In addition to the potential mating behavior described above, there is evidence that calving may be occurring north off Isla de Chiloé. A mother with a young calf was recorded nearshore on 22 October 2010 at 41º27′S, 73º51′W, about 18

nmi north of Isla de Chiloé. The video was reviewed by southern right whale experts,12 who reported that the smaller whale had the typical head shape of a calf, and that its body length appeared to be less than half of its mother’s body length. Other features that indicated that the smaller whale was a young calf were the shape of its blow holes, its wide back and its typical following behavior shown by young calves. Based on these observations, they agreed this animal was a calf born in 2010, and was probably <3 mo old. This is the southernmost record of mother-calf pair for this population. A possible birth occurred in central Chile (33º34′S, 71º48′W) in 1991, based on the sudden appearance of a small PF-01367338 supplier calf with a female that was previously seen alone.3 Clarke (1965) also observed a female and calf pair off Cartagena (33º32′S, 71º37′W) in August 1964. Although the data are limited, one small area in southern Chile appears to be more utilized by right whales than previously thought. Sixteen sightings have been reported off Chile south of 40ºS, with six of them in a small area off northwestern

Isla de Chiloé and five of them south of Isla de Chiloé (Table 1). Isla de Chiloé is the northern limit of the Chilean fjord system and was a former whaling ground for southern Y-27632 right whales. Between 1830 and 1832, 91 British whaling vessels operated around Isla de Chiloé (Gay 1847). Today, fewer than 1,000 people live in the coastal area of northwestern Isla de Chiloé and only about 10% of

them are involved in marine activities such as fishing, making it significant that 6 (6%) of the 108 sightings off Chile and Peru since 1964 were in this small area. In addition, the fact that at least six different individuals 17-DMAG (Alvespimycin) HCl were recorded between 20 September and 21 October 2011 (Fig. 3), potential reproductive behavior has been observed, and the southernmost record of a female-calf pair was just 18 nmi north of Isla de Chiloé, strongly suggest that northwestern Isla de Chiloé is an important area, although with as yet undetermined boundaries. Coastal and marine large-scale development projects may negatively impact these southern right whales, through habitat loss, marine degradation, or even direct mortality. Laist et al. (2001) suggested that right whales may be more vulnerable to ship strikes than other species because of their behavior, such as skim feeding, nursing, and mating, which occur at the surface. Mothers and calves may be the most vulnerable because they spend more time at or near the surface than other classes of right whales. Further, North Atlantic right whales did not respond to the playback of ship sounds (Nowacek et al.

e., inflammation see more and ductular reaction,

unpublished observations), the data clearly reveal a direct action of OPN on Collagen-I protein expression, a key event in liver fibrosis. Hence, OPN appears to induce scarring per se. This is, indeed, also supported by the finding that though ALT activity and the necrosis and inflammation scores were similar, there was increased portal, bridging and sinusoidal fibrosis, along with enhanced width of the collagenous septa in CCl4-injected OpnHEP Tg mice, compared to their WT littermates. Notably, OpnHEP Tg mice developed spontaneous fibrosis over time, whereas WT mice did not. Last, in line with the results using OpnHEP Tg mice and the in vitro data, fibrilar Collagen-I content and scar thickness was significantly lowered by OPN ablation in vivo. It is likely that secreted OPN allows paracrine signaling to HSCs, whereas endogenous OPN expression Small molecule library solubility dmso in HSCs signals in an autocrine fashion, amplifying fibrogenic response. The cell- and matrix-binding ability of OPN may also facilitate a proper stromal and fibrillar collagen network

organization. Overall, it is reasonable to propose that OPN may drive the fibrogenic response, among others, by directly regulating Collagen-I deposition. Thus, OPN emerges as a key soluble cytokine and ECM-bound molecule promoting liver fibrosis. The authors are very grateful to the following investigators: David T. Denhardt (Rutgers University, Newark, NJ) for his generous gift of the 2A1 Ab and for the Opn−/− mice in 129sv background; Satoshi Mochida (Saitama Medical University, Saitama, Japan) for providing the OpnHEP Tg mice; Andrea D. Branch (Mount Sinai School of Medicine, New York, NY) for donating the human liver protein lysates; Toshimitsu Uede (Hokkaido University, Sapporo, Japan) for the Ad-OPN and Ad-LacZ; John Engelhardt (University of Iowa, Iowa City, IA) for the recombinant Ad expressing the NFκB-Luc reporter; and Feng Hong (Mount Sinai School of Medicine) for supplying the primary human HSC isolated from normal liver margin of patients undergoing hepatic tumor resection. The authors are also very thankful to all former

