GENETIC POLYMORPHISMS INFLUENCING EFFICACY AND SAFETY OF METHOTREXATE IN RHEUMATOID ARTHRITIS

Objective: This review will summarize pharmacogenetic studies of single nucleotide polymorphisms in genes coding enzymes of methotrexate (MTX) pathway, related to its response and toxicity in rheumatoid arthritis (RA). In addition, this review focuses on the racial and ethnic differences in distribution of the polymorphisms in genes related to efficacy and toxicity of MTX in RA.Methods: Articles were searched using Pubmed database using the search term pharmacogenetics and MTX and arthritis.†The search revealed 72 articles, of which 27 were given special importance, due to open-access.Results: Many genes and single nucleotide polymorphisms are investigated in this context, and the highlighting genes are ATP-binding cassette proteins (ABCB1) reduced folate carrier (RFC), methylenetetrahydrofolatereductase (MTHFR), gamma-glutamyl hydrolase (GGH), serine hydroxyl methyltransferase (SHMT), 5-aminoimidazole-4-carboxamide ribonucleotidetransformylase (ATIC), methionine synthase reductase (MTRR), methionine synthase (MS), adenosine monophosphate deaminase1 (AMPD1), inosine triphosphate pyrophosphatase (ITPA). The study highlighted RFC-1 80AA, ITPA 94CC, and AMPD1 347CC as responders. The allelic types prone to toxicity were MTHFR 677TT, MTRR 2756AA, MS 66GG, SHMT 1420CC, ATIC 347GG, and thymidylate synthase *3/*2. The genotypes reported as non-responders were ABCB1 3434TT, MTHFR 1298AA, DHFR A317G, GGH 16CC, and GGH 401TT.Conclusion: Although these studies highlight inconsistency in results, due to the difference in sample size and assessment parameters and racial and ethnic differences, larger prospective studies are essential to reach the cornerstone of the concept of personalized medicine

Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the contribution of NTE components in induced CA, we measured CA with and without an NO scavenger in normal skin fibroblasts cells after exposure to 600 MeV/u and 1 GeV/u 56Fe ions, less than one direct particle traversal per cell nucleus. Yields of CA were significantly lower in fibroblasts exposed to the NO scavenger compared to controls, suggesting involvement of NO in cell signaling for induction of CA. Media transferred from irradiated cells induced CA in non-irradiated cells, and this effect was abrogated with NO scavengers. Our results strongly support the importance of NTE contributions in the formation of CA at low-particle fluence in fibroblasts. View Full-Tex

Improved Memoryless RNS Forward Converter Based on the Periodicity of Residues

The residue number system (RNS) is suitable for DSP architectures because of its ability to perform fast carry-free arithmetic. However, this advantage is over-shadowed by the complexity involved in the conversion of numbers between binary and RNS representations. Although the reverse conversion (RNS to binary) is more complex, the forward transformation is not simple either. Most forward converters make use of look-up tables (memory). Recently, a memoryless forward converter architecture for arbitrary moduli sets was proposed by Premkumar in 2002. In this paper, we present an extension to that architecture which results in 44% less hardware for parallel conversion and achieves 43% improvement in speed for serial conversions. It makes use of the periodicity properties of residues obtained using modular exponentiation

FIR Filter Implementation by Efficient Sharing of Horizontal and Vertical Common Sub-expressions

No abstract availabl

Race and Ethnic Group Dependent Space Radiation Cancer Risk Predictions

Future space missions by national space agencies and private industry, including space tourism, will include a diverse makeup of crewmembers with extensive variability in age, sex, and race or ethnic groups. The relative risk (RR) model is used to transfer epidemiology data between populations to estimate radiation risks. In the RR model cancer risk is assumed to be proportional to background cancer rates and limited by other causes of death, which are dependent on genetic, environmental and dietary factors that are population dependent. Here we apply the NSCR-2020 model to make the first predictions of age dependent space radiation cancer risks for several U.S. populations, which includes Asian-Pacific Islanders (API), Black, Hispanic (white and black), and White (non-Hispanic) populations. Results suggest that male API and Hispanic populations have the overall lowest cancer risks, while White females have the highest risk. Blacks have similar total cancer rates than Whites, however their reduced life expectancy leads to modestly lower lifetime radiation risks compared to Whites. There are diverse tissue specific cancer risk ranking across sex and race, which include sex specific organ risks, female’s having larger lung, stomach, and urinary-bladder radiation risks, and male’s having larger colon and brain risks

Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A meta-analysis of randomised controlled treatment trials

Small studies have shown positive effects from adding a variety of antipsychotic agents in patients with obsessive–compulsive disorder who are unresponsive to treatment with serotonin reuptake inhibitors. The evidence, however, is contradictory. This paper reports a meta-analysis of existing double-blind randomized placebo-controlled studies looking at the addition of the second-generation antipsychotic quetiapine in such cases. Three studies fulfilled the inclusion criteria. Altogether 102 individuals were subjected to analysis using Review Manager (4.2.7). The results showed evidence of efficacy for adjunctive quetiapine (< 400 mg/day) on the primary efficacy criterion, measured as changes from baseline in total Yale–Brown Obsessive Compulsive Scale scores (P = 0.008), the clinical significance of which was limited by between-study heterogeneity. The mechanism underlying the effect may involve serotonin and/or dopamine neurotransmission

Isolation and identification of bacterial strains from different tea growing areas against Macrophoma sp. in southern India tea plantation

Branch canker is an important secondary stem disease in tea caused by Macrophoma theicola. Three different Macrophoma spp. were identified from three tea growing regions of southern India and their identity was confirmed by 18S rRNA method. Bacterial biocontrol isolated from four different locations of south India were also identified through 16S rRNA method. The bacterial strains were identified and evaluated for their antagonistic potential for the control of branch canker. Dual plate technique revealed that among the four bacterial strains, Bacillus amyloliquefaciens (78.9±0.4) showed maximum level of antagonism against all the three strains of Macrophoma spp. followed by B. subtilis (72.9±0.6) and B. licheniformis (64.2±0.7). In culture filtrate studies also, B. amyloliquefaciens (80.2) was found to possess highest antagonistic activity against the test pathogen, followed by B. subtilis (74.8) and Pseudomonas fluorescens (69.0). Among these, one potent strain of B. amyloliquefaciens was taken for GC-MS study and their bioactive compounds were identified as 1H-indene, 1-methylene, 3-hexadecene (Z), benzene acetic acid, phenol, and caffeine. These compounds could be responsible for antifungal activity against branch canker pathogen