The results support the view that motor control in aging is influ

The results support the view that motor control in aging is influenced by executive control and have implications for theories

of cognitive training and transfer.”
“Many studies find more on the effects of acupuncture on brain activity have been concerned with the stimulation of specific acu-points. However, research on brain activity with the stimulation of the body-meridian line is still quite novel. The hypothesis of the present study is that heart meridian stimulations with different directions of line-magnet poles would elicit different effects on EEG activity. Twenty-three healthy young adults between the age of 19 and 22 years old participated in the experiment. Two tiny NEO line-magnets were applied to stimulate the heart meridian. EEG activities were changed significantly between different treatments on the heart meridian using line-magnet with different directions of magnetic poles (p < 0.05). The present study shows that the stimulation of the heart

meridian with the line-magnets has an effect on brain activity associated with the direction of the line-magnet pole. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Using data from the Italian SurveY on carDiac rEhabilitation-2008 (ISYDE-2008), this study provides insight into the level of implementation of cardiac rehabilitation (CR) in very old cardiac patients.

Data from 165 CR units were collected online from January 28 to February 10, 2008.

The study cohort Fedratinib in vivo consisted of 2,281 patients (66.9 +/- 11.8 years): 1,714 (62.4 +/- 9.6 years, 78% male) aged < 75 years and 567 aged >= 75 years (80.8 +/- 4.5 years, 59%

male). Compared with adults, a higher percentage of older patients were referred to CR programs after cardiac surgery or acute heart failure and showed more acute phase complications and comorbidity. Older patients were less likely discharged to home, more likely transferred to nursing homes, or discharged with social networks activation. Older patients had higher death rate during CR programs (odds ratio = 4.6; 95% confidence interval = 1.6-12.9; p = .004).

The ISYDE-2008 survey provided a detailed snapshot of CR in very old cardiac patients.”
“The neurotransmitter histamine is produced in the tuberomamillary nucleus of the posterior hypothalamus; these neurons project broadly Selleckchem Fedratinib throughout central nervous system. Histidine decarboxylase (HDC) synthesizes histamine from histidine; in the brain, its mRNA is expressed exclusively in the posterior hypothalamus. Histamine receptors are expressed throughout the forebrain, including in cortex, hippocampus, and basal ganglia, suggesting functional innervation of these structures. We investigated the distribution of HDC protein in dissected tissue from mouse and rat, anticipating that it would reflect the density of hypothalamic histaminergic axonal projections and thus qualitatively parallel the known distribution of histamine receptors.

All rights reserved “
“Inhalation of particles has been show

All rights reserved.”
“Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active cell division, which occurs during fetal development in females. We investigated the effects of prenatal

exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during this website fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6J mice were exposed four times during gestation by intratracheal instillation of 67 mu g/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed

F2 female offspring were Crenolanib research buy not statistically different from those of F2 female control offspring. (C) 2013 Elsevier Inc. All rights reserved.”
“The eye is particularly sensitive to ethanol’s teratogenic effects. Our previous work, using a chick embryo model system, has shown that ethanol acts rapidly to perturb vital processes of early eye development producing defects of the lens and retina. Ethanol-induced selleck kinase inhibitor disruption of the midline ventral telencephalon, a key site for expression of ocular morphogens such as sonic hedgehog (Shh), was further established. Consequently, in this study we have examined the effects of ethanol on the Shh pathway during the period of optic

vesicle/optic cup formation. Chick embryos were injected in ovo with 125 mu L of a 20% ethanol solution directly into the yolk-sac at HH-stage 7, resulting in peak ethanol uptake of 0.294 g/dL. Subsequent molecular analysis at 12, 24 and 48 h post-treatment revealed that ethanol had no affect on Shh transcription, while, a significant reduction in the expression of the active signalling Shh protein was found. Surprisingly, none of the downstream Shh pathway members (Ptc, Gli1 and Gli3) were significantly altered by ethanol exposure. Overall, our results indicate that ethanol’s disruption of Shh may be mediated through some alternative mechanism independent of the classical signalling pathway. However, the precise role of Shh in relation to ethanol teratogenicity continues to be debated. Thus, in conclusion, our findings are discussed in relation to the varied and often conflicting reports of ethanol-induced Shh perturbation found in the literature. (C) 2013 Elsevier Inc. All rights reserved.”
“Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models.

