Briefly, 1 mL of saliva sample with or without PI was concentrated with a 10 kDa membrane cut-off filter (Millipore). The fractions with high-molecular-weight proteins were separated check details on 1D SDS-PAGE (Novex Bis–Tris 4-12% gel; Invitrogen)

and stained with Coomassie Blue. The protein gel bands were excised from the 1D SDS-PAGE and subjected to in-gel reduction, alkylation, and trypsin digestion. The digestion was performed for 16 h at 37 °C. The peptides generated were extracted with 50% acetonitrile, washed twice with a solution containing 0.1% TFA and dried with a Speed-Vac. The dried peptide mixture was subjected to LC-MS/MS analysis. For LC-MS/MS analysis, the peptide mixture was separated by a 60-min gradient elution with the Dionex U3000 capillary/nano-HPLC system (Dionex, Sunnyvale, CA) at a flow rate of 0.25 μL min−1 directly interfaced with a Thermo-Fisher LTQ-Orbitrap mass spectrometer (Thermo-Fisher, San Jose, CA) operated in the

data-dependent scan mode. The analytical column was a homemade fused silica capillary column (75 μm i.d., 100 mm length; Upchurch, Oak Harbor, WA) packed with C-18 resin (300 A, 5 μm; Varian, Palo Alto, CA). Mobile phase A consisted of 0.1% formic acid, and mobile phase B consisted of 100% acetonitrile Ensartinib nmr and 0.1% formic acid. The 60-min gradients at 0.250 μL min−1 flow rate for solvent B increased from 0% to 55% in 30 min and then to 80% in 10 min. The experiment consisted of a single full-scan mass spectrum in the Orbitrap (400–1600 m/z, 30 000 resolutions), which was followed by six data-dependent MS/MS scans in the ion trap at 35% normalized collision energy. Data were analyzed using mascot software and manual inspection. The fraction with low-molecular-weight species was directly

new analyzed by LC-MS/MS using the method described above with an LTQ-Orbitrap mass spectrometer (Thermo-Fisher). Data management and analyses were performed using spss 17.0 software (SPSS Inc., Chicago, IL). All cultivable bacterial data were compiled and logarithmically transformed to normalize the variance distribution. Correlation analyses were performed to determine the correlation coefficients of the mean bacterial levels in the samples with and without PI addition. For DGGE profile analysis, levels of similarity between fingerprints were calculated according to the Dice coefficient. Dendrograms were constructed from the average matrix using the unweighted pair group method by means of arithmetic averages. Differences in mean bacterial counts (log10 value), the number of detected DGGE bands, and the degree of similarity were evaluated using the paired t-test. All P values <0.05 were two-tailed and considered significant. Based on conventional culturing techniques, the log10 values of the total cultivable bacteria in saliva with PI were similar to those of saliva without PI.

2). These spots from the SH treatment were excised, digested with trypsin and subjected to MS analysis. A mascot search identified spot 195 as GlnK, and spot 196 as a mixture of both GlnB and GlnK (these proteins have the same predicted pI and MW; Table 2). Several predicted peptides of both GlnB and GlnK have the same mass, as these proteins are 79% identical in sequence. DAPT order We identified two peptides that are characteristic for each protein in the mass spectrum of spot 196 (Table 2) and MS/MS analysis of these particular peptides confirmed that this spot is a mixture of GlnB and GlnK. The peptide

of m/z of 1359.76, which is predicted to derive from GlnB only, was also observed in the mass spectrum of spot 195 (Fig. 3). Although we could not obtain good MS/MS data for this particular peptide, its presence suggests that spot 195 might also be a mixture of GlnB and GlnK. The experimental

pI for spot 195 (pI=5.58) was 0.55 units different from the predicted pI of GlnB and GlnK (pI=6.13). It is known that the PII proteins from H. seropedicae are subject to uridylylation (Benelli et al., 2001) and, by analogy with the E. coli PII proteins, it is assumed that uridylylation occurs at the conserved Opaganib datasheet Y51 residue. A signal of m/z of 1543.67 was observed in the mass spectrum of spot 195 but was absent in that of spot 196 (Fig. 3). This signal matches the expected increment of mass for the addition of a UMP group (monoisotopic mass of 306.03) in the peptide of m/z 1237.64, which carries the Y51 uridylylation site of both GlnB and

