Whereas lower organisms such as Amoeba proteus and Dictyostelium discoidium rely entirely on bleb-based amoeboid motility,16, 36 there is evidence in diverse cellular circumstances that higher eukaryotic cells undergo a so-called “mesenchymal to amoeboid transition” in situations requiring rapid deformation

of cellular shape.36, 37 Examples of this transition include diapedesis of leukocytes,38 metastatic invasion,39 and embryogenesis. This mode of motility may be favored in microenvironments containing dense three-dimensional ECM, such as that seen in cirrhosis. Our data suggest that mode-switching toward amoeboid invasion may be a previously unrecognized, this website yet important mechanism in the development of blood vessels in fibrotic liver. The biophysics at

play in the dynamic expansion and retraction of blebs is complex, involving expansion by cytoplasmic streaming (a hydraulic force caused by contraction of the cytoskeletal cortex), and mechanical retraction (a force caused by myosin II activation). We propose that a third force also may be at play, an osmotic force, driving water influx and efflux. Indeed, we see localization of water channels at the periphery of dynamic membrane blebs, similar to the dynamic protrusions in C. parvum infection of cholangiocytes.23 Our data support a role for channel-mediated, trans-membrane water flux in membrane blebs that Neratinib manufacturer is sufficient to enhance FGF-induced blebbing and to promote invasive angiogenesis (Fig. 8). This provocative clonidine idea suggests that angiogenesis in general could be driven,

in part, by local osmotic gradients. Physiological interactions between AQPs and several ion/solute transporters, including the Na+/H+ exchanger,40, 41 the Cl−/HCO exchanger (AE2),24 the cystic fibrosis transmembrane regulator,24 and the Na+/glucose cotransporter 123 are well described in other cell types. However, the ion/solute transporters that create the osmotic gradients to help drive the expansion and retraction of endothelial blebs are currently unknown. Numerous small molecule inhibitors of AQPs are currently known, including mercurial agents, gold compounds, dimethyl sulfoxide, quaternary ammonium compounds, carbonic anhydrase inhibitors, and plant flavonoids such as phloretin.26, 42 However, none are suitable for clinical applications because of toxicity and lack of specificity. As rapid screening techniques for water channel function continue to become available,42 large-scale testing of pharmaceutical compounds should accelerate the discovery of new AQP inhibitors.43 Currently, mechnistic in vivo studies will require the use of genetic AQP knockout models. In summary, our findings identify a mechanism whereby LECs can adapt to the cirrhotic microenvironment and pursue invasion, despite the presence of fibrotic scar, thereby driving pathological angiogenesis and progression of fibrosis.

HPX is produced mainly by the liver, and other sites of HPX synthesis are the central and peripheral nerve systems, skeletal muscle, retina, and kidney, although the role and expression of HPX in the intestine remain unclear. The Navitoclax manufacturer low-density lipoprotein receptor-related protein (LRP)/CD91 has been identified as the receptor for the heme–HPX complex,17 and LRP/CD91 is expressed in various cell types, including hepatocytes and macrophages. Besides the scavenging of heme by HPX, accumulating data suggest that the heme–HPX complex activates a signaling pathway to modulate gene expressions, such as that of heme oxygenase-1 (HO-1). It has been demonstrated that the heme–HPX system protects

against stroke-related damage via the induction of HO-1 expression.18 Heme oxygenase-1 is the rate-limiting enzyme in heme degradation,

catalyzing the cleavage of the heme ring to form carbon monoxide, ferrous iron and biliverdin.19,20 Induction of HO-1 has been shown to protect against inflammatory processes and oxidative tissue injury. Recent evidence indicates that HO-1 plays a potent protective role against NSAID-induced small intestinal injuries.21,22 Disruption of Bach1 (Broad complex-Tramtrack-Bric-a-brac [BTB] and cap“n”collar [CNC] homology 1), which is a transcriptional repressor of HO-1, leads the intestinal HO-1 expression PD-332991 and inhibited indomethacin-induced intestinal mucosal injury. Yoda et al. have also reported that lansoprazole, which is a proton-pump inhibitor, inhibited indomethacin-induced small intestinal ulceration through the induction of HO-1 expression.23 Thus, HPX binding to heme might exert a tissue-protective effect against indomethacin-induced intestinal injury through induction of HO-1. On the other hand, Liang et al.