and current members from the Nieto Laboratory 17-DMAG (Alvespimycin) HCl for their helpful comments and suggestions throughout this project as well as for their critical review of the manuscript for this article. Special thanks go to Marcos Rojkind, Arthur I. Cederbaum and David T. Denhardt for their constant support and for their very helpful insight throughout the course of this project. Additional Supporting Information could be found in the online version of this article. “
“Pancreatic cancer is one of the major causes of cancer death. Most patients present with advanced disease and only 10–15% of patients can undergo resection. There are numerous molecular alterations that are involved in the pathogenesis of pancreatic cancer, and there are precursor lesions that progress to invasive cancer.

5% glutaraldehyde solution buffered at pH Ganetespib concentration 7.4 with 0.1 M Millonig’s phosphate, postfixed in 1% osmium tetroxide solution at 4°C for 1 hour, dehydrated in graded concentrations of ethanol, and embedded in Quetol 812 epoxy resin (Nisshin EM, Tokyo, Japan). Ultrathin sections (80 nm) cut on ultramicrotome were stained with uranyl acetate and lead citrate and examined with an H-7650 electron microscope (Hitachi

Ltd., Tokyo, Japan) at 80 kV. Data are presented as the mean ± SE. Differences between two groups were determined using the Mann-Whitney U test for unpaired observations. The survival curves were estimated using the Kaplan-Meier method and were tested by way of log-rank test. P < 0.05 was considered statistically significant. First, to examine the significance of Bak in hepatocellular apoptosis induced by Fas stimulation, Bak KO mice (bak−/−) and wild-type (WT) littermates (bak+/+) were intraperitoneally injected with 1.5 mg/kg Jo2 anti-Fas antibody and analyzed 3 hours later. Consistent with previous

reports,10, 19 WT mice showed severe elevation of serum ALT levels with massive hepatocellular apoptosis (Fig. 1A,B). Bak KO mice also developed liver injury, but the levels of serum ALT and the number of TUNEL-positive hepatocytes were significantly lower in Bak KO mice than in WT mice (Fig. 1A-C). Western blotting for cleaved caspase-3, caspase-7, and PARP revealed that activation of effector caspases were partially inhibited in KO livers compared with NVP-BKM120 purchase WT livers (Fig. 1D). Cleavage of procaspase-9, which Edoxaban is initiated by mitochondrial release of cytochrome c, was also suppressed in Bak KO livers compared with WT liver (Fig. 1D). The cleaved form of caspase-8, a direct downstream target of Fas activation, was detected in both mice, but its levels were reduced in Bak KO mice compared with WT mice (Fig. 1D). This reduction may be explained by the lesser activation of caspase-3/7, because it has been reported that caspase-3/7 could activate caspase-8 through an amplification loop during apoptosis.20 Collectively, these findings demonstrated that Bak deficiency partially ameliorated Fas-induced hepatocellular apoptosis associated with reduced

cleavage of caspase-9, caspase-3/7, and PARP. We then compared survival of mice after Jo2 injection but found that Bak KO mice also rapidly died with kinetics similar to those of WT mice, suggesting that partial amelioration of hepatocellular apoptosis induced by Bak deficiency did not lead to survival benefit under our experimental conditions (Fig. 1E). Because Bax residing in the cytosol moves to the mitochondria upon activation, where it undergoes oligomerization,21 we analyzed its translocation and oligomerization in the liver at 3 hours after Jo2 injection. Western blot analysis revealed that the levels of Bax expression clearly increased in the mitochondrial fraction in both WT livers and Bak KO livers (Fig. 1F). Signals for the Bax dimer were also detected in both livers (Fig. 1F).

