Thus, patients with continuous headache were excluded. Patients were also excluded if they had used any headache prophylactic medication within 4 weeks prior to start of baseline, or had previous exposure to any

botulinum toxin serotype or a positive urine pregnancy test. Randomization, Stratification, and Study Treatment.— The recruitment period was between January 2006 and July 2007, with a 56-week follow-up period after the last patient was enrolled. Eligible patients were randomized (1:1) in double-blind fashion to onabotulinumtoxinA or placebo. Randomization, which has been previously described,32,33 Midostaurin clinical trial was stratified in blocks of 4 for each investigator site and by whether or not patients were overusing acute headache pain medication (yes/no) during the 28-day baseline according to protocol-defined frequency of use. Investigators were trained not to enroll patients who frequently used opioids as their acute headache pain medication. OnabotulinumtoxinA 155 U or placebo was administered as 31 fixed-site, fixed-dose injections across 7 specific head/neck muscle areas. At the investigator’s discretion, an additional 40 U could be administered using a “follow-the-pain” strategy. The maximum dose was 195 U across 39 sites. Dosing and results of this study are specific

to the formulation of onabotulinumtoxinA manufactured by Allergan, Inc. Efficacy and Safety Measures.— For the pooled analyses, the primary efficacy endpoint was mean change from baseline in frequency of headache days for the 28-day period ending with week 24.

Secondary efficacy buy Vemurafenib variables evaluated in the pooled analyses included: frequency of migraine days, frequency of moderate/severe headache days, number of cumulative hours of headache on headache days, proportion of patients with severe (≥60 points) Headache Impact Test (HIT)-6 score,34 frequency of headache episodes, frequency of migraine episodes, and frequency of acute headache pain medication intakes (all categories; referred to hereafter as acute pain medication intakes). Other efficacy analyses included the incidence of patients with a 50% or more decrease from baseline in the frequency of headache days and, separately, headache selleck inhibitor episodes. Additional assessments of disability, functioning, and HRQoL (eg, mean changes in total HIT-6; Migraine-Specific Quality of Life questionnaire [MSQ v2.1]35,36 evaluations) are also reported. All efficacy analyses primarily examined the mean change from baseline for the 28-day period ending with week 24. All efficacy analyses were also analyzed for the medication overuse stratum. These results will be reported elsewhere. Statistical Analysis.— The pooled population sample provided >90% power to detect ≥1.75 between-group difference in mean change from baseline of the primary endpoint (headache days), using a 2-sided alpha = 0.05. The pooled population also had greater power than the individual studies32,33 to identify any safety and tolerability findings.

24–26 Granulocyte colony stimulating factor exerts potent immunomodulatory

effects, enhancing the generation of regulatory T cells27 and tolerogenic dendritic cells.28 Furthermore, it has recently been demonstrated that G-CSF therapy reduces inflammation in Crohn’s disease patients.29 Selleck Gefitinib This suggests that G-CSF given to HCV patients to counteract IFN-induced neutropenia may also have undesired effects on the antiviral immune response by enhancing the generation of tolerogenic DC and regulatory T cells. Stimulating G-CSF production in the context of activating the innate immune system as a whole by the use of TLR agonists may counteract IFN-induced neutropenia while also enhancing the anti-viral response. In GSK1120212 in vivo the present study, we show for the first time that TLR-7/8 signaling induces significant G-CSF production by human PBMCs and purified monocytes in the presence

of IFN-α (Fig. 3). Furthermore, PBMCs obtained from patients undergoing IFN-α therapy, that were stimulated in vitro with CL097 produced significant amounts of G-CSF (Fig. 4). PBMCs stimulated with CL097 in the presence of IFN-α also secreted granulocyte macrophage colony stimulating factor (GM-CSF) (data not shown). GM-CSF is a hematopoietic growth factor that has potent adjuvant properties,30 therefore the use of TLR7/8 agonists will have effects that go beyond the induction of G-CSF, possibly enhancing the efficacy of IFN/ribavirin treatment. Human monocytes express high levels of TLR8.31 In addition, IFN-treated dendritic cells have been demonstrated to respond efficiently to TLR7 stimulation.32 TLR7/8 agonists have previously demonstrated potential as anti-viral therapeutics.33–35 Therefore the use of TLR7/8 agonists during IFN-therapy may not only enhance the production of hematopoietic growth factors counteracting IFN-induced

