Lcn2 levels in PV after CCl4 treatment were significantly decreased in SPX mice compared to Sham mice (327.5 ± 35.0 ng/mL vs 465.9 ± 30.6 ng/mL, p<0.05). CCL2 and TNF-α mRNA levels were significantly decreased after rLcn2 treatment on LPS-stimulated KCs. Conclusion: Spleen

deficiency enhanced CCl4-induced liver fibrosis. The mechanism of exaggerated liver fibrosis most likely involves decreased Lcn2 levels in PV that led to excessive KC activation in this MAPK Inhibitor Library model. The spleen may have a protective role in the development of liver fibrosis by Lcn2 produced from Gr1-positive cells, and it could be a new therapeutic target against liver fibrosis. Disclosures: The following people have nothing to disclose: Tomonori Aoyama, Akira Uchiyama, Kazuyoshi Kon, Hironao

Okubo, Shunhei Yamashina, Kenichi Ikejima, Shigehiro Kokubu, Akihisa Miyazaki, Sumio Watanabe Introduction: Lysyl Oxidase Like 2 (LOXL2) is an extracellular copper-dependent amine oxidase that catalyzes the formation of crosslinks in collagen. We assessed the relationship of sLOXL2 levels with liver fibrosis and cirrhosis in patients with CHB treated with TDF. Methods: Subjects in the pivotal TDF registration trials who had stored serum samples available for analysis at baseline and weeks 12, 48 and 240 were included in the analysis. Liver biopsies were click here performed pre-treatment, at weeks 48 and 240. sLOXL2 was measured using a highly sensitive assay developed using 2 specific monoclonal antibodies on a Singulex® platform. Results: Of the 641 check details subjects originally randomized, 304 had stored serum available and were included in the analysis. Of these, 225 had liver biopsies at baseline and week 240. Characteristics (77% male, 63% white, 30% Asian and 13% obese) of the subjects included in the study matched well with those not included

in the analysis. sLOXL2 correlated with Ishak fibrosis stage at all time points. In cross sectional analyses at baseline, the median sLOXL2 level correlated with necroinflammation by Knodell score (p<0.0001) and with fibrosis by Ishak stage (791 pg/mL for Ishak stage 0-2, 1091 pg/mL for Ishak 3-4 and 1370 for pg/mL for Ishak 5-6; p<0.0001). In longitudinal analysis, sLOXL2 declined with treatment, with the largest decline seen in the first 12 weeks. For all fibrosis stage categories, patients experiencing fibrosis regression consistently had lower sLOXL2 levels than those without regression (Figure1). Conclusions: sLOXL2 correlates with fibrosis stage in patients with HBV. sLOXL2 declines with HBV treatment, likely indicating a decrease in fibrogenesis. Overall, the data suggest that sLOXL2 is a potential measure of ongoing fibrosing disease and may be useful not only to assess liver fibrosis at a given time but also to detect reversal of fibrosis and cirrhosis. Mean Serum L0XL2 (+/- SE) by Baseline Ishak Fibrosis Score, Stratified by Regression Status Disclosures: W.

26, 27 However, in ethanol- or TSA-treated cells, no such collars were detected. Although the class 3 profiles were invaginated, the necks were not elongated nor were the sides of the necks apposed, indicating that dynamin oligomers were likely

not assembling there. Furthermore, overexpressed wild-type dynamin failed to rescue the ethanol-induced defect and was not detected at the plasma membrane, indicating impaired dynamin membrane recruitment. Previously, we determined Saracatinib order that impaired clathrin-mediated internalization required ethanol metabolism and was likely mediated by acetaldehyde (see Supporting Fig. 1).15, 28 Thus, one exciting possibility is that a critical clathrin-coat component(s) is prone to adduction by acetaldehyde or other reactive metabolites, thereby impairing proper dynamin recruitment. Alternatively, (additionally?), hyperacetylation of key coat components may be at fault. This hypothesis is supported by the findings that actin and cortactin

are hyperacetylated upon ethanol exposure.4 Although how cortactin, actin, and dynamin function to promote vesicle release BVD-523 datasheet is not completely elucidated, acetylation of cortactin is known to prevent its association with actin.29 Thus, we propose that alcohol-induced hyperacetylation leads to decreased interactions between actin, cortactin, and/or dynamin, thereby inhibiting dynamin recruitment and subsequent vesicle fission. Although our coimmunoprecipitation results are fully consistent with this hypothesis, identification of the hyperacetylated lysines in both actin and cortactin (and dynamin?) is needed to test this hypothesis. Previously, we found that ethanol exposure led to increased microtubule acetylation and stability.6 In an effort to determine the

