Search results for: Nem1/Spo7 phosphatase
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 133

Search results for: Nem1/Spo7 phosphatase

73 Assessment of Diagnostic Enzymes as Indices of Heavy Metal Pollution in Tilapia Fish

Authors: Justina I. R. Udotong, Essien U. Essien

Abstract:

Diagnostic enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were determined as indices of heavy metal pollution in Tilapia guinensis. Three different sets of fishes treated with lead (Pb), iron (Fe) and copper (Cu) were used for the study while a fourth group with no heavy metal served as a control. Fishes in each of the groups were exposed to 2.65 mg/l of Pb, 0.85 mg/l of Fe and 0.35 mg/l of Cu in aerated aquaria for 96 hours. Tissue fractionation of the liver tissues was carried out and the three diagnostic enzymes (AST, ALT, and ALP) were estimated. Serum levels of the same diagnostic enzymes were also measured. The mean values of the serum enzyme activity for ALP in each experimental group were 19.5±1.62, 29.67±2.17 and 1.15±0.27 IU/L for Pb, Fe and Cu groups compared with 9.99±1.34 IU/L enzyme activity in the control. This result showed that Pb and Fe caused increased release of the enzyme into the blood circulation indicating increased tissue damage while Cu caused a reduction in the serum level as compared with the level in the control group. The mean values of enzyme activity obtained in the liver were 102.14±6.12, 140.17±2.06 and 168.23±3.52 IU/L for Pb, Fe and Cu groups, respectively compared to 91.20±9.42 IU/L enzyme activity for the control group. The serum and liver AST and ALT activities obtained in Pb, Fe, Cu and control groups are reported. It was generally noted that the presence of the heavy metal caused liver tissues damage and consequent increased level of the diagnostic enzymes in the serum.

Keywords: diagnostic enzymes, enzyme activity, heavy metals, tissues investigations

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72 Protective Role of Fish Oil against Hepatotoxicity Induced by Fipronil on Female Rats

Authors: Amel A. Refaie, Amal Ramadan, Abdel-Tawab H. Mossa

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This study was designed to evaluate the adverse effects of sub-chronic exposure to the fipronil on the liver of female rats at a dose equal to 400 mg /kg (1/10LD50) in drinking water and the protective role of fish oil at concentration 117.6 mg/Kg b.wt via oral routes daily for 28 days. Fipronil treatment caused a decrease in body weight gain and increase in relative liver weight. Fipronil induced a significant increase in the liver biomarkers enzymes such as alanine aminotransferases (ALT), aspartate aminotransferases (AST), alkaline phosphatase (ALP) and levels of total protein while fipronil caused a significant decrease in butyryl cholinesterase activity in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) were significantly decreased in liver tissue, while lipid peroxidation (LPO) was significantly increased in fipronil treating rats in a dose-dependent manner. FPN caused histopathological alterations in liver of female rats. From our results, it can be reported that FPN induced lipid peroxidation, oxidative stress, liver injury in female rats and fish oil used to protect animals against the adverse effect of pesticide exposure. These pathophysiological alterations in liver tissues could be due to the toxic effect of fipronil that associated with a generation of free radicals.

Keywords: fipronil (FPN), fish oil, hepatotoxicity, transaminases, antioxidant enzymes, female rats

Procedia PDF Downloads 113
71 Histopathological and Biochemical Evaluation of Hydroxyurea-Induced Hepato-Pulmonary Toxicity and Lymphoid Necrosis in Rats

Authors: Samah Oda, Asmaa Khafaga, Mohammed Hashim, Asmaa Khamis

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Toxicity of hydroxyurea (HU), a treatment for certain tumors, polycythemia, and thrombocytosis, was evaluated in rats in one-month toxicity study. Sixty male albino rats were equally classified into four groups. Rats received daily oral gavage of HU in 0, 250, 500, and 750 mg/kg b.wt. Chemical and histopathological assessment of liver, lung, spleen, and bone marrow was performed at 10, 20, and 30 days of the experiment. No significant change was reported in alanine aminotransferase (ALT), aspartate aminotransferase (AST), globulin, and albumin/ globulin ratio during the experiment. Significant decreases in alkaline phosphatase (ALP) and total albumin were reported in rats received 500 and 750 mg/kg b.wt of HU. In addition, total cholesterol level increased significantly after 10 days; however, it significantly decreased after 20 and 30 days of the experiment. Moreover, hepatocytic vacuolation and necrosis with portal inflammatory infiltrates were reported along experimental periods. Pulmonary congestion, hemorrhage, interstitial mononuclear infiltration, peribronchitis, and bronchial epithelial necrosis were also reported. Severe lymphocytic necrosis in spleen and severe loss of hematopoietic cells and replacement with corresponding adipose tissue in bone marrow tissues was demonstrated. In conclusion, HU could be able to induce severe dose and time-dependent hepato-pulmonary toxicity and lymphoid depression in rats.

