Top PDF Role of IRAK-M in alcohol induced liver injury.

Role of IRAK-M in alcohol induced liver injury.

Role of IRAK-M in alcohol induced liver injury.

sample was analyzed in triplicate and the experiments were repeated twice. All the samples were negative for 18S DNA indicating that there was no eukaryotic cell contamination. Figure 2. Liver injury after alcohol treatment in IRAK-M2/2 mice. To induce alcoholic liver damage, mice were fed with alcohol as described in Materials & Methods. (A) Serum ALT levels in control (CTL) and 10% alcohol treated (ALC, without binge) IRAK-M2/2 mice (red) compared with wild type B6 mice (blue). Data shown are from one of 4 experiments. (B) Serum ALT levels in control (CTL) and alcohol (10% and binge) treated (ALC) IRAK- M2/2 mice (red) compared with wild type B6 mice (blue). Data are from pooled 2 experiments. (C-F): Liver tissue was stained with standard H&E and liver histology was viewed under a light microscope (20X) by a blinded investigator. Data represent one of two independent experiments (n = 3–4 per group in each experiment). (C+D) Liver histology from a WT B6 mouse without (C) and with binge ALC exposure (D). (E+F) Liver histology from an IRAK-M2/2 B6 mouse without (E) and with binge ALC exposure (F). (G) Absolute number of LMNCs per gram liver tissue in control and alcohol treated mice. More infiltrating lymphocytes were found in IRAK-M2/2 mice (red) compared with wild type B6 mice (blue) after binge alcohol treatment. Data were from 2 pooled experiments and error bars represent the SD of samples within a group. The experiment was repeated twice. *P,0.05, **P,0.01, Two way ANOVA analysis.
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Bark Extract of Bathysa cuspidata in the Treatment of Liver Injury Induced by Carbon Tetrachloride in Rats

Bark Extract of Bathysa cuspidata in the Treatment of Liver Injury Induced by Carbon Tetrachloride in Rats

The samples of B. cuspidata were collected from a biome of Brazilian Atlantic forest in the municipality of Araponga in the state of Minas Gerais, Brazil (20°43`00.0``S e 42°29`10.8``W, 1.200 m altitude) and adequately documented in the herbarium of the Federal University of Viçosa under registration no VIC 21559. Stem bark samples were separated, dried for 48 h at room temperature in a darkened, well-ventilated room, pulverized in a knife mill and stored. The powered air-dried stem bark of B. cuspidata (500g) was extracted exhaustively with ethanol (95%) by percolation method. The extract was concentrated under vacuum at 50°C using a rotary evaporator and then lyophilized until complete removal of the solvent, yielding an ethanolic extract (139 g). Phytochemistry of the extract was performed on chromatography plates coated with silica gel GF 254 ® (Merck, Darmstadt, Germany) using different mobile phases and detection reagents in accordance with the protocol described by Wagner and Bladts (1996).
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Hepatoprotective effect of Alhagi sparsifolia against Alcoholic Liver injury in mice

Hepatoprotective effect of Alhagi sparsifolia against Alcoholic Liver injury in mice

conversion from alcohol to acetaldehyde, subsequently causing ROS over-production (Jimenezlopez, Cederbaum, 2005). The absence of CYP2E1 in knockout mice significantly lowered alcohol-induced oxidative stress and reduced lipid accumulation in the liver (Wang, 2010). Previous reports suggested that the great number of natural products and their active substances could inhibit CYP2E1. In the present study, the treatment of AH M (300 mg/kg) remarkably reduced the alcohol induced CYP2E1 expression. These findings demonstrate the protective effect of Alhagi sparsifolia alcoholic livery injury by reducing oxidative stress by down-regulating the CYP2E1 expression.
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The role of alveolar epithelium in radiation-induced lung injury.

The role of alveolar epithelium in radiation-induced lung injury.