mechanism responsible for this observation, we examined the distributions and biochemical properties of histone deacetylase-6 (HDAC6), a tubulin (and cortactin) deacetylase. We found that HDAC6 binding to endogenous microtubules was impaired in ethanol-treated cells, whereas its ability to bind or deacetylate exogenous tubulin did not change, suggesting fantofarone that tubulin from ethanol-treated cells was modified, thereby preventing HDAC6 binding.30 Because both impaired HDAC6 microtubule binding and tubulin hyperacetylation require ethanol metabolism and are likely mediated by acetaldehyde6, 30 and because tubulin can be acetaldehyde adducted,31, 32 we propose that tubulin-acetaldehyde adducts impede HDAC6-tubulin binding, thereby preventing deacetylation. It is possible that an analogous scenario may explain impaired clathrin-mediated internalization in ethanol-treated cells, a possibility we are currently exploring.

In this uniquely sized North American study, we extend the previous work by using for the first time in selleck chemical this context a more sensitive and disease-specific QOL measure for use in PBC. Our study showed that a higher

number of comorbidities (>2) as well as a higher number of medications (>3) was associated with higher fatigue scores. The association with depression is notable. Clearly we are not able to distinguish between direct potential causes for fatigue (for example, beta-blocker use) and surrogate associations (e.g. the possible increased prevalence of functional bowel disorders in those using a proton pump inhibitor). Our study design prevents us from doing this but this does not detract from the concept that fatigue is not specific to PBC, nor does it make less relevant the message to clinicians to think broadly about fatigue and its cause, if they are to successfully intervene. Others before have shown,

for example, that 12% of patients with PBC fulfilled criteria for irritable bowel syndrome and had more gastrointestinal symptoms and higher fatigue scores.11 The pruritus reported by our patients was also associated with higher fatigue scores, and at the time of evaluation 33 patients were currently using antipruritic prescription. Despite that, we show that PCI-32765 mouse patients who were on these medications scored high on the Fatigue domain of PBC-40 (34.5 ± 10.8 versus 26.5 ± 11.0, P < 0.0001). This could be attributed to the symptom being in need of better control as well as speculatively poor sleep quality because of itching. The associations we demonstrate with disease severity are complicated by unknown confounders. Therefore, although at the time of survey disease severity does seem

to associate with fatigue, it had an inverse relationship when factored backwards with regards to stage at presentation. Confounders regarding modes of presentation may help explain 3-mercaptopyruvate sulfurtransferase this apparent paradox, as might age at presentation, for example. Our multivariate analysis went on to provide a model for fatigue association that included BMI, disease severity, and clinical symptoms. The association with calcium and vitamin D use is presumably a surrogate for an unknown factor. Of note, AMA status was not related to the presence of fatigue. It is well recognized that AMA titers can fall during the course of treated PBC, and our failure to demonstrate a relationship between AMA titers and fatigue argues against the hypothesis that there is a direct metabolic link between mitochondrial antibodies and changes in mitochondrial function in patients.22, 31 For the symptom of fatigue, we were also not able to show an effect of treatment response, although intriguingly some components of the PBC-40 domains, Symptom and Itch, did seem to improve. This provides further support to the complex interactions that underpin fatigue in patients with PBC.

“
“Summary.  Our aim was to evaluate bone status in boys with haemophilia using dual energy X-ray absorptiometry (DXA) and quantitative ultraSonography (QUS), and in addition, to compare these two methods with the use of biochemical markers of bone turnover. Twenty-six boys with a mean decimal

age of 12.08 ± 4.44 years were included in the study which included a DXA scan at lumbar spine and radial, as well as tibial QUS. Serum levels of soluble receptor activator of nuclear factor κB ligand (sRANK-L), osteoprotegerin (OPG) and osteocalcin (OC) were measured and joint evaluation was performed using the Hemophilia Joint Health Score (HJHS). With regard to the study results, only 2 of 26 patients (7.7%) had bone mineral density (BMD) Z-scores <−2, and 4 patients (15.4%) had BMD Z-scores between −1 and −2. Only one patient had radial and other two had tibial QUS Z-scores <−2. No agreement was recorded between QUS and DXA in identifying RXDX-106 nmr patients at risk for osteoporosis (k = 0.275, P = 0.063). Haemophiliacs had significantly higher serum levels of sRANK-L (21.04 ± 4.78 vs. 18.58 ± 2.28 ng mL−1, P = 0.038) and of OC (5.35 ± 2.29 vs. 3.09 ± 0.61 ng

