Mais en fait, il est probable que l’étude du coût énergétique, du V˙O2, ne soit pas une méthode appropriée pour appréhender les contraintes cardiovasculaires liées l’activité sexuelle. Il s’agit en effet d’une activité brève, discontinue, avec un pic d’activité court et, de plus, une respiration irrégulière entrecoupée de courtes apnées (rendant PS-341 clinical trial l’analyse des échanges gazeux délicate). Tous ces éléments pourraient laisser penser qu’un certain niveau de capacité fonctionnelle est indispensable pour pouvoir réaliser un rapport sexuel. Cette vision est toutefois probablement trop restrictive et réductrice. On sait bien que des individus âgés conservent

une activité sexuelle régulière et satisfaisante alors même que leur performance, en termes de V˙O2, est probablement en deçà

des chiffres habituellement cités. Il est donc probablement peu pertinent de limiter l’activité sexuelle des patients cardiaques sur la seule base de leur capacité à l’effort, évaluée par la puissance développée lors d’un test d’effort, la mesure du V˙O2 ou, surtout, la capacité à monter deux étages. Une des questions fondamentales est bien sûr de savoir s’il existe un risque de complication cardiovasculaire, comme un infarctus ou une mort subite, au cours de l’activité sexuelle. C’est bien sûr le cas puisque toute activité physique accroît, temporairement au moins, le risque de complication cardiovasculaire. Ce risque est SB431542 cell line néanmoins très faible. L’une des études les plus importantes sur le sujet a été conduite par Parzeller et al. [15] and [16] à Francfort. Elle porte sur 27 années GBA3 entre 1972 et 2004 et concerne 32 000 autopsies. Seuls 68 cas de décès ont pu être reliés à la pratique d’une activité sexuelle, chez des femmes dans 5 cas et des hommes dans 63 cas. L’incidence annuelle de décès cardiovasculaire au cours de l’activité sexuelle dans cette étude est donc d’1,9 pour 1000 autopsies chez les hommes et 0,16 pour 1000 autopsies chez les femmes, ce qui montre d’ailleurs bien, indirectement,

la différence en termes de contrainte cardiovasculaire au cours de l’acte sexuel entre homme et femme. La cause du décès était un infarctus dans 28 cas, une récidive de nécrose dans 19 cas et un accident vasculaire cérébral hémorragique dans 7 cas. Il paraît intéressant de préciser que, dans la publication de 2001 [16], 36 décès sur les 48 constatés à l’époque (75 %) étaient survenus au cours de relations extraconjugales, en particulier avec des prostituées (n = 25). Les décès de femmes lors de relations extraconjugales sont en revanche particulièrement rares avec très peu de cas décrits dans la littérature [17]. Cette augmentation du risque de complication cardiovasculaire au cours de l’activité sexuelle concerne l’acte sexuel lui-même et, globalement, les deux heures suivantes [13].

We therefore assayed the supernates

from groups undergoing enhanced apoptosis for those 2 cytokines (some individuals were excluded), and a proportional increase of TNF-α levels was evident only for the HD group (Fig. 3a; p < 0.004). However, this finding did not mirror that of the UV group since the rates of TNF-α remained undetectable even in the presence of BCG infection at both time-points. Also, there was a statistically significant difference at 24 h of infection when HD and UV groups were compared (p = 0.03). The pro-inflammatory cytokine IL-1β, for which cell-death induction is also one of its main functions [8], was also assayed. There was a marked MG-132 purchase increase in IL-1β levels that were directly proportional to the time of BCG infection in the HD group ( Fig. 3b; p ≤ 0.02). This pattern was also a trend in the UV group, but opposite to TNF-α, although it did not attain a statistically significant difference when compared to the baseline condition. Also, no discrepancy was found when evaluating the IL-1β levels between the 2 cohorts Gefitinib cell line in this last, resting condition (p = 0.85). It has been previously shown that mycobacteria are able to induce macrophage apoptosis, and the inhibition of this critical mechanism might be considered an evasive strategy of the pathogen [Reviewed by 6]. Evasion of apoptosis

by M. tuberculosis can be achieved in human macrophages by enhanced release of sTNFR2 [6], Mcl-1 [10], bcl-2 PAK6 and Rb [11], and lower productions of prostaglandin E2 [12], bad and bax, and caspases-1, -3 and -10 [11]. On the other hand,