GlnK. Thus, spot 195 represents uridylylated monomers of GlnK and probably also of GlnB. We conclude that very low amounts of deuridylylated PII proteins are associated with the cell membrane in both +N and −N conditions and that more deuridylylated PII becomes membrane-associated after an ammonium shock (Fig. 2, compare signals of spot 196 in +N, −N and SH). To verify whether the membrane association of PII proteins occurs via interaction with AmtB we prepared membrane fractions from wild-type and amtB mutant strains collected before and after the ammonium shock. As attempts to localize the PII proteins in these Dichloromethane dehalogenase fractions by Western blot using polyclonal anti-PII antibodies from both E. coli and A. brasilense were unsuccessful, we decided to use a MS-based approach instead. These extracts were separated in a regular 12% SDS-PAGE and stained with Coomassie blue. A 1 cm region of molecular mass below the 14-kDa marker was excised from each lane, digested with trypsin and analyzed by MALDI-TOF MS/MS (Fig. S2A). The MS1 mass spectra indicate the presence of peaks with m/z of 1237.64 and 1330.78 in the samples from wild-type cell membrane extract collected both before and after the ammonium shock. These peaks match the expected peptide mass of 1237.64 and 1330.77 of GlnB and GlnK.

2b. Therefore, they may be responsible for click here the hydrolysis of RNA by a mechanism similar to RNase A. However, due to localization of aspartic acid (D535) on the surface of catalytic domain as shown in Fig. 2b, its role in RNA hydrolysis by mechanism similar to barnase and colicin E3 cannot be ruled out. Therefore, to determine individual role of conserved amino acid residues in the putative active site of catalytic domain of

xenocin, site-directed mutagenesis was performed. All the conserved amino acid residues were mutated to alanine, and endogenous toxicity assay was performed with each mutant strain. Growth profile of JSR4 strain–containing vector alone was considered as 100% and compared with growth profile of D535A, H538A, E542A, H551A, K564A and R570A strains. From the predicted structure of catalytic domain of xenocin as shown in Fig. 2b, it was observed that H538 was the most surface-exposed histidine residue among the four other present in the catalytic domain. Endogenous assay showed that mutation at H538 position results in the reduction of toxicity by more than 90% after 8 h postinduction as shown in Fig. 2c, which confirmed the role D535 as an important residue of the putative active site. As second conserved histidine residues H551 was nearer to H538 and exposed on the surface, it

may behave as the second histidine residue required for the hydrolysis of RNA by a mechanism similar to RNase A ribonuclease. Therefore, PS-341 mw H551 was mutated to alanine, and endogenous assay was performed. Results showed that there was only 50% reduction in endogenous toxicity in H551A strain after 8 h of induction as shown in Fig. 2c. One reason for such minimum reduction in endogenous toxicity in H551A strain is that it could be due to partial exposure of H551 to the surface as compared to H538 as revealed by the surface view model of catalytic domain as buy Sunitinib shown in

Fig. 2b. This result indicates that RNA hydrolysis mechanism of catalytic domain of xenocin is different from RNase A ribonuclease. D535 and E542 are two acidic amino acid residues that are conserved, exposed to surface as well as close to the H538 as shown in Fig. 2a and b. These two residues may be responsible for the hydrolysis of RNA by mechanism similar to barnase and colicin E3. Therefore, these two residues were mutated to alanine and analysed by endogenous assay. Endogenous toxicity assay result showed that toxicity was reduced by 70% after 8 h postinduction in E542A strain as shown in Fig. 2c. Structural studies showed that E542 was also a part of cleft formed by D535 and H538, which is exposed to the surface as shown in Fig. 2b. However, studies with D535 strain showed significant reduction (88%) in the endogenous toxicity after 8 h postinduction as shown in Fig. 2c; moreover, D535 was the closest amino acid residue with respect to H538 as shown in Fig. 2a.

NHT-2 possessed a high degree of sequence homology with R. gracialis, while Leucosporidium sp. BSS-1 possessed a high degree of sequence homology with Leu. antarcticum (Glaciozyma antarctica), and these two isolates demonstrated antifreeze activity. IGF-1R inhibitor All isolates examined were capable of growth at −1 °C. Mrakia spp., while capable of growth at −1 °C, did not demonstrate any antifreeze activity and exhibited only limited secretion of extracellular polysaccharides. Species

of the genus Mrakia possessed high amounts of unsaturated fatty acids, suggesting that members of this genus have adapted to cold environments by increasing their membrane fluidity. “
“Enterotoxins produced by Staphylococcus aureus are the key pathogenicity factors that can cause a variety of illnesses in humans, including staphylococcal gastroenteritis and food poisoning. It has been proven that licochalcone A is a potentially

