All ileo-cecal ulcers are not Crohn's:Changing perspectives of symptomatic ileocecal ulcers

AIM To investigated clinical,endoscopic and histopathological parameters of the patients presenting with ileocecal ulcers on colonoscopy.METHODS Consecutive symptomatic patients undergoing colonoscopy,and diagnosed to have ulcerations in the ileocecal(I/C) region,were enrolled.Biopsy was obtained and theirclinical presentation and outcome were recorded.RESULTS Out of 1632 colonoscopies,104 patients had ulcerations in the I/C region and were included in the study.Their median age was 44.5 years and 59% were males.The predominant presentation was lower GI bleed(55,53%),pain abdomen ± diarrhea(36,35%),fever(32,31%),and diarrhea alone(9,9%).On colonoscopy,terminal ileum was entered in 96(92%) cases.The distribution of ulcers was as follows:Ileum alone 40%(38/96),cecum alone 33%(32/96),and both ileum plus cecum 27%(26/96).The ulcers were multiple in 98% and in 34% there were additional ulcers elsewhere in colon.Based on clinical presentation and investigations,the etiology of ulcers was classified into infective causes(43%) and noninfective causes(57%).Fourteen patients(13%) were diagnosed to have Crohn's disease(CD).CONCLUSION Non-specific ileocecal ulcers are most common ulcers seen in ileo-cecal region.And if all infections are clubbed together then infection is the most common(> 40%) cause of ulcerations of the I/C region.Cecal involvement and fever are important clues to infective cause.On the contrary CD account for only 13% cases as a cause of ileo-cecalulcers.So all symptomatic patients with I/C ulcers on colonoscopy are not Crohn's.

Anti-cancer effects of sitagliptin,vildagliptin,and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line.We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate AMPK.This study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were examined.Treatment with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned medium.These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and HO-1.Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay.Thus,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect.Therapeutic response was in the order of:sitagliptin>vildagliptin>exendin-4.

Tay-Sachs carrier screening in the genomics age: Gene sequencing versus enzyme analysis in non-Jewish individuals

Purpose: To compare the sensitivity of Hexosaminidase A (HexA) enzyme-based testing to gene sequencing for carrier detection in non-Jewish individuals. Methods: Blood samples were obtained from parents and relatives of affected patients at an annual Tay-Sachs and Allied Diseases Foundation meeting. A family history was taken for each individual. Samples were analyzed for leukocyte HexA activity, serum HexA activity and subjected to extensive gene sequencing. The results from these analyses were combined with our previously published data describing 34 obligate Tay-Sachs disease (TSD) carriers. Results: Twelve additional TSD carriers were detected in this study. Gene sequencing successfully identified all 12 carriers whereas enzyme analysis identified 11 of 12 carriers. This individual is a carrier of the B1 variant that is known to cause false negative results with enzyme testing. Combined data from 46 non-Jewish TSD carriers revealed that gene sequencing had a higher sensitivity rate than HexA enzyme-based testing (94% versus 87%) in non-Jewish TSD carriers. In our series, approximately 4% of non-Jewish TSD carriers have this mutation. Conclusions: HexA gene sequencing provides a higher sensitivity for TSD carrier detection than HexA based enzyme analysis in non-Jewish patients primarily due to the presence of individuals with the B1 variant.

Abundance of Carbonic Fluid Inclusions in Hira-Buddini Gold Deposit, Hutti-Maski Greenstone Belt, India: Inferences from Petrography and Volume Ratio Estimation of Fluid Components

Low saline aqueous carbonic fluids are considered to be the ore forming solutions for orogenic lode gold deposits.Phase separation/fluid immiscibility of the ore fluid is quite common and is one of the major reasons for deposition of gold in these deposits.Abundant carbonic fluid inclusions have been observed in quartz grains of Hira-Buddnini Gold Deposit.Theoretical estimation indicates that more volume of H2O compared to CO2 is likely to be trapped in inclusions at different P-T conditions.Preferential loss of H2O from fluid inclusions during ductile deformation of quartz grains have been attributed as the suitable reason for abundance of carbonic fluid inclusions.