However, DEHP administered at high dose (30 mg/kg bw/day) to dams

However, DEHP administered at high dose (30 mg/kg bw/day) to dams produced a significant decrease in the inhibitory neurotransmitter GABA and an increase in the stimulatory neurotransmitter aspartate in prepubertal male offspring rats. These modifications were accompanied

click here by gonadotropin serum levels increase. On the contrary, in treated female rats this chemical increased both, aspartate and GABA, which exert a characteristic stimulatory action on gonadotropin in 15-day-old normal females. This study provides new data about changes produced by DEHP on the hypothalamic amino acid neurotransmitters involved in the neuroendocrine reproductive regulation, in prepubertal male and female rat offspring from dams exposed during gestational and lactational periods. These alterations induced by DEHP exposure could be related to the gonadotropin modifications also described in this work, and with changes in the production of sexual hormones previously reported by other authors. (C) 2011 Elsevier Inc. All rights reserved.”
“In plants

and some animals, posttranscriptional RNA silencing can be manifested beyond its sites of initiation, because of the movement of signaling molecules that must have RNA components to account for the Cyclosporin A supplier nucleotide sequence specificity of their effects. In a recent study carried out in Arabidopsis thaliana, interesting clues were provided that suggest mechanisms by which systemic RNA silencing signals might be produced and perceived between distant plant organs.”
“Gastric cancer has significant morbidity and mortality worldwide and locally. Good prognosis relies on an early diagnosis. However, this remains

a challenge due to the lack of specific and sensitive serum biomarkers for early detection. Hence, there BMS345541 in vitro is a constant search for these biomarkers for screening purposes. Proteomic profiling enables a new approach to the discovery of biomarkers in disease. This review presents recent attempts in search of gastric cancer serum biomarker using proteomics. Different methodologies and different types of samples were employed by different groups of researchers. Major difficulties were encountered in the discovery processes, including interference from abundant proteins and continuous changing serum proteomes from different individuals.”
“We develop and analyse a flexible compartmental model of the interaction between a plant host, a soilborne pathogen and a microbial antagonist, for use in optimising biological control. By extracting invasion and persistence thresholds of host, pathogen and biological control agent, performing an equilibrium analysis, and numerical investigation of sensitivity to parameters and initial conditions, we determine criteria for successful biological control. We identify conditions for biological control (i) to prevent a pathogen entering a system, (ii) to eradicate a pathogen that is already present and, if that is not possible, (iii) to reduce the density of the pathogen.

The performance of a one-step RT-PCR protocol, a more clinically

The performance of a one-step RT-PCR protocol, a more clinically practical approach, was evaluated. The VP1 and/or VP2 region of archived enterovirus isolates (n = 36, representing 32 serotypes), patient enterovirus isolates not typeable by immunofluorescence antibodies (n = 50), and enterovirus from direct patient specimens (48 cerebrospinal fluid, 2 plasma/serum, 1 blood) were amplified and sequenced for genotype identification. The analytical sensitivity Cyclosporin A concentration of the genotyping assays was 100-fold less than detection by RT-PCR of the 5′-untranslated region. Thirty-four of 36 archived isolates could be genotyped by combining results of VP1 and VP2 target sequencing. Non-typeable

isolates included 17 echovirus 18,6 enterovirus 68,6 rhinovirus, and 7 which could not be classified further. From clinical specimens, 23 of 51 (45%) could be identified using VP2 typing and the most common types were coxsackievirus B1, echovirus 30, and echovirus 6. Using a one-step RT-PCR without nesting, most enterovirus isolates and a subset of clinical samples with high viral titer could be genotyped. (C) 2009 Elsevier B.V. All rights reserved.”
“We recently showed that measures of cannabinoid 1 receptor (CB1R) mRNA and protein were significantly reduced in dorsolateral prefrontal cortex (DLPFC) area 9 in schizophrenia subjects relative to matched normal comparison subjects. However,