Recently, chromatin remodeling via posttranslational histone modification was found to function in a genome-wide manner and contributes to an extensive range of biological functions [55]. Histone deacetylases (HDACs) are known as modulators of gene transcription, which is important for cell function, proliferation and differentiation. HDAC inhibitors have been reported to induce protein hyperacetylation, chromatin remodeling, transcrip- tional activation and repression, cell-cycle arrest, and cell death [56,57]. Preclinical studies indicate that HDAC inhibitors can effectively block cardiac, skin, liver and renal fibrosis [58]. In vitro and in vivo investigations indicate that HDAC inhibitors modulate fibrosis by suppressing ECM production, inhibiting myofibroblast activation, blocking EMT, and/or reducing pro-inflammatory cytokine production [11,59–63]. Furthermore, recent studies suggest that topical treatment of rat skin with HDAC inhibitor 4-Phenyl butyrate has been shown to promote wound healing, reduce skin fibrosis, and decrease tumorigenesis after irradiation
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Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Fig 4. The role of different opioid receptors subtype affecting infarction size in preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury. In the I/R model, animals were randomly allocated into 6 groups as described in Methods. They were 1) sham RES group (n = 24); 2) RES preconditioning group (n = 20); 3) RES preconditioning pretreated with KOR blocker (n = 18); 4) RES preconditioning pretreated with DOR blocker (n = 10); 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active (n = 11); 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active (n = 9). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (A), area at risk (B) and infarcted size (C). Data are presented as mean ± S.E.M and were analyzed using repeated one-way analysis of variance (ANOVA) followed by the Dunnet’s test. A p value less than 0.05 is considered statistically significant. *, p<0.05, vs. sham RES; #, p<0.05, vs. RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
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Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

Endovanilloid profiles were measured by Lipidomics GmbH (Berlin, Germany). Briefly, kidney tissue samples were subjected to alkaline hydrolysis and subsequent solid phase extraction was performed as described previously [26] [27]. LC-MS/MS analysis of the extracted metabolites was performed using the Agilent 6460 Triplequad mass spectrometer with Jetstream ion source (Agilent Technolgies, Santa Clara, CA) coupled with Agilent 1200 HPLC (degasser, binary pump, well plate sampler, thermostated column compartment). The HPLC system was equipped with a Phenom- enex Kinetex Column (150 mm62.1 mm, 2.6 m m, Phenomenex, Aschaffenburg, Germany). Tissue samples were analysed in two separate series of experiments, each using independent internal standards (deuterated eicosanoids and metabolites) added to the samples before extraction for the quantification of groups of similar metabolites. The first series of experiments determined eicosanoid profiles in non-ischemic (Control) and ischemic (I) kidneys 25 min after ischemia (without reperfusion) from a group of wild-type mice with ischemia (I)-induced AKI; the second series of experiments determined the profiles in non-ischemic (I/R Control) and ischemic (I/R) kidneys after 25 min of ischemia and 24 hours of reperfusion from the above described four groups of mice with I/R-induced AKI, namely control wild-type mice, capsaicin treated wild-type mice, capsazepine treated wild-type mice, and Trpv12/2 mice.
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Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

