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ID PMID Title PublicationDate abstract
24652524 Polyacetylenes from Radix et Rhizoma Notopterygii incisi with an inhibitory effect on nitr 2014 Mar Notopterygium roots (Qiang Huo) have been used in traditional Chinese medicine for treating colds, inflammatory diseases like rheumatoid arthritis, and as an analgesic. The anti-inflammatory activity of the roots of Notopterygium incisum has been evaluated by testing the inhibitory activity on nitric oxide production by inducible nitric oxide synthase. The apparent authenticity of the sample was checked by DNA sequence comparison. Using activity-guided isolation, different compounds were isolated and structurally characterized by means of NMR and mass spectroscopy. Eight polyacetylenes could be identified and were tested on their inhibitory activity on nitric oxide production in RAW 264.7 mouse macrophages using the Griess assay. Different 3-hydroxy allyl polyacetylenes exhibited significant activity (IC50: 8-acetoxyfalcarinol, 20.1 µM; falcarindiol, 9.2 µM; 9-epoxyfalcarindiol, 8.8 µM; and crithmumdiol, 23.6 µM).
24599604 Potential roles of nucleotide-binding oligomerization domain 2 in the pathogenesis of syst 2014 Oct Nucleotide-binding oligomerization domain 2 (NOD2) is one of the most prominent member of the NOD-like receptors protein family that functions as intracellular pattern recognition receptors. Numerous studies have suggested the importance of NOD2 in defensing against microbial infections, regulation of the inflammatory process. It is shown that NOD2 contributes to the pathogenesis of various autoimmune and chronic inflammatory diseases, such as Crohn's disease, rheumatoid arthritis. The aim of this study is to summarize our current understandings of NOD2 function and the role of NOD2 in systemic lupus erythematosus (SLE). The following databases were searched: Pubmed, EMBASE and Web of Science for English-language sources, using the terms "lupus," "systemic lupus erythematosus," ''SLE," "immunity," "inflammatory" and "NOD2." Emerging data evidences that NOD2 has important biological effects in autoimmunity and inflammatory and might take part in the pathogenesis of SLE. Studies exploring the relationship between NOD2 and SLE are very limited. Whether NOD2 could be a potentially valuable therapeutic target for treatment for SLE, more understanding of the mechanism of NOD2 is needed in the future in SLE.
24433626 Prevalence of chronic conditions among Medicare Part A beneficiaries in 2008 and 2010: are 2014 Jan 16 INTRODUCTION: Medicare beneficiaries who have chronic conditions are responsible for a disproportionate share of Medicare fee-for-service expenditures. The objective of this study was to analyze the change in the health of Medicare beneficiaries enrolled in Part A (hospital insurance) between 2008 and 2010 by comparing the prevalence of 11 chronic conditions. METHODS: We conducted descriptive analyses using the 2008 and 2010 Chronic Conditions Public Use Files, which are newly available from the Centers for Medicare and Medicaid Services and have administrative (claims) data on 100% of the Medicare fee-for-service population. We examined the data by age, sex, and dual eligibility (eligibility for both Medicare and Medicaid). RESULTS: Medicare Part A beneficiaries had more chronic conditions on average in 2010 than in 2008. The percentage increase in the average number of chronic conditions was larger for dual-eligible beneficiaries (2.8%) than for nondual-eligible beneficiaries (1.2%). The prevalence of some chronic conditions, such as congestive heart failure, ischemic heart disease, and stroke/transient ischemic attack, decreased. The deterioration of average health was due to other chronic conditions: chronic kidney disease, depression, diabetes, osteoporosis, rheumatoid arthritis/osteoarthritis. Trends in Alzheimer's disease, cancer, and chronic obstructive pulmonary disease showed differences by sex or dual eligibility or both. CONCLUSION: Analyzing the prevalence of 11 chronic conditions by using Medicare claims data provides a monitoring tool that can guide health care providers and policy makers in devising strategies to address chronic conditions and rising health care costs.