report that HPX regulates Toll-like receptor 4 (TLR4) and TLR2-mediated cytokine production from macrophages.24 The starting point of their study was previously described research that mouse serum inhibited lipopolysaccharide-induced tumor-necrosis factor production by macrophages.25 Liang et al. used classical biochemical Orotidine 5′-phosphate decarboxylase fractionation techniques to identify this molecule contained in mouse serum, which inhibited cytokine production by macrophages. Interestingly, the mechanism by which HPX inhibited cytokine production by macrophages was independent of HO-1 induction. In conclusion, we identified HPX as an upregulated protein in the intestinal inflammation induced by indomethacin administration. Although further research is warranted to gain a better understanding of the role of HPX in the pathogenesis of intestinal inflammation, it is expected that HPX may be a novel therapeutic molecule and biomarker for NSAID-induced intestinal damage. This work was supported by a Grant-in-Aid for Scientific Research (C) to Tomohisa Takagi (Grant no. 22590706) and Challenging Exploratory Research to Yuji Naito (no.

“
“(Headache 2011;51:232-236) Objective.— To investigate the factors involved in the delayed diagnosis of migraine without aura among patients attending a tertiary center for headache diagnosis and management. Methods.— Two hundred consecutive patients were divided into 3 groups according to the time elapsed from the first clinical manifestations and the diagnosis of migraine at our center. Belinostat order Results.— The interval was <1 year in 16.5% of patients (n = 33); from 1 to 5 years in 30% (n = 60); and >5 years in 53.5% (n = 107). Younger age at migraine onset and a lower level of education were significantly associated with a longer time to diagnosis (P = .01

and P = .0001, respectively). Longer delays were significantly associated with a larger number of specialists consulted (P < .05). Conclusion.—

Our findings suggest an insufficient awareness of the diagnostic criteria of migraine by non-specialist physicians, who often prescribe expensive and unnecessary diagnostic investigations that do not alleviate patients’ symptoms while wasting health care resources. “
“The aim of this study was to investigate knowledge about medication overuse headache (MOH) among pharmacy staff. MOH is a public health problem both in Sweden see more and in many other countries. Persons with MOH have limited contact with health care, and medications used are to large extent over-the-counter (OTC) medications. Therefore, pharmacists have an important role in, eg, advising these individuals about their medication use. Little is, however, known about the actual level of knowledge about MOH among pharmacy staff, which determines the quality of their advice to MOH sufferers. A total of 326 questionnaires were distributed to 44 pharmacies in Gothenburg, Sweden. The questionnaire included background questions, questions about advice on headache treatment, source of knowledge about MOH, and questions on self-perceived and actual knowledge Vasopressin Receptor on MOH.

The response rate was 70%. A majority of the pharmacy staff (90.6%) considered themselves to have knowledge about MOH to some or a greater extent. Almost half had learned about MOH through their university/vocational education. Only 8.6% knew that all 5 headache medications listed in the questionnaire can cause development of MOH, but 40% responded correctly on which treatment advice one can give a person with MOH. Actual knowledge on treatment advice differed significantly between groups of self-perceived knowledge. The knowledge on MOH is insufficient among pharmacy staff, but with the proper knowledge, pharmacy staff is well positioned to effect both primary and secondary prevention of MOH. We suggest not only increasing educational efforts about MOH within pharmacy programs but also continuing education at the pharmacies for all staff.

Plasma renin activity (PRA; >4 ng/mL/hour) was used as a surrogate of effective arterial blood volume. Patients were followed up for 12 months. Thirty-seven patients had LVDD (19 with grade 1 and

18 with grade 2). Left ventricular hypertrophy, left atrial volume, AEVS, and natriuretic peptide levels were significantly greater in patients with LVDD than without LVDD. Patients with grade 2 LVDD, compared to grade 1 LVDD and without LVDD, had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E-wave transmitral/early diastolic mitral annular velocity (E/e’ ratio), cardiopulmonary pressures, PRA, and OSI-906 manufacturer natriuretic peptide levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade 2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites learn more but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) type 1 on follow-up. Survival was different according to degree of LVDD (without LVDD: 95%; grade 1 LVDD: 79%; grade 2 LVDD: 39%; P < 0.001). Independent predictive factors of mortality were MELD score and E/e' ratio. Conclusion:

LVDD occurs simultaneously with other changes in cardiac structure and function and is associated with an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type 1 HRS development, and mortality. (Hepatology 2013;58:1732–1741) Cirrhosis is associated with a specific subclinical cardiomyopathy[1-4] characterized by diminished systolic responsiveness to stress stimuli,[5, 6] impaired diastolic relaxation,[7, 8] electrophysiological abnormalities,[9]

and enlargement and hypertrophy of cardiac chambers,[10, 11] all in the absence of known cardiac disease. However, evidence suggests that patients with cirrhosis display primarily left ventricular diastolic dysfunction (LVDD) with normal systolic function at rest.[7] Doppler examination of mitral inflow has been the most common technique used in the evaluation of left ventricular (LV) diastolic Resveratrol function in cirrhosis.[7, 8, 10, 11] However, conventional Doppler echocardiographic indices (E/A ratio) have clear limitations (age and load conditions) and rarely allow the accurate differentiation between normal from pseudonormal pattern. Currently, the most sensitive and reproducible echocardiographic technique for the assessment of LV filling dynamics is tissue Doppler imaging (TDI), because TDI can overcome some of these factors. TDI is an ultrasound modality that applies the Doppler principle to record velocities within the myocardium. TDI velocities have demonstrated a significant correlation with invasive indices of LV relaxation and minimal effect of preload in the setting of impaired relaxation.

05), while CES-D scores were significantly higher in patients with interferon-based therapy at 12 weeks than those at start of treatment (8.3 ± 7.9 vs. 13.2 ± 6.0, p<0.001). Furthermore, the

relationship between CES-D scores and mean oxy-Hb changes in left temporal channels was significantly and positively correlated in patients with interferon-based therapy (r=0.74517, p<0.05). There was no significant difference in patients without interferon-based therapy. Conclusion: The decrease in oxy-Hb concentrations detected using NIRS probably reflects the prodromal phase of depression with decreasing activation Ixazomib in vivo of the frontal cortex and compensated left temporal blood volume. NIRS imaging is potentially

useful for the early detection of depression during interferon-based therapy for patients with CHC. Disclosures: The following people have nothing to disclose: Kazumichi Abe, Akira Wada, Sachie Oshima, Soichi Kono, Atsushi Takahashi, Yukiko Kanno, Hiromichi Imaizumi, Manabu Hayashi, Ken Okai, Shinichi Niwa, Hirooki Yabe, Hiromasa Ohira Purpose: Non-parenteral drug use, through insufflation AZD9668 mw or smoking, presents a risk for acquiring hepatitis C virus (HCV) infection, but the prevalence estimates of HCV among non-injection drug users (NIDU) lack precision due to limited published research and surveillance data. This review aims to determine the global prevalence of HCV infection among persons who use non-injection drugs. Methods: A systematic review of peer-reviewed and grey literature was conducted in Cochrane Database, PubMed, EMBASE, DARE, Web of Science and CINAHL from January 2006 through December 2013. Two investigators independently reviewed abstracts to determine inclusion based on English language, laboratory confirmed anti-HCV or HCV RNA diagnosis, method of drug administration (snorting, sniffing or smoking), and lifetime drug injection status. Full articles meeting inclusion criteria were abstracted. Study quality was assessed based on representativeness of the study population, participant eligibility criteria and

selection, sample size, determination of exposure, confounders, and ascertainment of the outcome of interest (HCV infection). Pooled prevalence estimates Y27632 were obtained through random-effects meta-analysis using Comprehensive Meta-Analysis software. Heterogeneity was assessed by I2 statistic and moderated by subgroup analysis. Results: The search identified 11,360 articles. Of the 144 full articles reviewed, 23 cross-sectional studies featuring 25 distinct samples (N=7889) met inclusion criteria. Regional breakdown of the samples included Mexico, Central and South America (7); North America (7); Europe (5); Asia (3); 1 each from Africa, Australia, and the Middle East. Overall HCV prevalence among NIDU ranged from 0.6-40%.

