The 10(5)-fold rate acceleration by Mg2+-protein interactions learn more therefore requires additional favorable protein-metal couplings. Examples include longer-range, i.e., allosteric, interactions previously illustrated by the remote F371 mutation, which both reduces k(cat) and enhances catalytic assist by Mn2+, relative to that by Mg2+. These data support a model linking metal-assisted phosphoryl transfer catalysis to domain movement, and hence to free-energy transduction

in a broad range of enzymes.”
“Objectives: To evaluate the prognostic value of maximum standardized uptake value (SUVmax) measured in [F-18]-fluorodeoxyglucose positron emission tomography (F-18-FDG PET) for patients with non-disseminated nasopharyngeal carcinoma (NPC).\n\nMaterials and methods: From January 2002 to July 2008, 371 NPC patients who underwent F-18-FDG-PET before radical intensity-modulated radiotherapy (IMRT) were recruited. The SUVmax was recorded AL3818 solubility dmso for the primary tumor (SUVmax-T) and neck lymph nodes (SUVmax-N).\n\nResults: The median follow-up was 64

months. The optimal cutoff value was 9.3 for SUVmax-T and 7.4 for SUVmax-N. Patients with a lower SUVmax-T or SUVmax-N had a significantly better 5-year distant metastasis-free survival (DMFS), but showed no significant difference in local control or regional control. Patients were divided into four groups by SUVmax, as follows: (a) both lower SUVmax-T and SUVmax-N, (b) higher SUVmax-T only, (c) higher SUVmax-N only, and d) both higher SUVmax-T and SUVmax-N. There were significant differences between these four groups in 5-year DMFS: (a) 95.5%, (b) 90.0%, (c) 83.3%, and (d) 79.9%, respectively (p = 0.004). see more When looking at the stage of disease, the 5-year DMFSs in group a, b, c, d were 96.9%, 94.6%, 97.4%, and 84.3%, respectively in stage I-III patients (p = 0.037) and were 91.6%, 82.9%, 68.5%, and 76.7% in stage IVA-B patients (p = 0.145). Using

multivariate analysis, the SUVmax grouping, gender, and stage were independent factors for DMFS.\n\nConclusion: The SUVmax of the primary tumor and neck lymph nodes were independent prognostic factors for DMFS in NPC patients treated with IMRT. (C) 2012 Elsevier Ltd. All rights reserved.”
“The primary goals of this critical literature review were to determine whether revision rates of primary total hip arthroplasty in patients with osteonecrosis differ based on the underlying associated risk factors and diagnoses, whether the outcomes of this procedure have improved over the past two decades, and to compare outcomes based on study level of evidence. A systematic literature review yielded 67 reports representing 3,277 hips in 2,593 patients who had a total hip arthroplasty for osteonecrosis of the femoral head.

Here we defined the growth-phase-dependent transcriptomes

of Haemophilus ducreyi, which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of hfq. Insertional inactivation of hfq altered the expression of similar to 16% of the H. ducreyi genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the hfq inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of hfq downregulated genes in the flp-tad and lspB-lspA2 operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation selleck screening library experiments, an unmarked hfq deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of hfq downregulated Flp1 and impaired the ability of H. ducreyi to form microcolonies, downregulated DsrA and rendered H. ducreyi serum susceptible, and downregulated LspB and LspA2, which allow H. ducreyi to resist learn more phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of H. ducreyi stationary-phase

and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog.\n\nIMPORTANCE Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully BEZ235 datasheet establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here,

we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.”
“Study design: Experimental trial based on the analytical study of radiographic standards of the sagittal spinal alignment in paraplegics in upright position under surface neuromuscular electrical stimulation (NMES).\n\nObjectives: To evaluate changes in radiographic standards of the sagittal spinal alignment of paraplegics under three different models of NMES used to optimize the global bipedal posture.\n\nSetting: The University Hospital Ambulatory (UNICAMP), Campinas, SP, Brazil.\n\nMethods: Ten paraplegic patients were selected.