other studies have reported unaltered or higher measures of CB1R levels in schizophrenia. To determine buy RepSox whether these discrepancies reflect differences across brain regions or across subject groups (eg, presence of depression, cannabis exposure, etc), we used immunocytochemical techniques to determine whether lower levels of CB1R immunoreactivity are (1) present in another DLPFC region, area 46, in the same subjects with schizophrenia, (2) present in area 46 in a new cohort of schizophrenia Citarinostat cell line subjects, (3) present in major depressive disorder (MDD) subjects, or (4) attributable to factors other than a diagnosis of schizophrenia, including

prior cannabis use. CB1R immunoreactivity levels in area 46 were significantly 19% lower in schizophrenia subjects relative to matched normal comparison subjects, a deficit similar to that observed in area 9 in the same subjects. In a new cohort of subjects, CB1R immunoreactivity levels were significantly 20 and 23% lower in schizophrenia subjects relative to matched comparison and MDD subjects, respectively. The lower levels of CB1R immunoreactivity in schizophrenia subjects were not explained by other factors such as cannabis use, suicide, or pharmacological treatment. In addition, CB1R immunoreactivity levels were not altered in monkeys chronically exposed to haloperidol. Thus, the lower levels of CB1R immunoreactivity may be common in schizophrenia, conserved across DLPFC regions, not present in MDD, and not attributable to other factors, and thus a reflection of the underlying disease process.

They demand a toxinological explanation


They demand a toxinological explanation.


Bites by several genera of African, Asian and Australasian tarantulas can cause systemic neurotoxic envenoming. In the absence of available antivenom, severe persistent muscle spasms, reminiscent of latrodectism, pose a serious therapeutic challenge. Discovery of the toxin responsible would be of scientific and potential clinical benefit. Tarantula keepers should be warned of the danger of handling these animals incautiously.”
“Melanopsin (OPN4) is a photosensitive pigment originally found in a subtype of retinal ganglion cells and is a 7-transmembrane G-protein-coupled receptor (GPCR). Several previous reports showed that ectopic expression of OPN4 can be used as an optogenetic tool to control check details neural and cellular activities in

various tissues. Compared with other optogenetic pigments, OPN4 is more sensitive to light, shows long-lasting activation, and can also control intracellular Ca2+ dynamics. Here, we review how the ectopic expression of OPN4 enables the control of neural and cellular activities in vivo. In the retina, the ectopic expression of melanopsin Selleck NU7026 in retinal ganglion cells successfully restored the vision of blind mice. It has also been reported that ectopic expression of melanopsin in orexin/hypocretin neurons enabled control of wakefulness in mice by blue light. In addition to neural activity, the ectopic expression of OPN4 has been reported to enable circuit control of the nuclear factor of activated T cells (NFAT) to enhance blood-glucose homeostasis in mice. We discuss the possibility of optogenetic control of other systems through the ectopic expression of OPN4. (C) 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“Objectives: Surgical management of tricuspid valve regurgitation

mainly consists of tricuspid valve annuloplasty, usually performed with implantation of a rigid ring or a flexible band.

Methods: We performed a retrospective analysis on 820 patients who underwent tricuspid valve repair between March 2002 and July 2009 with either a flexible Cosgrove-Edwards Liproxstatin-1 ic50 band (n = 415; Edwards Lifesciences LLC, Irvine, Calif) or a rigid Carpentier-Edwards Classic annuloplasty ring (n = 405; Edwards Lifesciences). Mean patient age was 69.2 +/- 9.5 years, 54.1% were female, and average logistic EuroSCORE was 13.3% +/- 12.5%. Concomitant procedures were performed in 94.6% of patients (mitral valve surgery, 80.6%; aortic valve surgery, 28.2%; coronary artery bypass grafting, 24.5%; atrial fibrillation ablation, 44.5%). One fifth of the operations were reoperative procedures. Follow-up was 94% complete, with mean duration of 21.0 +/- 19.0 months.