this website neutropenia, but also have beneficial effects on the anti-viral response by acting on monocytes and dendritic cells. In summary, we have shown that IFN-α has a suppressive effect on G-CSF production by PBMCs, this may contribute to the development of IFN-α-induced neutropenia. Furthermore, stimulation of PBMCs and monocytes with the TLR7/8 agonist CL097 induced both G-CSF and GM-CSF secretion even in the presence of IFN-α suggesting that this and other related compounds may be used to counteract IFN-induced neutropenia. The authors thank Carol McNulty, Sheila O’Toole, Aileen Murphy and Anne Grogan for their help in patient recruitment and sample collection; Catherine Keogh and Tatiana Dempsey for technical assistance and database management. This study was funded by the Irish Health Research Board. The Authors have no conflict of interest to declare. “
“A fatty liver, which is a common feature in insulin-resistant states, can lead to chronic liver disease.

24–26 Granulocyte colony stimulating factor exerts potent immunomodulatory

effects, enhancing the generation of regulatory T cells27 and tolerogenic dendritic cells.28 Furthermore, it has recently been demonstrated that G-CSF therapy reduces inflammation in Crohn’s disease patients.29 MG 132 This suggests that G-CSF given to HCV patients to counteract IFN-induced neutropenia may also have undesired effects on the antiviral immune response by enhancing the generation of tolerogenic DC and regulatory T cells. Stimulating G-CSF production in the context of activating the innate immune system as a whole by the use of TLR agonists may counteract IFN-induced neutropenia while also enhancing the anti-viral response. In SB203580 ic50 the present study, we show for the first time that TLR-7/8 signaling induces significant G-CSF production by human PBMCs and purified monocytes in the presence

of IFN-α (Fig. 3). Furthermore, PBMCs obtained from patients undergoing IFN-α therapy, that were stimulated in vitro with CL097 produced significant amounts of G-CSF (Fig. 4). PBMCs stimulated with CL097 in the presence of IFN-α also secreted granulocyte macrophage colony stimulating factor (GM-CSF) (data not shown). GM-CSF is a hematopoietic growth factor that has potent adjuvant properties,30 therefore the use of TLR7/8 agonists will have effects that go beyond the induction of G-CSF, possibly enhancing the efficacy of IFN/ribavirin treatment. Human monocytes express high levels of TLR8.31 In addition, IFN-treated dendritic cells have been demonstrated to respond efficiently to TLR7 stimulation.32 TLR7/8 agonists have previously demonstrated potential as anti-viral therapeutics.33–35 Therefore the use of TLR7/8 agonists during IFN-therapy may not only enhance the production of hematopoietic growth factors counteracting IFN-induced

this website neutropenia, but also have beneficial effects on the anti-viral response by acting on monocytes and dendritic cells. In summary, we have shown that IFN-α has a suppressive effect on G-CSF production by PBMCs, this may contribute to the development of IFN-α-induced neutropenia. Furthermore, stimulation of PBMCs and monocytes with the TLR7/8 agonist CL097 induced both G-CSF and GM-CSF secretion even in the presence of IFN-α suggesting that this and other related compounds may be used to counteract IFN-induced neutropenia. The authors thank Carol McNulty, Sheila O’Toole, Aileen Murphy and Anne Grogan for their help in patient recruitment and sample collection; Catherine Keogh and Tatiana Dempsey for technical assistance and database management. This study was funded by the Irish Health Research Board. The Authors have no conflict of interest to declare. “
“A fatty liver, which is a common feature in insulin-resistant states, can lead to chronic liver disease.

Disclosures: Shirish Barve – Speaking and Teaching: Abbott Craig J. McClain – Consulting: Vertex, Gilead, Baxter, CP 673451 Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing

to disclose: Qifa Xie, Mohammad K. Mohammad, Matthew C. Cave Alcoholic hepatitis (AH) is one of the most deadly liver diseases. AH often occurs in patients who have a background of chronic drinking and a history of recent excessive drinking. The development of new therapies is hampered by lack of an animal model. We have recently developed 10-day chronic plus single binge model, which induces significantly elevation of serum ALT but mild steatosis and inflammation in C57BL/6J female mice (Bertola et al, Nature Protein Tyrosine Kinase inhibitor Protocols 2013). By using various combinations of long-term plus one or multiple binges of ethanol feeding, we identified that 8- to 12-week chronic plus single binge induced the most severe form of alcoholic steatohepatitis among the several other combinations. This model induced histological changes similar to AH in humans, which include severe steatosis with ∼10-fold increase in liver triglyc-eride, significant infiltration of neutrophils evidenced by MPO staining, significant elevation of serum ALT (∼230 U/L) and AST