Administration of Vernonia cinerea, attenuated CCI induced rise in calcium ion and oxidative stress markers and it plays a critical role to produce the anti-nociceptive effects in painful peripheral neuropathy. The noted decrease in calcium levels with Vernonia cinerea may be attributed to its anti- oxidant effects and free radicals are well reported to increase calcium ions (Glass et al. 2002). However, the possibility of direct action of Vernonia cinerea decrease in calcium level remains to be explored. Moreover, increase in calcium ions is also associated with an increase in oxidative stress (Carriedo et al. 2000). So, the noted antioxidant effects of Vernonia cinerea may be the secondary effect in decrease of calcium ion level in sciatic nerve. Similar results were obtained in the pregabalin treated animals. Pregabalin is a potential voltage dependent calcium channel (α2–δ subunit) antagonist. It has also been reported to possess the potential role in the management of painful neuropathy in human and in experimental animals (Kumar et al. 2010). Vernonia cinerea extract was found to possess free radical scavenging activity and proinflammatory cytokine and TNF-alpha inhibition activity. Administration of Vernonia cinerea extracts in mice significantly increases the level of anti-oxidant markers such as catalase, superoxide dismutase, glutathione, glutathione peroxidase and glutathione-S transferase in blood and liver, whereas lipid peroxidation activity was significantly decreased (Pratheeshkumar and Kuttan 2010, Kumar and Kuttan 2009, Rajamurugan et al. 2011). Recent reports suggested that Vernonia cinerea has analgesic, anti-inflammatory, anti- oxidant, radical scavenging and inhibition of pro inflammatory cytokines like TNF-alpha (Pratheeshkumar and Kuttan 2010, Rajamurugan et al. 2011, Thiagarajan et al. in press).
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Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

methylprednisolone) or increasing doses of CNI were usually administered to these patients and, to some extent, precipitated the development of DILI. The x 2 test showed no correlation between DILI and acute rejection (AR) (p = 0.053) (Table 2). Percentage of AR recipient with DILI(20/112, 17.86%) was higher than no-AR (70/662, 10.57%), but in subanalysis, no statistical differences in genotype distribution and allelic frequencies of the CTLA4 polymorphisms were found yet in AR group and no-AR group. In our previous study [24], correlation between CTLA4SNPs and AR was found, whether AR is a risk of DILI or not need further discover. A larger sample size is necessary to confirm or reject the significance of this correlation. CTLA4 SNPs influencing to DILI was possibly an internal factor. The association between CTLA4 SNPs and liver damage has been studied in two papers. Kanno et al [17] identified that the CTLA4 +49 (rs231775) genotype was positively associated with liver damage in primary biliary cirrhosis (PBC) in Japanese populations and that PBC patients with the G/ G genotype had significantly higher serum levels of ALT, GGT, and IgM than did patients with the A/A or A/G genotype. Valenti et al [18] observed a significantly higher prevalence of the susceptible CTLA4 allele (both in the heterozygous [OR 2.5] and in the homozygous [OR 4.6] state) in patients with alcoholic liver disease (ALD) compared to healthy subjects; this relationship was independent of age, sex and geographical origin. The CTLA4 polymorphic G allele may confer susceptibility to ALD and, in the homozygous state, to alcoholic cirrhosis by interfering with the immune response. Ethnicity may influence a person’s susceptibility to DILI [25]. For instance, African-Americans were predisposed to anticonvulsant-induced DILI, while Caucasians are particularly prone to abacavir- and flucloxacillin-induced DILI [25]. The frequency of the G allele at the CTLA4 +49 (rs231775) locus was much higher in the Chinese population than in other populations [26]. This may indicate an even more significant role of this genetic bias. In addition, using log-rank analysis, we discovered that the rs231775 GG genotype was associated with an early onset of DILI (p = 0.039) (Table 5 and Figure 2).
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Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

Assessment of the Potential Role of Silymarin Alone or in Combination with Vitamin E and or Curcumin on the Carbon Tetrachloride Induced Liver Injury in Rat

Caspase-3-like protease was assayed according to the method described by Vaculova and Zhivotovsky (2008). For analysis of 8- Hydroxydeoxyguanosine ( 8-OHdG) formation, the DNA was extracted from the nuclear fraction with the DNA Extractor WB Kit (Asami et al.1996) To the extracted nuclear DNA (~ 100 mg/100 mL of 0.1 mM EDTA), 1 µL of 2 M sodium acetate, 4 µL of nuclease P1 (5 mg/mL, Yamasa Co., Japan, YA7801) and 2 µL of acid phosphatase (47 mg/mL, suspension in 1.8M (NH4)2SO4, Sigma, P-1435) were added and incubated at 37°C for 30 min. The 8-OH-dG content in the digested DNA was measured by an HPLC-ECD systems, as described previously (Nakaeet al.1995).TNF- α was measured using the ELISA assay Kit following the instructions supplied by the manufacturer (DuoSet kits; R&D Systems, Minneapolis, MN, USA). C-reactive protein (CRP) was estimated by immunonephelometric (Dade Behring N Latex High Sensitivity CRPTM mono assay) on a Behring Nephelometer II analyzer. In this method, polystyrene beads coated with rat monoclonal antibodies bind to serum CRP forming aggregates. The intensity of the scattered light is directly
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Identification of S-nitrosylated proteins in injury-induced neurogenesis