effective antimicrobial agent against S. aureus. In this study, Western blot assays, tumour necrosis factor release assays, murine T-cell proliferation assays, and real-time reverse transcriptase-PCR were performed Palbociclib molecular weight to evaluate the effect of subinhibitory concentrations of licochalcone A on the secretion of two major enterotoxins (SEA and SEB) by S. aureus. The results show that licochalcone A significantly decreased, in a dose-dependent manner, the secretion of SEA and SEB by both methicillin-sensitive Resveratrol S. aureus and methicillin-resistant S. aureus. These results may increase the desirability of using licochalcone A as a lead compound for the design of more potent antibacterial agents based on the chalcone template. Staphylococcus aureus is one of the most important community- and hospital-acquired pathogens, and it continues to cause a wide spectrum of serious diseases, including skin and soft tissue lesions, as well as lethal infections such as osteomyelitis, endocarditis,

pneumonia, and septicaemia (Liang et al., 2006). Owing to the development of drug resistance, the morbidity and mortality associated with S. aureus infections remain high in spite of antimicrobial therapy (Kuroda et al., 2007). In addition, S. aureus secretes a number of exotoxins (e.g. haemolysins, enterotoxins, protein A, TSST-1, and coagulase) that contribute to a variety of diseases (Ohlsen et al., 1997). Exotoxins are produced by S. aureus in a growth-phase-dependent manner, primarily during the postexponential phase of growth (Arvidson & Tegmark, 2001). Furthermore, the expression of virulence factors is generally modulated in response to alternations in cell-population density through a process referred to as quorum sensing (Miller & Bassler, 2001). Staphylococcal enterotoxins (SEs) are the major virulence factors that cause staphylococcal gastroenteritis and are one cause of food poisoning in humans (Tseng & Stewart, 2005; Bania et al., 2006).

5% bovine serum albumin in PBS; Calbiochem, Darmstadt, Germany) was added to each well. The plate was incubated at 37 °C for 30 min and washed three times with 1 × SSC. Following this, 100 μL of the substrate (4-methylumbelliferyl-β-d-galactopyranoside 100 μg mL−1) was added to each well and the fluorescence intensity was measured

using IWR-1 chemical structure a DTX 800 Multimode Detector (Beckman Coulter, Tokyo, Japan). DNA relatedness was expressed as a mean percentage of the homologous DNA-binding value. The G+C mol% content was determined by HPLC (Mesbah et al., 1989). A total of 5 μg of denatured DNA was hydrolyzed with P1 nuclease (Yamasa Syoyu, Chiba, Japan) for 1 h at 50 °C. Alkaline phosphatase (Sigma, MO) was then added, and the mixture was incubated at 37 °C for 30 min for nucleotide dephosphorylation. The nucleosides were quantified with a GC analysis standard (Yamasa Syoyu) using a model L-2400 HPLC system (Hitachi, Tokyo, Japan) and an Inertsil ODS-3 HPLC Column (GL Sciences, Tokyo, Japan). The nucleosides were eluted with a solvent containing 0.2 M NH4H2PO4 and acetonitrile (20 : 1, v/v). G+C mol% was determined using

the mean values of three experiments. Strains designated as belonging to Lancefield group M formed a precipitate with Lancefield group M antiserum and with no other Lancefield grouping sera, confirming that they were indeed Lancefield group M strains. Based on 16S rRNA gene analysis, species of the genus Streptococcus were separated Roscovitine in vivo into six major clusters (Kawamura et al., 1995). Group

M strains PAGU 653, PAGU 1331, PAGU 1332 and PAGU 1535 were located in the Epothilone B (EPO906, Patupilone) pyogenic group on the phylogenetic tree (Fig. 1) and were highly related to each other genetically (99.8–100.0% 16S rRNA gene sequence similarity). Streptococcus marimammalium strain CCUG 48494T was the closest relative to the Group M strains in this analysis. The homology values between PAGU 653 and all other streptococci were<95.6%. These data demonstrate that group M strains constitute a new species with>97% 16S rRNA gene sequence similarity between strains (Stackebrandt & Goebel, 1994). We collected additional data of the genetic relationship between group M strains and closely related species by DNA–DNA hybridization experiments including group M strains, PAGU 653, PAGU 1331 and PAGU 1332. Streptococcus marimammalium was selected for these experiments because this species was most closely related to the group M strains on the phylogenetic tree based on 16S rRNA gene, and showed similarities for some phenotypic characteristics compared with other streptococci. The DNA–DNA hybridization values obtained under optimal (30 °C) and stringent (40 °C) conditions (Table 1) indicate that group M strains possess significantly lower DNA relatedness with S. marimammalium than with each other.