Results: Thirty-day mortality was 10.1% (Cosgrove-Edwards, 11.9%; Carpentier-Edwards, 8.4%), and 5-year survival was 62.4% (Carpentier-Edwards, 64.7%; Cosgrove-Edwards, 60.3%).

“Earthquakes normally occur as frictional stick-slip insta

“Earthquakes normally occur as frictional stick-slip instabilities, resulting in catastrophic failure and seismic rupture. Tectonic faults Dactolisib also fail in slow earthquakes with rupture durations of months or more, yet their origin is poorly understood. Here, we present laboratory observations of repetitive, slow stick-slip in serpentinite fault zones and mechanical evidence for their origin. We document a transition from unstable to stable frictional behavior with increasing slip velocity, providing a mechanism to limit the speed of slow earthquakes. We also document reduction of P-wave speed within the active shear zone before stick-slip events. If similar mechanisms operate in nature, our results

suggest that higher-resolution studies of elastic properties in tectonic fault zones may aid in the search for reliable earthquake precursors.”
“Abiotic release of nitrous acid (HONO) in

equilibrium with soil nitrite (NO2-) was suggested as an important contributor to the missing source of atmospheric HONO and hydroxyl radicals (OH). The role of total soil-derived HONO in the biogeochemical and atmospheric nitrogen cycles, however, has remained unknown. In laboratory experiments, we found that for nonacidic soils from arid and arable areas, reactive nitrogen emitted as HONO is comparable with emissions of nitric oxide (NO). We show that ammonia-oxidizing bacteria can directly release HONO in quantities larger than expected from the acid-base and Henry’s law equilibria of the aqueous phase in soil. This component of the nitrogen cycle Epigenetics inhibitor constitutes an additional loss term for fixed nitrogen in soils and a source for reactive nitrogen in the atmosphere.”
“Ice shelves play a key role in the mass balance of

the Antarctic ice sheets by buttressing their seaward-flowing outlet glaciers; however, they are exposed to the underlying ocean and may weaken if ocean thermal forcing increases. An expedition to the ice shelf of the remote Pine Island Glacier, a major outlet of the West Antarctic Ice Sheet that has rapidly thinned and accelerated in recent decades, has been completed. Observations from geophysical surveys and long-term oceanographic instruments deployed down bore holes into the ocean cavity reveal a buoyancy-driven boundary layer within a basal channel that melts the channel apex by 0.06 meter per day, with near-zero melt rates along the flanks of the channel. A complex pattern of such channels is visible throughout the Pine Island Glacier shelf.”
“Organisms are expected to adapt or move in response to climate change, but observed distribution shifts span a wide range of directions and rates. Explanations often emphasize biological distinctions among species, but general mechanisms have been elusive. We tested an alternative hypothesis: that differences in climate velocity-the rate and direction that climate shifts across the landscape-can explain observed species shifts.

We exploited this type of stress, alone or in combination with ac

We exploited this type of stress, alone or in combination with acute immobilization, to define changes in the expression level and compartmental distribution of GR, Hsp90 and Hsp70 selleck screening library in HIPPO and PFC. The results indicated that in acute and combined stress, when CORT was increased, GR was translocated to the nucleus in both brain structures. Under chronic stress, when CORT was below the control level, GR was retained in the cytoplasm of PFC, and evenly distributed between compartments in HIPPO. Simultaneously, heat shock proteins partitioning in HIPPO seemed to be

mainly stress type-independent, while that of PFC was dependent on stress type. Thus, the stress type-specific responses of GR and heat shock proteins were mainly detected in PFC rather than in HIPPO of Wistar rats. The observed alterations in protein expression and cytoplasmic-nuclear partitioning of the GR, Hsp90 and Hsp70 proteins may be related to maladaptive response of the HPA axis under chronic PU-H71 mouse stress. Copyright (C) 2009 S. Karger AG, Basel”
“Objective: The aim of the present retrospective pilot study was to examine the clinical impact of the cytochrome P450 (CYP) enzyme CYP2D6 poor metabolizer (PM) genotype in patients taking

