An assessment of the efficacy and safety of diclofenac potassium liquid-filled capsules in patients with various levels of baseline pain intensity.

Context: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC; Zipsor*) is a novel formulation of diclofenac potassium used to treat mild to moderate acute pain.

Objective: To investigate whether DPSGC 25 mg provided significant reduction in pain intensity compared with placebo, regardless of baseline pain intensity, a post hoc analysis was performed of pooled data from two replicate randomized controlled trials (NCT00366444 and NCT00375934) that evaluated the safety and efficacy of DPSGC in postbunionectomy treatment.

Methods: Patients from the two randomized trials were assigned to one of two subgroups: patients with baseline numerical pain rating scale (NPRS) scores of 4 or greater to less than 7 and those with baseline NPRS scores of 7 or greater.

Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following bunionectomy surgery.

Objective: To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets * for the treatment of moderate-to-severe postoperative pain following bunionectomy surgery.

Research Design And Methods: Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069).

Diclofenac potassium liquid-filled soft gelatin capsules for the treatment of postbunionectomy pain.

Objective: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a rapidly absorbed formulation of diclofenac approved for the treatment of mild to moderate acute pain in adults (≥18 years of age). The objective of this study was to investigate the efficacy and safety of DPSGC 25 mg in a multicenter, randomized, double-blind, placebo-controlled study in patients experiencing pain following first metatarsal bunionectomy.

Research Design And Methods: Patients experiencing a requisite level of pain (≥4 based on an 11-point numeric pain rating scale [NPRS]; 0 = no pain, 10 = worst pain possible) on the day following surgery were randomized to receive DPSGC 25 mg or placebo.

Differential use of signal peptides and membrane domains is a common occurrence in the protein output of transcriptional units.

Membrane organization describes the orientation of a protein with respect to the membrane and can be determined by the presence, or absence, and organization within the protein sequence of two features: endoplasmic reticulum signal peptides and alpha-helical transmembrane domains. These features allow protein sequences to be classified into one of five membrane organization categories: soluble intracellular proteins, soluble secreted proteins, type I membrane proteins, type II membrane proteins, and multi-spanning membrane proteins. Generation of protein isoforms with variable membrane organizations can change a protein's subcellular localization or association with the membrane.

A class of human exons with predicted distant branch points revealed by analysis of AG dinucleotide exclusion zones.

Background: The three consensus elements at the 3' end of human introns--the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide--are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides.

Understanding alternative splicing: towards a cellular code.

In violation of the 'one gene, one polypeptide' rule, alternative splicing allows individual genes to produce multiple protein isoforms - thereby playing a central part in generating complex proteomes. Alternative splicing also has a largely hidden function in quantitative gene control, by targeting RNAs for nonsense-mediated decay. Traditional gene-by-gene investigations of alternative splicing mechanisms are now being complemented by global approaches.

ASD: the Alternative Splicing Database.

Alternative splicing is widespread in mammalian gene expression, and variant splice patterns are often specific to different stages of development, particular tissues or a disease state. There is a need to systematically collect data on alternatively spliced exons, introns and splice isoforms, and to annotate this data. The Alternative Splicing Database consortium has been addressing this need, and is committed to maintaining and developing a value-added database of alternative splice events, and of experimentally verified regulatory mechanisms that mediate splice variants.

Conservation of human alternative splice events in mouse.

Human and mouse genomes share similar long-range sequence organization, and have most of their genes being homologous. As alternative splicing is a frequent and important aspect of gene regulation, it is of interest to assess the level of conservation of alternative splicing. We examined mouse transcript data sets (EST and mRNA) for the presence of transcripts that both make spliced-alignment with the draft mouse genome sequence and demonstrate conservation of human transcript-confirmed alternative and constitutive splice junctions.

The molecular basis for the lack of immunostimulatory activity of vertebrate DNA.

Macrophages and B cells are activated by unmethylated CpG-containing sequences in bacterial DNA. The lack of activity of self DNA has generally been attributed to CpG suppression and methylation, although the role of methylation is in doubt. The frequency of CpG in the mouse genome is 12.

Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human.

By spliced alignment of human DNA and transcript sequence data we constructed a data set of transcript-confirmed exons and introns from 2793 genes, 796 of which (28%) were seen to have multiple isoforms. We find that over one-third of human exons can translate in more than one frame, and that this is highly correlated with G+C content. Introns containing adenosine at donor site position +3 (A3), rather than guanosine (G3), are more common in low G+C regions, while the converse is true in high G+C regions.