Keywords: hydroxyurea, hepato-pulmonary toxicity, lymphoid depression, histopathology

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70 Nanoparaquat Effects on Oxidative Stress Status and Liver Function in Male Rats

Authors: Zahra Azizi, Ashkan Karbasi, Farzin Firouzian, Sara Soleimani Asl, Akram Ranjbar

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Background: One of the most often used herbicides in agriculture is paraquat (PQ), which is very harmful to both people and animals. Chitosan is a well-known, non-toxic polymer commonly used in preparing particles via ionotropic gelation facilitated by negatively charged agents such as sodium alginate. This study aimed to compare the effects of PQ and nanoparaquat (PQNPs) on liver function in male rats. Materials & Methods: Rats were exposed to PQ & PQNPs (4 mg/kg/day, intraperitoneally) for seven days. Then, rats were anesthetized, and serum and liver samples were collected. Later, enzymatic activities such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in serum and oxidative stress biomarkers such as lipid peroxidation (LPO), total antioxidant capacity (TAC) and total thiol groups (TTG) levels in liver tissue were measured by colorimetric methods. Also, histological changes in the liver were evaluated. Results: PQ altered the levels of ALT, AST, and ALP while inducing oxidative stress in the liver. Additionally, liver homogenates with PQ exposure had challenged LPO, TAC, and TTG levels. The severe liver damage is indicated by a significant increase in the enzyme activity of AST, ALT, and ALP in serum. According to the results of the current study, PQNPs, as compared to PQ and the control group, lowered ALT, AST, ALP, and LPO levels while increasing TAC and TTG levels. Conclusion: According to biochemical and histological investigations, PQ loaded in chitosan-alginate particles is more efficient than free PQ at reducing liver toxicity.

Keywords: paraquat, paraquat nanoparticles, liver, oxidative stress

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69 Evaluation of Rhus lancea and Celtis africana as Browse for Mixed-Feeders in Captivity

Authors: France Phiri, Arnold Kanengoni, Dawood Hattas, Khanyisile Mbatha

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A study was carried out to determine seasonal changes in fiber composition and condensed tannin (CT) concentrations in Rhus lancea and Celtis africana and their effects on feed intake and blood metabolites in mixed-feeders. Rhus lancea and C. africana were analysed for dry matter (DM), acid detergent lignin (ADL), acid detergent fiber (ADF), neutral detergent fiber (NDF) and CT concentrations over four seasons; early wet (EWS), late wet (LWS), early dry (EDS) and late dry (LDS). Twelve indigenous male goats were kept in metabolic crates for periods of 21 days per season and fed one of two diet combinations; the test diet comprised R. lancea and C. africana (denoted as BROWSE) and the lucerne diet comprised lucerne (Medicago sativa and concentrates (CON). Feed intake, body weight and blood metabolites were determined in all goats over each study period. Goats fed BROWSE in the EDS, LDS and LWS lost weight while goats fed CON gained weight (P < 0.05). Goats fed CON had higher urea, alkaline phosphatase and gamma-glutamyl transferase concentrations than those fed BROWSE (P < 0.05). Creatinine and cholesterol concentrations in all goats across LWS, EDS and LDS were lower than the normal range, while total protein and globulin concentrations were higher. The goats fed BROWSE had higher creatinine concentrations (P < 0.05) than those fed CON. Cholesterol concentrations were higher (P < 0.05) in goats fed BROWSE than in those on CON fed. It was concluded that goats fed BROWSE lost weight, indicating insufficient nutrients for maintenance requirements.