(C) 2010 Elsevier Ltd. All rights reserved.”
“A LY2835219 purchase 3D-QSAR investigation of 95 diaminobenzophenone yeast farnesyltransferase (FT) inhibitors selected from the work of Schlitzer et al. showed that steric, electrostatic, and hydrophobic properties play key roles in the bioactivity of the series. A CoMFA/CoMSIA combined model using the steric and electrostatic fields of CoMFA together with the hydrophobic field of CoMSIA showed significant improvement in prediction compared with the CoMFA steric and electrostatic fields model. The similarity of the 3D-QSAR field maps for yeast FT inhibition activity (from this work) and for antimalarial

activity data (from previous work) and the correlation between those activities are discussed.”
“An ahpC mutant derivative of Azospirillum brasilense Sp245 (strain SK586) that encodes an alkyl hydroperoxide reductase was found to be more sensitive to oxidative stress caused by organic hydroperoxides compared with the wild-type. In addition, the ahpC mutant strain had multiple defects in a large array of cellular functions that were consistent with alteration of cell-surface properties, such as cell morphology in stationary phase, Calcofluor White-, Congo Red- and lectin-binding abilities, as well as cell-to-cell aggregation and flocculation. All phenotypes of the ahpC mutant were complemented by

in trans expression of AhpC, and overexpression of AhpC in the wild-type strain was PD-1/PD-L1 Inhibitor 3 found to affect the same set of phenotypes, suggesting that the pleiotropic effects were caused by the ahpC mutation. SK586 was also found to be fully motile, but it lost motility at a higher rate than the wild-type

during growth, such that most SK586 cells were non-motile in stationary phase. Despite these defects, the mutant did not differ from the wildtype in short-term colonization of sterile wheat roots when inoculated alone, and in competition with the wild-type strain; this implied that AhpC activity may not endow the cells with a competitive advantage in colonization under these conditions. Although the exact function of AhpC in affecting these phenotypes remains to be determined, changes in cell morphology, Bafilomycin A1 mechanism of action surface properties, cell-to-cell aggregation and flocculation are common adaptive responses to various stresses in bacteria, and the data obtained here suggest that AhpC contributes to modulating such stress responses in A. brasilense.”
“Bifunctional alkylating agent sulfur mustard (SM) and its analog nitrogen mustard (NM) cause DNA damage leading to cell death, and potentially activating Inflammation. Transcription factor p53 plays a critical role in DNA damage by regulating cell cycle progression and apoptosis. Earlier studies by our laboratory demonstrated phosphorylation of p53 at Ser15 and an increase in total p53 in epidermal cells both in vitro and in vivo following NM exposure.

Here we tested whether this effect can be observed in the absence of some of the visual areas showing a preferential response to faces as typically identified in neuroimaging. Event-related potentials were recorded in response to faces, cars, and their phase-scrambled versions in a well-known brain damaged case of prosopagnosia

(PS). Despite the patient’s right inferior occipital gyrus lesion encompassing the most posterior cortical area showing preferential response to faces (“occipital face area”), we identified an early face-sensitive component over the right occipito temporal hemisphere of the patient that was identified as the N170. A second experiment supported this conclusion, showing the typical N170 increase of latency and amplitude in response to inverted faces. In contrast, selleck compound there was no N170 in the left hemisphere, where PS has a lesion to the middle fusi form gyrus and shows no evidence of face preferential response in neuroimaging( no left “fusiform face area”). These results were replicated by a magnetoencephalographic investigation of the patient, disclosing a high throughput screening compounds M170 component only in the right

hemisphere. These observations indicate that face preferential activation in the inferior occipital cortex is not necessary to elicit early visual responses associated with face perception (N170/M170) on the human scalp. These results further suggest that when the right inferior occipital cortex is damaged, the integrity of the middle fusiform gyrus and/or the superior temporal sulcus – two areas showing face-preferential responses in the patient’s right hemisphere – might be necessary to generate the N170 effect.”
“Mitochondrial reactive oxygen species regulate many important biological selleckchem processes. We studied H2O2 formation by nonsynaptic brain mitochondria in response to the addition of low concentrations of glutamate, an excitatory neurotransmitter. We demonstrated that glutamate at concentrations from 10 to 50 mu M stimulated the H2O2 generation in mitochondria up to 4-fold, in a dose-dependent manner. The effect of glutamate was observed

