60 μg/ml in DPPH and 53 80 μg/ml in superoxide radical scavenging

60 μg/ml in DPPH and 53.80 μg/ml in superoxide radical scavenging model for E. viride roots. Histopathological findings indicated that administration of E. viride roots extract offered protection to the hepatocytes from damage induced by paracetamol, with mild fatty changes in the hepatic parenchymal cells, which corroborated the changes observed in the hepatic enzymes. It also showed regenerating liver cells around the necrotic area ( Fig. 4, Fig. 5 and Fig. 6). Paracetamol-induced acute liver damage as an experimental XL184 mw model of drug-induced acute hepatic necrosis is well-established.26, 27 and 28 The mechanism by which,

paracetamol-induced hepatocellular injury and death involves its conversion to a toxic highly reactive and cytotoxic intermediate metabolite, N-acetyl-para-benzoquinonimine (NAPQI). Normally, paracetamol is primarily metabolized via cytochrome P-450 to form the highly electrophilic NAPQI [26] which is eliminated by conjugation with glutathione (GSH) and further metabolized

to a mercapturic acid which is excreted in the urine. 29 In the present investigation it was observed that the administration of paracetamol increased the levels of serum marker PD0332991 enzymes significantly (P < 0.001) which is an evidence of existence of liver toxicity, ( Table 1). There was a significant (P < 0.001) restoration of these enzyme levels on administration of the E. viride roots extract in a dose dependent manner and also by silymarin at a dose of 25 mg/kg. The reversal of increased Rutecarpine serum enzymes in acetaminophen induced liver damage by the extract may be due to the prevention of the leakage of intracellular enzymes by its membrane stabilizing activity. The possible mechanism by which ethanolic extract of E. viride roots exhibited significant protection against paracetamol-induced hepatotoxicity may be due to the active constituents present in various ingredients like flavonoids, alkaloids, sterols etc and its free radical scavenging activity. Present investigation also revealed that ethanolic extract of E. viride roots decreases the formation of ROS and reactive nitrogen species (RNS) such as superoxide anion, hydroxyl

radical, and hydrogen peroxide, and nitro oxide and peroxynitrite, respectively, ( Table 2). Decrease levels of ROS and RNS can leads to decrease lipid peroxidation, and increase level of the antioxidant enzymes (SOD, CAT, GPx). In conclusion, the present study has demonstrated that the ethanolic extract of E. viride roots has hepatoprotective activity against paracetamol-induced hepatotoxicity in rats and it may be due to their anti-oxidant property. All authors have none to declare. The authors are grateful to Principal, Management of Vasavi Institute of Pharmaceutical Sciences, India for providing necessary facilities to carry out this research project and we thank JPR Solutions for funding in publication of this research.

The bergamot’s peel contains flavonoids and pectins, a potent sou

The bergamot’s peel contains flavonoids and pectins, a potent source of natural antioxidant/anti-inflammatory

phytochemicals. 12 The bergamot’s extract is found to be valuable in curing beta-thalassemia disease. Its extract has the ability to maintain differentiation of K562 cells and induction of erythroid production. Bergamot extract contains bergapten, bergamottin and citropten. Bergapten and citropten enhance the HbF level in K562 cells. Bergamot extract is less efficient in inducing erythroid cell differentiation and its activation value for erythroid differentiation is found to be same as hydroxyurea. Bergapten and citropten are responsible for erythroid differentiation and their biological activity is similar to that of ara-C and mithramycin. The biological activity of different bergamot extracts and the natural compound Etoposide ic50 have been checked by using three experimental cell systems (a) human leukemic K562 cell line (b) K562 cell clones, and (c) human erythroid progenitors isolated from normal donors. This approach may prove useful for identifying molecules capable of inducing HbF production in erythroid precursors (derived from normal donors and beta-thalassemic patients). 13