necrosis can be looked at as a good strategy induced by pathogenic mycobacteria to skew the protective host immune response. Since 2005, a novel form of proinflammatory programmed cell death, or pyroptosis, has been identified to be uniquely dependent on caspase-1, which is not involved in apoptosis, and prototypically induced by infection with flagellin-expressing bacteria, such as Salmonella and Shigella species [13]. To date, pyroptosis seems to play a significant role in specific biological systems. It has been previously shown that this mechanism releases bacteria from macrophages and exposes the bacteria to uptake and killing by reactive oxygen species in neutrophils [14]. Similarly, activation of caspase-1 cleared intracellular Legionella pneumophila and Burkholderia thailandensis in vivo by IL-1β-independent mechanisms, an efficient bactericidal mechanism by the innate immune system [14]. In this study, we did not check whether pyroptotic cell death takes place in our system; however, based on the latest notion highlighted by those authors, the increased IL-1β levels found in the cultures could not support this possibility. With this in mind, and regarding M.

However, very little is known of these responses shortly after booster vaccination or natural exposure in immunized children. Early measles vaccination primed IFN-γ memory T-cell responses to nucleoprotein peptides which were significantly greater at 9 months of age in immunized than unimmunized infants. However some of the unimmunized infants in group 1 had responded to these peptides suggesting that common infections such as cytomegalovirus or Epstein-Barr virus selleck chemicals llc prompt such responses [24]. At 18 and 48 months of age IFN-γ memory responses were readily detectable and similar in the two groups of children. Maternal

antibody had no effect on these responses nor were they influenced by the number of times the child had been immunized. Surprisingly ex vivo measles IFN-γ

effector responses two weeks after vaccination did not differ between those receiving primary vaccination (group 1) or secondary vaccination (group 2). After a further boost at 36 months of age effector responses to E-Z virus were similar in both groups and in neither group was there a rise after the boost. However there was a small but significant rise to fusion find more peptides which did not differ between the groups. Prime boost studies using recombinant Modified Vaccinia Ankara/TB vaccines in man [25] and DNA/measles vaccines in monkeys [17] indicate that maximum IFN-γ ELIspot responses occur 1–2 weeks after the booster immunization. Thus we are confident that the lack of a response after the booster

doses was real and not due to late sampling. However macaques primed with DNA/measles protein vaccines raise cytotoxic T-cell, IFN-γ and antibody responses within 14 days of challenge with live virus [17] and [26]. Perhaps in our study the attenuated vaccine virus did not multiply sufficiently in the presence of antibody to raise a cell mediated immune response. There were no significant Bay 11-7085 differences in plasma cytokine levels between the groups before or after the 36 month booster dose which resulted in a significant fall in IL-10, IL-2Rα and MIP-1β concentrations in both groups after the boost. This was not mirrored by changes in FOXP3 mRNA expression which were expected to increase [27]. We found no relationship between maternal or vaccine derived measles antibody concentrations and IFN-γ ELIspot numbers or cytokine levels after primary or secondary immunization. Similar findings have been noted following primary measles immunization in infants [23] or after secondary immunization in children [28] or after measles in children [29]. Intracellular cytokine staining showed that CD4 and CD8 T-cells were equally prominent producers of IFN-γ during the effector response and that both cell types a produced IL-2 in memory responses.

SDS-PAGE analysis showed purity of >95%. Its functionality was verified by its ability to form the stable C3-convertase [47]. The VCP http://www.selleckchem.com/products/epacadostat-incb024360.html specific mAbs were generated by immunizing 5–6 week old BALB/c mice with the rVCP. In brief, mice were immunized with 20 μg of rVCP in Freund’s complete adjuvant, followed by two boosts 15 days post prime at weekly intervals with the same dose, but in Freund’s incomplete adjuvant. Following immunization, spleen was removed and the spleen cells were fused in-house with myeloma cells as per established protocols [48] and [49]. The clones from the fusion were screened by ELISA and subcloned to isolate the individual clones.