5% glutaraldehyde solution buffered at pH buy AZD1208 7.4 with 0.1 M Millonig’s phosphate, postfixed in 1% osmium tetroxide solution at 4°C for 1 hour, dehydrated in graded concentrations of ethanol, and embedded in Quetol 812 epoxy resin (Nisshin EM, Tokyo, Japan). Ultrathin sections (80 nm) cut on ultramicrotome were stained with uranyl acetate and lead citrate and examined with an H-7650 electron microscope (Hitachi

Ltd., Tokyo, Japan) at 80 kV. Data are presented as the mean ± SE. Differences between two groups were determined using the Mann-Whitney U test for unpaired observations. The survival curves were estimated using the Kaplan-Meier method and were tested by way of log-rank test. P < 0.05 was considered statistically significant. First, to examine the significance of Bak in hepatocellular apoptosis induced by Fas stimulation, Bak KO mice (bak−/−) and wild-type (WT) littermates (bak+/+) were intraperitoneally injected with 1.5 mg/kg Jo2 anti-Fas antibody and analyzed 3 hours later. Consistent with previous

reports,10, 19 WT mice showed severe elevation of serum ALT levels with massive hepatocellular apoptosis (Fig. 1A,B). Bak KO mice also developed liver injury, but the levels of serum ALT and the number of TUNEL-positive hepatocytes were significantly lower in Bak KO mice than in WT mice (Fig. 1A-C). Western blotting for cleaved caspase-3, caspase-7, and PARP revealed that activation of effector caspases were partially inhibited in KO livers compared with XL765 purchase WT livers (Fig. 1D). Cleavage of procaspase-9, which Adenosine triphosphate is initiated by mitochondrial release of cytochrome c, was also suppressed in Bak KO livers compared with WT liver (Fig. 1D). The cleaved form of caspase-8, a direct downstream target of Fas activation, was detected in both mice, but its levels were reduced in Bak KO mice compared with WT mice (Fig. 1D). This reduction may be explained by the lesser activation of caspase-3/7, because it has been reported that caspase-3/7 could activate caspase-8 through an amplification loop during apoptosis.20 Collectively, these findings demonstrated that Bak deficiency partially ameliorated Fas-induced hepatocellular apoptosis associated with reduced

cleavage of caspase-9, caspase-3/7, and PARP. We then compared survival of mice after Jo2 injection but found that Bak KO mice also rapidly died with kinetics similar to those of WT mice, suggesting that partial amelioration of hepatocellular apoptosis induced by Bak deficiency did not lead to survival benefit under our experimental conditions (Fig. 1E). Because Bax residing in the cytosol moves to the mitochondria upon activation, where it undergoes oligomerization,21 we analyzed its translocation and oligomerization in the liver at 3 hours after Jo2 injection. Western blot analysis revealed that the levels of Bax expression clearly increased in the mitochondrial fraction in both WT livers and Bak KO livers (Fig. 1F). Signals for the Bax dimer were also detected in both livers (Fig. 1F).

This discovery complements growing evidence that Hh signaling guides repair of chronically injured livers, and it suggests that common mechanisms mediate fetal liver development and repair of adult liver injury. Therefore, progress in delineating how Hh-responsive mechanisms regulate liver growth and CDK inhibitor development might help to unravel conserved mechanisms that control regeneration

of injured livers in adults. Such knowledge has important implications for patients with various types of acute and chronic liver damage. The authors thank Dr. Xiaoling Wang (Gastroenterology, Duke University) and Dr. Gregory Michelotti (Anesthesiology, Duke University) for technical assistance, and Dr. Jiawen Huang (Gastroenterology, Duke University) for animal care assistance. The authors thank W. C. Stone (Gastroenterology, Duke University) for his administrative support

to this work. Additional Supporting Information may be Selleckchem CAL101 found in the online version of this article. “
“The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. Selleckchem Lumacaftor Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial

autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment. Conclusion: These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (HEPATOLOGY 2012) Primary biliary cirrhosis (PBC) is a female-predominant, organ-specific autoimmune disease characterized by nonsuppurative destructive cholangitis of the intrahepatic bile ducts.