Romidepsin is commonly referred by different names such as FK228, NSC 630176, FR 901228, istodax and depsipeptide. Romidepsin is a pentapeptide extracted from Chromobacterium violaceum found in the Japanese soil sample. Its chemical

structure consists of four different amino acids (l-valine, d-valine, Z-dehydrobutyrine, BKM120 chemical structure d-cysteine) and also (3S,4E)-3-hydroxy-7-mercapto-4-heptenoic acid. 14 The experimental results have shown that romidepsin is a potent inducer of HbF. It is effective even in picomolar concentration. It has been observed that when BFU-e (burst forming unit erythroid) cells are cultured in the presence of romidepsin of 100 pM concentration, the amount of F-erythroblasts gets increased from 13.3% to 34.9%. 15 Although romidepsin has many therapeutic applications but its production yield is very low. 14 Wheatgrass (Triticum aestivum) is an essential part of Indian culture since ages. 16 It belongs Methisazone to the Poaceae family whose members are generally grasses. The use of T. aestivum L. has been cited in Ayurveda, an Indian herbal medicine system. This grass has many beneficial properties and is known for its diuretic, laxative, antibacterial, antioxidant, wound healing properties. It prevents and suppresses conditions like Pitta and Kapha. Now-a-days, it is used to optimize the level of blood sugar in diabetic mellitus patients. 17 Wheatgrass is called green blood due to the presence of high amount of chlorophyll content in it. Chlorophyll is the key chemical constituent present in wheatgrass. The compounds, chlorophyll and hemoglobin are similar in structure as both contain a tetrapyrrole ring.

7–1 0 million child deaths every year worldwide Over 90 serotype

7–1.0 million child deaths every year worldwide. Over 90 serotypes of pneumococcus exist, and

most disease caused by a limited number of serotypes show regional differences in serotype distribution. Ten- and 13-valent polysaccharide conjugate vaccines are widely used in Europe, the US and Australia, and protection is related to IgG, assessed by ELISA. Two vaccine manufacturers are unlikely to meet global demand. Thus serological criteria are essential for the evaluation of new formulations and new serotypes, and head-to-head comparison with licensed product is the preferred method of efficacy evaluation. Recommendations for pneumococcal conjugated vaccines were revised in 2009 [5] and the 1st. International Standard for Human Pneumococcal Serum was established [6] and is available [7] for strengthening the capability and the breadth of expertise in vaccines and to facilitate development of new vaccines and diagnostics. Everolimus solubility dmso V. Halkjaer-Knudsen, from Sandia National Laboratories for biorisk management, provided an overview of vaccine GMP production and containment programs for eradicating, emerging, carcinogenic, genetically modified organisms Erlotinib and other risks related to the biotechnology and vaccine industry. While GMP aims to protect end-users from an unsafe agent, biosafety aims to protect the environment from harmful agents, and biosecurity,

to protect bio agents from harmful uses. Vaccine production facilities should thus identify the chain of potential infectivity, from storage of pathogens, buildings and equipment procedures, to administrative controls and decontamination, ensuring that risks are controlled through surveillance and quarantine, as needed. Regulatory best practices, codes and standards, such as ISO guidance are widely available to manage risk related processes [8], [9], [10], [11], [12], [13], [14] and [15]. An international biorisk management document (CWA 15793:2011) [16], used by the WHO Smallpox Lab inspection program, and the

WHO GAP III draft [17] lay out a risk based strategic approach for mitigation measures and controls for emerging and re-emerging infectious diseases. New tailored facilities evolved to single-use bioreactors widely implemented, that matured to a range of single use products for cell cultivation, upstream and downstream STK38 processes, resulting in cost-effective flexible and scalable production suites, requiring almost no-cleaning validation, for easy switch of products, projects, and low cost start up process, increasing the complexity of regulatory oversight on equipment, disposable, and leachables. She recommended that manufacturers study the guidelines, reflect on risk analysis, and decide on solutions to be discussed with health authorities. A satellite symposium on new technologies for vaccine development and supply was hosted by Merck Millipore. M. Payne and S.Y.