only in the presence of Ca2+ (20 mu M) in the incubation medium, and the rate of calcium uptake by the brain mitochondria was increased by up to 50% by glutamate. Glutamate-dependent effects were sensitive to the NMDA receptor inhibitors MK-801 (10 mu M) and D-AP5 (20 mu M) and the inhibitory neurotransmitter glycine (5 mM). We have shown that the H2O2 formation caused by glutamate is associated with complex II and is dependent on the mitochondrial potential. We have found that nonsynaptic brain mitochondria are a target of direct glutamate signaling, which can specifically activate H2O2 formation through mitochondrial respiratory chain complex II. The H2O2 formation induced by glutamate can be blocked by glycine, an inhibitory neurotransmitter that prevents the deleterious effects of glutamate in brain mitochondria. (C) 2013 Elsevier Inc. All rights reserved.

In this review, we discuss the ways in which the GIFT fusokines are able to alter the immune response, particularly in disease states, with a special emphasis on how these novel molecules may be translated into effective therapies in selleck chemicals the clinical setting.”
“A reliable chromatographic method for the determination of soy isoflavones (genistein, daidzein and glycitein) using a coulometric detection has been developed and applied to analyse plasma of postmenopausal women The chromatographic separation was performed on a C18 reversed phase column with a mobile phase composed

of acetonitrile-phosphate buffer mixture. Coulometric detection was carried out at +0.500 V A careful PARP activity and rapid solid phase extraction procedure on hydrophilic/lipophilic cartridges was chosen for plasma sample purification with and without hydrolysis obtaining good extraction yield values for all the analytes (>90 0%). The enzymatic hydrolysis step was necessary for the determination of the total amount of soy isoflavones The limit of quantitation was 05 ng mL(-1) for genistein and 025 ng mL(-1) for daidzein and glycitein. The method was found to be precise and accurate Thus, the proposed method is suitable for the analysis of soy isoflavones (free and total amounts)

in plasma of postmenopausal women under treatment with the SoymenGN (R) dietary supplement (C) 2010 Elsevier B.V All rights reserved”
“Background and Purpose-Based on thrombus location and nature and anatomic features of aorta and cerebral arteries, we hypothesized that cardiogenic embolisms (CE) and aortogenic embolisms

(AE) might have different right-left propensity and lesion patterns.\n\nMethods-We retrospectively reviewed patients with acute ischemic stroke with high-risk CE sources or moderate-or-severe aortic atherosclerotic plaques on transesophageal echocardiography. Lesion side and patterns on diffusion-weighted imaging were compared between CE and AE.\n\nResults-CE was identified in 123 and AE in 63. In multivariate analysis, right-sided lesions LY2835219 supplier and corticosubcortical infarcts were independently associated with CE, and left-sided lesions and pial infarcts were independently associated with AE.\n\nConclusions-CE and AE have different radiological characteristics, as shown by the right-left propensity and lesions patterns of cerebral infarcts. (Stroke. 2011;42:2323-2325.)”
“Objective: Between 31 and 35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology-based 8-week weight loss intervention among college students.

Moreover, the in vitro biocompatibility

of the prepared nanostructured apatite crystals was investigated using CCK-8 assay and alkaline phosphatase activity of osteoblast-like MC3T3-E1. Compared with HA synthesized by traditional method, the obtained apatite in agar-gelatin hybrid hydrogel could provide significantly higher cell viability and alkaline phosphatase activity. Through the study, we could better understand the role of gelatin and polysaccharide in bone formation process, and the product SBE-β-CD nmr is a promising candidate to be used in bone tissue engineering.”
“Human immunodeficiency virus (HIV-1) develops resistance to 3′-azido-2′,3′-deoxythymidine (AZT, zidovudine) by acquiring mutations in reverse transcriptase that enhance the ATP-mediated excision of AZT monophosphate from the 3′ end of the primer. The excision reaction occurs at the dNTP-binding site, uses ATP as a pyrophosphate