mL−1, P = 0.002) and significantly decreased levels of OPG (15.78 ± 2.53 vs. 23.79 ± 4.39 pg mL−1, P < 0.001) selleck screening library compared with controls. QUS Z-scores at tibia significantly correlated with HJH Scores (r = −0.450, P = 0.040), whereas lumbar BMD Z-scores significantly correlated with body mass index Z-scores (r = 0.500, P = 0.009). More studies are warranted to identify the most accurate densitometric method for assessing bone status in haemophiliacs. “
“Severe heritable protein C (PC) deficiency is quite rare, although heterozygous PROC mutation is the second leading cause of genetic predisposition to thrombosis in Japanese adults. The aim of the study was to search the optimal management, the paediatric onset and outcomes of PC deficiency were characterized in

Japan. The genetic study, postmarketing survey of activated PC (aPC) concentrate (Anact®C) and intensive review in Japan for 20 years enabled the analysis of the disease onset, genotype, treatment and prognosis. Symptomatic PC deficiency was determined in 27 Japanese children. All but two patients presented Liothyronine Sodium within 16 days after birth (three prenatal and six neonatal onsets). Postnatal-onset cases had normal growth at full-term delivery. Of the 27 patients, 19 suffered intracranial thrombosis or haemorrhage (ICTH) (three foetal hydrocephalies), 16 developed purpura fulminans (PF) and 10 had both at the first presentation. ICTH preceded PF in both affected cases. Low PC activities of 18 mothers and/or 12 fathers indicated 20 inherited PC deficiencies (2 homozygotes, 11 compound heterozygotes and 7 heterozygotes) and seven unidentified causes of PC deficiency. Nine of 11 patients studied had PROC mutations.

r-project. org) was employed to perform quantile normalization of probe intensity data, and to identify significantly differentially expressed genes. Data are presented as mean ± standard error of the mean (SEM). Data were analyzed using a two-way analysis Fulvestrant manufacturer of variance with a Bonferroni post hoc test (GraphPad PRISM, version 4.0). P < 0.05 was considered as significant. We validated

that deletion of the SOCS3 gene was limited to the liver in mice acutely injected with interleukin-6 (Fig. 1A and Supporting Information Fig. 1). As expected, the HFD increased liver SOCS3 expression in littermate control floxed WT mice but not in SOCS3 LKO mice (Fig. 1A). SOCS1 and SOCS3 are highly homologous, but we found no difference in HFD induction of SOCS1 between genotypes (data not shown). On a control chow diet, SOCS3 LKO mice weighed the same as WT littermates. However, when fed an HFD (from 6 weeks of age onward), they gained more weight (Fig. 1B). Epididymal fat pad weights were significantly larger in absolute terms (Fig. 1C) and as percentage of total body mass (data not shown) in SOCS3 LKO mice fed an HFD indicating that the increased weight gain in SOCS3 LKO mice was due to increased adiposity. To assess the mechanisms contributing to increased weight gain in SOCS3 LKO mice we measured food intake and energy expenditure. On an HFD, Decitabine price SOCS3 LKO mice consumed significantly

more food per day (Fig. 1D), even when corrected for body mass (data not shown), and expended less energy (Fig. 1E). Glucose oxidation rate was reduced in chow-fed and tended to

be reduced in HFD-fed SOCS3 LKO mice (data not shown). There was no difference in the rates of fat oxidation over a 24-hour light/dark cycle on either diet (data not shown). Taken together, these data suggest that increased adiposity in SOCS3 LKO mice on an HFD was due to reduced daily energy expenditure Oxalosuccinic acid and increased caloric intake. We measured serum glucose and insulin concentrations as well as glucose tolerance and found that on a chow diet SOCS3 LKO mice were comparable to WT littermates (Fig. 2A-C). In contrast, HFD-fed SOCS3 LKO mice developed hyperglycemia (Fig. 2A) and a greater degree of hyperinsulinemia (Fig. 2B) and glucose intolerance (Fig. 2D) than WT littermates. These data suggest that deletion of liver SOCS3 accelerates the onset of HFD-induced insulin resistance. To assess the specific contribution of hepatic versus peripheral insulin resistance to glucose homeostasis in SOCS3 LKO mice we conducted euglycemic-hyperinsulinemic clamps. Basal glucose turnover was similar between the two groups of mice on both diets (Supporting Table 1). In chow fed mice the glucose infusion rate (GIR), and the glucose disposal rate (GDR) were not different between groups (Fig. 3A,B). As anticipated, the HFD significantly reduced both GIR and GDR relative to chow fed mice, but this reduction was significantly greater in SOCS3 LKO mice (Fig.

