32, 33 The contribution of DNL to total IHTG production in normal subjects is small and accounts for less than 5% of FAs incorporated into secreted VLDL-TG (≈1–2 g/day).34 However, the contribution of

DNL to total IHTG production in subjects with NAFLD is much higher and accounts for 15% to 23% of the FAs within IHTG and secreted in VLDL-TG.34, 35 Forskolin Moreover, data from a study that used sophisticated magnetic resonance spectroscopy techniques to evaluate postprandial glucose metabolism in vivo suggest that the increase in DNL precedes the development of NAFLD.36 Compared with insulin-sensitive subjects, consumption of a high-carbohydrate meal was associated with a much PI3K Inhibitor Library manufacturer lower rate of muscle glycogen synthesis and a diversion of most of the ingested glucose toward hepatic DNL and IHTG synthesis

in insulin-resistant subjects who had normal IHTG content. These data suggest that insulin resistance in skeletal muscle could promote IHTG accumulation by diverting ingested carbohydrate away from storage as muscle glycogen and toward de novo FA synthesis. Although hepatic DNL is a quantitatively minor pathway for TG synthesis, the rate of DNL might have important metabolic regulatory functions. For example, intrahepatic FAs that have been synthesized de novo activate peroxisome proliferator-activated receptor α (PPAR-α) to maintain glucose and lipid homeostasis.37 In addition, malonyl-CoA, the first intermediate of DNL, inhibits carnitine palmitoyltransferase 1 activity (CPT-1), thereby preventing the entry of FFAs into the mitochondrion and inhibiting FAO.38 The notion of potential allosteric inhibition of FAO by DNL is supported by data that found hepatic CPT-1 expression is decreased in subjects with NAFLD.33 The complex metabolic processes performed by the liver require a considerable amount of energy; the metabolic rate

of liver tissue (≈0.28 kcal/g of tissue per day) is similar to that of the brain, and is nearly 20 times greater than the metabolic rate of resting skeletal muscle and 50 times greater than the metabolic rate of adipose tissue.39 Therefore, although the liver weighs only ≈1.5 kg in adults, representing a small portion of total body weight (≈2.5% selleck compound in lean persons), it consumes ≈450 kcal/d and accounts for ≈20% of total resting energy expenditure.39 The mix of fuels used by the liver in vivo is difficult to quantify accurately because of the complicated exchange of metabolites between multiple biochemical pathways and technical limitations. It is estimated that FA and amino acid oxidation provide ≈90% of the fuel for basal hepatic energy requirements, and that the use of FFA as a fuel decreases during the fed state.40 The oxidation of intrahepatocellular FA occurs primarily within mitochondria, and to a much lesser extent by peroxisomes and microsomes.

The highest growth rate and DHA accumulation of this strain were obtained in 6.0% glucose, 1.0% yeast extract, 50% artificial seawater (ASW), and pH 7 at 28°C. In addition, carbon and nitrogen sources could be replaced by glycerol, ammonium acetate, sodium nitrate, or fertilizer N–P–K. Total lipid content reached 38.67% of dry cell

weight (DCW), in which DHA and eicosapentaenoic acid (EPA, C20:5n-3) contents accounted for 43.58% and 0.75% of the total fatty acid (TFA), respectively. In 5 and 10 L fermenters, the cell density, DCW, total lipid content, and maximum DHA yield were 46.50 × 106 cells · mL−1, 23.7 g · L−1, 38.56% of DCW, and 8.71 g · L−1 (in 5 L fermenter), respectively, and 49.71 × 106 cells · mL−1, 25.34 g · L−1, 46.23% of DCW, and 11.55 g · L−1 (in 10 L fermenter), respectively. Biomass of PQ6 strain possessed high contents of Na, I, and Fe (167.185, 278.3, and 43.69 mg · kg−1 Protein Tyrosine Kinase inhibitor DCW, respectively). These