This discovery complements growing evidence that Hh signaling guides repair of chronically injured livers, and it suggests that common mechanisms mediate fetal liver development and repair of adult liver injury. Therefore, progress in delineating how Hh-responsive mechanisms regulate liver growth and Rucaparib price development might help to unravel conserved mechanisms that control regeneration

of injured livers in adults. Such knowledge has important implications for patients with various types of acute and chronic liver damage. The authors thank Dr. Xiaoling Wang (Gastroenterology, Duke University) and Dr. Gregory Michelotti (Anesthesiology, Duke University) for technical assistance, and Dr. Jiawen Huang (Gastroenterology, Duke University) for animal care assistance. The authors thank W. C. Stone (Gastroenterology, Duke University) for his administrative support

to this work. Additional Supporting Information may be BTK activity found in the online version of this article. “
“The aim of this study was to determine the safety and potential efficacy of B-cell depletion with the anti-CD20 monoclonal antibody rituximab in patients with primary biliary cirrhosis (PBC) and an incomplete response to ursodeoxycholic acid (UDCA). This open-label study enrolled six patients with PBC and incomplete responses to UDCA to be treated with 2 doses of 1000 mg rituximab separated by 2 weeks and followed for 52 weeks. The primary endpoints were safety and changes in B-cell function. mafosfamide Two patients received only 1 dose of rituximab, one due to activation of latent varicella and the other due to a viral upper respiratory infection. Serum levels of total IgG, IgM, and IgA as well as anti-mitochondrial

autoantibodies (AMAs) IgA and IgM decreased significantly from baseline by 16 weeks and returned to baseline levels by 36 weeks. Stimulation of B cells with CpG produced significantly less IgM at 52 weeks after treatment compared with B cells at baseline. In addition, transient decreases in memory B-cell and T-cell frequencies and an increase in CD25high CD4+ T cells were observed after treatment. These changes were associated with significant increases in mRNA levels of FoxP3 and transforming growth factor-β (TGF-β) and a decrease in tumor necrosis factor-α (TNF-α) in CD4+ T cells. Notably, serum alkaline phosphatase levels were significantly reduced up to 36 weeks following rituximab treatment. Conclusion: These data suggest that depletion of B cells influences the induction, maintenance, and activation of both B and T cells and provides a potential mechanism for treatment of patients with PBC with an incomplete response to UDCA. (HEPATOLOGY 2012) Primary biliary cirrhosis (PBC) is a female-predominant, organ-specific autoimmune disease characterized by nonsuppurative destructive cholangitis of the intrahepatic bile ducts.

Different from the study by Mederacke et al., where the authors did not observe any increase in LS values in patients with baseline values over 10 kPa, a cutoff value that allows predicting significant or advanced fibrosis but not cirrhosis,3 the 5-Fluoracil results of the present investigation clearly indicate that LS values increase after a standardized meal in patients with chronic HCV infection at any stage of fibrotic evolution and in patients with compensated cirrhosis. The increase in LS, with return to baseline values within 120 minutes, is not just related to the rapid assumption

of the liquid volume but rather associated with the overall caloric intake of the meal. The meal test with postmeal portal blood flow (PBF) measurements has been suggested as a reproducible

noninvasive test to evaluate the severity of portal hypertension in cirrhosis patients. The effect of postprandial hyperemia on portal pressure has been reported 30 minutes after the onset of the meal both by direct measurement18 and by Doppler sonography19 in cirrhosis patients. Data in normal subjects and in noncirrhosis patients with CLD are SCH727965 solubility dmso scarce and obtained only by Doppler sonography,20-22 but indicate that an increase in PBF is detectable by Doppler sonography also 30 minutes after the onset of the meal. Changes in LS values following a test meal are likely a consequence of the adaptation of the hepatic microcirculation to an increased PBF8, 9 and are in overall agreement with the