The outcome of supracondylar femoral extension osteotomy has not been extensively studied. Caviglia et al. [16] published the most extensive series with 19 patients who underwent extension osteotomies during a 30-year period. In six patients with fixed knees in flexion, the ROM was not regained. The arc of movement did not change in six, decreased in four

and increased in the three remaining patients by only 10°. Postoperative bleeding, temporary peroneal nerve paralysis, genu recurvatum and relapsed flexion deformity were the reported complications. They concluded that although this operation aligns the limb, it hardly influences the ROM. BGB324 solubility dmso Mortazavi et al. [17] reported the outcome of 11 trapezoid supracondylar extension osteotomy during a five-year period. The patients were followed up for an average 43.4 months after surgery. Investigators showed that all of the patients gained the ability to function more independently after the operation; they could walk, climb the stairs, bathe and use public means of transportation by themselves. The

arc of motion increased in all of the knees, which had some ROM before surgery. This was in contrast to results of previous studies on V-shaped osteotomies. Using rigid internal fixation and early physiotherapy ROM may well be a reason, but investigators proposed that the higher degrees of release of extensor mechanism PD0325901 gained by femoral shortening in trapezoid osteotomy compared with V-shaped ones could be another mechanism for this difference. This shortening may also reduce the risk of neurovascular complications. There were few minor postoperative complications and this operation seems to be safe. The trapezoid supracondylar femoral extension DCLK1 osteotomy could be considered an alternative in the management of severe, fixed flexion contracture of the knee joint that is unresponsive

to conservative measures in patients with haemophilia. The knee is the most commonly involved joint in haemophilia and certainly the one most responsible for pain and disability. The indications for knee replacement in haemophilia are incapacitating pain and impaired function. Many of these patients have severely restricted ROM, putting increased stress on other involved joints like the ipsilateral ankle and contralateral knee. Regaining a functional ROM following knee replacement in haemophilia patients is one of the greatest challenges in reconstructive orthopaedic surgery. With severe arthrofibrosis, extensive releases, as well as debridement, are necessary to evert the patella and get adequate flexion to prepare the distal femur. In severe cases of fibrous ankylosis, making the tibial cut first can greatly facilitate exposure [15]. However, this must be done very cautiously to avoid damage to popliteal neurovascular structures which may be adherent to the posterior capsule.

We did not estimate calf:cow ratios with sample sizes <20 groups, as optimization was problematic when there were few groups and observers typically classify >20 groups. Calf:cow ratios in all simulations

were estimated with function dbetabinom within package bbmle in Program R using the Nelder-Mead algorithm for optimization. Selecting an appropriate level of precision is difficult, as the desired level of precision will depend upon how the data are used. Clearly, we would like to be able to identify years in which reproduction fails and a relative precision of 20% should be sufficient to delineate years of high vs. low calf production. For example, attaining 20% relative precision for a calf:cow ratios would allow differentiation of ratios that differ by more than 1 calf per 100 cows for small ratios, such as 0.05

PI3K inhibitor drugs (i.e., 0.05 × 0.2 = 0.01), or 3 calves per 100 cows for larger see more ratios, such as 0.15 (i.e., 0.15 × 0.2 = 0.03). However, if calf:cow ratios are used as measures of fecundity in population models, more precision may be necessary. We chose to present relative precisions as functions of sample size, so users can decide what sample sizes are necessary. Nine surveys classified walrus groups along the ice edge between 1982 and 1999 (Fig. 3; Table 2). Two surveys occurred in 1981 and 1982, single surveys occurred in 1983, 1984, and 1998, and two surveys occurred in 1999. Walruses would sometimes enter the water before all individuals were counted and classified to