The signal transduction mechanisms

in response to nutritional stress and other abiotic stresses besides DNA damage have been shown in bacteria (Parkinson, 1993). In this study, we highlight, for the first time, the presence of a γ radiation-induced signaling mechanism in a prokaryote, D. radiodurans. We demonstrate that the DNA damage-induced synthesis of cAMP and ATP was possibly manifested by upregulation of AC and downregulation of 2′,3′ cAMP phosphodiesterase activities during PIR. The presence of different ACs and their involvement in bacterial signal transduction are well established (Linder & Schultz, 2003; Shenoy & Visweswariah, 2006). Although, the mechanism by which cAMP regulates DNA damage response is not clear; it can presumably act as an inducer of protein kinase NVP-AUY922 mw activity and a signaling molecule in bacteria, as is known in eukaryotes (De Gunzburg, 1985). Similarly, the effects of DNA damage and oxidative stress on AC and 2′,3′cyclic phosphodiesterase enzymes have not RAD001 been studied, but the regulation of cyclic phosphodiesterase and AC activities by a membrane receptor relaxin-mediated tyrosine phosphorylation has been demonstrated in mammalian cells (Bartsch et al., 2001). As cAMP is a

known activator of mitogen-activated protein kinases and other soluble as well as membrane-bound protein kinases (Stork & Schmitt, 2002; Sanz, 2008) in eukaryotes, it is likely that the higher levels of cAMP and AC activity in 1- and 0.5-h PIR samples, 3-oxoacyl-(acyl-carrier-protein) reductase respectively, regulate protein phosphorylation in this bacterium by similar mechanisms. Our results show that (1) the levels of cAMP and ATP change in response to DNA damage, possibly manifested by differential regulation of AC and cyclic phosphodiesterase enzymes and (2) DNA damage-inducible protein kinase-mediated ATP attenuation of nucleolytic activity is involved during PIR. This is consistent with the activation

of protein kinase by DNA damage in eukaryotes (Kitagawa & Kastan, 2005). Thus, there exists a DSB-induced signaling mechanism in this extremophile, which is known to have acquired the genetic elements from higher organisms through horizontal gene transfer (Makarova et al., 2001; Blasius et al., 2008). The possibility that this superbug has acquired the DNA damage-induced signaling pathway from other organisms during evolution cannot be ruled out and would be worth investigating. We express our sincere thanks to Dr S.K. Apte, Bhabha Atomic Research Centre, Mumbai, for the technical and critical comments in data interpretation and in the preparation of the manuscript. Prof. S.P. Modak, Pune University, and Ms Swathi Kota, Bhabha Atomic Research Centre, are thanked for their comments on scientific and technical aspects of the manuscript. “
“We agree with the authors that the maintenance of patients in care and, where appropriate, on treatment after diagnosis is vital for their continued good health.

Multiple mechanisms might be responsible for generating the observed

diversity in 5S rRNA genes in a genome. In organisms containing multiple rRNA genes, the homogeneity of primary structures is believed to be maintained through gene conversion by homologous recombination (Hashimoto et al., 2003), as a form of concerted evolution (Abdulkarim & Hughes, 1996). Although the observed homogeneity of 5S rRNA genes in the majority of species analyzed could be attributed to the effect of homologous recombination, the recombination appeared to be compartmentalized or ineffective in some genomes. The observed high degree of diversity in the primary structures of the 5S rRNA genes in partial or split rRNA gene operons and the rrnC operon in T. tengcongensis suggested that these rRNA genes have been excluded INK-128 from participation in concerted evolution. Such compartmentalization was also present in B. subtilis that has two similarity groups of rRNA genes appeared to have evolved

independently, as evidenced by their relation to different 5S rRNA genes-rrn23S spacers. Despite the lack of sequence homogeneity, secondary structures of these genes were well conserved, most likely due to the life and death driving force of ribosomal constraints. Compared with whole 16S and 23S rRNA genes, 5S rRNA genes are a less ideal taxonomical marker for use in analyses of complex microbiomes. The main reason is the widespread intragenomic 5S rRNA gene diversity. Approximately, 12.3% (96 of 779) GW-572016 research buy of the unique