observation that postprandial hyperemia is associated with a greater increase in portal pressure in cirrhosis patients. In this context, the progressive increase in postmeal delta LS values along with the fibrotic evolution of chronic HCV hepatitis could represent an indirect index of the progressive impairment of the mechanisms responsible for this adaptation, particularly sinusoidal clonidine circulation autoregulation, as a consequence of tissue fibrosis, inflammatory infiltration, and neoangiogenesis.23-25 Overall, these findings highlight an interesting potential of TE in detecting dynamic changes in LS related to both the anatomical modifications and hemodynamic alterations occurring in the progression of chronic HCV hepatitis. Accordingly, we tested whether or not the delta stiffness increase in postmeal LS values had advantages, when compared with premeal baseline LS values, in assessing the probability of liver fibrosis according to the Metavir staging system. While premeal baseline LS values were rather accurate in defining the probability of fibrosis stage and in agreement with previous observations by our group in a completely different cohort of patients with HCV-induced CLD,3 an analysis of the performance of the postmeal delta stiffness increase revealed that changes in LS values occurring after the meal test do not offer any advantage in the detection of different stages of fibrosis, whose definition becomes actually less accurate.

6, 18 We also found that TGFβ played a major role in the HCV-induced

elevation of Nox4 in hepatocytes, although other factors might also be involved (Fig. 8; unpublished findings, Wang, Ito, and Choi, 2010). Some of these findings were corroborated by a recent study by Boudreau et al.21 Importantly, hepatocellular carcinoma, associated with chronic hepatitis C, is typically preceded by cirrhosis. Therefore, hepatocyte Nox protein(s) may provide a link between inflammation, fibrogenesis, and hepatocarcinogenesis during chronic hepatitis C. In particular, nuclear Nox4 is likely Selleckchem p38 MAPK inhibitor to be highly significant in the HCV-induced DNA damage in the initiation of cancer as well as reversible and/or irreversible protein modifications in the modulation of cell signaling and host gene expression. The ability to regulate Nox proteins also makes them potential targets for therapy. Therefore, our study provides new insights into

a possible mechanism of HCV-induced pathogenesis and points to potential targets for therapy directed at the source of ROS. The authors thank Takaji Wakita for JFH1 constructs, Mark Zern for telomerase-reconstituted primary human hepatocytes, Balaraman Kalyanaraman for the 2-OH-E+ standard, and Henry Jay Forman for Daporinad cost the HPLC systems and discussion. They also thank Muhammad Sheikh, Michael David, Matthew Meyer, David Ojcius, Rui-Ming Liu, and the late T. S. Benedict Yen for discussion and Anna Nandipati, Simrita Kaur (McNair Scholars Program), Sam Chung, and Armand McGee (Basic and Advanced Science and Technology Academies of Research program) for technical

assistance. Additional Supporting Information may be found in the online version of this article. “
“Chronic infection with the human hepatitis B virus (HBV) is a global health problem and a main cause of progressive liver diseases. HBV exhibits a narrow host range, replicating primarily in hepatocytes. Both host and hepatocyte specificity presumably involve specific receptor interactions on the target cell; however, direct evidence for this hypothesis is missing. Following the observation that HBV entry is specifically blocked by L-protein-derived preS1-lipopeptides, we visualized specific HBV receptor/ligand complexes on hepatic Venetoclax cells and quantified the turnover kinetics. Using fluorescein isothiocyanate-labeled, myristoylated HBV preS1-peptides we demonstrate (1) the presence of a highly specific HBV receptor on the plasma membrane of HBV-susceptible primary human and tupaia hepatocytes and HepaRG cells but also on hepatocytes from the nonsusceptible species mouse, rat, rabbit and dog; (2) the requirement of a differentiated state of the hepatocyte for specific preS1-binding; (3) the lack of detectable amounts of the receptor on HepG2 and HuH7 cells; (4) a slow receptor turnover at the hepatocyte membrane; and (5) an association of the receptor with actin microfilaments.

6, 18 We also found that TGFβ played a major role in the HCV-induced

elevation of Nox4 in hepatocytes, although other factors might also be involved (Fig. 8; unpublished findings, Wang, Ito, and Choi, 2010). Some of these findings were corroborated by a recent study by Boudreau et al.21 Importantly, hepatocellular carcinoma, associated with chronic hepatitis C, is typically preceded by cirrhosis. Therefore, hepatocyte Nox protein(s) may provide a link between inflammation, fibrogenesis, and hepatocarcinogenesis during chronic hepatitis C. In particular, nuclear Nox4 is likely buy Vismodegib to be highly significant in the HCV-induced DNA damage in the initiation of cancer as well as reversible and/or irreversible protein modifications in the modulation of cell signaling and host gene expression. The ability to regulate Nox proteins also makes them potential targets for therapy. Therefore, our study provides new insights into

