Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats.

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer.

Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging.

BACKGROUND AND PURPOSE: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow-up imaging of patients with head trauma. MATERIALS AND METHODS: A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases. RESULTS: There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (κ = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (κ = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (κ = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (κ = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%. CONCLUSIONS: Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT.

Enlargement of a vestibular schwannoma after stereotactic radiotherapy.

BACKGROUND: Radiosurgery has been increasingly advocated as a primary treatment for vestibular schwannoma (VS), and recently fractionation of the dose has been proposed as a method to decrease the risk of radiation injury when treating larger tumors. METHOD: The authors describe a 48-year-old woman who presented with right-sided hearing loss and new-onset tinnitus, with a progressive decrease in facial sensation. The diagnosis of a large right cerebellopontine angle VS was made on magnetic resonance imaging (MRI). The patient was treated with a course of fractionated stereotactic radiotherapy (SRT) (5 treatments of 4 Gy to the 90% isodose line over a 3-week period). FINDINGS: Six months after the initiation of therapy, her symptoms increased, and a repeat MRI scan demonstrated that her tumor had increased in size, producing significant brainstem compression. She then underwent complete surgical resection of the tumor, with resolution of her symptoms. INTERPRETATION: Stereotactic radiosurgery has been effective in controlling small VSs with low complication rates. Larger tumors pose a risk for increasing in size and producing symptoms from mass effect with SRT. There are at present limited data demonstrating safety and efficacy of fractionated SRT for the treatment of larger tumors.

Aging and DNA methylation in colorectal mucosa and cancer.

DNA methylation of promoter-associated CpG islands may function as an alternate mechanism of silencing tumor suppressor genes in multiple neoplasias including colorectal cancer. De novo methylation of genes appears to be an early and frequent event in most neoplasias. For the ER and IGF2 genes, we have previously shown that methylation actually begins in the normal colon mucosa as an age-related event and progresses to hypermethylation in cancer. In this study, we have determined the frequency of age-related methylation in normal colonic mucosa among the genes hypermethylated in colorectal cancer. We studied six genes, including N33, MYOD, p16, HIC-1, THBS1, and CALCA. The N33 gene showed partial methylation in normal colon mucosa, which was age-related (r = 0.7; P = 0.003 using regression analysis). Adenomas and cancers showed further hypermethylation at this locus. Similarly, the MYOD gene showed age-related methylation in normal colon mucosa (r = 0.7; P < 0.00001 using regression analysis) and hypermethylation in cancers. Age-related methylation seems to be gene specific, because p16, THBS1, HIC-1, and CALCA were not affected. Furthermore, this process may also be modulated by tissue-specific factors. Our study suggests that aging is a major contributing factor to hypermethylation in cancer.

Association between CpG island methylation and microsatellite instability in colorectal cancer.

De novo methylation of promoter region CpG islands has been increasingly associated with transcriptional inactivation of important genes in neoplasia. To study the potential mechanisms underlying aberrant methylation in cancer, we have determined the methylation patterns of selected genes in colorectal cancers with and without microsatellite instability (MI), which results from defects in one of several base mismatch repair genes. A total of 47 colorectal cancers were analyzed, of which 15 were MI+ (32%). We now report that both the frequency and the extent of de novo methylation are strikingly increased in MI+ cancers. Hypermethylation of the p16 gene was found in 60% of MI+ cancers, compared to only 22% in MI- cancers (P = 0.02). Similarly, hypermethylation of the thrombospondin-1 (TSP-1) gene, an angiogenesis inhibitor, was increased in MI+ cancers (27% versus 0%; P = 0.008). Extensive methylation of insulin-like growth factor II (IGF2) and hypermethylated in cancer-1 (HIC-1) genes was observed in 60 and 80% of MI+ cancers, respectively, as contrasted with 6 and 38% of MI- cancers (P = 0.0002 and 0.01, respectively). Furthermore, 60% of the MI+ cancers displayed the hypermethylation events at two or more loci in a concordant manner compared to only 9% of the MI- cancers (P < 0.001). These results demonstrate a strong link between promoter hypermethylation and genetic instability due to deficient DNA repair.