Identification of S-nitrosylated proteins in injury-induced neurogenesis

proliferation experiments, as we were able to analyze only the transfected cells. Treatment of NSC with 10 M CysNO for 5 min increases P-ERK levels detected by Western Blot (Ana I Santos, unpublished results), so we tested if we could detect this effect by immunocytochemistry. CysNO and NOC-18 increased P-ERK levels of NSC. We used EGF, the EGFR agonist and an activator of the ERK/MAPK pathway as the positive control in the experiments of ERK phosphorylation, since its effect in activation of this pathway should be independent of the effect of NO. That way we could assure that possible differences in ERK phosphorylation between mutant forms of PEBP-1 were not due to a secondary effect caused by the mutations that affect protein function in such a way that it affects by itself the signaling pathway. Treatment with EGF induced ERK phosphorylation in PEBP-1-overexpressing NSC regardless of cysteine mutation, which shows that PEBP-1 mutants are functional and respond to EGF stimulation as normal PEBP-1. In NSC overexpressing normal PEBP-1, P-ERK levels were significantly increased by treatment with CysNO. However, in NSC transfected with C13S/C133S construct this effect was abolished, and also at a lower extent in NSC transfected with C133S. This may indicate that C133S is important for S-nitrosylation of PEBP-1 and that this reaction lowers its inhibitory effect in the ERK/MAPK pathway activation. PEBP-1 binds to and inhibits c-Raf (Yeung et al. 1999) so, in order to allow ERK/MAPK activation and thus cell proliferation, its inhibitory effect on c-Raf must be released. The fact that prevention of ERK phosphorylation is more evident in the double mutant indicates that both C13 and C133 may be potential sites for S-nitrosylation of NO, but with C133 being the most important and preferential site for reacting with NO. In the absence of C133, C13 S-nitrosylation may be able to compensate at some extent, while in the opposite scenario C133 S-nitrosylation appears to be enough to increase ERK phosphorylation. In hippocampal stem cells, we observed S-nitrosylation of PEBP-1 induced by treatment with CysNO, dependent on its concentration. C13 is only present in mouse PEBP-1, being replaced by a serine in human and rat forms of PEBP-1. So, it makes sense that C133 can be more relevant than C13, with its biological role being present across different species.
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Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling.

Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling.

Endoplasmic reticulum (ER), an intracellular membranous network, plays a crucial role in the maintenance of normal cardiac function through managing intracellular Ca 2+ storage, folding and processing of proteins, lipid and sterol. External stimuli including hypoxia, glucose depri- vation, oxidative stress, disorder of Ca 2+ and infection may interrupt ER function [1], leading to a state of ER stress, which then activates unfolded protein response (UPR) [2]. Although UPR is a defense mechanism through a complex network to maintain ER homeostasis, exces- sive ER stress causes inappropriate activation of UPR, resulting in cell death through apoptosis or autophagy [3, 4]. A number of acute and chronic diseases including obesity [5], diabetes mellitus [6, 7], heart failure [8, 9], cardiac and cerebral ischemia/reperfusion injury [10, 11] have been consolidated with presence of ER stress, suggesting the therapeutic potential of tar- geting ER stress in these comorbidities. However, the mechanisms under ER stress-induced cardiac dysfunction have not been fully elucidated. Tunicamycin, a mixture of homologous nucleoside antibiotics, has been used as an ER stress inducer by blocking N-linked glycosyla- tion of newly synthesized glycoproteins, thus resulting activation of UPR [12].
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Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