donor, unblocks the primer terminus and allows reverse transcriptase to continue viral DNA synthesis. The excision product is AZT adenosine dinucleoside tetraphosphate ( AZTppppA). We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; selleck chemicals AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at dNTP-and primer-binding sites; and AZTr apo reverse transcriptase. The AMP part of AZTppppA

bound differently to wild-type and AZTr reverse transcriptases, whereas the AZT triphosphate part bound the two enzymes similarly. Thus, the resistance mutations create a high-affinity ATP-binding site. The structure of the site provides an opportunity to design inhibitors of AZT-monophosphate excision.”
“Background: Caloramator celer is a strict anaerobic, alkalitolerant, thermophilic AS1842856 purchase bacterium capable of converting glucose to hydrogen (H-2), carbon dioxide, acetate, ethanol and formate by a mixed acid fermentation. Depending on the growth conditions C. celer can produce H-2 at high yields. For a biotechnological exploitation of this bacterium for H-2 production it is crucial to understand the factors that regulate carbon and electron fluxes and therefore the final distribution of metabolites to channel the metabolic flux towards the desired product.\n\nResults: Combining experimental results from batch fermentations with genome analysis, reconstruction of central carbon metabolism and metabolic flux analysis (MFA), this study shed light on glucose catabolism of the thermophilic alkalitolerant bacterium C. celer. Two innate factors pertaining to culture conditions have been identified to significantly affect the metabolic flux distribution: culture pH and partial pressures of H-2 (P-H2).

(Arterioscler Thromb Vasc Biol. 2010;30:962-967.)”
“The PM2.5 and PM10 samples

were collected during Diwali celebration from study area and characterized for ionic concentration of four anions (NO3 (-), NO2 (-), Cl-, SO4 (2-)) and five cations (K+, Mg2+, NH4 (+), Ca2+, Na+). The results showed that the ionic concentrations were three times compared to those on pre and post Diwali days. Predominant ions for PM2.5 were K+ 33.7 mu g/m(3), Mg+ 31.6 mu g/m(3), SO4 (2-) 22.1 mu g/m(3), NH4 (+) 17.5 mu g/m(3) and NO3 (-) 18 mu g/m(3) and for PM10 the ionic concentrations were Mg+ 29.6 mu g/m(3), K+ 26 mu g/m(3), SO4 (2-) 19.9 mu g/m(3), NH4 (+) 16.8 mu g/m(3) and NO3 (-) 16 mu g/m(3). While concentration of SO2 and NO2 were 17.23, 70.33 mu g/m(3) respectively.”
“In Xenopus oocytes, the water permeability of AQP0 (P(f)) increases with removal of external DNA Synthesis inhibitor calcium, an effect that is mediated by cytoplasmic calmodulin (CaM) bound to the C terminus of AQP0. To investigate the effects of serine phosphorylation on CaM-mediated Ca(2+) regulation of Pf, we tested the effects of kinase activation, CaM inhibition,

and a series of mutations in the C terminus CaM binding site. Calcium regulation of AQP0 Pf manifests four distinct phenotypes: Group 1, with high Pf upon removal of external Ca(2+) (wild-type, S229N, R233A, S235A, S235K, K238A, and this website R241E); Group 2, with high Pf in elevated ( 5 mM) external Ca(2+) (S235D and R241A); Group 3, with high Pf and no Ca(2+) regulation (S229D, S231N, S231D, S235N, and S235N/I236S); and Group 4, with low Pf and no Ca(2+) regulation ( protein kinase A and protein kinase C activators, S229D/S235D and S235N/I236S). Within each group, we tested whether CaM binding mediates the phenotype, as shown previously for wild-type AQP0. EPZ004777 solubility dmso In the presence of calmidazolium, a CaM inhibitor, S235D showed high Pf and no Ca(2+) regulation, suggesting that S235D still binds CaM. Contrarily, S229D showed a decrease in recruitment of CaM, suggesting that S229D