Sixteen denture wearers, candidates for a new set of complete dentures, were selected. OHIP-14 scores were recorded at the beginning of the study, 6 weeks after fitting of the new set (T0), 15 days (T1), and finally 30 days (T2) after daily use of a denture adhesive as instructed. The KIS and KID were clinically examined and rated according to the Kapur Index. Statistical analyses were based on repeated-measures ANOVA, Mann-Whitney test, regression analysis, and Friedman test at a = 0.05. The OHIP-14 scale was found to have a high reliability (alpha = 0.847) and a high test-retest consistency (ICC = 0.889); however, domain 1 had the lowest item-total correlation (rho = 0.144) and item 7 a negative one (rho

= -0.414). Trend analysis indicated a significant negative linear trend over time (slope = -3.156, p = 0.002), while repeated-measures

ANOVA showed ZD1839 ic50 differences in OHIP-14 between T2 and T1 (p = 0.003) or T0 (p = 0.005) intervals. OHIP-14 groups were found to be positively associated with KIS (p = 0.010) and negatively with KID (p selleckchem = 0.047) groups, but not with gender (p = 0.272). The study shows that OHIP-14 has a high internal reliability and consistency when applied to new denture wearers, and its score decreases if denture adhesives are used for at least 15 days. Low KIS and high KID contributes to this trend. Some OHIP-14 items are more associated than others with the total score trend over time. “
“The prosthodontic management of a 7-year-old girl with induced dental agenesis is described. The mandibular posterior tooth germs had been removed during surgical excision of a melanotic neuroectodermal tumor of infancy, at the age of 2 months. The ongoing prosthodontic treatment, now in its eighth Oxymatrine year, was implemented by regular follow-up of the operation outcome and by targeted orthodontic intervention. The treatment plan included the provision of four successive interim removable partial dentures. Care was taken to preserve the oral structures, adapt to the morphological changes, and satisfy the needs of the child. Due to the unfavorable biomechanical

conditions, retention and stability problems were encountered. These were resolved by engaging the mechanism of neuromuscular adaptation through optimization of the shape of the denture base. For children and adolescents with extensive dental agenesis, prosthodontic management with interim removable dentures supports function, restores esthetics, and provides a solid basis for the definitive treatment. “
“To report the 5-year outcome of the All-on-4 treatment concept comparing double full-arch (G1) and single-arch (G2) groups. This retrospective cohort study included 110 patients (68 women and 42 men, average age of 55.5 years) with 440 NobelSpeedy groovy implants. One hundred sixty-five full-arch, fixed, immediately loaded prostheses in both jaws were followed for 5 years.

pylori eradication

was analyzed using the Kaplan–Meier method, and the difference between the curves of open- and closed-type was tested by Log-rank test. A Cox’s proportional hazards regression model was used to analyze independence of the association Bortezomib clinical trial between the extent of green mucosa in AFI images and development of metachronous EGC. Age, sex, intestinal metaplasia in the lesser curvature of the corpus, serum pepsinogen status, and H. pylori status were selected as candidate covariates for multivariate analysis. P < 0.05 was considered to indicate statistical significance. Eighteen patients in whom AFI endoscopy was not available and who did not undergo AFI observation were excluded, which left a total of 82 patients who were followed up and analyzed. The patients' demographic and clinical characteristics are shown in Table 1. In the AFI images, 31 patients had open-type, chronic atrophic fundic gastritis, and 51 had closed type. PD0325901 manufacturer Among 82 patients who were analyzed, 73 were H. pylori-positive and received eradication therapy, while the remaining nine patients were negative and were not prescribed anti-H. pylori treatment. In 58 of 73 H. pylori-positive patients, the first eradication therapy was successful,

and second-line therapy was successful in five patients. Thus, a total of 72 patients were followed up as an H. pylori negative group. Ten patients who failed first- and second-line eradication therapy were followed up as a persistent H. pylori infection group (Fig. 3). All participants received follow-up endoscopy (median duration of follow-up period, 55 months; range, 14–72 months). Metachronous EGC developed