24369933 Respirable dust and respirable silica exposure in Ontario gold mines. 2014 A comprehensive survey of respirable dust and respirable silica in Ontario gold mines was conducted by the Ontario Ministry of Labor during 1978-1979. The aim was to assess the feasibility of introducing gravimetric sampling to replace the assessment method which used konimeters, a device which gave results in terms of number of particles per cubic centimeter (ppcc) of air. The study involved both laboratory and field assessments. The field assessment involved measurement of airborne respirable dust and respirable silica at all eight operating gold mines of the time. This article describes the details of the field assessment. A total of 288 long-term (7-8 hr) personal respirable dust air samples were collected from seven occupational categories in eight gold mines. The respirable silica (α-quartz) was determined by x-ray diffraction method. The results show that during 1978-1979, the industry wide mean respirable dust was about 1 mg/m(3), and the mean respirable silica was 0.08 mg/m(3.)The mean% silica in respirable dust was 7.5%. The data set would be useful in future epidemiological and health studies, as well as in assessment of workers' compensation claims for occupational diseases such as silicosis, chronic obstructive pulmonary disease (COPD), and autoimmune diseases such as renal disease and rheumatoid arthritis.
24260977 Autoimmune phenotype in patients with common variable immunodeficiency. 2013 BACKGROUND AND OBJECTIVE: Autoimmune disorders occur with a higher incidence in common variable immunodeficiency (CVID) patients than in the general population. To describe the clinical features of the autoimmune phenotype in patients with CVID. METHODS: The hospital records of all diagnosed CVID patients referred to the Children's Medical Center Hospital in Tehran, Iran between 2000 and 2010 were reviewed. Patients were also classified according to the presence or absence of autoimmune disease. RESULTS: Of 52 patients studied, 26.9% (n=14) had shown at least 1 autoimmune manifestation during the study period. Autoimmune cytopenias and juvenile rheumatoid arthritis were the most common form of autoimmunity in our series. Autoimmunity was significantly associated with polyclonal lymphocytic infiltrative disorders (P = .017), increased serum Immunoglobulin (Ig) M levels (P < .001), decreased IgE values (P = .04) and diminished switched memory B-cell count (P < .001). CONCLUSIONS: Because autoimmunity is one of the first manifestations in CVID, humoral immune system tests should be considered in autoimmune patients with a history of recurrent infection. The presence of polyclonal lymphocytic infiltrative disorders and decreased switched memory B-cells may predispose CVID patients to autoimmunity.
24199951 Glucocorticoids and estrogens modulate the NF-κB pathway differently in the micro- and ma 2013 Dec Estrogens and glucocorticoids have synergistic effects in the micro and macrovasculature of endothelial cells (ECs), having pro-inflammatory effects in the former and inhibiting the expression of adhesion molecules in the latter. The molecular basis of these effects in the endothelium has not yet been clarified. We postulate that the ECs of the micro- and macrovasculature have different non-genomic mechanisms that regulate levels of preexisting complexes of glucocorticoids and estrogens with their respective receptors. Since these receptors are regulated by NF-κB, their expression could be critical to the activation of a pro- or anti-inflammatory response. In the macrovasculature the synergistic effects of estrogens and glucocorticoids on ECs may be through the inhibition of NF-κB, leading to the inhibition of the expression of inflammatory molecules. It seems likely that glucocorticoid-receptor and estrogen-receptor complexes directly bind to NF-κB proteins in the macrovasculature, resulting in the inhibition of an excessive proinflammatory response. Further insights into these processes may help clarify the role of the endothelial cells of different vascular beds during the inflammatory response and chronic inflammation, and thus contribute to the design of more effective therapeutic strategies for the prevention of diseases related to inflammation, including atherosclerosis, systemic lupus erythematosus and rheumatoid arthritis.
