Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload.

Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis.

Pharmacokinetics of intravenous ibuprofen: implications of time of infusion in the treatment of pain and fever.

Intravenous NSAIDs are playing an increasingly large role in analgesia, anti-inflammation and antipyresis in the hospitalized setting. For many years, ketorolac was the only intravenous NSAID available in the US, but in 2009 intravenous ibuprofen was approved by the US FDA for the treatment of pain and fever in adults. In developing intravenous ibuprofen, a range of times of infusion and dosing levels have been utilized and compared with the oral route of administration.

Pharmacokinetics, safety, and tolerability of a rapid infusion of i.v. ibuprofen in healthy adults.

Purpose: The pharmacokinetics, safety, and tolerability of a rapid infusion of i.v. ibuprofen in healthy adults were evaluated.

A prospective, multicenter, randomized, double-blind trial of IV ibuprofen for treatment of fever and pain in burn patients.

This prospective study evaluated the efficacy and safety of IV ibuprofen for the reduction of fever and treatment of pain in patients with thermal burn injury. A total of 61 patients with second- and/or third-degree thermal burns covering >10% TBSA were randomly assigned in a 2:1 ratio to receive either 800 mg IV ibuprofen or placebo every 6 hours for 120 hours (5 days). Antipyretic medications were restricted during the first 24 hours of the study, but analgesics were allowed throughout.

Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review.

Objective: To evaluate the analgesic and antipyretic efficacy and safety of ibuprofen compared to acetaminophen in children and adults.

Data Sources: Literature searches were performed using PubMed/MEDLINE (through August 2009) and EMBASE (through January 2008) and were restricted to the English language. In PubMed/MEDLINE, search terms used were ibuprofen, acetaminophen, paracetamol, clinical trials, and randomized controlled trials.

Comparison of preference and safety of powder and liquid lactulose in adult patients with chronic constipation.

Background: Chronic constipation is an important clinical condition which can result in serious discomfort and even require hospitalization. Powder and liquid lactulose are designated as clinically equivalent for the treatment of constipation, but there are significant differences in the taste, consistency, and portability of the products, which may affect patient compliance and therefore clinical outcome.

Aim: To evaluate patient preference between powder and liquid lactulose in terms of overall preference, taste, consistency, and portability, and safety in terms of adverse events.

Suboptimal activation of protease-activated receptors enhances alpha2beta1 integrin-mediated platelet adhesion to collagen.

Thrombin and fibrillar collagen are potent activators of platelets at sites of vascular injury. Both agonists cause platelet shape change, granule secretion, and aggregation to form the primary hemostatic plug. Human platelets express two thrombin receptors, protease-activated receptors 1 and 4 (PAR1 and PAR4) and two collagen receptors, the alpha(2)beta(1) integrin (alpha(2)beta(1)) and the glycoprotein VI (GPVI)/FcRgamma chain complex.

PAR1, but not PAR4, activates human platelets through a Gi/o/phosphoinositide-3 kinase signaling axis.

Thrombin-mediated activation of platelets is critical for hemostasis, but the signaling pathways responsible for this process are not completely understood. In addition, signaling within this cascade can also lead to thrombosis. In this study, we have defined a new signaling pathway for the thrombin receptor protease activated receptor-1 (PAR1) in human platelets.

Dendritic molecular transporters provide control of delivery to intracellular compartments.

Novel biocompatible macromolecular vectors were developed that not only enable transport of bioactive cargo across the cell membrane but also control the delivery into defined intracellular compartments. This work describes the synthesis and design of two non-peptidic fluorescently labeled Newkome-type dendrimers, differentiated over a varied alkyl spacer with guanidine end moieties. The internalization of the fluorescein-labeled molecular transporter into mammalian cells showed strong subcellular localizations, evident with both live cells and fixed cells costained with DAPI, a nuclear stain.

Protease-activated receptors differentially regulate human platelet activation through a phosphatidic acid-dependent pathway.

Pathological conditions such as coronary artery disease are clinically controlled via therapeutic regulation of platelet activity. Thrombin, through protease-activated receptor (PAR) 1 and PAR4, plays a central role in regulation of human platelet function in that it is known to be the most potent activator of human platelets. Currently, direct thrombin inhibitors used to block platelet activation result in unwanted side effects of excessive bleeding.

PAR4, but not PAR1, signals human platelet aggregation via Ca2+ mobilization and synergistic P2Y12 receptor activation.

Regulation of platelet activation plays a central role in hemostasis and pathophysiological processes such as coronary artery disease. Thrombin is the most potent activator of platelets. Human platelets express two thrombin receptors, PAR1 and PAR4, both of which signal platelet activation.