Sulfasalazine-induced renal and hepatic injury in rats and the protective role of taurine

Taurine (2‑amino‑ethane sulfonic acid) was ob‑ tained from Acros (New Jersey, USA). Trichloroacetic acid (TCA),Thiobarbituric acid (TBA), Ethylenedi‑ aminetetraacetic acid (EDTA), phosphoric acid, 2‑Ami‑ no‑2‑hydroxymethyl‑propane‑1, 3‑diol (Tris) were ob‑ tained from Merck (Darmstadt, Germany). Kits for eval‑ uating biomarkers of renal and liver injury were obtained from Pars Azmun (Tehran, Iran). All salts used for prepar‑ ing buffer solutions were of analytical grade and obtained from Merck (Darmstadt, Germany).

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Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

Role of hypoxia inducing factor-1β in alcohol-induced autophagy, steatosis and liver injury in mice.

hepatocyte-specific HIF-1b knockout mouse livers compared to wild type mice but did not reach statistical difference. AKT is one of the major kinases that phosphorylates FoxO3a resulting in reduced nuclear FoxO3a retention [30, 31]. We found that Gao-binge treatment markedly reduced levels of phosphorylated AKT in hepatocyte-specific HIF-1b knockout mice but that it only had mild effects in wild type mice (Fig. 8A). Interestingly, levels of phosphorylated 4EBP-1, one of the mammalian target of rapamycin (mTOR) substrates, were markedly decreased in both wild type and hepatocyte-specific HIF-1b knockout mice after Gao-binge treatment (Fig. 8A). We recently demonstrated that activation of FoxO3a promotes hepatic autophagy and protects against acute ethanol-induced liver injury [19]. Indeed, we found that hepatic p62, which is normally degraded in the autolysosomes as a result of increased autophagic flux, were markedly decreased in hepatocyte-specific HIF-1b knockout mice but only mildly decreased in wild type mice following Gao-binge treatment (Fig. 8B). We did not find significant changes in the levels of LC3-II in both wild type and hepatocyte- specific HIF-1b knockout mice. It is likely that LC3-II could be degraded in the autolysosomes to offset the possible increased autophagosome formation induced by ethanol treatment (Fig. 8B). Moreover, we also found that MnSOD, another FoxO3a target gene, was markedly elevated in hepatocyte-specific HIF-1b knockout mouse livers when compared to wild type mice, whereas induction of CYP2E1 was very comparable in both wild type and hepatocyte-specific HIF-1b knockout mice after Gao-binge treatment (Fig. 8B). In line with our western blot analysis, EM studies revealed that Gao-binge treatment slightly increased the number of autophagosome/autolysosomes (AVs) in wild type mouse livers. The number of AVs was increased by two fold in hepatocyte-specific HIF-1b knockout mouse livers compared to wild type mice at baseline, and was further increased by Gao-binge treatment in hepatocyte-specific HIF-1b knockout mouse livers although differences were not significant (Fig. 8C & D).
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Carvedilol improves inflammatory response, oxidative stress and fibrosis in the alcoholinduced li injury in rats by regulating kuppfer cells and hepatic stellate cells

Carvedilol improves inflammatory response, oxidative stress and fibrosis in the alcoholinduced li injury in rats by regulating kuppfer cells and hepatic stellate cells

Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransfer- ase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemi- cal analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1β and NF-κB expression and real- time quantitative PCR analysis for TNFα, PCI, PCIII, and NF-κB were performed.
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Ferro e Doena Heptica Alcolica

Ferro e Doena Heptica Alcolica

Não é surpreendente que se tenha verificado experimentalmente que o etanol provocava uma diminuição da expressão do ácido ribonu- cleico mensageiro (ARNm) da hepcidina, in vitro e in vivo. O efeito não era dependente do etanol em si, mas do seu metabolismo, pois com a administração concomitante de 4-metilpirazol, um inibidor es- pecífico das enzimas metabolizadoras do álcool, não se verificava qualquer alteração da transcrição. Para além disso, o acetaldeído isolado era também capaz de inibir a transcrição da hepcidina. Apu- nos de 3 mg de ferro.