24194771 Combination with methotrexate and cyclophosphamide attenuated maturation of dendritic cell 2013 Immune disorder is considered the main pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA). The balance of the two special subsets of CD4⁺T cells, T helper cell 17 (Th17), and Regulator T cell (Treg) is the key factor of maintaining a normal immune response. Dendritic cells (DCs), which are the most powerful antigen-presenting cells, play an important role in regulating the balance of Th17 and Treg. The combination of disease modifying antirheumatic drugs (DMARDs) is an important strategy of RA therapy. In this study, we investigated the effect of MTX and CTX on DC maturation in ovalbumin (OVA) immunized mice. Th17 inflammatory response is stronger, while the level of DCs maturity is higher. In contrast, the immunosuppression of Treg is stronger. We found that MTX combined with CTX significantly inhibited the DCs maturity and downregulated the antigen presenting capacity of DCs. As a result, it reestablished a balance of Th17 and Treg. Our study adds a novel mechanism and therapeutic target of MTX combined with CTX for autoimmune disease treatment.
24074306 Design and characterization of microcrystals for enhanced dissolution rate of celecoxib. 2013 Dec Poor aqueous solubility and bioavailability of drugs are one of the important factors affecting the absorption of drugs and consequently their therapeutic effectiveness. Celecoxib is a widely used anti-inflammatory agent, with special use in rheumatoid arthritis. It belongs to biopharmaceutical classification system (BCS) class II drug with low solubility and high permeability. The present study was aimed to prepare and characterize the microcrystals of celecoxib, employing in situ micronization technique by rapid solvent change approach to enhance the solubility and dissolution rate and to optimize the solvent and anti-solvent ratio (v/v) using hydrophilic stabilizers such as guar gum, maltodextrin and PVP K30. The prepared formulations were evaluated for percentage crystal yield, mean particle size, drug content and in vitro dissolution studies. Amongst the formulations prepared (F1-F9), F6 formulation containing maltodextrin as stabilizing agent at 0.1% w/v concentration with 1:6 ratio of solvent to anti-solvent (v/v) respectively was considered as optimized formulation in which percentage drug release was found to be 89.33% within 60 minutes in comparison with that of the pure drug dissolution of 30.26% only within 60 minutes. Characterization studies like SEM, DSC and XRD indicate the solubility enhancement of celecoxib microcrystals due to decrease in particle size when compared to that of pure drug. FT-IR spectroscopy studies revealed that there is no chemical interaction between the drug and stabilizer and crystalline habit modification occurs in the microcrystals without any polymorphic changes.
24029143 β-Arrestins 1 and 2 are critical regulators of inflammation. 2014 Jul β-Arrestins 1 and 2 couple to seven trans-membrane receptors and regulate G protein-dependent signaling, receptor endocytosis and ubiquitylation. Recent studies have uncovered several unanticipated functions of β-arrestins, suggesting that the role of β-arrestins in cell signaling is much broader than originally thought. It is now recognized that β-arrestins can transduce receptor signaling independent of G proteins. The expression of β-arrestins is differentially regulated in immune cells and tissues in response to specific inflammatory stimuli, and β-arrestins are critical regulators of the inflammatory response. This review will focus on β-arrestins in immune cells and the impact of altered expression on the pathogenesis of specific inflammatory diseases. Understanding the role of β-arrestins in inflammation may lead to new strategies to treat inflammatory diseases, such as sepsis, rheumatoid arthritis, asthma, multiple sclerosis, inflammatory bowel disease and atherosclerosis.