a possible mechanism of HCV-induced pathogenesis and points to potential targets for therapy directed at the source of ROS. The authors thank Takaji Wakita for JFH1 constructs, Mark Zern for telomerase-reconstituted primary human hepatocytes, Balaraman Kalyanaraman for the 2-OH-E+ standard, and Henry Jay Forman for selleck chemicals llc the HPLC systems and discussion. They also thank Muhammad Sheikh, Michael David, Matthew Meyer, David Ojcius, Rui-Ming Liu, and the late T. S. Benedict Yen for discussion and Anna Nandipati, Simrita Kaur (McNair Scholars Program), Sam Chung, and Armand McGee (Basic and Advanced Science and Technology Academies of Research program) for technical

assistance. Additional Supporting Information may be found in the online version of this article. “
“Chronic infection with the human hepatitis B virus (HBV) is a global health problem and a main cause of progressive liver diseases. HBV exhibits a narrow host range, replicating primarily in hepatocytes. Both host and hepatocyte specificity presumably involve specific receptor interactions on the target cell; however, direct evidence for this hypothesis is missing. Following the observation that HBV entry is specifically blocked by L-protein-derived preS1-lipopeptides, we visualized specific HBV receptor/ligand complexes on hepatic LY294002 cells and quantified the turnover kinetics. Using fluorescein isothiocyanate-labeled, myristoylated HBV preS1-peptides we demonstrate (1) the presence of a highly specific HBV receptor on the plasma membrane of HBV-susceptible primary human and tupaia hepatocytes and HepaRG cells but also on hepatocytes from the nonsusceptible species mouse, rat, rabbit and dog; (2) the requirement of a differentiated state of the hepatocyte for specific preS1-binding; (3) the lack of detectable amounts of the receptor on HepG2 and HuH7 cells; (4) a slow receptor turnover at the hepatocyte membrane; and (5) an association of the receptor with actin microfilaments.

Methods.— Cross-sectional data were collected from respondents in 10 countries via a Web-based survey. Respondents were classified as chronic migraine Palbociclib chemical structure (≥15 headache days/month) or episodic migraine (<15 headache days/month). Data collection included socio-demographic and clinical characteristics and medical resource use for headache (clinician and emergency department visits and hospitalizations over the preceding 3 months and medications over the preceding 4 weeks). Unit cost data were collected outside of the Web-based survey using publicly available sources and then applied to resource use profiles. Cost estimates are presented in 2010 US and Canadian

dollars. Results.— In this manuscript, the analysis included data from respondents with migraine in the USA (N = 1204) and Canada (N = 681). The most common medical services utilized by all respondents included headache-specific medication, healthcare provider visits, emergency department visits, and diagnostic testing. In the USA, approximately one-quarter (26.2%) of chronic migraine participants vs 13.9% of episodic migraine participants reported visiting a primary care physician in the preceding 3 months (P < .001). In Canada, one-half (48.2%) of chronic migraine participants had a primary

care physician visit, compared with 12.3% of episodic migraine subjects Selleckchem PF 01367338 (P < .0001). Total mean headache-related costs for participants with chronic migraine in the USA were $1036 (±$1334) over 3 months compared

to $383 (±807, P < .001) for persons with episodic migraine. In Canada, total Selleckchem Ixazomib mean headache-related costs among chronic migraine subjects were $471 (±1022) compared to $172 (±920, P < .001) for episodic migraine subjects. Conclusions.— Chronic migraine was associated with higher medical resource use and total costs compared to episodic migraine. Therapies that reduce headache frequency could become important approaches for containing or reducing headache-related medical costs. "
“(Headache 2011;51:544-553) Background.— Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine-like attacks in FHM patients without known mutations is unknown. Objective.— In the present study we therefore examined the migraine-inducing effect of CGRP in FHM patients without known mutations and healthy controls. Methods and design.— Eleven patients suffering from FHM without known mutations and 11 controls received an intravenous infusion of 1.5 µg/minute CGRP over 20 minutes. The study design was a balanced and controlled provocation study.