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Male-Specific Alleviation of Iron-Induced Striatal Injury by Inhibition of Autophagy.

Male-Specific Alleviation of Iron-Induced Striatal Injury by Inhibition of Autophagy.

In mouse striatum, the caudate nucleus and the putamen are not distinguishable. Therefore, three microliters of rapamycin (50 nmol/L; LC Laboratories, Woburn, USA)[19], was infused into the right striatum (coordinates: 0.2 mm anterior, 2.5 mm lateral, and 3.5 mm ventral to bregma) using a microinfusion pump (CMA Microdialysis, Kista, Sweden) at a rate of 1 μL/min [15]. Five hours after rapamycin-pre-treatment [15], 3 μL of FC (1 mmol/L) (Sigma-Aldrich, St. Louis, USA) was infused into the right striatum at the same stereotaxic coordinates as the rapamycin injection. Two days later, the forelimb use asymmetry test was performed to evaluate FC-induced functional deficits. Then, mice were sacrificed and the brain tissue containing stria- tum was sampled for histological examination and immunihistochemical analysis. The samples for Western blot were dissected at 2 mm anterior and 2 mm posterior of the injection site, then separated the outer cortex and isolated the striatum. The iron overload was confirmed by Prus- sian blue assay on brain sections from mice infused with FC as shown in S1 Fig.
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Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat.

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat.

medicinal properties, particularly with regard to liver complaints [20]. However, the A. cinna- momea fruiting body is expensive, therefore, its application is limited. Currently, most of the commercially available A. cinnamomea comes from artificial cultures, such as submerged liq- uid and solid-state mycelia cultures. In this study, we investigated the hepatoprotective effect of A. cinnamomea obtained by wheat-based solid-state fermentation. For an appropriate conver- sion of drug doses from humans to rats, we converted the human dose to an animal dose based on the body surface area, and not by a simple conversion based on body weight, because body surface area correlates well with several physiological parameters in mammals, including blood volume, circulating plasma proteins, basal metabolism, oxygen utilization, caloric expenditure, and renal function [33]. In this study, the animal dose for the rat was calculated by considering the suggested daily usage doses of solid-state fermented A. cinnamomea (2 g/ day in human). The dose calculation was performed on the basis of body surface area using a conversion factor of 0.018 (200 g rat/70 kg human) [34]. Therefore, rats were administered 180 mg/ kg WFAC, which is equal to 2 g/70 kg in humans. However, 180 mg/kg WFAC was ineffective in prevent- ing liver cirrhosis induced by CCl 4 in rats. To get significant hepatoprotective effect, WFAC
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IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

