Drug–drug Interactions in Hospitalized Cardiac Patients

Drug–drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. DDI in patients receiving multidrug therapy is a major concern. The aim of the present study was to assess the incidence and risk factors of DDIs in patients admitted in cardiology unit of a teaching hospital. A prospective, observational study was carried out for a period of 3 months (April–July 2009). During the study period, a total of 600 prescriptions were analyzed and it was found that 88 patients had at least one DDI. The percentage of DDIs was higher in females compared to males (56.82% vs. 43.18%). DDIs were observed more in the age group of 60 years and above (57.96). Patients with more than 10 prescribed drugs developed DDIs more frequently [58 (65.91%)]. Heparin [55 (62.25%)] and aspirin [42 (47.72%)] were the most common drugs responsible for DDIs. Bleeding was the commonest clinical consequence [76 (86.63%)] found in this study population. On assessment of severity of DDIs, majority of the cases were classified as moderate in severity (61.36%). Aging, female gender and increase in concurrent medications were found to be associated with increased DDIs. Patients having these risk factors can be actively monitored during their stay in the cardiology department to identify DDIs

A redetermination of the structure of the triple mutant(K53,56,120M) of phospholipase A2 at 1.6 Å resolution using sulfur-SAS at 1.54 Å wavelength

The crystal structure of the triple mutant K53,56,120M of bovine pancreatic phospholipase A(2) has been redetermined using sulfur single-wavelength anomalous scattering. The synchrotron data-were collected at lambda = 1.54 Angstrom and the crystal diffracted to 1.6 Angstrom resolution. The program SOLVE was used to locate the heavy atoms and to estimate the initial phases and the resulting map was then subjected to RESOLVE. The output of 455 non-H atoms, including 12 S atoms, one calcium ion and one chloride ion, were then subjected toARP/wARP followed by REFMAC With the improved phases, the automaticmodel building successfully built more than 85%, of the 123 residues, excluding the N- and C-terminal residues. The final crystallographic R factor is 17.7% (R-free = 21.7%). The refined model consists of 954 non-H protein atoms, 165 water 0 atoms, three 2-methyl-2,4-pentanediol (MPD) molecules, one calcium ion and one chloride ion. The present work is yet another example that shows the utility of single-wavelength anomalous scattering data for solving a protein structure

Structure of the C-Terminal Domain of the Multifunctional ICP27 Protein from Herpes Simplex Virus 1

Herpesviruses are nuclear-replicating viruses that have successfully evolved to evade the immune system of humans, establishing lifelong infections. ICP27 from herpes simplex virus is a multifunctional regulatory protein that is functionally conserved in all known human herpesviruses. It has the potential to interact with an array of cellular proteins, as well as intronless viral RNAs. ICP27 plays an essential role in viral transcription, nuclear export of intronless RNAs, translation of viral transcripts, and virion host shutoff function. It has also been implicated in several signaling pathways and the prevention of apoptosis. Although much is known about its central role in viral replication and infection, very little is known about the structure and mechanistic properties of ICP27 and its homologs. We present the first crystal structure of ICP27 C-terminal domain at a resolution of 2.0 Å. The structure reveals the C-terminal half of ICP27 to have a novel fold consisting of α-helices and long loops, along with a unique CHCC-type of zinc-binding motif. The two termini of this domain extend from the central core and hint to possibilities of making interactions. ICP27 essential domain is capable of forming self-dimers as seen in the structure, which is confirmed by analytical ultracentrifugation study. Preliminary in vitro phosphorylation assays reveal that this domain may be regulated by cellular kinases. IMPORTANCE ICP27 is a key regulatory protein of the herpes simplex virus and has functional homologs in all known human herpesviruses. Understanding the structure of this protein is a step ahead in deciphering the mechanism by which the virus thrives. In this study, we present the first structure of the C-terminal domain of ICP27 and describe its novel features. We critically analyze the structure and compare our results to the information available form earlier studies. This structure can act as a guide in future experimental designs and can add to a better understanding of mechanism of ICP27, as well as that of its homologs

Enzymes involved in lipid digestion

International audienceLipid digestion is a complex process that takes place at the lipid-water interface and involves various lipolytic enzymes present predominantly in the stomach and the small intestine [34]. These enzymes catalyse the hydrolysis of a variety of dietary lipids from animal and plant sources, such as triacylglycerols (TAGs), phospholipids, galactolipids, cholesterol and vitamin esters. They include gastric lipase, colipase-dependent pancreatic lipase, pancreatic lipase-related proteins 2 (PLRP2), carboxyl ester hydrolase or bile salt-stimulated lipase (CEH, BSSL), and pancreatic phospholipase A2. A debate still exist about the existence of a lingual lipase in human [30, 86, 140], an enzyme that has been demonstrated to be present and active in rat and mice tongue only and which is the product of a gene ortholog [53] to the gene of gastric lipase [24] in humans and many other species. Bakala N’Goma et al. [12] have reviewed the key findings that support the existence of lingual or gastric lipases in several species in term of gene expression, enzyme immunocytolocalization and lipase activity. So far, no supporter of the existence of a lingual lipase in humans has been able to provide similar data