Keywords: fiber, maintenance, condense tannins, blood metabolites

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68 Effect of Feed Additive on Cryopreservation of Barki Ram Semen

Authors: Abdurzag Kerban, Mostfa M. Abou-Ahmed, Abdelrof M. Ghallab, Mona H. Shaker

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Preservation of semen had a major impact on sheep genetic breeding. The aim of this study was to evaluate the effect of protected fat, probiotic and zinc-enriched diets on semen freezability. Twenty two Barki rams were randomly assigned into four groups; Group I (n=5) was fed the basal diet enriched with 3.7% of dry fat/kg concentration/day, Group II (n=5) was fed a basal diet-enriched with 10gm of probiotic /head/day, Group III (n=6) was fed on the basal diet enriched with 100 ppm of 10% zinc chelated with methionine/kg dry matter/day and Group IV (n=6) was served as control. A pool of three to four ejaculates were pooled from rams within a period of ten weeks. Semen was diluted in egg yolk-Tris diluent and processed in 0.25 ml straw. Motility was evaluated after dilution, before freezing and post-thawing at 0, 1, 2 and 3 hour incubation. Viability index, acrosome integrity and leakage of intracellular enzymes (Aspartat aminotransferase and Alkline phosphatase) were also evaluated. Spermatozoa exhibited highly significant (P<0.01) percentages of motility at 0, 1, 2, and 3 hours incubation after thawing, viability index and acrosome integrity in rams fed a diet enriched with protected fat and zinc groups as compared with probiotic and control groups. Also, the mean value of extracellular leakage of AST was significantly lower in fat and zinc group as compared with probiotic and control groups. In conclusion, semen freezability was improved in animals fed a diet fortified with fat and zinc with no significant improvement in animals fed the probiotic-enriched diet.

Keywords: Barki ram semen, freezing, straw, feed additives

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67 Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Authors: Nazmul Huda, Ashik Mosaddik, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi

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Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Keywords: polyherbal formulation, sharbat deenar, carbon tetrachloride, silymarin, hepatoprotective

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66 Meld of Lactobacillus and Rangiferinus for Emendation of Endotoxemia in Alcoholic Liver Damage in Rats

Authors: Shukla Ila, Azmi Lubna, S. S. Gupta, Ch. V. Rao

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Oxidative stress has been increasingly associated with the induction and progression of liver damage. The current study was conducted to record the effect of combination of Lactobacillus and Lichen rangiferinus extract (LRE + Lac) on the severity of injury in experimental alcoholic liver disease and how it affects plasma levels of prostaglandin E2, endotoxin, thromboxane B2, and leukotriene B4. Male Wistar rats were grouped into five comprising six animals in each group. Group 1 served as negative control. Groups 2-5 were administered 10% ethanol for six weeks. Group 3 was administered with extract (200 mg/kg), group 4 received the diet containing 10% ethanol plus a bolus of lactobacilli GG (1010 CFU), and group 5 animals were given silymarin along with alcohol and it served as positive control. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein content, γ-glutamyltransferase, glutathione S-transferase, oxidative stress markers, glutathione, malondialdehyde and glutathione reductase were determined using standard diagnostic kits. Histopathological analysis of liver tissue was also made. A positive relation was found between plasma endotoxin levels and degree of liver injury. The pathology records were also related positively with leukotriene B4 and thromboxane B2. But a negative correlation was obtained with PgE2 levels. This study led us to hypothesize that the increased endotoxin levels modulate liver metabolism of eicosanoid, which gradually leads to liver injury. Endotoxemia increases leukotriene and thromboxane levels in plasma.

Keywords: lactobacillus, Lichen rangiferinus, endotoxemia, silymarin

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65 Synthesis and in vitro Characterization of a Gel-Derived SiO2-CaO-P2O5-SrO-Li2O Bioactive Glass

Authors: Mehrnaz Aminitabar, Moghan Amirhosseinian, Morteza Elsa

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Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO2-CaO-P2O5 glass with nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of opposite effect of Sr and Li of the dissolution of BG in the SBF but also, stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S BG exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: antibacterial activity, bioactive glass, sol-gel, strontium

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64 Effect of Leaf Essential Oil of Citrus sinensis at Different Harvest Time on Some Liver and Kidney Function Indices of Diabetic Rats

Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa

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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.

Keywords: C. sinensis, function indices, harvest time, leaf essential oil.

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63 Bifunctional Electrospun Fibers Based on Poly(Lactic Acid)/Calcium Oxide Nanocomposites as a Potential Scaffold for Bone Tissue Engineering

Authors: Daniel Canales, Fabián Alvarez, Pablo Varela, Marcela Saavedra, Claudio García, Paula Zapata