After translation and back translation, NEWS-A and the IPAQ were

After translation and back translation, NEWS-A and the IPAQ were tested for their reliability and validity in a previous study conducted among 168 Hangzhou residents who had similar characteristics with the current study population. The results click here showed moderate to good test–retest reliability, construct validity, and criterion validity for the questionnaires (waiting to be published). Neighborhood-level built environment correlates

were assessed through in-the-field audits of neighborhood street segments. A typical neighborhood in most urban areas of China usually shows a shape of square or rectangle with 0.2 to 0.5 km2 in area. In this study, we extended 400 m out from each side of the original administrative boundaries to form a study area with 1.0 to 1.5 km2 in area. All the street segments in these 30 extended study areas were evaluated using environmental audit instrument, the China Urban Built Environment Scan Tool (CUBEST). A GDC-0941 concentration street segment was defined as a section of street or road between two intersections with a maximum length of 400 m. Street audit

was conducted by trained graduated students. A standard operating procedure for environmental audit was developed using detailed written instructions and field pictures to achieve uniformity in the performance of evaluation. A two-day intensive rater training was developed, including explanation of the principles, operation, potential problems and solutions of the CUBEST and GPS Resminostat positioning device. Seven aspects of neighborhood-level built environment were assessed, including: 1)

Access to commercial destinations; 2) Access to physical activity destinations; 3) Street connectivity; 4) Sidewalk quality; 5) Bike lane quality; 6) Esthetic quality; and 7) Safety from traffic. All environmental scans were conducted during daylight hours. The average time required for data collection was 6.2 min per segment. The CUBEST is a reliable and valid instrument that can be used to assess the physical activity-related urban built environment. Additional details about its development, reliability and validity test results are available in print (Su et al., 2014). Descriptive statistics were calculated for demographic, anthropometric, and SES variables. Body mass index (BMI) was calculated as weight divided by the square of height (kg/m2). The median and inter-quartile range was calculated for LTPA and LTW due to their skewed distributions. Participants who did not meet the moderate or high physical activity criteria were classified as physically inactive according to the IPAQ scoring procedure. After logarithmic transformation of MET-min score, t-test was used to compare physical activity between genders. The chi-square test was used to compare the proportion of physically inactive between genders.

However cellulose based materials are highly modifiable (Klemm et

However cellulose based materials are highly modifiable (Klemm et al., 2011), with which it is possible to improve the properties of NFC in drug release and retaining. Furthermore, this study did not focus on physical nor SP600125 price chemical properties of the molecules; however the native NFC is known to have a slight negative surface charge (Kolakovic et al., 2012 and Wang et al., 2011), thus it can be expected to have some repelling forces between the negatively charged 123I-NaI and 99mTc-HSA. Indeed, the results indicated that in the dual-radionuclide imaging study, the release of 123I-NaI was more rapid from the hydrogels than

from the control saline injections. The chemical properties are more important in smaller scale, thus the repulsion forces by the negative charges are greater than the hindrance of the nanofibrous matrix of the hydrogel itself, which relates to molecular size, www.selleckchem.com/products/Bosutinib.html a physical factor. 99mTc-HSA also has a negative charge; however

the size of the molecule is considerably larger than 123I-NaI, therefore the physical effect of the NFC matrix in the controlled release is more dominant. Positively charged molecules were not investigated in this study, however considering the effects of the negatively charged molecules (123I-NaI and 99mTc-HSA); it is likely that a more noticeable sustained release effect would be observed with positively charged molecules. In addition, during the study on 99mTc-HSA and hydrogel preparations, it is unlikely but possible that a small amount of the free/unbound pertechnetate from the HSA radiotracer would label the NFC matrix while mixing the 99mTc-HSA solutions with the biomaterial prior to injection. The labeling for both 99mTc-HSA and 99mTc-NFC utilized spontaneous stannous chloride reduction methods; therefore we believed the second labeling mechanism could be the same. In the case of erroneous