Measurement of gene expression was performed utilizing the ABI Prism 7000 Sequence Detection System (Applied Biosystems) as previously described [15]. Briefly, the primers and probe for b-actin was designed using Primer Express software (Applied Biosystems). The primers, placed in different exons, were tested to ensure that they do not amplify genomic DNA. Primers and probe nucleotide sequences for mTNF-a were as follows: forward 59-CAGCC- GATGGGTTGTACCTT-39, reverse 59-TGTGGGTGAGGAG- CACGTAGT-3 9, probe 59-TCCCAGGTTCTCTTCAAGGGA- CAAGGC-39; for mIL-12p40: forward 59-AGACCCTGCCCA- TTGAACTG-39, reverse 59-GAAGCTGGTGCTGTAGTTCT- CATATT-3 9, probe 59-CGTTGGAAGCACGGCAGCAGAA-39; for mIRAK-M: forward 5 9-TGAGCAACGGGACGCTTT-39, reverse 59-GATTCGAACGTGCCAGGAA-39, probe 59-TTA- CAGTGCACAAATGGCACAACCCC-3 9; miNOS forward, 59- CCC TCC TGA TCT TGT GTT GGA-3 9; reverse, 59-CAA CCC GAG CTC CTG GAA-39; and probe, 59-TGA CCA TGG AGC ATC CCA AGT ACG AGT-39; for mLcn2 forward, 59-GG- GCAGGTGGTACGTTGTG-3 9; reverse, 59-CAT CGT AAA GCT GCC TTC TGTTT-39; and probe, 59-CCTGGCAGG- CAATGCGGTCC-39;for mHDAC-1 forward 59-CTGGGAG- GAGGTGGCTACAC-3 9, reverse 59-GCCACCGCTGTTTCG- TAAGT-3 9, and probe 59-ATCCGGAATGTTGCTCGCTGC- TG-39; for mHDAC-2: forward 59-GAAGATTGTCCGGTG- TTTGATG-3 9, reverse 50-CACAGCCCCAGCAACTGAA-39, and probe 5 9-ACTCTTTGAGTTTTGTCAGCTCTCCACGGG-39 for mHDAC-3: forward 59-CCCAGTGTCCAGATTCATGATG-39, reverse 59-GGCCTCGTCAGTCCTGTCA-39, and probe 59- CCCGGCAGACCTCCTGACGT-3 9 for mHDAC-7: forward 59- CTTTCCCTTGCGTAAAACAGTGT-39, reverse 59-GCGTCTC- TCCAGGGATTTCTT, and probe 59-CCCAACCTGAAGT- TGCGCTACAAACC-3 9; for mb-actin: forward 59-CCGTGAAAA- GATGACCCAGATC-39, reverse 59-CACAGCCTGGATGGC- TACGT-39, probe 59-TTTGAGACCTTCAACACCCCAGCCA- 3 9. Specific thermal cycling parameters used with the TaqMan One- Step RT-PCR Master Mix Reagents kit (Applied Biosystems, USA) included 30 minutes at 48uC, 10 minutes at 95uC, and 40 cycles involving denaturation at 95 uC for 15 seconds, annealing/ extension at 60 uC for 1 minute. Relative quantitation of cytokine mRNA levels was plotted as fold change relative to untreated control cells of the lung. All experiments were performed in triplicate.
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Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

specificity there is also increased interest in their use due to reduced toxicity concerns as a result siRNAs being directly and transiently delivered ex vivo, by pluronic gel or in studies using bypass grafts This in turn greatly reduces the potential for systemic toxicity and also represents a powerful tool in inhibiting the restenosis event, which follows balloon angioplasty for example, by introducing a suitable inhibitor of vessel remodeling [12]. Another therapeutic possibility is to utilize drug-eluting stents to deliver Notch siRNAs to the site of lesions in injured vessels in an attempt to inhibit or reverse injury-induced remodeling. Taking together their specificity and potential for reduced systemic toxicity, it is hoped that this localized treatment of stenosed vessels with Notch1 specific siRNA, could represent a novel therapy for either restenosis which may accompany vein grafting, post angioplasty or atherosclerosis.
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Rev. Assoc. Med. Bras.  vol.58 número3 en v58n3a07

Rev. Assoc. Med. Bras. vol.58 número3 en v58n3a07

he study included 144 individuals with class III obesity, of both genders, with a mean age of 36.5 (11.7) years, from a private clinic in the city of Rio de Janeiro in the period from January to December 2006, representing ap- proximately 60% of the total annual attendance. Pregnant women, nursing mothers, individuals with liver disease other than NAFLD (positive serology for hepatitis B and C), with daily intake of more than 20 grams of ethanol, and those using hepatotoxic drugs were excluded from the study. NAFLD diagnosis was achieved by magnetic reso- nance imaging assessment.
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