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Calcium oxide nanoparticles (n-CaO) ca. 8 nm were obtained from eggshell waste. The n-CaO was incorporated into Poly(lactic acid) PLA matrix in 10 and 20 wt.% of filler content by electrospinning process to obtain PLA/n-CaO nanocomposite fibers as a potential use in scaffold for bone tissue regeneration. The fibers morphology and diameter were homogeneity, the PLA had a diameter of 2.2 ± 0.8 µm and, with the nanoparticles incorporation (20wt.%), reached ca. 2.9 ± 0.9 µm. The PLA/n-CaO nanocomposites fibers showed in vitro bioactivity, capable of inducing the precipitation of hydroxyapatite (HA) layer in the fiber surface after 7 days in Simulated Body Solution (SBF). The biocidal and biological properties of PLA/n-Cao with 20 wt.% were evaluated, showing a 30% reduction in bacterial viability against S. aureus and 11% for E. coli after 6 hours of bacterial suspensions exposure. Furthermore, the fibers did not show a cytotoxic effect on the bone marrow ST-2 cell line, permitting the cell adhesion and proliferation in Roswell Park Memorial Institute medium (RPMI). The PLA/n-CaO with 20 wt.% of nanoparticles showed a higher capacity to promote the osteogenic differentiation, significantly increasing the alkaline phosphatase (ALP) expression after 7 days compared to PLA and cell control. The in vivo analysis corroborated the biocompatibility of scaffolds prepared, the presence of n-CaO in PLA reduced the formation of fibrous encapsulation of the material improve the healing process.

Keywords: electrospun scaffolds, PLA based nanocomposites, calcium oxide nanoparticles, bioactive materials, tissue engineering

Procedia PDF Downloads 63
62 Anticancer Effect of Isolated from the Methanolic Extract of Triticum Aestivum Straw in Mice

Authors: Savita Dixit

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Rutin is the bioactive flavonoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7, 12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight) continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen-treated control. Rutin produced a significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH), superoxide dismutase (SOD) and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results of the present study suggest the chemopreventive effect of rutin in DMBA and croton oil-induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

Keywords: chemoprevention, papilloma, rutin, skin carcinogenesis

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61 Organotin (IV) Based Complexes as Promiscuous Antibacterials: Synthesis in vitro, in Silico Pharmacokinetic, and Docking Studies

Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid

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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.

Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance

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60 Effect of Supplemental Bacterial Phytase at Different Dietary Levels of Phosphorus on Tibial Bone Characteristics and Body Weight Gain in Broilers

Authors: Saqib Saleem Abdullah, Saima Masood, Hafsa Zaneb, Shela Gul Bokhari, Muti Ur Rehman, Jamil Akbar

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A 5- weeks feeding trial was carried out to determine the effectiveness of Bacterial Phytase (Phyzyme®) in broilers, at different dietary levels of Phosphorous. 140 d-old broilers (Hubbard) were randomly divided into 4 groups (n=4). Birds were fed corn-based basal diet or the same diet supplemented with 3 different levels of non Phytate Phosphorous (NPP) (0.45 %, 0.30 % and 0.15 %). Furthermore, the diets were supplemented with bacterial Phytase. Birds were fed ad libitum and kept under thermo neutral conditions. The parameters studied were; body weight gain (BWG), tibial bone characteristics (TBC), serum Calcium (Ca), Phosphorus (P) and Alkaline Phosphatase (AP) levels and tibia ash percentage (TAP). BWG of the broilers was calculated at weekly interval and remaining parameters were calculated after slaughtering the birds at 35thday. Results suggested that Phytase supplementation at 0.30% NPP (Non Phytate Phosphorus + Bacterial Phytase) increased (P < 0.05) the BWG, bone length, bone weight, tibiotarsal index, medullary canal diameter and diaphysis diameter however, rubosticity index was reduced to minimum (P < 0.05) at this dietary level of phosphorous when compared with other groups. Maximum (P < 0.05) rubosticity index was observed in control group with 0% Phytase. Furthermore, Phytase addition at 0.30 % NPP also improved (P < 0.05) Ca, P and AP levels in the blood. Phytase supplementation at lower phosphorus level (0.30%NPP) improved BWG and TBC including bone density and bone quality in broilers hence it can be concluded that addition of Phytase at 0.30% NPP may prove beneficial for bone and overall performance in broilers.