(AST/ALT>2), remarkable increase of TUNEL positive liver cells, and learn more mild fibrosis identified by MASSON staining and increased expression of collagen genes (eg. Col1a1, col3a1, col4a2, col5a2, col12a 1). We next assessed whether this new model reproduces the changes in the hepatic transcriptome recently described in patients with AH (Affo et al, Gut 2013). Microarray and qPCR analyses revealed a marked up-regula-tion of key pro-inflammatory and pro-apoptotic genes (eg. Fn14, TRAIL-R2, CD137, TNFR1, TNFR2, DR6, CXCL1, CXCL2, CXCL4, LCN2, et al.), which were also found overexpressed in the livers from patients with AH. In conclusion, this novel model closely simulates

the histological and molecular features of human alcoholic hepatitis. Disclosures: Jim Lu – Employment: GoPath Pathology Associates, SC; Independent Contractor: GoPath Laboratories LLC; Management Position: GoPath Global LLC The following people have nothing to disclose: Ming-Jiang Xu, Yan Cai, Hua Wang, Adeline Bertola, Ramón Bataller, Bin Gao Background: Steatosis is the initial, most frequent hepatic manifestation that occurs in response to acute as well as chronic ethanol consumption. Alcohol-induced hepatic steatosis is no longer considered to be a benign state; it is now regarded as a significant risk factor for more progressive disease. Steatotic hepatocytes have increased sensitivity to injury produced by inflammatory cytokines, particularly TNF. Cyclic adenosine monophosphate (cAMP) plays a significant role in the regulation of both hepatic lipogenesis and fatty acid oxidation.

Disclosures: Shirish Barve – Speaking and Teaching: Abbott Craig J. McClain – Consulting: Vertex, Gilead, Baxter, Sotrastaurin in vivo Celgene, Nestle, Danisco, Abbott, Genentech; Grant/Research Support: Ocera, Merck, Glaxo SmithKline; Speaking and Teaching: Roche The following people have nothing

to disclose: Qifa Xie, Mohammad K. Mohammad, Matthew C. Cave Alcoholic hepatitis (AH) is one of the most deadly liver diseases. AH often occurs in patients who have a background of chronic drinking and a history of recent excessive drinking. The development of new therapies is hampered by lack of an animal model. We have recently developed 10-day chronic plus single binge model, which induces significantly elevation of serum ALT but mild steatosis and inflammation in C57BL/6J female mice (Bertola et al, Nature see more Protocols 2013). By using various combinations of long-term plus one or multiple binges of ethanol feeding, we identified that 8- to 12-week chronic plus single binge induced the most severe form of alcoholic steatohepatitis among the several other combinations. This model induced histological changes similar to AH in humans, which include severe steatosis with ∼10-fold increase in liver triglyc-eride, significant infiltration of neutrophils evidenced by MPO staining, significant elevation of serum ALT (∼230 U/L) and AST

(AST/ALT>2), remarkable increase of TUNEL positive liver cells, and selleck compound mild fibrosis identified by MASSON staining and increased expression of collagen genes (eg. Col1a1, col3a1, col4a2, col5a2, col12a 1). We next assessed whether this new model reproduces the changes in the hepatic transcriptome recently described in patients with AH (Affo et al, Gut 2013). Microarray and qPCR analyses revealed a marked up-regula-tion of key pro-inflammatory and pro-apoptotic genes (eg. Fn14, TRAIL-R2, CD137, TNFR1, TNFR2, DR6, CXCL1, CXCL2, CXCL4, LCN2, et al.), which were also found overexpressed in the livers from patients with AH. In conclusion, this novel model closely simulates

the histological and molecular features of human alcoholic hepatitis. Disclosures: Jim Lu – Employment: GoPath Pathology Associates, SC; Independent Contractor: GoPath Laboratories LLC; Management Position: GoPath Global LLC The following people have nothing to disclose: Ming-Jiang Xu, Yan Cai, Hua Wang, Adeline Bertola, Ramón Bataller, Bin Gao Background: Steatosis is the initial, most frequent hepatic manifestation that occurs in response to acute as well as chronic ethanol consumption. Alcohol-induced hepatic steatosis is no longer considered to be a benign state; it is now regarded as a significant risk factor for more progressive disease. Steatotic hepatocytes have increased sensitivity to injury produced by inflammatory cytokines, particularly TNF. Cyclic adenosine monophosphate (cAMP) plays a significant role in the regulation of both hepatic lipogenesis and fatty acid oxidation.