Antibody isotyping was performed by an ELISA-based hybridoma isotyping kit (BD Biosciences, San Diego, CA, USA). The IgG mAbs were purified by capryllic acid precipitation method or by Hi-Trap affinity protein G column (GE Healthcare Bio-Sciences, Sweden). Homogeneity of mAbs was assured by SDS-PAGE analysis. VACV pathogenicity studies were performed in rabbits using skin lesion model [36]. In brief, 104 pfu of VACV-WR strain in sterile PBS in a total volume of 100 μl were injected intradermally with or without the mAb on the shaved backs of two New Zealand White GDC-0941 molecular weight rabbits (age 6–7 months) in duplicate and lesions formed (scabs) were measured after every 24 h using calipers. The mean of four measurements was used for graphical representation

of individual time point per site. To study the role of complement during infection, similar experiments were also performed in two additional rabbits depleted of complement by administering 100 U/kg of cobra venom factor.

All the results were grouped and statistically evaluated by performing Mann–Whitney Rank Sum test (SigmaStat). The experimental protocol was approved by the Institute’s Animal Care and Use Committee. The ELISA plates were coated overnight at 4 °C with rVCP or VCP mutants (CCP 1–3, CCP 2–4, CCP 1–2, CCP 2–3, CCP 3–4; 200 ng/well), blocked by adding 5% milk and incubated with mAbs (1 μg/well) for 1 h at room temperature. Binding was probed by adding 1:2000 diluted anti-mouse HRP conjugate (Biorad, Hercules, Tolmetin CA) and detected with 2,2′-Azino-bis (3-ethylbenzthiazoline) 6-sulfonic acid (ABTS) (Roche, Mannheim, Germany) at 414 nm. Inhibition of factor I cofactor activity of VCP by mAbs was determined as described below. rVCP (0.5 μg) was mixed with 3 μg of mAb and incubated for 15 min at 37 °C. Thereafter, 3 μg of C3b or C4b and 0.1 μg of factor I was added to the reaction mixture and the volume was adjusted to 20 μl using PBS. It was then further incubated at 37 °C for 2 h. The reaction was stopped by adding SDS-PAGE sample buffer containing DTT and C3b/C4b cleavages were analyzed on a 10% SDS-PAGE gel [40]. Inhibition of the classical pathway decay-accelerating activity of VCP by mAbs was determined by utilizing a hemolytic assay [42] and [50].

The company has to assess the epidemiologic data and balance the costs. In Africa, opinion leaders support vaccine manufacturers, and investors can expect the economic improvement in the future. A. Muktadir from Incepta (Bangladesh), shared the story of how he started the business and illustrated the biggest challenges. One challenge comes from the PQ barrier because the local NRA is not considered fully functional. The simple motivation is to develop high quality vaccines for those people who need them. Dr. Muktadir expressed appreciation for the platform provided by DCVMN and expressed his interest in seeking partners for vaccine technology transfer to Bangladesh.

A. Poonawalla from Serum Institute PD0332991 solubility dmso of India, shared his successful business experience, and noted that patience and continuous investment are very important while fostering cooperation with international organizations, particularly to achieve PQ. Challenges such buy Talazoparib as to integrate the manufacturers, the donors and the NGOs into one common philosophy do exist. He gave two suggestions to DCVMN members: to establish strong R&D and quality systems and to register the

products in as many countries as possible. All CEOs agreed that DCVMN created a remarkable and vibrant platform to share knowledge and communicate solutions to emerging issues. It was concluded that entrepreneurial thinking is important to make changes happen and the Network community

is serving a society where access to preventive vaccination will be fully met everywhere to assure supply of needed vaccines for future generations. The authors are employees of the respective indicated organizations, and have no conflict of interest to declare. DCVMN International did not provide any financial support to speakers or moderators to participate at this meeting. We are grateful to all speakers and moderators, whose gracious participation and contributions made the conference possible. We are indebted to the US Human and Health Services (HHS) Department for the in-kind support of the registration website. We are grateful to the local organizing committee and to all volunteers who helped preparing and during the conference, especially Ms. Lan Huong for coordination Chlormezanone of many logistic aspects of the conference. We thank Vabiotech and corporate partners for supporting DCVMN educational activities in 2013 with grants:Polyvac, Merck Millipore, Temptime, Bioengeneering, SGS, Alfa Wassermann, GEA, Bosch. This conference was partly supported by a grant of the Bill and Melinda Gates Foundation, Grant no. OPP1097005. “
“An update of Intravacc’s Sabin IPV technology Transfer Initiative to developing countries vaccine manufacturers as a Private Public Partnership directly under the Ministry of Health in The Netherlands was provided by A. Hamidi.