biomaterial labeling during the study, results would show as a false positive data of slower 99mTc-HSA release from the biomaterial, as some of the NFC would be labeled to 99mTc-NFC instead of the 99mTc-HSA. However, during the radiochemical purity test of the 99mTc-HSA, the amount of free pertechnetate was observed very low (impurities were found below the allowed 5% indicated by the manufacturer). Therefore, only the free portion of the radiolabel amongst the impurities of the total activity is theoretically able to form bonds with the NFC biomaterial, which would still amount to much less than 5% of the whole activity. This suggests that the 99mTc-HSA related data obtained in this study is still reliable, as the amount of possible erroneous activity detected from the biomaterial during the image acquisition is considerably lower. Most injectable biomaterials are prepared in solution, while the gelation is triggered by an external signal, for example phototriggering (Zhang et al.

The cost savings might

The cost savings might Caspase inhibitor clinical trial be the result of a preventive effect on knee injuries in the intervention group. Future research should primarily

focus on the preventive effect of specific exercises from The11 in relation to knee injuries, and the possible cost savings. Despite the lack of a proven preventive effect, the potential of a structured prevention program to reduce costs associated with injuries is of particular interest in view of the increasing healthcare costs worldwide. eAddenda: Figure 1, Table 4 available at jop.physiotherapy.asn.au Ethics: The study protocol was approved by the Medical Ethics Committee of the University Medical Centre Utrecht, The Netherlands; reference number 08/263.

All participants provided written informed consent before the start of the study. Funding: This study was funded by the Netherlands Organization for Health Research and Development (ZonMw), reference number 50-50110-96-554, and the Royal Netherlands Football Association (KNVB). The authors declare no conflicts of interest regarding the authorship or publication of this contribution. The authors gratefully acknowledge the financial support provided by the Netherlands Organization for Health Research and Development (ZonMw) and the Royal Netherlands Football selleck chemicals llc Association (KNVB). In addition, we would like to extend a special word of thanks to the Royal Netherlands Football Association (KNVB) for their support and co-operation. The authors appreciate the co-operation of the coaches, medical staff and soccer players of all participating soccer clubs who provided the data for this project. “
“Osteoarthritis

is the most prevalent articular disorder worldwide (Bijlsma 2002), with thumb carpometacarpal osteoarthritis being a common manifestation in Electron transport chain middle or older aged people (Pellegrini 2005). Thumb carpometacarpal osteoarthritis involves degeneration of the joint articular surfaces, with associated hyaline cartilage loss, ligament laxity, osteophyte formation, synovial inflammation, and muscle weakness (Pellegrini 2005). Advanced thumb carpometacarpal osteoarthritis is characterised by deterioration of the superficial surfaces of the joint and ectopic bone regeneration (Wajon and Ada 2005, Im et al 2010). The main symptom of this condition is pain at the base of the thumb, usually resulting in functional impairments in the performance of activities of daily living, and occupational and recreational tasks (Slatkowsky-Christensen et al 2007). In advanced disease, adduction contracture of the first web space with secondary thumb carpometacarpal hyperextension is also commonly seen (Wajon and Ada 2005).

Soluble proteins were purified from bacterial lysates by glutathi

Soluble proteins were purified from bacterial lysates by glutathione-affinity chromatography

as previously described [29], then analysed by sodium-dodecyl-sulphate (SDS) polyacrylamide gel electrophoresis (PAGE). GST-fused proteins from inclusion bodies (insoluble fraction) were dissolved in a CAPS buffer (CAPS 50 mM, DTT 1 mM and Sarkosyl 0.3%), hence denaturing the proteins [30]. The dissolved and denatured protein was dialyzed overnight against 20 mM Tris–HCl pH 8.5. Insoluble proteins dissolved in CAPS buffer/dialysed are referred find more to as ‘CAPS-denatured proteins’ throughout the text. Purified proteins were quantified by two different methods: (i) a Bradford assay at 595 nm and (ii) UV spectrophotometry at 280 nm (extinction coefficient determined from aa sequences of each fusion protein). Concentration measurements were consistent using both methods. Relative amounts of proteins to be injected were based on copy number considerations in a BTV particle, as determined by X-ray crystallography (780 copies for VP7, 360 copies for VP5 and 180 copies for VP2 [1]). Seven