Examination of C/EBPβ and HDAC1 revealed that C/EBPβ and HDAC1 were increased in the livers of Little mice (Fig. 7D). We found that the amounts of C/EBPβ-HDAC1 complexes are higher in Little mice and that these complexes occupy and repress the gankyrin promoter in Little mice treated with DEN (Fig. 7E). Gankyrin is a protein that is activated in liver cancer and causes degradation or elimination of activities of five tumor suppressor proteins; Rb, p53, C/EBPα, HNF4α,

and p16.1, selleck 5-7, 22 This places gankyrin in a unique position to be a target for therapeutic approaches in the prevention of liver cancer. In this study, we elucidated the mechanisms of activation of gankyrin during the development of liver cancer. Four lines of evidence show that development of liver cancer involves the reduction of FXR and subsequent activation of gankyrin. First, DEN-mediated carcinogenesis in WT mice reduces FXR, leading to the reduction of HDAC1-C/EBPβ complexes and activation of the gankyrin promoter. Second, the deletion of FXR signaling in

FXR/SHP selleck chemicals llc KO mice activates gankyrin in the liver, leading to development of liver cancer. Third, high levels of FXR in Little mice prevent development of age-associated liver cancer and development of cancer under DEN protocol. Fourth, levels of FXR are reduced in spontaneously developed mouse and human liver tumors, whereas gankyrin is elevated. Fig. 7F summarizes our studies and presents our hypothesis, according to which the elevation of gankyrin triggers degradation of four tumor suppressor proteins and leads to liver cancer. Based on the literature and our observations, we suggest that the gankyrin-mediated

elimination of C/EBPα is associated with phosphorylation at S193, while other proteins might be degraded by additional mechanisms such as activation of MDM2 (for p53) and direct interactions of gankyrin with Rb. These findings provide a basis for the generation of gankyrin-based therapeutic approaches in the prevention of liver cancer. Additional Supporting Information may be found in the online version of this article. “
“Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has been documented that it can suppress pro-inflammatory selleck chemicals cytokines synthesis in alleviating non-alcoholic steatohepatitis (NASH) in vivo. TLR4 is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines. It has been reported that TLR4 is up-regulated in NAFLD and plays an important role in the pathogenesis of NASH. This study aimed to examine the changes of TLR4 and its signaling pathways in sophocarpine’s anti-inflammatory process on experimental NASH in vitro. Primary hepatocytes were isolated and oleic acid-induced steatosis model was established. CCK-8 assay was used to detect the number of metabolically active mitochondria and viable cells.

Examination of C/EBPβ and HDAC1 revealed that C/EBPβ and HDAC1 were increased in the livers of Little mice (Fig. 7D). We found that the amounts of C/EBPβ-HDAC1 complexes are higher in Little mice and that these complexes occupy and repress the gankyrin promoter in Little mice treated with DEN (Fig. 7E). Gankyrin is a protein that is activated in liver cancer and causes degradation or elimination of activities of five tumor suppressor proteins; Rb, p53, C/EBPα, HNF4α,

and p16.1, selleck 5-7, 22 This places gankyrin in a unique position to be a target for therapeutic approaches in the prevention of liver cancer. In this study, we elucidated the mechanisms of activation of gankyrin during the development of liver cancer. Four lines of evidence show that development of liver cancer involves the reduction of FXR and subsequent activation of gankyrin. First, DEN-mediated carcinogenesis in WT mice reduces FXR, leading to the reduction of HDAC1-C/EBPβ complexes and activation of the gankyrin promoter. Second, the deletion of FXR signaling in

