Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) is known as one of the most common irritating gastrointestinal disorders. The mechanism behind IBS is still under investigation and it is thought that it may arose from multi factors among which free radicals have been previously mentioned. Studies have found an association between oxidative stress and IBS; however, little is known about the mechanisms and oxidative stress components status during IBS. One of the key factors playing a central role in oxidative stress network is glutathione reductase (GR). Here we report the GR activity in colon tissue samples during IBS to explore a part of contributing components in IBS pathogenesis. METHODS: The GR enzyme activity was measured in 15 active IBS colon biopsy samples and was compared to our best available age and sex matched colorectal tissue samples from normal marginal tissue of resected colon cancers (n=15). The enzyme activity in the two groups was determined and compared using a commercial GR Assay Kit (Cayman chemical). RESULTS: A significant decrease in GR activity among IBS tissue samples was observed compared to anatomically normal marginal colon tissue samples (p=0.007). CONCLUSIONS: Lower GR activity may increase oxidized glutathione there by in turn could contribute as a main component in oxidative stress network. The lower GR activity results in hampered defense mechanism against produced free radical species. This finding may clarify a part of IBS pathogenesis.

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer.

Colorectal cancer (CRC) is known as the most common form of malignancies in the world and its occurrence is annually increasing. Due to the relatively high death rates in patients, finding better diagnostic and prognostic factors are required. Substance P (SP) belongs to the tachykinin family that acts as an immunomodulator by binding to the neurokinin-1 receptor (NK1R). The interaction of SP with NK1R might be involved in tumor cell proliferation, angiogenesis, and migration. Hence, this study was aimed to evaluate the serum SP level and tissue distribution of NK1Rs in CRC. Also, we assessed the relationship between tissue distribution of NK1R and some different tumor characteristics, including tumor size, and lymph node status. Recruiting 38 patients primarily diagnosed with CRC, the tissue distribution of NK1R was immunohistochemically evaluated in tumor tissues and their adjacent normal tissue. The serum level of SP was measured using an ELISA method in both cases and healthy control group. The SP value was significantly increased in the serum of patients in comparison with the healthy group (p = 0.001). Tumor tissues expressed a higher number of NK1R than adjacent normal tissues (p = 0.01) considering both the percentage of stained cells and intensity of staining. However, there was not any statistically significant relevance between NK1R distribution and tumor characteristics. The SP/NK1R system is involved in tumorigenesis of CRC, and might be suggested as a potent prognostic or diagnostic factor, or a new target in the treatment of CRC.

Assessing subtype and drug-resistance-associated mutations among antiretroviral-treated HIV-infected patients.

BACKGROUND: Several studies have reported an increasing number of therapeutic failures with antiretroviral drugs in HIV-infected patients. The emergence of viral-resistant strains is a major problem for the medical management of infected individuals. The aim of this study is to determine viral subtypes and drug-resistance mutations among antiretroviral-treated HIV-infected patients. METHODS: A total of 42 antiretroviral-treated but still viremic HIV-infected patients were enrolled. The HIV pol regions were amplified and sequenced to determine subtypes and antiretroviral-resistant mutations. RESULTS: The subtype distribution was 48% A/D recombinants, 43% subtype B, 5% subtype A and 5% CRF01-AE recombinants. Drug-resistant mutations were most common in subtype B (53%) and A/D recombinant strains (44%). Virus samples from 19% of participants had no drug-resistant mutations; 2, 2 and 76% of samples carried one, two and at least three drug-resistant mutations, respectively. The prevalence of nucleoside transcriptase inhibitor mutations was 76%, with M184V and L74V present in 60 and 38% of samples, respectively. The prevalence of nonnucleoside transcriptase inhibitor mutations was 74%, with P225H present in 55% of study specimens. The prevalence of protease inhibitor mutations was 45%, with major mutation L90M seen in 33% and minor mutation A71V in 36% of samples. Of note, the P225H and A71V are 'minor' drug-resistance mutations conferring only minimal drug-resistance phenotypes in the absence of major mutations. CONCLUSION: Our study found a high prevalence of drug-resistant mutations in Iranian HIV-infected patients. Our data support the need for continued surveillance of resistance patterns to help guide therapeutic approaches and limit transmission of these variants.