antipsychotic medication. The impaired metabolic capacity of the PM genotype results in higher steady-state plasma concentrations at a given dose, thus increasing the risk of toxic effects from medication. Methods: We identified 18 PM patients with a schizophrenia

spectrum diagnosis from a clinical database covering all patients who have been analyzed in an ongoing standardized CYP2D6 screening program. Each PM patient was carefully matched on age, gender and diagnosis with an intermediate metabolizer (IM) and an extensive metabolizer (EM) from the same database to generate 18 triplets. Clinical data, primarily on side effects of treatment, were obtained from medical records by an experienced research and consultant Birinapant cell line psychiatrist, who was blinded to the results of the genotyping. Results: We found that extrapyramidal syndrome or tardive dyskinesia (EPS/TD) was significantly more frequent among PM patients than among the matched IM and EM control subjects. This finding was further supported by the significantly higher prevalence of noncompliance among the same PM patients. Importantly, this association was not due to differences in the use of CYP2D6-dependent or EPS/TD-causing medication across the 3 matched patient groups. Conclusions: This leads us to conclude that genetically encoded differences in the rate of drug metabolism through CYP2D6 can predict antipsychotic side effects and prompts the question of whether genotyping early in the course of illness to facilitate adjustment of pharmacotherapy will improve treatment outcomes and reduce side effects. Copyright (C) 2009 S.

MVA lacks many genes associated with virulence and/or regulation

MVA lacks many genes associated with virulence and/or regulation of virus tropism. The 68-kDa ankyrin-like protein (68k-ank) is the only ankyrin repeat-containing protein that is encoded by the MVA genome and is highly conserved throughout the Orthopoxvirus genus. We showed previously that 68k-ank is composed of ankyrin repeats and an F-box-like domain and forms an SCF ubiquitin ligase complex

together with the cellular proteins Skp1a and Cullin-1. We now report that 68k-ank (MVA open reading frame 186R) is an essential factor for completion of the MVA intracellular life cycle in nonpermissive human and murine cells. Infection of mouse NIH 3T3 and human HaCaT cells with MVA with a deletion of the 68k-ank gene (MVA-Delta 68k-ank) was characterized by an extensive reduction of viral intermediate RNA and protein, as well as late transcripts and drastically impaired late protein synthesis. Furthermore, infections with MVA-Delta Defactinib clinical trial 68k-ank failed to induce the host protein shutoff that is characteristic of VACV infections. Although we demonstrated that proteasome function P5091 concentration in general is essential for the completion of the MVA molecular life cycle, we found that a mutant 68k-ank protein with a deletion of the F-box-like domain

was able to fully complement the deficiency of MVA-Delta 68k-ank to express all classes of viral genes. Thus, our data demonstrate that the 68k-ank protein contains another critical domain that may function independently of SCF ubiquitin ligase complex formation,

suggesting multiple activities of this interesting regulatory protein.”
“Motor involvement in speech perception has been recently studied using a variety of techniques. In the current study, EEG measurements from Cz, C3 and C4 electrodes were used to examine the relative power of the mu rhythm (i.e., 8-13 Hz) in response to various audio-visual speech and non-speech stimuli, as suppression of these rhythms is considered an index of ‘mirror neuron’ (i.e., motor) activity. Fourteen adult native English speaking females watched and listened to nine audio-video stimuli clips assembled from three different auditory stimuli (speech, noise, and pure tone) combined 3-deazaneplanocin A concentration with three different video stimuli (speech, noise, and kaleidoscope-made from scrambling an image from the visual speech). Relative to the noise-noise (baseline condition), all visual speech conditions resulted in significant levels of suppression, a finding that is consistent with previous reports of mirror activity to visual speech and mu suppression to ‘biological’ stimuli. None of the non-speech conditions or conditions in which speech was presented via audition only resulted in any significant suppression of the mu rhythm in this population. Thus, visual speech perception appears to be more closely associated with motor activity than acoustic speech perception.

