A simulating interaction: The P-glycoprotein (P-gp) ligand 13 displays high P-gp interacting activity (EC(50) =2.90 μM) and selectivity in tumor cell lines. Here, this promising compound was further evaluated ex vivo in an everted gut sac assay and found to behave as a P-gp stimulator, making this agent a potential lead ...

A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-β in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-β from the brain may lead to these elevated amyloid-β levels. One of the clearance pathways of amyloid-β is transport across the blood-brain barrier via efflux ...

Background: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease. Since current treatments are unsatisfactory for many patients, there is a high need for effective drugs for this debilitating disease. Recent pathogenic insights suggest inflammasome activation and IL-1β production are important in HS. Colchicine is efficacious in the IL-1β- and ...

The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting interventions. This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients ...

Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic compounds. Importantly, dysfunctional BBB ...

The Coronary Artery Disease in gENeral practiCE (CADENCE) study examined chronic stable angina (CSA). This further analysis examined atherosclerotic risk factors, symptomatic status, clinical management, and quality of life in patients with CSA with and without peripheral arterial disease (PAD). The CADENCE study involved 207 Australian general practitioners (GPs) recruiting ...

Objectives  Several studies have suggested the efflux transporter P-glycoprotein (P-gp) to play a role in the etiology of Alzheimer's disease through the clearance of amyloid beta (Aβ) from the brain. In this study, we aimed to investigate the possibility of P-gp as a potential therapeutic target for Alzheimer's disease by ...

What is already known about this subject: Inflammatory conditions such as Crohn's are associated with cardiovascular complications. Inflammation also substantially reduces clearance of some cardiovascular drugs. It has also been shown that in rheumatoid arthritis, an elevation in verapamil concentration does not result in increased response. What this study adds ...

Rare diseases are a serious public health problem and are a threat to the health of EU citizens. Important role in the area of rare diseases have the medical specialists who diagnose and monitor the course of the disease of each patient. General practitioners (GPs) are usually the first to ...

Smallpox was "the most terrible of all the ministers of death," wrote English historian Thomas Macaulay. In the 17th century, the "small pox was always present," unlike the plague, which visited on occasion. Before this time, the disease did not pose a serious threat to the English or other nations ...

The relationship of predementia stage with cerebrovascular disease (CVD) has not been fully clarified. Following our Prevalence Study 1998 in Tajiri, Japan, Incidence Study 2003 disclosed that 17.9% of subjects developed vascular dementia (VaD). Some cases developed after stroke (type I), whereas others already met the criteria for subcortical VaD ...

Background: Good medical care results in long survival for patients with Parkinson's disease (PD). However, little is known about the burden of PD comorbidity and mortality in Japan. This is the first study to examine comorbid diseases of PD decedents and extrapolate PD death rates from multiple-cause coding mortality data ...

Juvenile idiopathic arthritis (JIA) is one of the most frequent autoimmune diseases in childhood and is characterized by chronic inflammation of the synovial fluid in joints. Several drugs are available for the treatment of JIA, including various biological agents that interfere with critical cytokine pathways. Though very effective in suppressing ...

Hyperphosphatemia is a major risk factor for death, CVE, and vascular calcification among patients with and without kidney disease. Even serum phosphate levels within the "normal laboratory range" associate with a greater risk of death and CVE. Potential mechanisms by which increased phosphate results in adverse outcomes are not fully ...

Neurodegenerative diseases that include amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, stroke, brain trauma and spinal cord injury, are associated with the inappropriate activation of a neuronal cell-suicide program called apoptosis. Given that central nervous system tissue has very limited regenerative capacity it is of extreme importance to ...

OBJECTIVES:The objective of the study was to compare cause-specific mortality risks in the periods before and after the introduction of accurate and specific serological tests for diagnosing celiac disease.METHODS:This was a prospective cohort study of people with celiac disease diagnosed in Southern Derbyshire, United Kingdom, from the late 1950s onward, ...

While rheumatoid factor (RF) testing has been previously used in the detection of rheumatoid arthritis (RA), its effectiveness has been limited by poor rates of sensitivity and specificity and its positivity in multiple other disease states. Given its enhanced specificity, quantification of anticyclic-citrullinated protein (anti-CCP) antibodies has emerged as a ...

Caspases, initially identified as a family of proteases regulating cell death, have been found to have nonapoptotic functions as well. Some family members are critical for mediating programmed cell death in development. After development, caspases are downregulated in the nervous system, but continue to perform important nonapoptotic functions relevant for ...

Lyme disease was listed as an underlying or multiple cause of death on 114 death records during 1999-2003. Upon review, only 1 record was consistent with clinical manifestations of Lyme disease. This analysis indicates that Lyme disease is rare as a cause of death in the United States.

AIM: The aim of this study is to identify small areas in Germany burdened by exceptionally high rates of amenable mortality using the 439 counties as unit of analysis. METHODS: To overcome shortcomings of conventional mortality measures, we construct an indicator for amenable mortality (AM) which captures deaths that should ...

Parasitic bronchitis in cattle; sudden deaths due to hypomagnesaemia in adult cattle; louping ill confirmed in adult cattle and young sheep; copper poisoning in Lleyn ewes associated with access to clover herbage with high copper and low molybdenum; polyarthritis due to Mycoplasma hyorhinis in growing pigs. These are among matters ...

IgG4-related disease has been identified in various organs, but whether or not there are organ-specific characteristics related to the etiologic factors is still unknown. Here, we carried out a cross-sectional study of 114 patients with IgG4-related disease. On the basis of the location of the lesions, the patients were classified ...

Rheumatoid arthritis is an inflammatory disease of the joints causing pain and stiffness, pathologically characterized by chronic synovitis. Without proper treatment, it progresses to cause joint deformity that results in significant loss of function. Extra-articular disease can also occur, which exacerbates morbidity and mortality associated with the disease. Patients from ...