sex and age. A total of 1,200 groups of walruses were encountered; of these, 1,107 (92%) were completely Adenosine counted and 886 were completely classified to sex and age. A total of 773 groups were completely classified and contained at least one cow. Pooling within sample years, the number of groups with cows that were classified ranged from 59 in 1983 and 1998 to 218 in 1982 (Table 2). The average size of groups with cows was 7.03 (SD = 10.35) and ranged from 5.52 (SD = 4.92) in 1982 to 9.48 (SD = 16.47) in 1981. The maximum observed sizes of groups with cows were 133 in 1981, 109 in 1982, 22 in 1983, 62 in 1984, 32 in 1998, and 30 in 1999. The entire sea ice front, from Alaska to Russia, was surveyed in 1982, 1998, and 1999 (Fig. 3). In 1981, during the Polar Star survey, time of day was not recorded for 30 cow groups (115 individual cows) and these data were not used for covariate modeling. The data were more appropriately modeled with a beta-binomial distribution (Δ AIC = 0; 2 parameters) than a zero-inflated beta-binomial distribution (Δ AIC = 2.1; 3 parameters), a zero-inflated binomial distribution (Δ AIC = 78.6; 2 parameters), or a binomial distribution (Δ AIC = 127.1; 2 parameters). Hence, a beta-binomial distribution was assumed for subsequent analyses.

Methods: A total of 21 Patients with Portal hypertension from the First Affiliated Hospital of Nanchang University were exeeuted TIPS with Covered Stent in rencent 2 years and

were followed up for 4 to 14 months. The portal venous pressure pertosystemic pressure gradients, alimentary tract hemorrhage, stent reocclusion, hepatic encephalopath, blood coagulation, hepatic function, blood ammonia, iconography and endoscopy results were monitored before and after Tips treatment. Results: In all of the 21 Patients,18 cases were sueeessfully completed the operation. The rate of hemostatsis in 24 hours was 1 00%. HVPG dropped from (41.9 ± 15.9)cm H20 to (25.5 ± 13.5)cm H20, there was significant selleck statistical signifieance. During in the 4 months–14 months of follow-up, RGFP966 concentration The relapse rate of rehaemorrhagia was 26.7% (4/15), and occurred in 1, 2, 6, 8 month after the operation. Esophageal varices of 11 cases release, another 6 cases did not change significantly. Stent reocclusion rate 16.7% (3/18), and the total of 3 cases rehaemorrhagia. The incidence rate of hepatic encephalopathy was16.7% (3/18), symptoms of every cases disappear after symptomatic

treatment. Refractory ascites of all cases remission obviously and even disappear. The difference of hepatic function and platelet between before and after operation was not significant statistically (P > 0.05). Conclusion: The curative effect of TIPS in treating portal hypertension caused by liver cirrhosis

is exact, and is worthy of clinical application. Key Word(s): 1. TIPS; 2. Portal HyPenension; 3. Liver cirrhosis; Presenting Author: CHAO DU Additional Authors: MINGDE JIANG Corresponding Author: CHAO DU Affiliations: Chengdu Military Command Objective: Liver fibrosis is the pathological basis of chronic liver disease and it must lead to the cirrhosis. There is still no effects of drugs to reverse the liver fibrosis. In recent years Fossariinae numerous studies have confirmed that bone marrow-derived mesenchymal stem cells in the the body and outward have the potential of differentiation to liver cell, it is expected to repair or reverse the process of liver fibrosis. The genetically modified stem cells maintain the directly differentiation characteristics, while corresponding factor can improve the efficacy and is compensate for the lack of simple MSCs transplantation therapy. Matrix metalloproteinases in the liver was expressed and secreted by hepatic stellate cells (HSC) and Kupffer cell. It was zinc – calcium-dependent family of endogenous proteolytic enzymes involved in extracellular matrix degradation. It was the only enzyme that breaks down collagen fiber and almostly breaks down the ECM components outside the polysaccharide, it plays an important role in physiological and pathological processes.