Despite extensive investigations demonstrating that immune responses are induced by many experimental DNA vaccines and that their character and magnitude can be readily manipulated, many of the processes noted above, related to DNA vaccines are still a “black box” with respect to the precise cell phenotypes, cell–cell interactions and

anatomical and temporal aspects of the initiation and maintenance of DNA vaccine immune responses. Studies such as these are difficult because of the paucity of tools necessary Akt cancer to investigate these low frequency events, but crucial for the rational design and application of DNA vaccines. We have therefore applied a variety of novel tools to address these questions directly in vivo for the first time. Following intramuscular injection, free and cell-associated pDNA has been found in muscle, peripheral blood [24], lymph nodes draining the injection site [19] and other sites including the bone marrow [25], minutes to months after injection [19], [26], [27] and [28]. Similar to others [19], we found labelled, cell-associated pDNA in the peripheral blood within 1 h of DNA injection and within cells of distal LNs, spleen and bone marrow by 24 h. We have not excluded the possibility that cells may be responsible for pDNA transport to the spleen and bone marrow, however our finding of pDNA in peripheral

blood within 1 h suggests that pDNA is carried as free DNA. Contrary to recent reports [29] we found no evidence for naïve CD4 T cell priming in the BM following pDNA injection. Our finding of pDNA-bearing selleck products cells in this site may have important consequences for both mobilisation of APC precursors from the BM into the periphery, as well as the maintenance of long-term memory following DNA vaccination. Our data suggests that CD11b+B220−MHCIIlow cells in the BM acquire pDNA. This phenotype is consistent with monocytes or neutrophils [30] which migrate from sites of inflammation to the BM and lead to antigen presentation directly or following engulfment by another APC [30]. Although it is understood that DNA vaccines

result in sustained Ag expression at the site of injection [31], in some cases more than 12 months [16], [31], [32], [33] and [34], the exact contribution of this Ag to initiating and maintaining immune responses is far from clear. Phosphatidylinositol diacylglycerol-lyase The cell types engaged in antigen production following intramuscular pDNA injection are predominantly myocytes, although direct transfection of, and antigen expression by, haematopoietic cells (including CD11b+ cells) at the injection site, has been reported [21], [35] and [36]. Although it is believed that somatic cells such as myocytes serve as Ag factories, that continue to “tickle” naïve and perhaps memory cells, precisely how and when Ag gets from these Ag depots to CD4 and CD8 T cells in secondary lymphoid tissue is not clear.

Pyruvate kinase (PK) is a ubiquitously expressed key glycolytic enzyme that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the generation of ATP and the altered expression could be expected to impair the glucose metabolism and energy production. PK is regulated by its own substrate phosphoenolpyruvate and fructose-1, 6-bisphosphate, an intermediate in glycolysis which both up-regulate PK. The observed decrease in the activity of PK in the liver http://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html and kidney of STZ induced diabetic rats readily accounts for the decreased utilization of glucose (glycolysis) and increased production of glucose (gluconeogenesis) by liver and kidney indicating

that these two pathways are altered in diabetes.48 Oral administration of MFE to STZ-induced diabetic rats resulted in a significant increase in the activity of PK. The improved activities of hexokinase and PK advocate the active utilization JNJ-26481585 of glucose. Pozzilli et al 49 has shown increased activity of LDH in diabetes mellitus. An increase from the resting level of lactate induces the pathway of gluconeogenesis which is indicated by a rise in the activity of lactate dehydrogenase. The LDH system reflects the NAD+/NADH ratio indicated by the lactate/pyruvate ratio in hepatocyte cytosol. 50MFE treated diabetic rats restored

the LDH activity probably by regulating the NAD+/NADH ratio thereby stimulating the oxidation of NADH. Normal LDH activity

is indicative of improved channeling of (pyruvate) glucose for mitochondrial oxidation. Glucose-6-phosphatase, a gluconeogenic enzyme, catalyzes the dephosphorylation of glucose-6-phosphate to glucose.51 Fructose-1, 6-bisphosphatase is another gluconeogenic enzyme that catalyzes the dephosphorylation of fructose-1, 6-bisphosphate to fructose-6-phosphate serves as a site for the regulation of gluconeogenesis.52 The increased activities of Sodium butyrate glucose-6-phosphatase and fructose-1, 6-diphosphatase in liver and kidney of the STZ induced diabetic rats may be due to insulin inadequacy. Upon treatment with the MFE the activities of glucose-6-phosphatase, fructose-1, 6-diphosphatase were found to be dwindled. This might be due to improved insulin secretion, which is responsible for the repression of the gluconeogenic key enzymes. Glucose-6-phosphate dehydrogenase is the rate-limiting enzyme of the pentose phosphate pathway.53 The activity of glucose-6-phosphate dehydrogenase is found to be decreased in diabetic conditions.54 Oral treatment of MFE to STZ induced diabetic rats significantly increased the activity of glucose-6-phosphate dehydrogenase. It seems to increase the influx of glucose into the pentose monophosphate shunt in an exertion to cut high blood glucose level.

