High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells

Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.     

Synthesis, potent anti-staphylococcal activity and QSARs of some novel 2-anilinobenzazoles

Synthesis and anti-staphylococcal activity of a number of substituted 2-anilinobenzimidazoles, benzothiazoles and benzoxazoles are reported. The anti-staphylococcal activities were evaluated in standard in vitro MIC assay method. While anilinobenzimidazole derivatives 11-45 showed very potent anti-staphylococcal activities (greatest activity with an MIC value of 0.095 microg/mL), none of the 2-anilinobenzothiazoles and benzoxazole derivatives exhibited inhibitory activity. QSAR analysis of the anilinobenzimidazoles was studied on the relationship between the anti-staphylococcal activity (MIC in mug/ml) and extrapolated log k(w) values.     

Is there an association between Helicobacter pylori in the inlet patch and globus sensation?

AIM:To determine the association between Helicobacter pylori(H.pylori)and globus sensation(GS)in the patients with cervical inlet patch. METHODS:Sixty-eight patients with esophageal inlet patches were identified from 6760 consecutive patients undergoing upper gastrointestinal endoscopy prospectively.In these 68 patients with cervical inlet patches, symptoms of globus sensation(lump in the throat), hoarseness,sore throat,frequent clearing of the throat,cough,dysphagia,odynophagia of at least 3 mo duration wa...     

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model

Purpose

The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis.

Methods

Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups.

Results

Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).

Conclusion

Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.     

Biliary fistula after treatment for hydatid disease of the liver:When to intervene

AIM:To determine the outcome of patients with biliary fistula(BF)after treatment for hydatid disease of the liver. METHODS:Between January 2000 and December 2010,out of 301 patients with a diagnosis of hydatid cyst of the liver,282 patients who underwent treatment [either surgery or puncture,aspiration,injection and reaspiration(PAIR)procedure]were analysed.Patients were grouped according to the presence or absence of postoperative biliary fistula(PBF)(PBF vs no-PBF groups,respectively).Preoperative clinical,radiological and laboratory characteristics,operative characteristics including type of surgery,peroperative detection of BF,postoperative drain output,morbidity,mortality and length of hospital stays of patients were compared amongst groups.Multivariate analysis was performed to detect factors predictive of PBF.Receiver operative characteristics(ROC)curve analysis were used to determine ideal cutoff values for those variables found to be significant.A comparison was also made between patients whose fistula closed spontaneously(CS)and those with intervention in order to find predictive fac-tors associated with spontaneous closure. RESULTS:Among 282 patients[median(range)age, 23(16-78)years;77.0%male];210(74.5%)were treated with conservative surgery,33(11.7%)radical surgery and 39(13.8%)underwent percutaneous drainage with PAIR procedure A PBF developed in 46(16.3%) patients,all within 5 d after operation.The maximum cyst diameter and preoperative alkaline phosphatase levels(U/L)were significantly higher in the PBF group than in the no-PBF group[10.5±3.7 U/L vs 8.4±3.5 U/L(P<0.001)and 40.0±235.1 U/Lvs 190.0±167.3 U/L(P=0.02),respectively].Hospitalization time was also significantly longer in the PBF group than in the no-PBF group[37.4±18.0 d vs 22.4±17.9 d(P< 0.001)].A preoperative high alanine aminotransferase level(>40 U/L)and a peroperative attempt for fistula closure were significant predictors of PBF development (P=0.02,95%CI:-0.03-0.5 and P=0.001,95%CI:0.1-0.4),respectively.Comparison of