is unable to bind CaM. Taken together, our results suggest a model in which CaM acts as an inhibitor of AQP0 P(f). CaM binding is associated with a low P(f) state, and a lack of CaM binding is associated with a high P(f) state. Pathological conditions of inappropriate phosphorylation or calcium/CaM regulation could induce P(f) changes contributing to the development of a cataract.”
“Chronic obstructive pulmonary disease (COPD), characterized by progressive inflammation in the small airways and lung parenchyma, is mediated by the increased expression of multiple inflammatory genes. The increased expression of these genes is regulated by acetylation of core histones, whereas histone deacetylase 2 (HDAC2) suppresses inflammatory gene expression. In COPD, HDAC2 activity and expression are reduced in peripheral lung and in alveolar microphages, resulting in amplification of the inflammatory response.

PBO-4

is a putative Na+/H+ ion exchanger expressed on the basolateral membrane of the intestine, juxtaposed to the posterior body muscles. In pbo-4 mutants the extracellular space is not acidified and the muscles fail to contract. The pbo-5 and pbo-6 genes encode subunits of a “cysloop” proton-gated cation channel required for muscles to respond https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html to acidification. In heterologous expression assays the PBO receptor is half-maximally activated at a pH of 6.8. The identification of the mechanisms for release and reception of proton signals establishes a highly unusual mechanism for intercellular communication.”
“3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) exert pleiotropic effects on the cardiovascular system, in part through a decrease in reactive oxygen species (ROS) formation and reduction of vascular inflammation. To elucidate the molecular mechanisms involved in these effects, we investigated the effect of statins on TNF-alpha-induced ROS production, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression

in human aortic endothelial cells (HAECs). Exposure selleck screening library of HAECs to TNF-alpha caused production of ROS via Rac-1 membrane translocation and activation. The Rac-1 activation and ROS liberation mediated TNF-stimulated NF-kappa B activation and the subsequent VCAM-1 and ICAM-1 expression. Extracellular-signal-regulated kinase 5 (ERK5) plays a central role in inhibiting endothelial inflammation. Immune complex kinase assay of protein extracts from HAECs treated with atorvastatin revealed increased ERK5 activity in a time- and dose-dependent manner. In addition, pretreatment with atorvastatin inhibited TNF-alpha-induced LY2090314 order ROS production and VCAM-1 and ICAM-1 expression. Chemical or genetic inhibition of ERK5 ablated the statins inhibition of Rac-1 activation,

ROS formation, NF-kappa B, VCAM-1 and ICAM-1 expression induced by TNF-alpha. Taken together, statins, via ERK5 activation, suppress TNF-stimulated Rac-1 activation, ROS generation, NF-kappa B activation and VCAM-1 and ICAM-1 expression in human ECs, which provides a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system. 2013 Elsevier Inc. All rights reserved.”
“Objectives: To examine the sexual behaviors and reproductive concerns among patients with moderate to complex congenital heart disease (CHD).\n\nBackground: There is a growing need to understand and address the psychosocial issues for older adolescents and young adults with CHD. Emerging sexuality is an issue for this age group and pregnancy for many women with CHD is risky. But, patients’ sexual behavior and reproductive concerns have not been studied.\n\nMethods: Young adults (19 – 20 years old; n=212) and adolescents (16 – 18 years old; n=144) with moderate to complex CHD reported their sexual behaviors and reproductive concerns. Data were compared to non-native samples from Canada and the United States.

The antioxidant activity of the compounds isolated was evaluated with two methods. Three published antitumor E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones entered the same tests to search whether they are endowed with antioxidant activity too. 3,3-Bis(4-amino-2,5-dimethoxyphenyl)-1,3-dihydroindol-2-one and the three antitumor agents showed a good chemical antioxidant activity.