NZW rabbits (n = 6/group) were immunized by two 0.5 ml injections into the right quadricep muscles find protocol with 1 × 1010 particle units of antigen expressing adenovirus vector using a 26G needle. For T cell studies, spleen cells from immunized or control mice

were harvested for use in IFN-γ ELIspot assays (n = 6 mice/group, assayed in pools) or intracellular cytokine staining assays (n = 6 mice/group, assayed individually) at 2 or 6 weeks after the final immunization. For antibody studies, sera from immunized or control mice (n = 6 mice/group, assayed individually) were collected 2 or 6 weeks after each immunization. A549 cells in a 12-well plate were infected at 70% confluence with various adenovectors at a MOI of 200 pu/cell for 1 h and then overlayed with DMEM medium containing 5% FBS. Twenty-four hours later, cells were washed 3 times for 5 min each with PBS and fixed with 4% paraformaldehyde (1 ml) for 30 min at room temperature. Cells were washed with PBS again and incubated for 2 h at 37 °C with primary antibody (1:200) in PBS containing 0.5% BSA ± 0.1% saponin for cell permeablization. Cells were again washed 3 times with PBS and incubated for 1 h at 37 °C with secondary antibody conjugated with fluorescein isothiocyanate (FITC) (1:200) in PBS containing 0.5% BSA. Cells were viewed using a Nikon Labophot II microscope and images were acquired using

a Spot RT digital camera. The 4G2 monoclonal antibody was used for analysis of AMA1 expression and the polyclonal R94256 antibody was used for analysis

of MSP142 expression. A549 cells in a 12-well plate were infected at 70% confluence with various adenovectors Epigenetic inhibitor at a MOI of 200 pu/cell for 1 h and then overlayed with DMEM medium containing 5% FBS. Twenty-four hours later, cells were trypinized, collected, and prepared for FACS analysis. For cell surface staining, cells were directly fixed with CytoFix/CytoPerm (BD Biosciences, San Jose, CA); for intracellular protein staining, Adenylyl cyclase cells were treated with cytoperm/cytofix (BD Biosciences) to fix and permeablize the cell membrane, prior to staining with the MSP-specific polyclonal antibody R94256. Glycosylation of AMA1 or MSP142 variants was analyzed with N-glycosidase PNGase F or Endo H (New England Biolabs, Ipswich, MA). PNGase F is an amidase that cleaves between the innermost GlcNAc and asparagine residues of complex oligosaccharides from N-linked glycoproteins. Endo H is a recombinant glycosidase which cleaves within the chitobiose core of high mannose and some hybrid oligosaccharides from N-linked glycoproteins. A549 cells at 80% confluence were infected at a MOI of 200 pu/cell with the indicated vectors expressing either AMA1 or MSP142. Twenty-four hours later the media was removed, the wells were washed 3 times with PBS and the cells were lysed in 3 ml of RIPA buffer (20 mM Tris [pH 7.4], 137 mM NaCl, 10% glycerol, 0.1% sodium dodecyl sulfate [SDS], 0.5% deoxycholate, 1% Triton X-100, 2 mM EDTA).

Use of P0 was found to improve the correlation as compared to the conventional in vitro Papp ( Avdeef, 2011). In Avdeef (2011), the IVIVC P0 analysis for published data from porcine models gave a correlation coefficient, r2 of 0.58 (P < 0.001).