results serve as a foundation for the efficient production of PQ6 biomass that can be used as a food supplement for Selleckchem Kinase Inhibitor Library humans and aquaculture in the future. “
“There is increasing interest in naturally produced colorants, and microalgae represent a bio-technologically interesting source due to their wide range of colored pigments, including chlorophylls (green), carotenoids (red, orange and yellow), and phycobiliproteins (red and blue). However, the concentration of these pigments, under optimal growth conditions, is often too low to make microalgal-based pigment production economically feasible. In some Chlorophyta (green algae), specific process conditions such as oversaturating light intensities or a high salt concentration induce the overproduction of secondary carotenoids (β-carotene in Dunaliella salina (Dunal) Teodoresco and astaxanthin in selleck products Haematococcus pluvialis (Flotow)). Overproduction of all other pigments (including

lutein, fucoxanthin, and phycocyanin) requires modification in gene expression or enzyme activity, most likely combined with the creation of storage space outside of the photosystems. The success of such modification strategies depends on an adequate understanding of the metabolic pathways and the functional roles of all the pigments involved. In this review, the distribution of commercially interesting pigments across the most common microalgal groups, the roles of these pigments in vivo and their biosynthesis routes are reviewed, and constraints and opportunities for overproduction of both primary and secondary pigments are presented. “
“Transcripts and enzyme activities of antioxidative enzymes were increased by hypersalinity (90‰) in a marine macroalga, Ulva fasciata Delile (Lu et al. 2006, Sung et al. 2009). This study examined the effects of polyamines (PAs) on the induction of hypersalinity tolerance through the modulation of expression of antioxidative defense enzymes. Incubation of U.

, Minneapolis, MN), according to the manufacturer’s instructions. Real-time polymerase chain reaction (PCR) was performed as described previously.13 The primers used are summarized in Supporting Table 2. Liver tissue content of malondialdehyde (MDA) was measured by the thiobarbituric acid reduction method using a commercially available kit (#10009055; Cayman Chemical, Ann Arbor, MI). Values were obtained after 30-minute incubation at 90°C under acidic conditions. Human umbilical vein endothelial cells (HUVECs) were

used at passages 3-6. For analysis of reactive oxygen species (ROS), H2O2 (Thermo Fisher Scientific, Waltham, MA) and N-acetylcysteine (NAC; Calbiochem, San Diego, CA) were used as an ROS inducer and an ROS Bafilomycin A1 in vivo scavenger, respectively. To examine the effects of H2O2 on TSP-1 expression, HUVECs were seeded on 0.1% gelatin-coated culture plates and incubated overnight. Without change of medium, H2O2 was applied at final concentrations of 0.01, 0.05, and 0.1 mM and incubated for 10 minutes. For immunocytochemistry (ICC), HUVECs were plated into Lab-Tek Permanox slides precoated with 0.1% gelatin and incubated overnight. Then, the cells, with or without pretreatment with 30 mM of NAC for 60 minutes, were treated with 0.1 mM of H2O2 for 10 minutes. To examine the effects

of HUVEC-derived TSP-1 on TGF-β/Smad signaling and proliferation in primary hepatocyte cultures, primary hepatocytes were isolated from 8- to 12-week-old adult WT mouse livers using collagenase perfusion as previously described.15 Isolated hepatocytes were plated on type I collagen