Keywords: diaphysis diameter, phytase, rubosticity index, tibia

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59 DUSP16 Inhibition Rescues Neurogenic and Cognitive Deficits in Alzheimer's Disease Mice Models

Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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58 Protective Effect of Saponin Extract from the Root of Garcinia kola (Bitter Kola) against Paracetamol-Induced Hepatotoxicity in Albino Rats

Authors: Alli Smith Yemisi Rufina, Adanlawo Isaac Gbadura

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Liver disorders are one of the major problems of the world. Despite its frequent occurrence, high morbidity, and high mortality, its medical management is currently inadequate. This study was designed to evaluate the Hepatoprotective effect of saponin extract of the root of Garcinia kola on the integrity of the liver of paracetamol induced Wistar albino rats. Twenty-five male adult Wistar albino rats were divided into five (5) groups. Group I, was the Control group that received distilled water only, group II was the negative control that received 2 g/kg of paracetamol on the 13th day, and group III, IV, and V were pre-treated with 100, 200 and 400 mg/kg of the saponin extract before inducing the liver damage on the 13th day with 2 g/kg of paracetamol. Twenty-four hours after administration, the rats were sacrificed, and blood samples were collected. The serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP) activities, Bilirubin and Conjugated Bilirubin, Glucose and Protein concentrations were evaluated. The liver was fixed immediately in Formalin and was processed and stained with Haematoxylin and Eosin (H&E). Administration of saponin extract from the root of Garcinia kola significantly decreased paracetamol induced elevated enzymes in the test group. Also, histological observations showed that saponin extract of the root of Garcinia kola exhibited a significant liver protection against the toxicant as evident by the cells trying to return to normal. Saponin extract from the root of Garcinia kola indicated a protection of the structural integrity of the hepatocytic cell membrane and regeneration of the damaged liver.

Keywords: hepatoprotective, liver damage, Garcinia kola, saponin, paracetamol

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57 Osteoprotective Effect of Lawsonia inermis

Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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56 Hemato-Biochemical Studies on Naturally Infected Camels with Trypanosomiasis

Authors: Khalid Mehmood, Riaz Hussain, Rao Z. Abbas, Tariq Abbas, Abdul Ghaffar, Ahmad J. Sabir

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Blood born diseases such as trypanosomiasis have negative impacts on health, production and working efficiency of camels in different camel-rearing areas of the world including Pakistan. In present study blood samples were collected from camels kept at the desert condition of cholistan to estimate the prevalence of trypanosomiasis and hemato-biochemical changes in naturally infected cases. Results showed an overall 9.31% prevalence of trypanosomiasis in camels. Various clinical signs such as pyrexia, occasional shivering, inappetence, urticaria, swelling, lethargy, going down in condition and edema of pads were observed in few cases. The statistical analysis did not show significant association of age and sex with trypanosomiasis. However, results revealed significantly decreased values of total erythrocyte counts, packed cell volume, hemoglobin concentration, mean corpuscular hemoglobin concentration, serum total proteins and albumin while increased values of mean corpuscular volume was recorded in infected animals as compared to healthy. A significant (P<0.01) increased values of total leukocyte count, monocyte, lymphocyte, neutrophils, and eosinophils was recorded in infected animals. Moreover, microscopic examination of blood films obtained from naturally infected cases showed the presence of parasite and various morphological changes in cells such as stomatocyte, hyperchromasia, and polychromasia. Significantly increased values of different hepatic enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also recorded.

Keywords: camel, hematological indices, serum enzymes, Trypanosomiasis

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55 The Effect of Simultaneous Doping of Silicate Bioglass with Alkaline and Alkaline-Earth Elements on Biological Behavior

Authors: Tannaz Alimardani, Amirhossein Moghanian, Morteza Elsa

Abstract:

Bioactive glasses (BGs) are a group of surface-reactive biomaterials used in clinical applications as implants or filler materials in the human body to repair and replace diseased or damaged bone. Sol-gel technique was employed to prepare a SiO₂-CaO-P₂O₅ glass with a nominal composition of 58S BG with the addition of Sr and Li modifiers which imparts special properties to the BG. The effect of simultaneous addition of Sr and Li on bioactivity and biocompatibility, proliferation, alkaline phosphatase (ALP) activity of osteoblast cell line MC3T3-E1 and antibacterial property against methicillin-resistant Staphylococcus aureus (MRSA) bacteria were examined. BGs were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy before and after soaking the samples in the simulated body fluid (SBF) for different time intervals to characterize the formation of hydroxyapatite (HA) formed on the surface of BGs. Structural characterization indicated that the simultaneous presence of 5% Sr and 5% Li in 58S-BG composition not only did not retard HA formation because of the opposite effect of Sr and Li of the dissolution of BG in the SBF, but also stimulated the differentiation and proliferation of MC3T3-E1s. Moreover, the presence of Sr and Li on the dissolution of the ions resulted in an increase in the mean number of DAPI-labeled nuclei which was in good agreement with the live/dead assay. The result of antibacterial tests revealed that Sr and Li-substituted 58S bioactive glass exhibited a potential antibacterial effect against MRSA bacteria. Because of optimal proliferation and ALP activity of MC3T3-E1cells, proper bioactivity and high antibacterial potential against MRSA, BG-5/5 is suggested as a multifunctional candidate for bone tissue engineering.