FXR/SHP Selleckchem Roxadustat KO mice activates gankyrin in the liver, leading to development of liver cancer. Third, high levels of FXR in Little mice prevent development of age-associated liver cancer and development of cancer under DEN protocol. Fourth, levels of FXR are reduced in spontaneously developed mouse and human liver tumors, whereas gankyrin is elevated. Fig. 7F summarizes our studies and presents our hypothesis, according to which the elevation of gankyrin triggers degradation of four tumor suppressor proteins and leads to liver cancer. Based on the literature and our observations, we suggest that the gankyrin-mediated

elimination of C/EBPα is associated with phosphorylation at S193, while other proteins might be degraded by additional mechanisms such as activation of MDM2 (for p53) and direct interactions of gankyrin with Rb. These findings provide a basis for the generation of gankyrin-based therapeutic approaches in the prevention of liver cancer. Additional Supporting Information may be found in the online version of this article. “
“Sophocarpine, a tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has been documented that it can suppress pro-inflammatory selleck kinase inhibitor cytokines synthesis in alleviating non-alcoholic steatohepatitis (NASH) in vivo. TLR4 is a pattern recognition receptor whose activation results in the production of several pro-inflammatory cytokines. It has been reported that TLR4 is up-regulated in NAFLD and plays an important role in the pathogenesis of NASH. This study aimed to examine the changes of TLR4 and its signaling pathways in sophocarpine’s anti-inflammatory process on experimental NASH in vitro. Primary hepatocytes were isolated and oleic acid-induced steatosis model was established. CCK-8 assay was used to detect the number of metabolically active mitochondria and viable cells.

This study was to investigate the role of STIM1 on metastatic potential of human CRC. Methods: We examined the expression of STIM1 in four CRC cell lines with different metastatic potentials using real-time PCR and Western Blot, SW620

and LOVO (high metastatic potential), SW480 and HT29 (low metastatic potential). Expression of STIM1 in CRC tissues was explored using immunohistochemisty. The relationships between STIM1 expression and clinicopathologic factors were assessed using theχ2 test. Effects of stable expression of STIM1 and its siRNA inhibitors were studied in the human CRC cell lines SW480 and SW620; transwell experiments were performed to evaluate cellular migration and invasion. Results: Expression of STIM1 was increased in highly invasive CRC cell lines and lymph node-positive CRC specimens. Enhancing the expression of STIM1 promoted CRC cell migration and invasion, while silencing Alectinib purchase its expression BIBW2992 supplier resulted in reduced migration and invasion. STIM1 overexpression was significantly associated

with advanced clinicalTNM stage and lymph node metastasis. Conclusion: These results suggest that STIM1 is a novel metastasis marker in CRC and might be a potential target for diagnosis and therapy. Key Word(s): 1. STIM1; 2. SOCE; 3. Colorector cancer; 4. Metastasis; Presenting Author: BANGMAO WANG Additional Authors: HAILONG CAO Corresponding Author: BANGMAO WANG Affiliations: General Hospital, Tianjin Medical University Objective: Berberine, an isoquinoline plant alkaloid, has shown antineoplastic effects on a variety of cancer cells in vitro. The aim of this study was to investigate chemopreventive effects of berberine on intestinal tumor development in APCmin/+ mice. Methods: Four-week old APCmin/+ mice were treated with 0.05% or 0.1% berberine in drinking water for twelve weeks. Parameters of intestinal tumor development, cell proliferation and apoptosis, and tumor promoting signaling pathways were determined. Results: The total number of the intestine tumor was decreased by

39.6% in 0.05% berberine treatment group 18.50 ± 1.51) and by 62.5% in 0.1% treatment group (11.50 ± 2.05) compared with untreated group (30.63 ± 1.69). All sizes of tumor (>2 mm, 1–2 mm, and <1 mm) were significantly reduced in both berberine treatment groups. selleck compound In 0.1% berberine-treated group, tumors in proximal, middle, distal segments of small intestine were significantly reduced by 53.7%, 55.3%, and 76.5%, and the percentage of PCNA and Ki-67 positive cells were decreased by 32% and 55%, respectively, expression of cyclin Dl was also decreased, and apoptotic cell number was increased by 2.14 fold in the tumors. Gene microarray indicated different gene expression profiles, and Wnt and EGFR pathways may be involved. Furthermore, berberine treatment suppressed β-catenin and epidermal growth factor receptor activation, and down-regulated the expression of cyclooxygenase-2 and prostaglandin E2 production.