(10-μg/mL)-coated dishes Napabucasin cost in Williams’ E medium, supplemented see more with 5 μg/mL of insulin, 5 μg/mL of transferrin, 10 ng/mL of endothelial growth factor, 10−5 M aprotinin, 10−5 M of dexamethasone, 10−3 M of nicotinamide, and 10% fetal bovine serum and incubated at 37°C for 24 hours. To examine the effect of HUVEC-derived TSP-1 on TGF-β/Smad signaling in hepatocytes, the conditioned media from HUVECs (treated with 1.0 mM of H2O2 for 2 hours) were added to primary hepatocytes with or without pretreatment of 5 μM of LSKL or SLLK peptide (GenScript, Piscataway, NJ),16, 17 cultured for an additional 4 hours, and the cells were used for the analysis. To examine the effect of HUVEC-derived TSP-1 on hepatocyte proliferation, the conditioned media from HUVECs were added to primary hepatocytes, cultured for an additional 24 hours, and the cells were used for the analysis. All experiments were performed in triplicate, and the data shown are representative of results consistently observed. Data are expressed as the mean ± standard deviation. Data analysis was performed with SPSS 12.0.1 for Windows (SPSS, Inc., Chicago, IL). Statistical analyses were performed using the Student’s t test or analysis of variance, followed by Bonferroni’s multiple comparison tests, when appropriate.

Fifty selleck chemicals llc microliters of tissue extract was used for GSH measurement. GSH was measured according to the manufacturer’s instructions with a GSH assay kit (Promega, Madison, WI). Luminescence was detected with a Synergy 2 multimode microplate reader with Gen5 data analysis software (BioTek, Winooski, VT). DNA was extracted from 25 mg of mouse liver. Total DNA purification was performed with a DNeasy blood and tissue kit (Qiagen, Germantown, MA) according to the manufacturer’s instructions. RNA was eliminated by incubation in 5 μg/mL RNase (Roche, Indianapolis, IN). A 1.5-μg DNA aliquot was loaded onto 1.5% agarose gel for separation to assess for DNA fragmentation.

TUNEL staining was conducted with an in situ apoptosis detection kit from R&D Systems according to the manufacturer’s instructions. Six to seven animals were SCH727965 datasheet used per time point per treatment group. At least 1000 cells (TUNEL-positive cells and TUNEL-negative cells) were counted in each of eight separate low-power fields for each animal, and the percentage of TUNEL-positive cells was calculated. Two hours prior to sacrifice, animals received 30 μg of BrdU/g of body weight intraperitoneally. Liver

specimens were obtained, fixed in 4% paraformaldehyde, processed for histological analysis, and stained with the Amersham cell proliferation kit (Amersham Pharmacia Biotech, Ltd., United Kingdom). BrdU incorporation was measured at 24, 36, 48, and 72 hours. There were four to seven mice per treatment group per time point. At least 1000 cells (BrdU-positive cells 上海皓元 and BrdU-negative cells) were counted

in each of eight separate low-power fields for each animal, and the percentage of BrdU-positive cells was calculated. Hepatic cytoplasmic and nuclear proteins were extracted with the NE-PER nuclear and cytoplasmic extraction reagent kit (Pierce Biotechnology, Rockford, IL) according to the manufacturer’s instructions. Liver samples were homogenized in a radioimmunoprecipitation assay buffer (50 mM trishydroxymethylaminomethane–hydrochloric acid, pH 7.4, 150 mM sodium chloride, 1% Nonidet P40, 0.1% sodium dodecyl sulfate, 0.25% sodium deoxycholate, 1 mM ethylene diamine tetraacetic acid, and protease and phosphatase inhibitors). Four hundred micrograms of protein was used for immunoprecipitation. The lysate was precleared with 1 μg of isotype immunoglobulin G (IgG) and 50 μL of protein A/G agarose at 4°C for 1 hour. Five micrograms of an immunoprecipitating antibody or isotype IgG was added to the supernatant, and it was rocked overnight at 4°C. Next, 50 μL of protein agarose was added, and the mixture was rocked for 2 hours at 4°C. The protein bound to the agarose conjugate was centrifuged, and the pellet was washed three times with a radioimmunoprecipitation assay buffer.