in nine (12.5%) of 72 patients without H. pylori infection, and in three (30.0%) of 10 patients who had persistent H. pylori infection (Fig. 3). All metachronous EGC detected had a small size (mean tumor size, 6.0 ± 3.6 mm), was confined to the mucosa, Metalloexopeptidase and could be treated by ESD. Pathologically, all EGC was of the differentiated type. The most suitable cut-off points for pepsinogen for metachronous EGC, obtained by receiver operating characteristic curve, were pepsinogen I ≤ 22 ng/mL or pepsinogen I/II ratio ≤ 1.8. Using the most suitable cut-off point for pepsinogen I/II ratio, the sensitivity and specificity for metachronous EGC was 63.6% and 41.0%, respectively. Investigating predictive factors by univariate analysis, age (P = 0.028), intestinal metaplasia in the lesser curvature of the corpus (P = 0.012), and open-type atrophic fundic gastritis diagnosed by AFI (P < 0.001) were significantly associated with the development of metachronous EGC (Table 2). The cumulative 4-year incidence of metachronous EGC was 27.8% in patients with open-type atrophic fundic gastritis diagnosed by AFI and 4.1% in those with closed type, respectively (P < 0.001, Fig. 4).

Results:  In 10 HVOD patients, find more the diagnoses of MDCT were coincident with clinical results. All patients had ascites and pleural fluid, hepatomegaly except the caudate lobe in MDCT. Failure to view hepatic veins in hepatic 3 phase scans, but portal veins and inferior vena cava were unobstructed. In portal-phase, hepatic enhancements were non-uniform. Three patients were incorrectly diagnosed before hospital admission. All patients improved significantly after hepato-protection and supporting therapy. No ascites, hydrothorax, hepatomegaly and obstruction of hepatic veins were observed by MDCT before patients were discharged from hospital. Conclusion: 

Multidetector computed tomography combined with MPR and liver CTA images are helpful in the diagnosis and differential diagnosis of HVOD and in the evaluation of clinical therapeutic effects. “
“Background and Aim:  The objective of this study was to evaluate the association between high-resolution

manometry (HRM) and impedance findings and symptoms in patients with nutcracker esophagus (NE). Methods:  After institutional review board approval retrospective review of a prospectively maintained database identified patients click here who were diagnosed with NE as per the Chicago classification (distal contractile integral [DCI] > 5000 mmHg-s-cm) at Creighton University between October 2008 and October 2010. Patients with achalasia or a history of previous foregut surgery

were excluded. NE patients were sub-divided into: (i) Segmental (mean distal esophageal amplitude [DEA] at 3 and 8 cm above lower esophageal sphincter [LES] < 180 mmHg) (ii) Diffuse (mean DEA at 3 and 8 cm above LES > 180 mmHg) and (iii) Spastic (DCI > 8000 mmHg-s-cm). Results:  Forty-one patients (segmental: 13, diffuse: 4, spastic: 24) satisfied study criteria. Patients with segmental NE would have been missed by conventional manometry criteria as their DEA < 180 mmHg. A higher percentage of patients with spastic NE (63%) had chest pain when compared to patients with segmental NE (23%) and Tyrosine-protein kinase BLK diffuse NE (25%). There was a significant positive correlation between chest pain severity score and DCI while there was no significant correlation between dysphagia severity and DCI. Conclusions:  In patients diagnosed with NE using the Chicago classification presence and intensity of chest pain increases with increasing DCI. The present criteria (> 5000 mmHg-s-cm) seems to be too sensitive and has poor symptom correlation. Adjusting the criteria to 8000 mmHg-s-cm is more relevant clinically. “
“We read with great interest the article by Teixera-Clerc et al.,1 regarding the hepatoprotective properties displayed by cannabinoid receptor 2 (CB2) agonists in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.

Applicability for all NAFLD cases, diverse ethnic populations, and logistics/ low cost are other issues. To provide higher diagnostic accuracy with readily available tests, we explored conventional and extended clinicopathological variables, LSM and biomarkers, then combined modalities in a clinical model to stratify as many as possible NAFLD cases into advanced or no fibrosis, and also to identify NASH versus simple steatosis. Patients and Methods: From our combined clinical database of 200 biopsied NAFLD patients (steatosis ≥5%), 169 with LSM data were analyzed: 135 from Hong Kong, 18 Perth, 16 Canberra. A further