23910608 Psychological characteristics of systemic sclerosis patients and their correlation with ma 2013 Mar OBJECTIVES: The aim of this paper is to assess the psychological characteristics of personality, depression, anxiety, social support and coping strategies of systemic sclerosis (SSc) patients, their inter-correlations and their association with clinical symptoms. METHODS: Patients with SSc (n=85) were interviewed and compared to rheumatoid arthritis (RA) patients (n=120) and healthy controls (HCs [n=125]). Psychological characteristics were assessed by the following psychometric scales: centre of epidemiological studies of depression (CES-D), hospital anxiety and depression scale (HAD), Eysenck personality questionnaire (EPQ), short form of social support (SSq), life experiences survey (LES) and ways of coping (WoC). Clinical data were collected at the same time of the interview. Both control groups were matched to SSc patients in terms of gender, age and educational status. Data were analysed with SPSS software. RESULTS: Compared to control groups, SSc patients expressed more symptoms of depression and anxiety, showed less extraversion and reported more negative life events. They coped less often with positive reappraisal, problem solving, seeking of support and assertiveness, while they sought more often divine help, and they expressed wishing and denial. Inactive disease was associated with a lower probability of reporting depressive symptoms and negative life events and with a higher probability of positively reevaluating a problem. Lung dysfunction, skin involvement, esophageal problems and oral aperture correlated with psychological features. CONCLUSIONS: Complications in psychological well-being characterise patients with SSc. This finding, as well as that of psychological characteristics correlating with organic factors, is an indication for designing supportive psycho-educational programmes as complementary therapies.
23917087 Inhibitors of switch kinase 'spleen tyrosine kinase' in inflammation and immune-mediated d 2013 Sep Spleen tyrosine kinase (Syk), a member of Syk family of non-receptor protein tyrosine kinases plays a significant role in the immune cell signaling in B cells, mast cells, macrophages and neutrophils. Anomalous regulation of this kinase can lead to different allergic disorders and antibody-mediated autoimmune diseases such as rheumatoid arthritis, asthma, psoriasis and allergic rhinitis. Being involved in the growth and survive mechanism of B cells, its inhibition can be beneficial in B-cell lymphoma. Thus, Syk can be sited as a therapeutically relevant target for various allergic and autoimmune disorders. This review article describes the structure of Syk and its role in B-cell signaling. In addition to this, data regarding small molecule inhibitors of Syk has also been reviewed from different papers and patents published.
23885887 Hospital admissions for vitamin D related conditions and subsequent immune-mediated diseas 2013 Jul 25 BACKGROUND: Previous studies have suggested that there may be an association between vitamin D deficiency and the risk of developing immune-mediated diseases. METHODS: We analyzed a database of linked statistical records of hospital admissions and death registrations for the whole of England (from 1999 to 2011). Rate ratios for immune-mediated disease were determined, comparing vitamin D deficient cohorts (individuals admitted for vitamin D deficiency or markers of vitamin D deficiency) with comparison cohorts. RESULTS: After hospital admission for either vitamin D deficiency, osteomalacia or rickets, there were significantly elevated rates of Addison's disease, ankylosing spondylitis, autoimmune hemolytic anemia, chronic active hepatitis, celiac disease, Crohn's disease, diabetes mellitus, pemphigoid, pernicious anemia, primary biliary cirrhosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, thyrotoxicosis, and significantly reduced risks for asthma and myxoedema. CONCLUSIONS: This study shows that patients with vitamin D deficiency may have an increased risk of developing some immune-mediated diseases, although we cannot rule out reverse causality or confounding. Further study of these associations is warranted and these data may aid further public health studies.
23843149 Kinase in motion: insights into the dynamic nature of p38α by high-pressure NMR spectrosc 2013 Sep 23 Protein kinases are highly dynamic and complex molecules. Here we present high-pressure and relaxation studies of the activated p38α mitogen-activated protein kinase (MAPK). p38α plays a central role in inflammatory diseases such as rheumatoid arthritis and is therefore a highly attractive pharmaceutical target. The combination of high pressure and NMR spectroscopy allowed for a detailed per-residue based assessment of the structural plasticity of p38α and the accessibility of low-lying excited-energy conformations throughout the kinase structure. Such information is uniquely accessible through the combination of liquid-state NMR and high pressure and is of considerable value for the drug discovery process. The interactions of p38α and DFG-in and DFG-out ligands were studied under the application of high pressure, and we demonstrate how we can alter kinase dynamics by pressure in a similar way to what has previously only been observed by ligand binding. Pressure is shown to be a mild and efficient tool for manipulation of intermediate-timescale dynamics.