Keywords: alkaline, alkaline earth, bioglass, co-doping, ion release

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54 Comparative Study of Calcium Content on in vitro Biological and Antibacterial Properties of Silicon-Based Bioglass

Authors: Morteza Elsa, Amirhossein Moghanian

Abstract:

The major aim of this study was to evaluate the effect of CaO content on in vitro hydroxyapatite formation, MC3T3 cells cytotoxicity and proliferation as well as antibacterial efficiency of sol-gel derived SiO2–CaO–P2O5 ternary system. For this purpose, first two grades of bioactive glass (BG); BG-58s (mol%: 60%SiO2–36%CaO–4%P2O5) and BG-68s (mol%: 70%SiO2–26%CaO–4%P2O5)) were synthesized by sol-gel method. Second, the effect of CaO content in their composition on in vitro bioactivity was investigated by soaking the BG-58s and BG-68s powders in simulated body fluid (SBF) for time periods up to 14 days and followed by characterization inductively coupled plasma atomic emission spectrometry (ICP-AES), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. Additionally, live/dead staining, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and alkaline phosphatase (ALP) activity assays were conducted respectively, as qualitatively and quantitatively assess for cell viability, proliferation and differentiations of MC3T3 cells in presence of 58s and 68s BGs. Results showed that BG-58s with higher CaO content showed higher in vitro bioactivity with respect to BG-68s. Moreover, the dissolution rate was inversely proportional to oxygen density of the BG. Live/dead assay revealed that both 58s and 68s increased the mean number live cells which were in good accordance with MTT assay. Furthermore, BG-58s showed more potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Taken together, BG-58s with enhanced MC3T3 cells proliferation and ALP activity, acceptable bioactivity and significant high antibacterial effect against MRSA bacteria is suggested as a suitable candidate in order to further functionalizing for delivery of therapeutic ions and growth factors in bone tissue engineering.

Keywords: antibacterial, bioactive glass, hydroxyapatite, proliferation, sol-gel processes

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53 Comparative Study on the Effect of Substitution of Li and Mg Instead of Ca on Structural and Biological Behaviors of Silicate Bioactive Glass

Authors: Alireza Arab, Morteza Elsa, Amirhossein Moghanian

Abstract:

In this study, experiments were carried out to achieve a promising multifunctional and modified silicate based bioactive glass (BG). The main aim of the study was investigating the effect of lithium (Li) and magnesium (Mg) substitution, on in vitro bioactivity of substituted-58S BG. Moreover, it is noteworthy to state that modified BGs were synthesized in 60SiO2–(36-x)CaO–4P2O5–(x)Li2O and 60SiO2–(36-x)CaO–4P2O5–(x)MgO (where x = 0, 5, 10 mol.%) quaternary systems, by sol-gel method. Their performance was investigated through different aspects such as biocompatibility, antibacterial activity as well as their effect on alkaline phosphatase (ALP) activity, and proliferation of MC3T3 cells. The antibacterial efficiency was evaluated against methicillin-resistant Staphylococcus aureus bacteria. To do so, CaO was substituted with Li2O and MgO up to 10 mol % in 58S-BGs and then samples were immersed in simulated body fluid up to 14 days and then, characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry, and scanning electron microscopy. Results indicated that this modification led to a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium revealed further pronounced effect. The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and ALP analysis illustrated that substitutions of both Li2O and MgO, up to 5 mol %, had increasing effect on biocompatibility and stimulating proliferation of the pre-osteoblast MC3T3 cells in comparison to the control specimen. Regarding to bactericidal efficiency, the substitution of either Li or Mg for Ca in the 58s BG composition led to statistically significant difference in antibacterial behaviors of substituted-BGs. Meanwhile, the sample containing 5 mol % CaO/Li2O substitution (BG-5L) was selected as a multifunctional biomaterial in bone repair/regeneration due to the improved biocompatibility, enhanced ALP activity and antibacterial efficiency among all of the synthesized L-BGs and M-BGs.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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52 Phytochemical Screening, Antioxidant and Hepatoprotection Assessment of Extracts of Coriandrum sativm L. on Wistar Rats

Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub

Abstract:

This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.

Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening

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51 Protective Effect of Celosia Argentea Leaf Extract on Cadmium Induced Toxicity and Oxidative Stress in Rats

Authors: Sulyman Abdulhakeem Olarewaju, S. O. Malomo, M. T. Yakubu, J. O. Akolade

Abstract:

The ameliorative effect of Celosia argentea var. cristata leaf extract against cadmium (Cd) induced oxidative stress and toxicity in selected tissues of rats was investigated. Toxicity coupled with oxidative stress was induced in rats by oral administration of Cd (8 mg/kg b. wt). Preliminary quantitative phytochemical and in vitro antioxidant analyses showed that the methanolic extract of C. argentea leaves was constituted by polyphenols (5.72%), saponins (3.20%), tannins (0.65%) and cadenolides (0.006%). IC50 of 9800, 7406, and 45.04 μg/ml were recorded for inhibition of linoleic acid oxidation, 2, 2-diphenyl-1-picrylhydrazyl and hydrogen peroxide radicals respectively. Simultaneous administration of C. argentea leaf extract with Cd significantly attenuated Cd-induced elevation of serum enzyme markers such as aspartate and alanine transaminase, alkaline and acid phosphatase as well as γ-glutaryltransferase in a dose-dependent fashion, while their reduced level in the liver were significantly increased. Higher levels of enzymatic antioxidants; superoxide dismutase and catalase activities were observed in the liver, brain, kidney and testes of the Cd-induced rats treated with C. argentea extract, while lipid peroxidation expressed in malondialdehyde concentrations were lower when compared to values in rats administered Cd only. Other Cd-induced toxicity and stress markers in the serum viz. reduced uric acid and albumin levels as well as elevated total and unconjugated bilirubin were attenuated by the extract and their values compared favorably with those animals co-administered cadmium with ascorbic acid. Data from the study showed that oral administration of extract from the leaf C. argentea may ameliorate Cd-induced oxidative stress and toxicity in rats.

Keywords: toxicity, cadmium, celosia, antioxidants, oxidative stress

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50 Biosafety Study of Genetically Modified CEMB Sugarcane on Animals for Glyphosate Tolerance

Authors: Aminah Salim, Idrees Ahmed Nasir, Abdul Qayyum Rao, Muhammad Ali, Muhammad Sohail Anjum, Ayesha Hameed, Bushra Tabassum, Anwar Khan, Arfan Ali, Mariyam Zameer, Tayyab Husnain

Abstract:

Risk assessment of transgenic herbicide tolerant sugarcane having CEMB codon optimized cp4EPSPS gene was done in present study. Fifteen days old chicks taken from K&Ns Company were randomly assorted into four groups with eight chicks in each group namely control chicken group fed with commercial diet, non-transgenic group fed with non-experimental sugarcane and transgenic group fed with transgenic sugarcane with minimum and maximum level. Body weights, biochemical analysis for Urea, alkaline phosphatase, alanine transferase, aspartate transferase, creatinine and bilirubin determination and histological examination of chicks fed with four types of feed was taken at fifteen days interval and no significant difference was observed in body weight biochemical and histological studies of all four groups. Protein isolated from the serum sample was analyzed through dipstick and SDS-PAGE, showing the absence of transgene protein in the serum sample of control and experimental groups. Moreover the amplification of cp4EPSPS gene with gene specific primers of DNA isolated from chicks blood and also from commercial diet was done to determine the presence and mobility of any nucleotide fragment of the transgene in/from feed and no amplification was obtained in feed as well as in blood extracted DNA of any group. Also no mRNA expression of cp4EPSPS gene was obtained in any tissue of four groups of chicks. From the results it is clear that there is no deleterious or harmful effect of the CEMB codon optimized transgenic cp4EPSPS sugarcane on the chicks health.

Keywords: chicks, cp4EPSPS, glyphosate, sugarcane

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49 Possible Modulation of FAS and PTP-1B Signaling in Ameliorative Potential of Bombax ceiba against High Fat Diet Induced Obesity

Authors: Paras Gupta, Rohit Goyal, Yamini Chauhan, Pyare Lal Sharma

Abstract:

Background: Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods: Male Wistar albino rats weighing 180–220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. Results: Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. Conclusion: On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol.