groups of six Balb/c mice were injected subcutaneously at days 0, 14 and 28 with 100 μl of soluble protein/Montanide ISA 50V emulsion (Table 1). Three groups of six Balb/c mice were injected subcutaneously at days 0, 14 and 28 with 100 μl of CAPS-denatured protein/Montanide ISA 50V emulsion (Table 1). A group of six Balb/c mice were injected subcutaneously at days 0, 14 and 28 each with 100 μl of Zulvac-4® Bovis. Sera were used for normalisation of ELISA results. A group of six control Balb/c mice which were not immunised with any of the antigens was PFI-2 also included. Six groups of six IFNAR−/− mice were injected subcutaneously at days 0, 14 and 28 with: a mixture of VP2 Idoxuridine domain 1 (VP2D1) and VP2 domain 2 (VP2D2) in Montanide, then challenged with (i) BTV-4 or (ii)

BTV-8; or a mixture of VP2D1 + VP2D2 + VP5Δ1–100/Montanide, then challenged with (iii) BTV-4 or (iv) BTV-8; or a mixture VP2D1 + VP2D2 + VP5Δ1–100 + VP7/Montanide, then challenged with (v) BTV-4 or (vi) BTV-8 (Table 1). Blood samples were collected at day 0 and day 28. The mice received an intravenous lethal [31] challenge on day 40, with 103 pfu of BTV-4-italy03 (homologous-challenge), or 10 pfu of BTV-8-28 (heterologous-challenge). Blood was collected on the day of challenge (day 40), then at days 2, 3, 4, 5, 7, 10 and 12 p.i. Sera were tested for anti-VP2, anti-VP5 and anti-VP7 antibodies by ELISA and immunofluorescence and for NAbs by PRNT. Two groups of six IFNAR−/− mice were injected subcutaneously with VP5Δ1–100 on days 0, 14 and 28. These groups were not challenged with BTV-4 or BTV-8. Two additional groups of six IFNAR−/− mice were immunised with VP7 on days 0, 14 and 28, then challenged at day 40 with either BTV-4 or BTV-8. Two groups of non-immunised mice were used as positive controls, to confirm lethality of BTV-4 or BTV-8 challenge-strains.

7, 166 9, 151 4, 144 5, 136 7, 131 6 (2C), 130 1, 129 8 (2C), 113

ESIMS: m/z 575 (M+Na)+. Amorphous powder, [α]D25 + 12.7° (c 0.5,

MeOH); IR(KBr) νmax: 3409, 2923, 2853, 1501, 1370, 1198; 1H NMR (300 MHz, CD3OD): δ 7.06 (2H, s, H-2′, H-6′), 6.97 (1H, s, H-8), 6.89 (1H, s, H-5), 4.56 (1H, d, J = 6.3 Hz, H-4), 4.23 (2H, m), 3.80 (3H, s, OCH3), 3.76 (6H, s, 2 × OCH3), 3.32 (2H, m), 2.52 (2H, m, Ha-1, Hb-1), 2.12 (1H, m, H-3), 1.73 (1H, m, H-2). 13C NMR (75 MHz, CD3OD): δ selleck products 148.9 (2C), 147.2, 139.0, 138.6, 134.5, 129.9, 126.2, 107.7, 106.6 (2C), 104.5, 71.4, 66.1, 56.9 (2C), 56.6, 48.8, 46.6, 42.6, 33.8. ESIMS: m/z 391 (M+H)+. Amorphous powder, [α]D25 + 4°(c 0.5, MeOH); IR(KBr) νmax: 3406, 2923, 2853, 1502, 1370, 1198, 1H NMR (300 MHz, http://www.selleckchem.com/products/bmn-673.html CD3OD): δ 7.05 (2H, s, H-2′, H-6′), 6.97 (1H, s, H-8), 6.58 (1H,