23833442 Safety Assessment of TLPL/AY/03/2008, A Polyherbal Formulation in Sprague Dawley Rats. 2013 Jan OBJECTIVES: TLPL/AY/03/2008 is a polyherbal formulation intended for treatment of osteoarthritis, rheumatoid arthritis, lumbago, spondylitis etc., Acute and repeated dose 90-days studies were conducted to evaluate the safety profile of TLPL/AY/03/2008 in rats. MATERIALS AND METHODS: In acute study, TLPL/AY/03/2008 was orally administered to Sprague Dawley rats at 2000 mg/kg. In repeated dose study, TLPL/AY/03/2008 was administered to rats at 200, 500 and 1000 mg/kg through oral gavage for 90 days and assessed for treatment related changes in body weight, feed consumption, hematological, biochemical and pathological parameters. Histopathological examination was conducted for tissues from control and the high dose groups and was extended to target organs from the lower dose and recovery groups. RESULTS: In acute study, the test item did not produce any mortality or adverse clinical signs. In the 90-days oral toxicity study, animals did not exhibit any toxicity symptoms and no deaths were observed. No significant changes were found in hematological and biochemical endpoints. Also, toxicologically significant alterations in relative organ weights were not observed. Microscopic findings of mild to marked, diffuse hepatocellular degeneration (vacuolar changes with granular of cytoplasm and pyknotic nuclei of hepatocytes) was noticed in males at 1000 mg/kg body weight. Animals of recovery group (1000 mg/kg) did not show any changes when compared with control group animals indicating the complete reversal. CONCLUSIONS: Based on the findings of the study, the median lethal dose of TLPL/AY/03/2008 was found to be more than 2000 mg/kg. The No Observed Adverse Effect Level (NOAEL) of TLPL/AY/03/2008 can be considered as 1000 mg/kg in both male and female rats, under the experimental conditions and doses employed.
23782298 Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cas 2013 Sep Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well-tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish-gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.
23761225 Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug 2013 Jul Biotherapeutic-reactive antibodies in treatment-naïve subjects (i.e., pre-existing antibodies) have been commonly detected during clinical immunogenicity assessments; however information on pre-existing antibody prevalence, physiological effects, and impact on posttreatment anti-drug antibody (ADA) induction remains limited. In this analysis, pre-existing antibody prevalence and impact on posttreatment ADA induction were determined using ADA data from 12 biotherapeutics analyzed in 32 clinical studies. Approximately half (58%) of the biotherapeutics were associated with some level of pre-existing antibodies and 67% of those were associated with posttreatment ADA induction. Across all studies, 5.6% of study subjects demonstrated presence of pre-existing antibodies, among which, 17% of the individual subjects had posttreatment increases in their ADA titers while 16% had decreased titers and 67% had no change in titers. However, in studies conducted in the rheumatoid arthritis (RA) population, 14.8% of RA patients were associated with pre-existing antibodies and 30% of those had posttreatment titer increases. The results suggest that in most study subjects, pre-existing antibodies pose a low risk for posttreatment ADA induction. That said, the high risk of induction implicated for RA patients, primarily observed in treatments evaluating novel antibody-based constructs, indicates that further understanding of the contribution of product and disease-specific factors is needed. Cross-industry efforts to collect and analyze a larger data set would enhance understanding of the prevalence, nature, and physiological consequences of pre-existing antibodies, better inform the immunogenicity risk profiles of products associated with these antibodies and lead to better fit-for-purpose immunogenicity management and mitigation strategies.