Alzheimer's disease (AD) is a progressive chronic disorder and is characterized by β-amyloid plaques and angiopathy, tau pathology, neuronal cell death, and inflammatory responses. The reasons for this disease are not known. This review proposes the hypothesis that a chronic mild longlasting cerebrovascular dysfunction could initiate a cascade of events ...

Objectives. RA is associated with early ischaemic heart disease. This appears to be driven largely by the presence of chronic inflammation. Studies suggest that treatment with disease-modifying drugs such as MTX may reduce the incidence of cardiovascular events in RA. Anti-TNF therapies significantly reduce inflammation in RA. However, the extent ...

The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia(®), UCB Inc., GA, USA), which targets TNF-α with a different mechanism of action than ...

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with significant functional disability and morbidity. Treatment with conventional disease-modifying anti-rheumatic drugs has substantial limitations including partial efficacy and poor tolerability. Advances in our understanding of the pathogenesis of RA over the past decade have fostered development of targeted therapies and ...

Rheumatoid arthritis (RA) is a common systemic disease that manifests as inflammatory arthritis of multiple joints. Interstitial lung disease (ILD) is the most common manifestation of rheumatoid lung disease. The ILDs associated with RA are diverse and it is very important for the general radiologist to differentiate one from another. ...

The understanding of the pathogenesis and optimal therapeutics for rheumatoid arthritis (RA) has advanced remarkably over the last decade. This review highlights these key advances, particularly the outcomes of genome-wide scans which have provided an increasingly robust appraisal of the complex genetics that underpin RA. Such observations are placed in ...

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in ...

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, most of which differ from the main adult-onset inflammatory joint diseases. Nonsystemic forms of JIA (oligoarthritis, polyarthritis with or without rheumatoid factors, and spondyloarthropathies) are managed similarly to adult-onset rheumatoid arthritis or spondylarthritis, with a few differences. More specifically, JIA-associated ...

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, ...

Objective: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting ...

With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. ...

OBJECTIVES: (1) To determine 6-month follow-up adherence and persistence with disease-modifying antirheumatic drugs in patients with early rheumatoid arthritis with disease under control. (2) To compare disease flares across adherent, nonadherent, persistent and nonpersistent patients. (3) To identify differences in adherent and persistent rates among therapeutic regimens. (4) To identify ...

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease in the United States, affecting 1% to 2% of the adult population. Although joints and synovium are the primary targets in this disorder, extra-articular manifestations involving the lungs can lead to significant morbidity and excess mortality. Among the various pulmonary ...

Rheumatoid arthritis (RA) is associated with enhanced atherosclerosis and impaired endothelial function early after the onset of the disease and cardiovascular (CV) disease represents one of the leading causes of morbidity and mortality. It is well known that disease modifying antirheumatic drugs (DMARDs) are able to improve the course of ...

To assess gender differences in disease characteristics and treatment responses over time in a disease-modifying antirheumatic drug (DMARD)-naive seropositive early rheumatoid arthritis (RA) cohort. Patients with polyarticular disease who were DMARD-naive and had seropositive early RA (< 14 months) were recruited by the Western Consortium of Practicing Rheumatologists. Each patient ...

Rationale: Mortality rates from rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are largely unknown. Objectives: We sought to determine mortality rates from rheumatoid arthritis-associated interstitial lung disease in the United States from 1988 through 2004. Methods: Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from ...

Pulmonary disease is a major source of morbidity and mortality in rheumatoid arthritis, manifesting most commonly as interstitial lung disease, airways disease, rheumatoid nodules, and pleural effusions. The diagnostic assessment of respiratory abnormalities is complicated by underlying risk for infection, the use of drugs with known pulmonary toxicity, and the ...

Patient-reported measures can quickly provide assessments of rheumatoid arthritis (RA) disease activity in the office setting and do not require a laboratory test or physician examination. The goal of our study was to establish the validity of patient-reported indices compared to the C-reactive protein-based Disease Activity Score (DAS28-CRP4). Baseline and ...

Rheumatoid arthritis is a chronic disease that can cause irreversible joint damage and significant disability. With a prevalence of 1%, it has a considerable cost to the community. Diagnosis is based on a combination of clinical and laboratory features. Patients typically present with a symmetrical polyarthritis of the small joints ...

The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European ...

OBJECTIVE: The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. METHODS: A joint working group from the ACR and ...

The disease modifying antirheumatic drug (DMARD) methotrexate (MTX) is widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). In ankylosing spondylitis (AS), the use of MTX is not recommended for the axial manifestations and may have some efficacy in the peripheral involvement. For this disease ...

This study investigates the association of rheumatoid arthritis-associated single nucleotide polymorphisms in endometriosis. We found an association of CCL21 (rs2812378) and HLA-DRB1 (rs660895) with moderate to severe endometriosis.

Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we ...

Epigenetics is a steadily growing research area. In many human diseases, especially in cancers, but also in autoimmune diseases, epigenetic aberrations have been found. Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation and destruction of synovial joints. Even though the etiology is not yet fully understood, rheumatoid arthritis ...

Psoriatic arthritis is a systemic disorder that causes chronic pain, altered physical appearance, and loss of function. The clinical features are diverse, but the core manifestations are psoriasis, peripheral arthritis, axial disease, enthesitis, and dactylitis. Our understanding about the psoriatic arthritis disease state, assessment, and treatment has advanced thanks to ...

Randomized controlled trials (RCTs) have demonstrated the efficacy of biologic agents in the treatment of rheumatic diseases. However, results from RCTs may not be generalizable to clinical practice because of their strict inclusion and exclusion criteria. Assessment of safety using RCT data also is limited by short duration of follow-up ...