(C) 2009 Elsevier Masson SAS. All rights reserved.”
“A series of small molecules consisting of a heterocyclic core flanked by two basic functionalities were synthesized and selleck chemicals llc screened for in vitro affinity at the human histamine H-3 receptor (hH(3)R). Nine of the twenty-eight compounds tested were found to possess a hH(3)R K-i of less than 5 nM and consisted of a diverse range of central hetero-aromatic linkers (pyridine, pyrazine, oxazole, isoxazole, thiazole, furan, thiophene, and pyrrole). One member of this series,

(4-isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone (37), was found to be a high affinity, selective antagonist that crosses the blood-brain barrier and occupies H-3 receptors after oral administration in the rat. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“The enkephalin signaling pathway regulates A-1155463 molecular weight various neural functions and can be altered by neurodegenerative disorders. In Alzheimer’s disease (AD), elevated enkephalin levels may reflect compensatory find protocol processes or contribute to cognitive impairments. To differentiate between these possibilities, we studied transgenic mice that express human amyloid precursor protein (hAPP) and amyloid-beta(A beta) peptides in neurons and exhibit key aspects of AD. Met-enkephalin levels in neuronal projections from the entorhinal cortex and dentate gyrus (brain regions important for memory that are affected in early stages of AD) were increased in hAPP mice, as were preproenkephalin mRNA levels. Genetic manipulations that exacerbate or prevent excitotoxicity also exacerbated or prevented the enkephalin alterations. In human AD brains, enkephalin levels in the dentate gyrus were also increased. In hAPP mice, enkephalin elevations correlated with the extent of A beta-dependent

neuronal and behavioral alterations, and memory deficits were reduced by irreversible blockade of mu-opioid receptors with the antagonist beta-funaltrexamine. We conclude that enkephalin elevations may contribute to cognitive impairments in hAPP mice and possibly in humans with AD. The therapeutic potential of reducing enkephalin production or signaling merits further exploration.”
“Objective: Controlled inpatient studies on the effects of food, physical activity (PA), and insulin dosing on glucose excursions exist, but such outpatient data are limited. We report here outpatient data on glucose excursions and its key determinants over 5 days in 30 adolescents with type 1 diabetes (T1D) as a proof-of-principle pilot study.

However, some patients suffer www.selleckchem.com/products/AZD7762.html from cognitive and emotional changes. These side effects are most likely caused by current spread to the cognitive and limbic territories in the subthalamic nucleus. The aim of this study was to identify the motor part of the subthalamic nucleus to reduce stimulation-induced behavioral side effects, by using motor cortex stimulation.\n\nMethods:

We describe the results of subthalamic nucleus neuronal responses to stimulation of the hand area of the motor cortex and evaluate the safety of this novel technique.\n\nResults: Responses differed between regions within the subthalamic nucleus. In the anterior and lateral electrode at dorsal levels of the subthalamic nucleus, an early excitation (similar to 5-45 ms) and subsequent inhibition (45-105 ms) were seen. The lateral electrode also showed a late excitation this website (similar to 125-160 ms). Focal seizures were observed following motor cortex stimulation.\n\nConclusions: To prevent seizures the current density should be lowered, so that motor cortex stimulationevoked responses can be safely used during deep brain stimulation surgery. (C) 2011 Movement Disorder Society”
“Bile acids are increasingly gaining attention since they were discovered to be activators of the transcription factor farnesoid X receptor (FXR) in addition to their well-established role in dietary lipid emulsification. Moreover,

the differential activation potency of bile acids on FXR,

which is due to structural variation of the ligands, generates the need for new analytical tools that are sensitive and specific enough PD-1/PD-L1 inhibitor to quantify the individual species of this complex class of compounds. Because bile acids undergo enterohepatic circulation, the additional assessment of a bile acid precursor as a marker for bile acid biosynthesis is used to differentiate between newly synthesised bile acids and bile acids reabsorbed from the intestine. This paper describes two new methods using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of the major unconjugated bile acids in human serum (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid and ursodeoxycholic acid) with their glycine- and taurine-conjugates as well as their precursor 7 alpha-hydroxy-4-cholesten-3-one (C4). Intra- and inter-day variation was less than 12% and accuracy was between 84% and 102% for all analytes. Extraction recovery was between 78% and 100% for the bile acids whereas it was 62% for C4 and limit of quantification values ranged from 2 nmol/l to 50 nmol/l for all compounds. These two methods have the practical advantage of requiring low sample volume (100 mu l serum for each method) and identical eluents, stationary phase as well as ionisation technique, so that they can be used in a combined way.