species analyzed had > 3% intragenomic variation of 5S rRNA genes, compared to only about 1% of species with similar degree of variation in 16S and 23S rRNA genes (Coenye & Vandamme, 2003; Acinas et al., 2004; Pei et al., 2010). This high degree of diversity most often occurs between a standalone 5S rRNA pentoxifylline gene (orphan or split) and a 5S rRNA gene in a complete rRNA operon. The lack of standalone 16S or 23 S rRNA genes appears to be the main reason for the lower intragenomic diversity among 16S or 23S rRNA genes. Orphan 5S rRNA genes are sometimes overlooked by a whole-genome annotation program because of their small size. Compared with rrnDB (Lee et al., 2009), a publically accessible database that collects existing data on structure RNA genes from whole-genome sequencing projects, 11 genomes listed in Table 1 that had additional 5S rRNA genes in our study are not listed in rrnDB. The additional 5S rRNA genes would have been invisible if blast search of 5S rRNA genes against the whole genomes were not performed. Nevertheless, in 26 of the 52 genomes listed in Table 1, correct records of the orphan 5S rRNA genes can be found in rrnDB. The remaining 15 of the 52 genomes have no entries in rrnDB. Divergent evolution between paralogous 5S rRNA genes in a genome may corrupt the record of evolutionary history and obscure the true identity of an organism.

Although both pharmacy and medical students valued the IPE experience, the interviews have helped identify minor changes to further increase the value of these sessions to pharmacy students, for example, providing some

additional preparation for medical students prior to the IPE sessions. 1. John DN, Premji A, Coulman SA, Hayes J, Sweetland H, Thompson JP, Routledge PA. Evaluating an Interprofessional Education Therapeutics and Prescribing Activity for Third Year Medicine and Pharmacy Undergraduates. International Journal of Pharmacy Practice 2012; 20(S2): 3. Samuel Jee, Ellen Schafheutle, Peter Noyce The University of Manchester, Greater Manchester, UK Qualitative interviews explored the views of newly qualified pharmacists (NQPs)’

on how they adjusted to their role following training All NQPs found the responsibility and accountability they faced learn more challenging; NQPs in community felt unprepared for managerial tasks and delivering services they were unfamiliar with; NQPs in hospital found it difficult to manage their time and workload Providing trainees with more responsibilities and learning opportunities in, for example, a range of services during training as well as providing formal support to NQPs may ease the transition from trainee to pharmacist Pre-registration training (PRT) can Selleck Apoptosis Compound Library play a major role in instilling professionalism1 and facilitating MycoClean Mycoplasma Removal Kit the development of skills required to practise as a pharmacist. Little is known, however, on how successful the pre-registration year is in preparing NQPs for practice as a pharmacist. The aim of this paper is to explore the views of NQPs on how successful PRT was in preparing them for their role and the challenges they faced. A purposive sample of trainees from community and hospital pharmacies were recruited in August / September 2011 across the North-West of England as part of a longitudinal study exploring the role of PRT in the professional socialisation of trainees. Semi-structured telephone interviews were conducted

with NQPs approximately three months after registration. Interviews were audio-recorded, transcribed verbatim and analysed thematically using template analysis and the framework technique.2 The topic guide included how well PRT prepared NQPs for their role, the challenges faced and who had supported them as NQPs. NHS ethics approval was granted. Interviews were carried out with 19 NQPs (10 female; mean age = 23.53, SD = .90). All NQPs were working in the same sector they trained in: 13 in community, six in hospital. Fourteen were working at a different pharmacy than where they trained. They were working as pharmacy managers (n = 3), second pharmacists (n = 3), relief pharmacists (n = 3); and locums (n = 4) in community and band six (n = 4) and resident pharmacists (n = 2) in hospital.

To understand

the role of the striatum in value- and strategy-based decision-making, we recorded striatal neurons in macaque monkeys performing a behavioral task in which they searched for a reward target by trial-and-error among three alternatives, earned a reward for a target choice, and then earned additional rewards for choosing the same target. This task allowed us to examine whether and how values of targets and strategy, which were defined as negative-then-search and positive-then-repeat (or win-stay-lose-switch), selleck compound are represented in the striatum. Large subsets of striatal neurons encoded positive and negative outcome feedbacks of individual decisions and actions. Once monkeys made a choice, signals related http://www.selleckchem.com/products/sch-900776.html to chosen actions, their values and search- or repeat-type actions increased and persisted until the outcome feedback appeared. Subsets of neurons exhibited a tonic increase in activity after the search- and repeat-choices following negative and positive feedback in the last trials as the task strategy monkeys adapted. These activity profiles as a heterogeneous representation of decision variables may underlie a part of the process for reinforcement- and strategy-based evaluation of selected actions