s, H-5), 4.25 (1H, d, J = 6.5 Hz, H-4), 4.23 (2H, m), 3.80 (3H, s, OCH3), 3.76 (6H, s, 2 × OCH3), 3.40 (2H, m), 2.89 (2H, m, Ha-1, Hb-1), 2.01 (1H, m, H-2), 1.98 (1H, m, H-3). 13C NMR (75 MHz, CD3OD): δ 148.9 (2C), 147.2, 139.1, 138.7, 134.5, 129.9, 126.2, 107.7, 106.6 (2C), 104.5, 70.4, 66.3, 56.9 (2C), 56.6, 48.8, 46.6, 42.6, 33.8. ESIMS: m/z 391 (M + H)+. Amorphous powder, [α]D25 + 127° (c 0.5, MeOH); IR(KBr) νmax: 3409, 2932, 1703, 11273, 1176, 1094; 1H NMR (300 MHz, CD3OD): δ 7.32 (1H, s, H-3), 5.56 (1H, d, J = 3.7 Hz, H-1), 4.56 (1H, d, J = 7.7 Hz, H-1′), 3.91 (1H, dd, J = 5.3 and1.3 Hz, H-7), 3.89 (3H, s, COOMe), 3.78 (2H, m), 3.42–3.10 (4H, m), 2.85 (1H, d, J = 8. 9 Hz, H-9), 2.35 (m, 2H), 1.13 (3H, s, H3-10). 13C

NMR (75 MHz, CD3OD): δ 167.8, 152.3, 99.8, 93.4, 79.7, 78.8, 78.7, 78.5, 78.1, 77.5, 73.9, 70.9, 62.3, 57.8, 51.7, 45.6, 21.7. ESIMS: m/z 445 (M + Na)+. Decolorization of ABTS+ and DPPH free radicals scavenging activity of compounds was analyzed spectrophotometrically10 and inhibitory potential of compounds against glucose induced glycation of bovine serum albumin (BSA) was estimated spectrofluorometrically.11 From crude methanol extract of D. repens, seven compounds namely Caryoptoside (1), 8 Duraterectoside A(2), 7 Durantoside Resminostat III (3), 7 Durantoside I (4), 7 and (+) 5′Methoxyisolariciresinol (5), 9 (−)5′Methoxyisolariciresinol (6), 9 Lamiide (7) 7 were isolated based on a bioassay-guided fractionation and identified by comparison of their physicochemical and spectrometric data with reported in the literature. The structure of these compounds is shown in Fig. 1.

The metabolites specifically present in eight different classes o

The metabolites specifically present in eight different classes of S. asoca and two drugs were listed out. Further, the abundant metabolites which can act as representative of their groups were identified. UPLC have several advantages over the conventional techniques being a tool to give rapid and effective phytochemical fingerprints along with the quantization of selleck screening library marker compounds. The length of the column [250 mm] increased the column efficiency and concomitant resolution resulted separation of 4 peaks per min over a range of 4–40 min [Fig. 1]. With the help of

infused standards reproducibility of data was analyzed and retention time variability was found to be 2 s and a relative standard deviation of less than 4% was observed. Crude cold and hot water extracts of various parts of S. asoca and drugs samples were analyzed without considering any specific group of metabolites. Furthermore, no pretreatment was given to the samples to avoid discrimination and to get maximum number of metabolites. Fig. 1 shows total ion chromatograms to distinguish between bark, regenerated bark, leaves, flowers and drugs prepared from bark. A visual examination shows the differences between the samples employed in the study. Along with several unique peaks across the samples, a prominent peak at 39.9 min in the chromatograms

