Combined models for data from in vitro-in vivo correlation experiments.

A method is presented to describe the in vitro-in vivo correlation (IVIVC) of an extended release drug formulation. This extended release drug product is overencapsulated with immediate release material. The heterogeneity of the capsule is modelled using a combined model of an extended release and an immediate release pharmacokinetic profile.

Efficacy and tolerability of lumiracoxib, a highly selective cyclo-oxygenase-2 (COX2) inhibitor, in the management of pain and osteoarthritis.

Lumiracoxib is a COX2 inhibitor that is highly selective, is more effective than placebo on pain in osteoarthritis (OA), with similar analgesic and anti-inflammatory effects as non-selective NSAIDs and the selective COX2 inhibitor celecoxib, has a lower incidence of upper gastrointestinal (GI) side effects in patients not taking aspirin, and a similar incidence of cardiovascular (CV) side effects compared to naproxen or ibuprofen. In the context of earlier guidelines and taking into account the GI and CV safety results of the TARGET study, lumiracoxib had secured European Medicines Agency (EMEA) approval with as indication symptomatic treatment of OA as well as short-term management of acute pain associated with primary dysmenorrhea and following orthopedic or dental surgery. In the complex clinical context of efficiency and safety of selective and non-selective COX inhibitors, its prescription and use should be based on the risk and safety profile of the patient.

Impact of systematic implementation of a clinical case finding strategy on diagnosis and therapy of postmenopausal osteoporosis.

Introduction: Case finding for osteoporosis in postmenopausal women is advocated in guidelines of osteoporosis, but implementation is unsatisfactory. We studied, in daily practice, the impact of systematic implementation of a previously validated clinical decision rule and fracture history on referral for bone densitometry (DXA) and drug prescription for osteoporosis.

Materials And Methods: Before-after impact analysis in 41,478 consecutive consulting postmenopausal women, included by 1080 general practitioners (GPs) during 2 mo, using the osteoporosis self-assessment (OST) index (based on age and weight, indicating women at low [LR], moderate [MR], and high risk [HR] for having osteoporosis [T-score < -2.

The PreCardio-study protocol--a randomized clinical trial of a multidisciplinary electronic cardiovascular prevention programme.

Background: Cardiovascular diseases (CVD) are the leading cause of death and the third cause of disability in Europe. Prevention programmes should include interventions aimed at a reduction of medical risk factors (hypertension, hypercholesterol, hyperglycemia, overweight and obesity) as well as behavioural risk factors (sedentary lifestyle, high fat intake and low fruit and vegetable intake, smoking). The aim of this study is to investigate the effects of a multifaceted, multidisciplinary electronic prevention programme on cardiovascular risk factors.

Dose response for infectivity of several strains of Campylobacter jejuni in chickens.

Although some major risk studies have been done for Campylobacter jejuni, its dose response is not well characterized. Only a single human study is available, providing dose-response information for only a single isolate. As substantial heterogeneity in infectivity has been acknowledged for other pathogens, it remains unknown how well this single study represents the dose-response relation for this pathogen.

The structural proteome of Pseudomonas aeruginosa bacteriophage phiKMV.

The structural proteome of phiKMV, a lytic bacteriophage infecting Pseudomonas aeruginosa, was analysed using two approaches. In one approach, structural proteins of the phage were fractionated by SDS-PAGE for identification by liquid chromatography-mass spectrometry (LC-MS). In a second approach, a whole-phage shotgun analysis (WSA) was applied.

Newer drug treatments: their effects on fracture prevention.

Drug treatment of osteoporosis is based on the knowledge of mechanisms of bone turnover and the manipulation of the cellular components of bone turnover in terms of recruitment, activation and apoptosis of the cells involved. Based on their mechanisms of action, drugs used in the treatment of osteoporosis can be divided into those that inhibit bone turnover (bisphosphonates, SERMs, calcitonin), those that stimulate bone turnover (parathyroid hormone), and those with mixed effects (strontium ranelate). In this chapter we discuss the anti-fracture effects of some newer drugs together with innovative aspects of intake (monthly oral intake for ibandronate) or mechanisms of action (parathyroid hormone and strontium ranelate).

Role of mitochondrial Na+ concentration, measured by CoroNa red, in the protection of metabolically inhibited MDCK cells.

In ischemic or hypoxic tissues, elevated cytosolic calcium levels can induce lethal processes. Mitochondria, besides the endoplasmic reticulum, play a key role in clearing excessive cytosolic Ca2+. In a previous study, it was suggested that the clearance of cytosolic Ca2+, after approximately 18 min of metabolic inhibition (MI) in renal epithelial cells, occurs via the reverse action of the mitochondrial Na+/Ca2+ exchanger (NCX).