Methods: 34 human hepatocyte chimeric mice were allocated into five

experimental groups. 15 mice were PD-0332991 ic50 infected with HBV, 13 were infected with HCV, and 6 were used as an uninfected control group. Mice were inoculated via the tail vein with human serum containing HBV or HCV genotype 1b particles. 5 HBV-infected mice and 5 HCVinfected mice were sacrificed 10 days after infection, whereas the remaining 18 mice were sacrificed 8 weeks after infection. Human hepatocytes were extracted from mouse livers and analyzed using Toray 3D-Gene Human Oigo chip 25k microarray. Results: Pairwise comparisons revealed a number of short and long-term differences in gene expression in response to HBV and HCV infection. Fuzzy c-means cluster analysis was used to identify patterns in gene expression among the experimental groups, and gene set enrichment analysis was used to characterize clusters based on enrichment of gene ontology terms and Reactome pathways. Response of interferon stimulated genes was faster in HCV infection than in HBV infection, whereas HBV infection resulted in stronger and more sustained induction of acute phase genes (CRP, SAA1, SAA2). Distinct patterns of gene expression were detected using fuzzy c-means clustering, and each cluster was significantly associated with one or more Reactome pathways involving, e. g., innate and

adaptive immune responses, cytokine JQ1 cost signaling, cholesterol biosynthesis, signal transduction, and cell cycle regulation. Conclusions: Analysis

of early and late changes in gene expression following HBV versus HCV infection revealed diverging patterns of immune response. Better understanding of differences in the molecular pathogenesis of inflammation in HBV versus HCV infection may help to reduce immune-mediated liver damage and improve response to therapy. Disclosures: Kazuaki Chayama – Consulting: Abbvie; Grant/Research Support: Dainippon Sumitomo, Chugai, Mitsubishi Tanabe, DaIICHI SANKYO, Toray, BMS, MSD; Speaking and Teaching: Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, KYORIN, Nihon Medi-Physics, BMS, Dainippon Sumitomo, MSD, ASKA, Astellas, AstraZeneca, Eisai, Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shinyaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people Carnitine palmitoyltransferase II have nothing to disclose: C. Nelson Hayes, Sakura Akamatsu, Masataka Tsuge, Daiki Miki, Nobuhiko Hiraga, Hiromi Abe, Michio Imamura, Shoichi Takahashi, Hidenori Ochi Background and Aim: Expression levels of interferon stimulated genes negatively correlate with the rate of sustained virological response in chronic hepatitis C patients treated with peg-IFN and ribavirin. In this study we investigated whether gene expression profiles in pre-treatment liver biopsies of patients with chronic hepatitis B (CHB) were associated with treatment outcome.

Objectives.— The aim of this study was to analyze the prevalence of RILES in a

consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce-TCD. Methods.— A total of 159 consecutive MA patients underwent ce-TCD with air-mixed saline to disclose RILES. RILES was characterized in terms of MB amount (small-moderate or large) and occurrence at rest and/or during Valsalva maneuver (permanent or latent). Results.— RILES was revealed in 79/159 patients (∼50%). Permanent RILES were detected in 56/79 (71%) and latent RILES in 23/79 (29%) MA patients. The occurrence of a typical MA attack was overall observed in 12/159 patients (7.5%; 95% CI: 4-12.8%), but arose only in RILES-positive ones, immediately after ce-TCD (12/79; 15.2%; P < .001). All 12 patients had permanent RILES (12/56; 21.4%; P = .015) C646 price and MA

attack was mostly observed in large RILES-positive patients, even without statistical significance (P = .118). Conclusions.— Microembolic air load could act as a trigger of MA attack. According to recent studies and to the clinical characteristics observed in our patients, microembolization because of MB injection might provoke a decrease this website in cerebral oxygen saturation, thus triggering cortical spreading depression and, thereafter, MA attack. Larger and prospective studies will be necessary to confirm our data and observe a wider correlation. “
“Orbitofrontal cortex (OFC) dysfunction and poor decision making have been described in patients with chronic migraine and medication Astemizole overuse. These neurobiological underpinnings might explain dependency-like behaviors often described in this condition, such as loss of control over painkillers,

high rates of relapse after detoxification, and compromised social functioning. We investigate whether the OFC impairment was a persistent trait in migraine, independent of clinical and affective features, a dynamic result of the need to cope with the increased pain and disability, or a temporary consequence of medication overuse. For this purpose, we compared 40 chronic migraineurs with medication overuse, 40 episodic migraineurs, and 40 matched healthy controls. The examination consisted of a clinical interview, Anxiety and Depression Hamilton Scales, Severity of Dependence Scale, and Migraine Disability Assessment questionnaire. A neuropsychological assessment of orbitofrontal function was made through the Iowa Gambling Task (IGT). Chronic migraineurs with medication overuse were followed for a year after detoxification. We found an impaired decision-making performance among chronic and episodic migraineurs that seems independent of the patients’ clinical and affective status. Contrary to the psychiatric and clinical improvement shown 1 year after the detox, CM patients exhibited a persistent IGT deficit.