We excluded trials of patients with organ transplants or who need

We excluded trials of patients with organ transplants or who needed haemodialysis. We used the 12 statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes

with random-effect meta-analysis.

Findings We identified 13 statin trials with 91140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% CI 1.02-1.17), with little heterogeneity (I(2)=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150-852) patients with statins AS1842856 in vivo for 4 years resulted in one extra case of diabetes.

Interpretation Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not

“Background Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood selleck products glucose in young people.

Methods We undertook three randomised crossover studies in 19 patients aged 5-18 years with type 1 diabetes of duration 6.4 years (SD 4.0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed

every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, selleck compound patients’ standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3.91-8.00 mmol/L or 3.90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883.

Findings 17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR. 43-83] closed loop vs 39% [15-51] standard treatment, p=0.06; <= 3.90 mmol/L, 1% [0-7] vs 2% [0-41], p=0.13), APCam02 (six analysed; target range, rapidly 53% [48-57] vs slowly absorbed meal 55% [37-64], p=0.97; <= 3.90 mmol/L, 0% [0-4] vs 0% [0-0], p=0.

The current data therefore suggest that upregulation of adenosine

The current data therefore suggest that upregulation of adenosine production abolished OSI-027 the suppressive effect of MTX on osteoclastic bone destruction. Involvement of the adenosine-A(2b)AR system may explain MTX resistance in

RA. Laboratory Investigation (2011) 91, 719-731; doi:10.1038/labinvest.2011.9; published online 21 February 2011″
“Imidazolium salts (IMSs) are precursors to N-heterocyclic carbenes (NHCs), which are routinely used as ligands or organo-catalysts in synthetic chemistry. We recently identified several IMSs as anti-fibrotic agents in liver fibrosis, which often has a consequence in the oncogenesis of hepatocellular carcinoma (HCC). Here, we investigate the potential anti-tumor property of three IMSs (named IBN-1, IBN-9, and DPIM) in HCC cell lines and in a xenograft mouse model. Our results showed that both IBN-1 and IBN-9 significantly inhibited the cell proliferation and arrested HCC cells in the G1-phase, whereas DPIM did not have any anti-tumor activity. When tested in a Huh7 HCC xenograft mouse model, IBN-1 reduced the tumor volume by 31% (P < 0.05), however accompanied by a 9% loss in body weight (P < 0.005), suggesting a general toxicity. In contrast, IBN-9 significantly reduced the tumor volume by 45% (P < 0.05) and 60% (P < 0.01) at doses of 0.6 and 1.5 g/l in drinking Panobinostat water, respectively, without any loss in body weight. Our in

vitro and in vivo data suggested that IBN-1 and IBN-9 inhibited the growth of HCC by suppressing the expression of Survivin and Cyclin-dependent kinases. The current study provides a proof of concept for using the metal-free IMSs to develop novel anti-cancer agents. Laboratory Investigation (2011) 91, 744-751; doi:10.1038/labinvest.2011.4; published online 21 February 2011″
“Hepatic fibrosis is the result of chronic liver injuries underlined by diverse etiologies. The massive accumulation of extracellular matrix (ECM) proteins during fibrogenesis

leads to structural distortion and functional disruption of the click here liver. There is currently no effective standard treatment for liver fibrosis. We previously identified a class of imidazolium salts (IMSs) with anti-fibrotic properties in a cell-based screen. In this report, we investigated the anti-fibrotic efficacy and mechanisms of a small IMS, 1,3-diisopropylimidazolium tetrafluoroborate (DPIM), in a hepatic fibrosis model induced by bile duct ligation (BDL) in mice. The orally available DPIM was administered to BDL mice via drinking water at three concentrations (0.5, 0.75, and 1 g/l) for 4 weeks. We observed a significant reduction in inflammation and collagen deposition in the liver, which could be mediated by a reduction in the expression of monocyte chemoattractant protein-1 (MCP-1) and by an enhancement in the matrix metalloproteinase-mediated ECM remodeling.