Matching-adjusted indirect comparison of phase 3 clinical trial outcomes: OC-01 (varenicline solution) nasal spray and cyclosporine a 0.05% ophthalmic emulsion for the treatment of dry eye disease.

Matching-adjusted indirect comparison (MAIC) is a validated and widely accepted statistical method that derives indirect comparisons between treatments when head-to-head studies have not been performed. To compare the efficacy of OC-01 varenicline nasal spray (OC-01 VNS) 0.03 mg to cyclosporine A (CsA) 0.

Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery.

Purpose: To assess the effectiveness of intracameral phenylephrine-ketorolac during cataract surgery compared with postoperative topical steroids in reducing the incidence of postoperative clinical cystoid macular edema (CME) confirmed via optical coherence tomography (OCT), breakthrough iritis, pain, and photophobia.

Setting: Ambulatory surgical center/clinical practice.

Design: Retrospective 2-cohort study.

Femtosecond laser-assisted arcuate keratotomy at the time of cataract surgery for the management of preexisting astigmatism.

Purpose: To evaluate the outcomes of femtosecond laser-assisted arcuate keratotomy combined with cataract surgery in eyes with low-to-moderate corneal astigmatism.

Setting: Eyes of York Private Practice Ophthalmology Clinic, York, Pennsylvania, USA.

Design: Retrospective case series.

Effect of phenylephrine/ketorolac on iris fixation ring use and surgical times in patients at risk of intraoperative miosis.

Purpose: To evaluate the effect of intracameral phenylephrine/ketorolac (1%/0.3%) during cataract surgery on the use of iris fixation ring and surgical time in patients with poor pupil dilation (≤5.0 mm) or intraoperative floppy iris syndrome (IFIS).

Discovery of N-[Bis(4-methoxyphenyl)methyl]-4-hydroxy-2-(pyridazin-3-yl)pyrimidine-5-carboxamide (MK-8617), an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3) for the Treatment of Anemia.

The discovery of novel 4-hydroxy-2-(heterocyclic)pyrimidine-5-carboxamide inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD) is described. These are potent, selective, orally bioavailable across several species, and active in stimulating erythropoiesis. Mouse and rat studies showed hematological changes with elevations of plasma EPO and circulating reticulocytes following single oral dose administration, while 4-week q.

Optimization of erythropoietin production with controlled glycosylation-PEGylated erythropoietin produced in glycoengineered Pichia pastoris.

Pichia pastoris is a methylotropic yeast that has gained great importance as an organism for protein expression in recent years. Here, we report the expression of recombinant human erythropoietin (rhEPO) in glycoengineered P. pastoris.

Discovery of betamethasone 17alpha-carbamates as dissociated glucocorticoid receptor modulators in the rat.

A series of betamethasone 17alpha-carbamates were designed, synthesized, and evaluated for their ability to dissociate the two main functions of the glucocorticoid receptor, that is, transactivation and transrepression, in rat cell lines. A number of alkyl substituted betamethasone 17alpha-carbamates were identified with excellent affinity for the glucocorticoid receptor (e.g.

Chemical genetics define the roles of p38alpha and p38beta in acute and chronic inflammation.

The p38 MAP kinase signal transduction pathway is an important regulator of proinflammatory cytokine production and inflammation. Defining the roles of the various p38 family members, specifically p38alpha and p38beta, in these processes has been difficult. Here we use a chemical genetics approach using knock-in mice in which either p38alpha or p38beta kinase has been rendered resistant to the effects of specific inhibitors along with p38beta knock-out mice to dissect the biological function of these specific kinase isoforms.

p38 MAP kinase inhibitors. Part 5: discovery of an orally bio-available and highly efficacious compound based on the 7-amino-naphthyridone scaffold.

A new sub-class of p38 inhibitors represented by 7-amino-naphthyridone have been discovered. Benchmark compound 16 potently inhibited p38 in vitro, was functionally active, and displayed excellent pharmacokinetic profiles in two animal species. Compound 16 reduced inflammation in animal disease models at EC(50) doses as low as 0.

Evaluation of a potential stress effect in rat adjuvant arthritis by using a new and efficient plethysmograph.

We describe the basis of a new design for a user-friendly and easily reproduced mercury-displacement plethysmograph. This system was validated using the rat adjuvant-induced arthritis model in female Lewis rats. Furthermore, 2 different caging systems were evaluated to ensure that caging did not have an effect on disease progression and severity.

Effects of relaxin in a model of rat adjuvant-induced arthritis.

A reduction in the incidence and severity of rheumatoid arthritis is seen in pregnant women. Relaxin, a hormone of pregnancy, has been implicated in decreased immune responsiveness. Consequently, the effects of relaxin and estradiol valerate, alone or in combination, were assessed in the development of adjuvant-induced arthritis in the rat.

Gene deletion of either interleukin-1beta, interleukin-1beta-converting enzyme, inducible nitric oxide synthase, or stromelysin 1 accelerates the development of knee osteoarthritis in mice after surgical transection of the medial collateral ligament and partial medial meniscectomy.

Objective: To investigate the development of osteoarthritis (OA) after transection of the medial collateral ligament and partial medial meniscectomy in mice in which genes encoding either interleukin-1beta (IL-1beta), IL-1beta-converting enzyme (ICE), stromelysin 1, or inducible nitric oxide synthase (iNOS) were deleted.

Methods: Sectioning of the medial collateral ligament and partial medial meniscectomy were performed on right knee joints of wild-type and knockout mice. Left joints served as unoperated controls.

Discovery of a potent and selective COX-2 inhibitor in the alkoxy lactone series with optimized metabolic profile.

The COX-2 inhibitor DFP [5,5-dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone] was found to have a long half-life in humans. Analogues have been characterized in order to optimize pharmacokinetics. This has lead to the discovery of 5(S)-(5-ethyl-5-methyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone analogue 11 a potent and selective COX-2 inhibitor which is metabolized to a greater extent than DFP upon incubation with rat and human hepatocytes, suggesting a shorter half-life in humans.