In the present study, the r2 improved slightly from 0.58 to 0.61 for the pooled data, for a total of 35 measurements (22 compounds). The r2 obtained for the P0 IVIVC analysis in the present study is lower than reported for an in vitro bovine BBB co-culture model ( Lundquist et al., 2002 and Cecchelli et al., 2007). In those studies, linear correlation was tested for in vitro Papp vs. in vivo BUI data of ten compounds; r2 of 0.86 was reported. The lower r2 in the present study could result from uncertainties in P0 derivation, e.g. when the GDC-0199 price measured data were too close to one of the DRW boundaries (either

ABL or paracellular limit), or when judgement has to be made to determine pKaFLUX AUY-922 price from assays for ionizable compounds conducted at a single pH of 7.4, which is common for BBB research. The low r2 may also reflect the use of pCEL-X predicted in situ P0 values (acetylsalicylic acid and neramexane) and Caco-2 values (dexamethasone and metoprolol) to fill in gaps in the rodent in situ brain perfusion database. The focus of the applications so far has been to derive or predict the transcellular passive permeability in vivo. Hence, in situ data for the training set were selected from studies which used transporter knock-out animals, transporter inhibitors or high concentration of compounds to saturate transporters Metalloexopeptidase ( Dagenais et al., 2009). Compounds reported to show saturable transport were excluded. In the present study, the assays for uptake compounds were not conducted in the presence of inhibitors or saturating concentrations.

Therefore, the permeability values obtained were in some cases different from predictions. The differences in transporter expression in different species (pig and rodent) and also in different models used i.e. in vitro and in vivo could also influence the r2. In the present study, the data collected reflect evolution of the in vitro PBEC model from a low TEER cell monolayer (below 200 Ω cm2) to high TEER cell monolayer (>1000 Ω cm2) used for permeability assays and the new knowledge of the restrictive effect of polyester filter membrane (Transwell®-Clear) on permeability of lipophilic compounds. The cell monolayer tightness and filter boundary define the DRW which influences P0 derivation, hence could also influence r2. The larger numbers of compounds in the IVIVC analysis in the present study cover a wider chemical space compared to the correlation analysis of ten compounds reported by Lundquist et al. (2002) which will also influence r2.

17 Male Wistar rats weighing between 150 and 200 g were used for this study. The animals

selleck screening library were placed at random and allocated to treatment groups in polypropylene cages with paddy husk as bedding. Animals were housed at a temperature of 24 ± 26 °C and relative humidity of 30–70%. A 12:12 light:day cycle was followed. All animals were allowed to free access to water and fed with standard commercial pelleted rat chaw (M/s. Hindustan Lever Ltd, Mumbai). The Institutional Animal Ethics Committee approved (Project No. 864) the animal experiments and the guidelines for animal care were followed, as recommended by the Indian National Science Academy. Test materials were administered as mg/kg body weight CB-839 in vitro of animals. Rats were divided into 5 groups (G-I to G-V) of six each. G-I served as normal control and received 0.5% (CMC) carboxy methyl cellulose suspension (1 ml/kg) once daily for 7 days. G-II served as PCM control, received paracetamol (2 g/kg) for seven days. G-III served as reference control, received silymarin (200 mg/kg) once daily for 7 days along with PCM (2 g/kg). G-IV and G-V were treated with MEMV (100 mg/kg and 200 mg/kg respectively) once daily for 7 days along with PCM (2 g/kg). All the test drugs and PCM were administered

orally by suspending in 0.5% CMC solution. After 24 h of last dose of PCM, the blood was collected from retro plexus, after blood collection, the animals were sacrificed by cervical dislocation and the liver was dissected out and used for biochemical studies and histological examination. The blood for collected from the rats was used for biochemical analysis. The blood was allowed to clot and centrifuged

(Remi, Mumbai) for separation of serum. The serum was separated and used for assay of Alanine amino transferase (ALT), Aspartate amino transferase (AST), Alkaline phosphatase (ALP) by standard methods using enzyme assay kits. Albumin, triglycerides and serum bilirubin were also measured by kits method according to the instructions provided by the company (E–Merck, Germany). The catalase activity was measured according to method of Sinha et al.18 The level of lipid peroxidation in liver homogenate was determined by the method of Buege and Aust.19 Hepatic reduced glutathione (GSH) level was determined by the method of Ellman modified by Jollow et al.20 Liver pieces preserved in 10% formaldehyde solution were used for histopathological study. The liver tissues were placed in plastic cassettes and immersed in neutral buffered formalin for 24 h. The fixed tissues were processed routinely, embedded in paraffin, cut into 4 μm-thick sections and stained with hematoxylin and eosin (H&E). The extent of paracetamol-induced hepatic damage was evaluated by assessing the morphological changes in the liver sections.