Hepatic expression of PlGF and serum PlGF levels were assessed in liver specimens and blood samples from patients with alcoholic hepatitis, chronic hepatitis C, nonalcoholic steatohepatitis, and normal liver specimens. For PlGF immunohistochemistry, biopsy samples were obtained from patients with hepatitis C. The demographic and clinical characteristics of the patients included in the study are further represented in the Supporting Information Methods and in Supporting Information Tables 2 and 3. The effect of PlGF deficiency in cirrhosis was first studied in PlGF−/− mice. CCl4 and saline (n = 8 in each group) were administered to

PlGF+/+ and PlGF−/− mice. After 25 weeks of CCl4 treatment, animals were sacrificed and experiments were performed. For the therapeutic study, control (n = 5) and CCl4-treated mice (n = 9) were treated with 25-mg/kg intraperitoneal injections of αPlGF (ThromboGenics NV, Leuven, Belgium) that were administered twice weekly on days Nutlin-3 supplier 0 and 3 from week 12 until week 20 of the CCl4 treatment. To eliminate the possibility of passive immunization, a group of matched control (n = 5) and a group of CCl4-treated mice (n = 7) were injected with mouse immunoglobulin G1 (IgG1) (ThromboGenics NV) at the same dose and times as mice in the

αPlGF groups. The dosing schedule of αPlGF was based on previous published pharmacokinetic studies that were performed in mice.9, 10 To provide therapeutic data for end-stage cirrhotic mice, αPlGF was administered at the same dosage as described above, but was given from week 18 to week 25 of the CCl4 treatment. Selleck Quizartinib Hemodynamic studies, vascular corrosion casting, histology (Sirius Red, periodic acid-Schiff–diastase), immunohistochemistry (CD31, α-smooth muscle actin), immunofluorescence (PlGF and vascular cell adhesion molecule 1), cytology (phalloidin), antibodyarray assay, statistical analysis, and all other methods 上海皓元医药股份有限公司 are described in the Supporting Information Methods. Changes in the expression of PlGF that occur in the setting of cirrhosis were investigated in experimental models of cirrhosis in mice and rats as well as in patients with cirrhosis. After treating mice with CCl4, hepatic PlGF protein

levels increased after 4 weeks and remained elevated during 16 weeks of treatment (P < 0.05 versus control mice) (Fig. 1A). Increased hepatic PlGF expression was also detected via western blot analysis of rats with established cirrhosis. As seen in Fig. 1B, there was an approximately four-fold increase in PlGF protein levels in cirrhotic rat livers compared with control livers (4.2±1.4 versus 0.7 ± 1.1 relative densitometric units, respectively; P < 0.05). To determine whether PlGF was also overexpressed in human liver cirrhosis, we measured PlGF messenger RNA (mRNA) and protein levels in livers of patients with cirrhosis. A prominent up-regulation of hepatic PlGF mRNA levels was observed in patients with and without cirrhosis (3.5 ± 0.9 versus 0.9 ± 0.

8%) were tested for HIV status. Conclusion:  It is essential to monitor the trends of this communicable

and preventable disease. The establishment and distribution of appropriate clinical evidence and guidelines are vital to improve the clinical practices for acute hepatitis B. “
“Recent reports demonstrated signaling pathway that the PNPLA3 (patatin-like phospholipase domain containing-3) isoleucine-to-methionine variant at residue 148 (I148M) influences steatosis and liver damage progression in chronic hepatitis C (CHC).1-4 The article by do O and coworkers now report that in 176 German patients with CHC who underwent liver transplantation, there was no significant effect of PNPLA3 genotype on fibrosis after 5 years of follow-up.5 Unfortunately, steatosis assessment was not available. Other major drawbacks limit the validity of these findings. First, previous studies have shown that the effect of PNPLA3 on fibrosis in CHC follow a recessive model,1-4 so that this study5 had only 30% power to detect a two-fold increased risk. Furthermore, the effect might be less relevant in patients carrying genotype-3 hepatitis C virus, but viral features were not reported. Most importantly, the authors could only evaluate recipient genotype, so that they had no information on PNPLA3 status in the transplanted liver. However, it is most commonly held that the 148M PNPLA3 variant predisposes