in the striatum. “
“In the last few years it has become clear that AMPA-type glutamate neurotransmitter receptors are rapidly transported into and out of synapses to strengthen or weaken their function. The remarkable dynamics of AMPA receptor (AMPAR) synaptic localization provides a compelling mechanism for understanding the cellular basis of learning and memory, as well as disease states involving cognitive dysfunction. Here, we summarize the evidence for AMPAR trafficking

as a mechanism underlying a variety of learned responses derived from both behavioral and P-type ATPase cellular studies. Evidence is also reviewed supporting synaptic dysfunction related to impaired AMPAR trafficking as a mechanism underlying learning and memory deficits in Alzheimer’s disease. We conclude that emerging data support the concept of multistage AMPAR trafficking during learning and that a broad approach to include examination of all of the AMPAR subunits will provide a more complete view of the mechanisms underlying multiple forms of learning. “
“Recent studies have shown a continued maturation of visual responsiveness and synaptic activity of retina after eye opening, including the size of receptive fields of retinal ganglion cells (RGCs), light-evoked synaptic output of RGCs, bipolar cell spontaneous synaptic inputs to RGCs, and the synaptic connections between RGCs and ON and OFF bipolar cells. Light deprivation retarded some of these age-dependent changes. However, many other functional and morphological features of RGCs are not sensitive to visual experience.

This is a retrospective chart review with convenience sampling of patients on NSAIDs (at least five tablets a

week, for at least 3 months prior to the study), attending the Rheumatology clinic of a tertiary care institution in south India between June 2004 and November 2004. Those with pre-existing heart disease, hypertension, thrombo-embolic disease, peptic Ipatasertib ulcer and patients on corticosteroids were excluded. All the recorded adverse events were noted and compared between the Celecoxib and non-selective NSAID users. Univariate analysis using Chi-square test was performed. Of the 1387 patients included, 915 were on Celecoxib. In the NSAID group, 204 had used multiple NSAIDs in sequence. Of the Celecoxib users, 164 had switched over to an NSAID during the study period. New onset of hypertension was significantly higher in the Celecoxib users as compared to non-selective NSAID users (3.06% vs. 1.27%, P = 0.04). However, those who had switched over to NSAIDs

did not show this trend. NSAID users, on the other hand, had significant gastrointestinal (GI) toxicity (2.54% vs. 0.327%, P = 0.001). A significant number of Celecoxib users who switched over to NSAIDs also developed GI toxicity (6.1% vs. 1.21%, P = 0.018) over a shorter time span, as compared to the continuous NSAID users. Multiple NSAID users had higher adverse events (6.37% vs. 2.23%, P = 0.023) as compared to single NSAID users. Celecoxib significantly increased the incidence of new onset hypertension in this cohort of Indian patients with rheumatic diseases. No thromboembolic events were documented. Non-steroidal anti-inflammatory drugs MK-8669 price (NSAIDs) are widely acclaimed for their anti-inflammatory, analgesic and antipyretic properties. The non-selective NSAIDs act by inhibiting both isoforms of the enzyme cyclo-oxygenase (COX-1 and COX-2).

COX-2 inhibition is mainly responsible for anti-inflammatory actions and COX-1 inhibition leads to NSAID-induced gastrointestinal damage.[1] Ribose-5-phosphate isomerase The hypothesis that selective inhibition of COX-2 isoform may help in reducing pain and inflammation without compromising the gastric mucosa led to discovery of the selective COX-2 inhibitors. Celecoxib was developed first in this group and was found to possess analgesic and anti-inflammatory efficacy comparable to the non-selective NSAIDs in treatment of inflammatory arthritic conditions.[2] In view of their gastrointestinal safety profile, within a short span of time COX-2 inhibitors gained popularity over non-selective NSAIDs.[3] However, COX-2 inhibition reduces vascular prostacyclin (PGI2) production, thus affecting the balance between prothrombotic and anti-thrombotic eicosanoids.[4] This property can tip the balance in favor of prothrombotic eicosanoids, which can lead to increased cardiovascular thrombotic events.[5] Serious concerns regarding the cardiovascular safety of Rofecoxib were expressed following the Vioxx Gastrointestinal Outcomes Research (VIGOR) study.