3. Two referees are ackmowledged for their comments and suggestions that helped improve the paper. “
“Sexual conflict drives evolution of sexually antagonistic adaptations that give advantages to the bearer. As a consequence of sexual conflict, male scorpionflies (Mecoptera: Panorpidae) provide nuptial gifts for the female and use grasping organs to repress female resistance. These organs, except

notal organ, have not been satisfactorily studied. In this paper, selleckchem the mating behavior of Dicerapanorpa magna (Chou) was investigated to reveal the role of the anal horns (a pair of posterior processes on tergum VI) of males. The males initiate copulation through grasping the female with the notal organ and anal horns, prolonging copulation by providing salivary masses to the female as nuptial gifts and maintaining copulation after the female consumed the salivary masses. The results of a manipulative experiment show that the anal horns play a significant role in the mating success for the males of D. magna by promoting male domination in copulation through increasing the duration of pre- and post-gift-providing copulatory BGJ398 price stages against female resistance and by avoiding wasting of nuptial gifts. The anal horns of male D. magna seem to be a male adaptation

evolved to overcome female mating resistance. “
“The grey wolf Canis lupus has the largest geographical range of large mammalian carnivores in west Asia. However, it is one of the least studied species, particularly in Iran. Feeding ecology is a critical aspect of predator ecology and has important implications when formulating species and ecosystem management strategies. Also, predation on livestock is a crucial cause of wolf–human conflicts throughout the wolf’s global range. Accordingly, we investigated the diet

of the grey wolf in Ghamishlou, an area with high population densities of wild and domestic ungulates in central Iran, between July 2007 and April 2009. Scat analysis indicated that livestock was the single most important prey species for wolves with 47.1% of total biomass consumed, whereas Persian gazelle comprised 27.0% and wild sheep 15.9%. Wild kills selleck chemicals llc were significantly skewed towards males relative to their proportion in the population, and were mainly preyed on during post-rutting months. Based on interview surveys, less than 1% of mean herd size was lost to wolf depredation; however, almost six times more died from non-depredation causes during each winter. We concluded that the high occurrence of livestock in the wolves’ diet is mainly because of scavenging rather than depredation; however, owing to high pressure of wolves on local herds during non-winter seasons in other areas with depleted prey populations, local people dislike wolves and try to eradicate them. Finally, management implications are discussed and solutions are recommended.

3. Two referees are ackmowledged for their comments and suggestions that helped improve the paper. “
“Sexual conflict drives evolution of sexually antagonistic adaptations that give advantages to the bearer. As a consequence of sexual conflict, male scorpionflies (Mecoptera: Panorpidae) provide nuptial gifts for the female and use grasping organs to repress female resistance. These organs, except

notal organ, have not been satisfactorily studied. In this paper, Small molecule library in vitro the mating behavior of Dicerapanorpa magna (Chou) was investigated to reveal the role of the anal horns (a pair of posterior processes on tergum VI) of males. The males initiate copulation through grasping the female with the notal organ and anal horns, prolonging copulation by providing salivary masses to the female as nuptial gifts and maintaining copulation after the female consumed the salivary masses. The results of a manipulative experiment show that the anal horns play a significant role in the mating success for the males of D. magna by promoting male domination in copulation through increasing the duration of pre- and post-gift-providing copulatory Acalabrutinib manufacturer stages against female resistance and by avoiding wasting of nuptial gifts. The anal horns of male D. magna seem to be a male adaptation

evolved to overcome female mating resistance. “
“The grey wolf Canis lupus has the largest geographical range of large mammalian carnivores in west Asia. However, it is one of the least studied species, particularly in Iran. Feeding ecology is a critical aspect of predator ecology and has important implications when formulating species and ecosystem management strategies. Also, predation on livestock is a crucial cause of wolf–human conflicts throughout the wolf’s global range. Accordingly, we investigated the diet

of the grey wolf in Ghamishlou, an area with high population densities of wild and domestic ungulates in central Iran, between July 2007 and April 2009. Scat analysis indicated that livestock was the single most important prey species for wolves with 47.1% of total biomass consumed, whereas Persian gazelle comprised 27.0% and wild sheep 15.9%. Wild kills selleck were significantly skewed towards males relative to their proportion in the population, and were mainly preyed on during post-rutting months. Based on interview surveys, less than 1% of mean herd size was lost to wolf depredation; however, almost six times more died from non-depredation causes during each winter. We concluded that the high occurrence of livestock in the wolves’ diet is mainly because of scavenging rather than depredation; however, owing to high pressure of wolves on local herds during non-winter seasons in other areas with depleted prey populations, local people dislike wolves and try to eradicate them. Finally, management implications are discussed and solutions are recommended.