to liver damage by acting directly at the level of hepatocytes.6 R788 purchase Therefore, the purported evidence does not exclude a clinically relevant role of PNPLA3 genotype in determining the outcome of orthotopic liver transplantation for CHC, opposite to what has been suggested. Additional, adequately powered studies with systematic evaluation of steatosis, viral features, and both donor and recipient PNPLA3 genotype are required to clarify this issue. Indeed, such a study would be of utmost importance for the following reasons: (1) it would clarify the cell type (hepatocytes versus adipocytes, or both) whose metabolic function is deranged due to PNPLA3 variants,

which has not been possible in mouse studies due to different expression medchemexpress pattern and mechanism of regulation of this gene, with implications for the design of new therapies, and (2) it would possibly provide useful information for organ allocation. A cooperative effort is warranted to achieve these goals. Luca Valenti M.D.*, Silvia Fargion M.D.*, * Centro Malattie Metaboliche del Fegato, Department of Internal Medicine, Università degli Studi Fondazione Ca’ Granda IRCCS, Ospedale Maggiore Policlinico, Padiglione Granelli, Milan, Italy. “
“Transarterial radioembolization with yttrium-90 microspheres is one treatment option for inoperable hepatocellular carcinoma. We compared the survival in a cohort of patients receiving radioembolization or no radioembolization. The data of 46 patients referred for radioembolization was retrospectively reviewed. The patient, tumor characteristics, and the survival were compared in the two groups.

Second, the potential interactive buy BAY 73-4506 effects of known hepatitis B viral factors on the development of HCC are not incorporated into this model. In a prospective study, Yu et al. provide strong evidence that male patients with both HBV genotype C and very high HBV viral loads had a 26-fold higher risk of HCC than those with other genotypes and low or undetectable viral loads.[72] Our case–control studies also revealed

that BCP A1762T/G1764A mutation combined with high viral load was independently associated with the risk of HCC, irrespective of the presence of cirrhosis.[22, 23] In addition, combination of mutations of pre-S, precore, and BCP regions, rather than single mutation, was significantly associated with the development of progressive liver diseases and HCC.[33, 37, 73] Furthermore, the relationships between HCC risk and dynamic changes of serum HBV-DNA, HBsAg, and ALT levels were determined in the ERADICATE-B study. Compared with patients with persistently low levels of HBV-DNA, HBsAg, or ALT, those with persistently high levels of these three factors were at a higher risk of HCC.[64] Therefore, it is essential to incorporate qualitative and

quantitative hepatitis B viral factors in risk calculation model to make it more comprehensive and to be clinically http://www.selleckchem.com/products/iwr-1-endo.html useful in various forms of chronic liver disease, including inactive carrier state, chronic hepatitis, and cirrhosis (Fig. 3). Over the past decade, extensive research on HBV has identified several hepatitis B viral factors

such as serum HBsAg level, viral load, genotype, and mutants as powerful contributors to disease progression of CHB patients. According to several population and hospital-based cohort studies, risk stratification for HCC in patients with chronic HBV infection has been established in a preliminary manner. Low risk factors for HBV-related HCC include female gender, younger age (≦ 50 years old), HBV genotype A/B, and low serum levels of ALT, HBV-DNA, and HBsAg. In contrast, high risk factors for HBV-related HCC include male gender, advanced age (> 50 years 上海皓元 old), HBV genotype C/D, BCP A1762T/G1764A mutations, pre-S deletion mutations, and high serum levels of ALT, HBV-DNA, and HBsAg. Among them, the modifiable risk factors are serum levels of ALT, HBV-DNA, and HBsAg. In the future, multivariate risk assessment profiles for HCC should be integrated with current HBV treatment guidelines to enable practicing physicians to have better management of HBV carriers with different HCC risks. Finally, risk modification through antiviral therapy may lead to the prevention of disease progression and eventually reduce the risk of HCC development even among those who start treatment with substantial risk (Fig. 4).