23756375 [Surface proteins of bacteria of the genus Bifidobacterium]. 2013 May 13 Beneficial effects due to the presence of probiotic bacteria of the genus Bifidobacterium in the human intestinal tract are still an interesting object of study. So far activities have been confirmed of bifidobacteria in stimulation of the host immune system, stimulation of tumor cell apoptosis, improvement of bowel motility, alleviation of symptoms of lactose intolerance, cholesterol lowering capacity, prevention and treatment of diarrhea and irritable bowel syndrome, alleviation of allergy or atopic dermatitis, maintenance of homeostasis of the intestine, and stimulation of the development of normal intestinal microflora in infants. A multitude of therapeutic properties encourages researchers to investigate the possibility of using the potential of Bifidobacterium in the prevention and treatment of other conditions such as rheumatoid arthritis and depression. Although it is known that the beneficial effects are due to intestinal mucosal colonization by these bacteria, the cell components responsible for the colonization are still not determined. In addition to the beneficial effects of probiotic administration, there were also negative effects including sepsis. Therefore research has been directed to identify specific components of Bifidobacterium responsible for probiotic effects. Currently researchers are focused on identifying, isolating and evaluating the properties of surface proteins that are probably involved in the adhesion of bacterial cells to the intestinal epithelium, improving colonization. This paper is an overview of current knowledge on Bifidobacterium surface proteins. The ways of transport and anchoring proteins in Gram-positive bacterial cells, the assembly of cell wall, and a description of the genus Bifidobacterium are presented.
23742177 The primary vascular dysregulation syndrome: implications for eye diseases. 2013 Jun 7 Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood-brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person.
23678770 [Mental and behavioral abnormalities after arthroplasty and incomplete cerebral fat emboli 2013 Feb OBJECTIVE: To investigate the relationship between mild consciousness and mental disorders after arthroplasty and incomplete cerebral fat embolism. METHODS: A retrospective analysis of 12 patients with incomplete cerebral fat embolism after arthroplasty was performed from June 2004 to December 2011. There were 5 males and 7 females,ranging in age from 36 to 82 years old,averaged 56.8 years old. Four patients had femoral neck fractures; 3 patients had avascular necrosis of the femoral head; 3 patients had rheumatoid arthritis; 1 patient had ankylosed hip and 1 patient had knee osteoarthritis. The patients had consciousness and mental disorders after arthroplasty (femoral head replacement in 3 cases, total hip replacement in 7 cases, and knee joint surface replacement in 2 cases), changes of vital sign and abnormal brain MRI examination. RESULTS: Twelve patients had mild consciousness and mental disorders,and the NIHSS score was 1.92+/-3.78,which was correlated with incomplete cerebral fat embolism after arthroplasty. The patients recovered conscious within 24 to 72 hours after treatment with expansion of blood volume,dehydrating agent and neuroprotective drugs,improving respiratory and circulatory function, hormone protection and antibiotic application. The patients were followed up with a mean period of 18 months (ranging from 10 to 36 months). The patients had neurological function recovering to normal without sequelae, and the NIHSS score decreased to 0. CONCLUSION: Incomplete cerebral fat embolism after arthroplasty is the main reason causing mild awareness and mental disorders, which is often to be misdiagnosed or ignored because of not typical clinical manifestations.
23613975 Interindividual variation in the proteome of human peripheral blood mononuclear cells. 2013 Peripheral blood mononuclear cells (PBMCs) are main actors in inflammatory processes and linked to many diseases, including rheumatoid arthritis, atherosclerosis, asthma, HIV and cancer. Moreover, they seem an interesting 'surrogate tissue' that can be used in biomarker discovery. In order to get a good experimental design for quantitative expression studies, the knowledge of the interindividual variation is an essential part. Therefore, PBMCs were isolated from 24 healthy volunteers (15 males, 9 females, ages 63-86) with no clinical signs of inflammation. The extracted proteins were separated using the two dimensional difference in gel electrophoresis technology (2D-DIGE), and the gel images were processed with the DeCyder 2D software. Protein spots present in at least 22 out of 24 healthy volunteers were selected for further statistical analysis. Determination of the coefficient of variation (CV) of the normalized spot volume values of these proteins, reveals that the total variation of the PBMC proteome varies between 12,99% to 148,45%, with a mean value of 28%. A supplemental look at the causes of technical variation showed that the isolation of PBMCs from whole blood is the factor which influences the experimental variance the most. This isolation should be handled with extra care and an additional washing step would be beneficial. Knowing the extent of variation, we show that at least 10 independent samples per group are needed to obtain statistical powerful data. This study demonstrates the importance of considering variance of a human population for a good experimental design for future protein profiling or biomarker studies.