18 cases were excluded due to missing data (final n = 151). According to NAFLD activity score (0–3 = simple steatosis, 4 = excluded, 5–8 = NASH) and Brunt’s fibrosis score (0, 1 or 2, 3 or 4), cases were grouped into 3 categories Z-VAD-FMK nmr (simple steatosis, NASH, F3/4 [NB, this third category could include NASH or “not NASH” NAFLD). Biomarkers included: serum ferritin, M30 (apoptosis GPCR Compound Library solubility dmso marker), M65ed (overall cell death marker), hyaluronic acid (HA), P3NP, annexin V-positive microparticles (MP), and genetic predisposition (PNPLA3). Using generalized linear models in SPSS v22.0, a parsimonious

decision tree was created to predict the three NAFLD categories. Results: Age, waist circumference (not BMI), hypertension, diabetes/fasting blood

glucose, ALT, platelet count, INR, LSM, all biomarkers except ferritin, and NAFLD fibrosis score significantly correlated with NAFLD category. In the multivariate analysis of the above candidate indicators, LSM was found to be the dominant predictor (OR 1.22, 95% CI 1.09–1.34, p < 0.0001). Consequently, LSM was stratified into 3 bands (<5.8, 5.8–30.3, >30.3 kPa) to maximize NAFLD category discrimination. Within each LSM stratum, the candidate variables were used 3-mercaptopyruvate sulfurtransferase to further predict NAFLD categories. The significant factors entering the decision tree were P3NP (cut-off 8.7 ng/mL), ALT (cut-off of 55 U/L within the lower band, and 60 U/L within the middle LSM stratum), hypertension and LSM< or >10. Overall, 72% (109/151) agreement between predicted and histologically-observed NAFLD categories was found across the tree. The sensitivities and specificities varied by LSM band. For LSM < 5.8 kPa (27 SS, 22 NASH, 1 F3/F4), achieved sensitivity for simple steatosis was 89% (24/27), and sensitivity for NASH was 55% (12/22), with predictive values of 71% and 80%, respectively. In contrast, the middle LSM band (LSM 5.8–30.3 kPa, [25 SS, 48 NASH, 23 F3/F4]) achieved 81% (39/48) sensitivity for NASH and 40% (10/25) for simple steatosis, with predictive values of 67% and 100%, respectively.

It is not known, however, whether CRP is merely a marker of accompanying inflammation or whether it contributes causally to insulin learn more resistance. The objective of this study is to investigate the role that CRP may play in the development of insulin resistance. We examined the effect of single-dose intravenous

administration of purified human (h)CRP on insulin sensitivity in Sprague-Dawley rats using the euglycemic, hyperinsulinemic clamp technique. hCRP was associated with impaired insulin suppression of endogenous glucose production with no reduction in peripheral tissue glucose uptake, suggesting that hCRP mediated insulin resistance in the liver but not extrahepatic tissues. We further assessed components of the insulin signaling pathway and mitogen-activated protein kinases (MAPKs) in the liver. Liver tissues derived from hCRP-treated rats showed reduced insulin-stimulated insulin receptor substrate (IRS) tyrosine phosphorylation, IRS/phosphatidylinositol 3-kinase (PI3K) association, and Akt phosphorylation, consistent with hCRP-induced impairment of hepatic insulin signaling. Furthermore, hCRP enhanced phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK as well as IRS-1 Ser612. Finally, we observed in primary cultured rat hepatocytes that U0126 (a selective inhibitor of MAPK/ERK kinase1/2) corrected

U0126 supplier hCRP-induced impairment of insulin signaling. Conclusions: hCRP plays an active role in inducing hepatic insulin resistance in the rat, at least in part by activating ERK1/2, with downstream

impairment in the insulin signaling pathway. (HEPATOLOGY 2011) The appreciation that inflammation is a hallmark of the metabolic syndrome1, 2 has stimulated interest in whether systemic inflammatory Buspirone HCl biomarkers such as C-reactive protein (CRP) contribute to the development of insulin resistance. The acute-phase protein CRP is a member of the pentaxin protein family involved in pattern recognition and innate immunity; it is synthesized primarily by the liver in response to inflammation.3 In addition to being an independent predictor of cardiovascular events,4 CRP is also closely associated with insulin resistance5 and related metabolic disturbances such as fatty liver disease and hyperglycemia.6, 7 It remains unclear, however, whether this association simply reflects the inflammatory milieu or whether it suggests a causative role of CRP in the progression of insulin resistance. In vitro studies have shown that human (h)CRP impairs insulin action and the insulin receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway, and/or activates proinflammatory pathways in various cell types.8–10 To date, in vivo data concerning the effect of hCRP on insulin action are still lacking.