In addition, when there is an excess

of 25(OH)D, 24-OHase in the kidneys can convert it to 24,25(OH)2D14 to prevent over-production of 1α,25(OH)2D. Of note, originally it was believed that 1α-OHase and 24-OHase exist exclusively in the kidneys, however, the two enzymes have been demonstrated in many extra-renal tissues.15–17 Given that anephric individuals had no detectable 1α,25(OH)2D in their circulation, it is believed that 1α,25(OH)2D generated in the extra-renal tissues acts and degrades only locally in an autocrine/paracrine fashion. This autocrine pathway seems to be regulated in a tissue-specific manner, which is not associated with systemic calcium homeostasis. Once 25(OH)D is internalized into the cells, the fate of 25(OH)D may depend on the relative expression levels of 24-OHase to 1α-OHase. In the cells with dominant expression of 1α-OHase, 25(OH)D will be converted Nutlin-3 mw to 1α,25(OH)2D to exert its non-calcemic functions. At the same time, the locally generated 1α,25(OH)2D will

upregulate the expression of 24-OHase within the cells to hydroxylate 1α,25(OH)2D and excess 25(OH)D to form 24-hydroxylated metabolites leading to their catabolism. On the other hand, in cells dominated with the expression of 24-OHase, the generated 1α,25(OH)2D will be degraded very quickly with little or no biological actions. The genomic action of 1α,25(OH)2D is mediated through its binding to vitamin D receptor (VDR) to modulate the expression of genes in a cell- and tissue-specific manner18 MCE公司 (Fig. 2). VDR is an endocrine member of the nuclear receptor superfamily.19 So far, there are 2776 VDR binding sites being identified selleckchem by a chip-sequencing method located within

229 vitamin-D-regulated genes.20 Since the initial identification of VDR in tissues not associated with the regulation of calcium and bone metabolism by Stumpf et al.21 in 1979, many non-calcemic actions of vitamin D have been described. At the present time, the 1α,25(OH)2D-induced antiproliferation, anti-inflammatory response, pro-differentiation, pro-apoptosis and immune regulation are well established and found to be tissue- and cell-specific.17,22 For example, at least 23 human cancer cell lines have been found to express VDR23–26 and 1α,25(OH)2D has been shown to exhibit growth inhibitory effect on those cells, including prostate, breast, lung, liver, and pancreatic cancer cells. Similar to other members of the nuclear receptor family, the liganded VDR requires further dimerization with retinoid X receptor (RXR) to form a heterodimer to bind to vitamin D response element (VDRE)27 located in the promoter region of vitamin D responsive genes to exert its genomic functions, including the inhibition of cancer cell growth and the prevention of cells from malignant transformation. The VDR-mediated gene expression is further modulated by a multiple of co-factors.

Of these patients, 149 participated in the associated LTFU study.12 The study was conducted in accordance with the guidelines of the Declaration of Helsinki and the principles of Good Clinical Practice. All patients gave written informed consent according to standards

of the local ethics committees. Serum HBsAg was quantified in samples taken at baseline, during the treatment period (weeks 4, 8, 12, 24, and 52) and during follow-up (week 78) using the ARCHITECT HBsAg assay (Abbott Laboratories; range 0.05-250 IU/mL).22 HBV DNA quantification for the initial study was performed with 4-week intervals using an in-house-developed TaqMan polymerase chain reaction assay (lower limit of quantification = 400 copies/mL) based on the EuroHep standard.23 For the LTFU Selleck INCB018424 study, HBV DNA was measured with the Cobas TaqMan HBV assay (Roche Molecular Systems, Branchburg, NJ), with a dynamic range of MG132 quantification of 174-6.4 × 108 copies/mL (30-1.1 × 108 IU/mL). It has previously been demonstrated that there is an excellent correlation between the two assays.12 HBeAg was assessed using enzyme immunoassay (AxSYM; Abbott Laboratories, Abbott Park, IL) or enzyme-linked immunosorbent assay (DiaSorin SpA, Saluggia, Italy). ALT was measured locally in accordance with standard procedures and is presented as multiples of the ULN. HBV genotype was assessed using the INNO-LiPA assay (Innogenetics). For the current study, a composite endpoint of HBeAg loss