was observed only in regenerated bark samples [ Fig. 1A and B] which can be further exploited find more as a marker peak of regenerating bark. Q-TOF-MS provides accurate MS/MS spectra due to internal mass calibration during acquisition and mass drift compensation. In the present study, mass accuracy less than 3 ppm was obtained when compared with internal and external standards. Q-TOF-MS was operated in positive ion mode with a ramp setting for collision energy. On-an average 8261 molecular features were observed per sample when analyzed with a threshold 5000 counts per second. Most abundant metabolites were inspected carefully and marker compounds of different parts of plants and drugs were identified [Table 1]. Some of the compounds were identified by their characteristic

mass fragments and later on comparing the m/z pattern with MS/MS spectra available with http://spectra.psc.riken.jp. One unique and un-identified metabolite of 385.9094 m/z Sitaxentan was observed at retention time 39.98 min in the regenerated bark sample along with others described in Table 1. Prunasin was observed in both the Askokarishta samples at m/z 296.7617 with product ion m/z 276.76 due to prominent water loss from the molecule. These most abundant molecular features can be used as biomarkers of various plant parts. It also produces challenge for further research to identify these metabolites and the potential of scopes in natural product research. Furthermore, derivatives of catechin and protocatechualdehyde [data not shown] were found to be elevated during the qualitative analysis, in the re-generated bark along with feruloyl CoA.

Le handicap lié à la sévérité de la BPCO doit aussi être évalué,

Le handicap lié à la sévérité de la BPCO doit aussi être évalué, notamment l’impact sur les activités sociales. Plusieurs auto-questionnaires simples et courts peuvent contribuer à l’évaluation Alectinib du retentissement global de la maladie. Deux ont fait l’objet d’une validation internationale incluant la France :

le questionnaire CAT (COPD Assessment test), qui a même fait l’objet d’une validation spécifique en langue française [7], et le CCQ (Clinical COPD Questionnaire). Tous deux sont intégrés dans les recommandations internationales GOLD (Global Initiative on Obstructive Lung Disease) sur la prise en charge de la BPCO [8]. Enfin, le nombre d’exacerbations par an, c’est-à-dire les périodes d’aggravation aiguë des symptômes, non systématiquement d’origine infectieuse, qui ont justifié une intervention médicale, doit être pris en compte. Selon l’étude ECLIPSE, la fréquence annuelle des exacerbations est stable sur plusieurs années chez un même patient ; environ un quart des patients ne fait aucune exacerbation de BPCO en trois ans mais un quart en fait au moins quatre

sur cette même période buy STI571 [9]. Ce dernier quart correspond aux patients considérés comme des « exacerbateurs » fréquents. Le risque d’exacerbation est d’autant plus élevé que le VEMS est diminué et qu’il existe des symptômes de reflux gastro-œsophagien [9] and [10]. L’évaluation de la sévérité de la BPCO selon le niveau d’obstruction bronchique, la dyspnée et/ou le retentissement global de la maladie (score CAT),

et la fréquence des exacerbations a conduit à un nouveau classement des patients selon quatre catégories dans les recommandations internationales GOLD en 2011 [8]. Ce classement et sa déclinaison en stratégies thérapeutiques n’ont pas été entérinés par la SPLF [11] et la HAS, et ne seront pas décrits dans cet article. Outre l’atteinte respiratoire, la BPCO peut avoir des conséquences systémiques ayant un impact pronostique comme la dénutrition, l’atteinte musculaire, un Etomidate syndrome anxiodépressif avec un retentissement sur la tolérance à l’effort et la qualité de vie. Ainsi, l’index de BODE qui prend en compte l’obstruction bronchique avec le VEMS, la capacité d’exercice (test de marche de six minutes), les symptômes avec le score de dyspnée et l’indice de masse corporelle (IMC) est supérieur au seul VEMS pour prédire la mortalité. Les objectifs de la prise en charge sont résumés dans l’encadré 2[1] and [2]. Deux composantes ont souvent été opposées : les objectifs symptomatiques (dyspnée, tolérance à l’exercice, qualité de vie) et la modification de « l’histoire naturelle » de la maladie (mortalité, déclin fonctionnel respiratoire).