sulindac against large intestine carcinoma].

OBJECTIVE: To compare effects of sulindac, PPARgamma activator and PPARgamma antagonist on the proliferation and apoptosis of the colonic cancer cells, and to investigate whether sulindac exerts its colonic neoplasm inhibiting activity through pathway of PPARgamma. METHODS: Cell strain HT-29 of colonic cancer was divided into six groups: the control group, sulindac group, 15d-PGJ2 (PPARgamma activator) group, GW9662 (PPARgamma antagonist) group, sulindac+GW9662 group and 15d-PGJ2+ GW9662 group. After 24 and 48 hours' culturing, proliferation status of each group was determined by immunocytochemical staining of PCNA, and cell apoptosis status was determined by double staining method of AnnexinV-FITC/PI, examined on flow cytometer. RESULTS: (1) Proliferation status of the colonic cancer cells of each group: 24 and 48 hours after medication, PCNA positive ratios were 33.2%+/- 4.5% and 25.0%+/-4.7% of the control group, 11.8%+/-3.7% and 8.6%+/-1.9% of sulindac group, 11.2%+/-2.5% and 11.4%+/-2.1% of 15d-PGJ2 group, 35.3%+/-4.3% and 26.8%+/-3.9% of GW9662 group, 16.5%+/-5.3% and 12.2 %+/-2.4% of sulindac + GW9662 group, 21.0%+/-4.8% and 21.5%+/-4.2% of 15d-PGJ2+GW9662 group. (2) Apoptosis ratio of colonic cancer cells of each group: 24 hours after medication, apoptosis rate of colonic cancer cells was 13.0%+/-1.0% of the control group, 41.0%+/-2.6% of sulindac group, 11.5%+/-0.6% of 15d-PGJ2 group, 12.4%+/-0.9% of GW9662 group,33.6%+/-2.3% of sulindac+GW9662 group, and 13.0%+/-1.0% of 15d-PGJ2 + GW9662 group. 48 hours after medication, apoptosis rate was 14.0%+/-3.4% of the control group, 95.3%+/-1.5% of sulindac group, 31.5%+/-2.3% of 15d-PGJ2 group, 13.0%+/-1.9% of GW9662 group, 86.8%+/-0.4% of sulindac+GW9662 group, and 12.9%+/-1.0% of 15d-PGJ2+GW9662 group. CONCLUSION: Both sulindac and PPARgamma activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPARgamma antagonist, which indicates that as a kind of PPARgamma ligand, sulindac can inhibit proliferation of colonic cancer cells via activating PPARgamma.

[Current diagnostic status, clinical and pathologic manifestation for a Crohn's disease].

OBJECTIVE: To evaluate the contemporary diagnostic and therapeutic status for Crohn's disease (CD), and analyze its clinical and pathologic manifestation. METHODS: Retrospectively we reviewed 220 hospitalized inflammatory bowel disease (IBD) cases in which 48 were diagnosed as CD. Data of diagnostic and therapeutic details were recorded. RESULTS: In the past 10 years 44 of the 48 CD cases were diagnosed in recent and 75.0% of the cases were in the onset age range from 17 to 40 years. The most common symptoms were abdominal pain, diarrhea and bloody stool. 16 (33.3%) of the cases were accompanied with extra-intestinal manifestations, 3 (6.3%) with perianal abscess, and 2 (4.2%) with intestinal fistulation. The main findings through colonoscopy were ulceration, obstruction and cobble stone sign, with a diagnostic correspondence of 85.7% (36/42). Non-caseous granulomas were totally identified in 43.2% (19/44) of the histology. Thirty cases were administrated with Sulfasalazine/Mesalazine (SASP/5-ASA) or corticosteroids/immuno-suppressor in which 27 got clinically improved. Thirteen patients underwent surgery. CONCLUSION: The diagnostic incidence of Crohn's disease has been increased in recent years. The combination of endoscopy, radiography and histology is the best way for the diagnosis of CD. Small intestinal endoscopy and capsule endoscopy with repeated histopathology and follow-up are helpful for the diagnosis.

[The effects of sulindac on the pathology of colorectal remnant polyps of familial adenomatous polyposis (FAP) patients].

OBJECTIVE: To evaluate the long-term effectiveness of sulindac on the pathology of colorectal adenomas of familial adenomatous polyposis (FAP) patients. METHODS: FAP patients were treated with sulindac 400 mg per day. The change of colorectal polyps was assessed every 3 months in the first year. After the significant regression of colorectal polyps was achieved, sulindac was used to maintain the effects. The patients received colonoscopy examination regularly. Biopsies of remnant polyps and other lesions were obtained. The type and dysplasia grade of biopsies were evaluated and compared with baseline. RESULTS: Before the study, 90.8% of adenoma biopsies were tubular, while 9.2% was tubulovillous adenoma. The dysplasia of grades I, II and III were 42.1%, 45.6% and 12.3%, respectively. After sulindac treatment, 99.8% of adenoma biopsies were tubular, while 0.2% tubulovillous adenoma. There was significant difference compared with baseline (P<0.01). The dysplasia of grades I, II and III were 55.8%, 41.8% and 2.4% respectively, which had significant difference with baseline (P<0.01). Minor flat elevation and erythema were found during the treatment, in which approximately 65% was adenoma. CONCLUSION: Long-term use of sulindac seems to be effective in reducing dysplasia grade and tubulovillous adenoma of retained colorectal adenoma of FAP patients. Minor flat elevation and erythema may be the lesions appearing during the regression of adenoma.