and HBV DNA level <10,000 copies/mL was chosen for definition of response.24 Patients who were retreated after the initial study were considered nonresponders at LTFU. Associations between variables were tested using Student t test, chi-squared test, Pearson correlation, or their nonparametric equivalents when appropriate. The differences in HBsAg decline between treatment arms and (non)responders were analyzed using repeated measurement models with an unstructured covariance allowing heterogeneity across compared groups. Discrimination, or the ability of HBsAg concentration and decline at various time points to distinguish patients medchemexpress who will develop a response from those who will not, was quantified

by the area under the receiver-operating characteristic curve (AUC). Our aim was to use on-treatment HBsAg levels to identify a stopping rule that would enable a clinician to discontinue patients who had a very low chance of response as early as possible, while maintaining >90% of responders on treatment. The optimal cutoff in HBsAg decline was identified using a grid-search of possible cutoff points at weeks 4, 8, 12, and 24. For each cutoff point, the chi-squared test was calculated together with the sensitivity and the negative predictive value (NPV). The highest chi-squared test identified the optimal cutoff point.25 SPSS, version 15.0 (SPSS Inc., Chicago, IL) and the SAS 9.2 program (SAS Institute Inc., Cary, NC) were used to perform statistical analyses.

The pathogenetic substrate of these changes might include adaptive remodeling of neural circuits and secondary reactive gliosis in brain regions that undergo significant functional changes during

the migraine attacks. Although VBM holds the potential to yield valuable advances, the data it generates still have to be considered with caution. The method, although largely automated and applicable throughout the entire brain, requires large sample sizes to provide stable results and may lack consistency across studies.86 Its robustness is affected by the type and level of correction, modulation of data, adjustment for brain size, software version, and other parameters and analyses.87 Diffusion tensor imaging (DTI), a sensitive MRI technique based on water diffusion through brain

tissue, allows visualization of the orientation and anisotropy of white IWR 1 selleck chemicals llc and grey matter, and identifies microstructural damage that affects water diffusivity (such as degree of myelination, and density or orientation of axons). Patients with migraine with and without aura had reduced mean diffusivity peaks in apparently normal brain tissue compared with controls.88 DaSilva and collaborators89 showed that migraineurs displayed a thicker somatosensory cortex than controls, especially in the caudal part, where the trigeminal area, including head and face, is somatotopically represented. Of note, this study also concluded that migraineurs without aura had lower fractional anisotropy 上海皓元 in the ventrolateral PAG. A larger study, however,90 failed to identify

any alterations in the thickness of somatosensory, cingulated, and visual motion-processing cortices in migraineurs. A recent study aimed at finding microstructural alterations in the brain of migraine patients by means of diffusion-weighted imaging used a novel approach based on fine-tuned nonlinear registration and non-parametric permutation test in an alignment-invariant tract representation (Tract-Based Spatial Statistics).91 Investigators reported diminished fractional anisotropy in the right frontal white matter cluster of migraine patients. In the same region, increased mean diffusivity and increased radial diffusivity were noted. The probabilistic tractography revealed this cluster’s connection to other parts of the pain network (orbitofrontal cortex, insula, thalamus, dorsal midbrain). These findings point to potential maladaptive plastic changes or white matter disintegration in the brain of migraineurs. Functional and Metabolic Correlates.— Several reports noted that migraine sufferers show abnormalities in visual motion perception during and between attacks. High-resolution cortical thickness measurement and DTI of the visual motion-processing network found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared with HCs.92 Cortical thickness increases were accompanied by abnormalities of the subjacent white matter.