Keywords: obesity, Bombax ceiba, free fatty acid, protein tyrosine phosphatase-1B, fatty acid synthase

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48 Phytochemical Screening and Hepatotoxic Effect of Datura metel Linn. Aqueous Seed Extract in Albino Wistar Rats

Authors: I. M. Fakai, A. Abdulhamid, I. Sani, F. Bello, E. O. Olusesi

Abstract:

The phytochemical screening and hepatotoxic effect of Datura metel aqueous seeds extract in Albino Wistar rats were evaluated. Phytochemicals were screened using standard methods. The enzymes activity and liver function indices were also determined using standard methods of analysis. The phytochemicals screening revealed the presence of alkaloid, tannin, glycoside and flavonoid. The organ-body weight decreased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The activity of alkaline phosphatase decreased significantly (P<0.05) in the liver and increased significantly in the serum at all the doses of the extract treated groups compared to the control. The activity of serum alanine transaminase increased significantly (P<0.05) while there is no significant difference (P>0.05) in the activity liver alanine transaminase at all the doses of the extract treated groups compared to the control. The result also revealed significant increase (P<0.05) in the aspartate transaminase activity in both liver and serum at all doses of the extract treated groups compared to the control. Serum total protein, albumin, globulin, and total bilirubin concentration decreased significantly (P<0.05), while direct bilirubin concentration increased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The present study therefore revealed that, the present of some phytochemicals in the plant extract attributed the plant to its hepatotoxic effects as revealed in the alteration of marker enzymes and some liver function indices analyzed.

Keywords: datura metel, transaminases, hepatotoxic effect, phytochemicals, rats

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47 Chemical and Physical Properties and Biocompatibility of Ti–6Al–4V Produced by Electron Beam Rapid Manufacturing and Selective Laser Melting for Biomedical Applications

Authors: Bing–Jing Zhao, Chang-Kui Liu, Hong Wang, Min Hu

Abstract:

Electron beam rapid manufacturing (EBRM) or Selective laser melting is an additive manufacturing process that uses 3D CAD data as a digital information source and energy in the form of a high-power laser beam or electron beam to create three-dimensional metal parts by fusing fine metallic powders together.Object:The present study was conducted to evaluate the mechanical properties ,the phase transformation,the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM,SLM and forging technique.Method: Ti-6Al-4V alloy standard test pieces were manufactured by EBRM, SLM and forging technique according to AMS4999,GB/T228 and ISO 10993.The mechanical properties were analyzed by universal test machine. The phase transformation was analyzed by X-ray diffraction and scanning electron microscopy. The corrosivity was analyzed by electrochemical method. The biocompatibility was analyzed by co-culturing with mesenchymal stem cell and analyzed by scanning electron microscopy (SEM) and alkaline phosphatase assay (ALP) to evaluate cell adhesion and differentiation, respectively. Results: The mechanical properties, the phase transformation, the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM、SLM were similar to forging and meet the mechanical property requirements of AMS4999 standard. a­phase microstructure for the EBM production contrast to the a’­phase microstructure of the SLM product. Mesenchymal stem cell adhesion and differentiation were well. Conclusion: The property of the Ti-6Al-4V alloy manufactured by EBRM and SLM technique can meet the medical standard from this study. But some further study should be proceeded in order to applying well in clinical practice.

Keywords: 3D printing, Electron Beam Rapid Manufacturing (EBRM), Selective Laser Melting (SLM), Computer Aided Design (CAD)

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46 Epstein, Barr Virus Alters ATM-Dependent DNA Damage Responses in Germinal Centre B-Cells during Early Infection

Authors: Esther N. Maina, Anna Skowronska, Sridhar Chaganti, Malcolm A. Taylor, Paul G. Murray, Tatjana Stankovic

Abstract:

Epstein-Barr virus (EBV) has been implicated in the pathogenesis of human tumours of B-cell origin. The demonstration that a proportion of Hodgkin lymphomas and all Burkitt’s lymphomas harbour EBV suggests that the virus contributes to the development of these malignancies. However, the mechanisms of lymphomagenesis remain largely unknown. To determine whether EBV causes DNA damage and alters DNA damage response in cells of EBV-driven lymphoma origin, Germinal Centre (GC) B cells were infected with EBV and DNA damage responses to gamma ionising radiation (IR) assessed at early time points (12hr – 72hr) after infection and prior to establishment of lymphoblastoid (LCL) cell lines. In the presence of EBV, we observed induction of spontaneous DNA DSBs and downregulation of ATM-dependent phosphorylation in response to IR. This downregulation coincided with reduced ability of infected cells to repair IR-induced DNA double-strand breaks, as measured by the kinetics of gamma H2AX, a marker of double-strand breaks, and by the tail moment of the comet assay. Furthermore, we found that alteration of DNA damage responses coincided with the expression of LMP-1 protein. The presence of the EBV virus did not affect the localization of the ATM-dependent DNA repair proteins to sites of damage but instead lead to an increased expression of PP5, a phosphatase that regulates ATM function. The impact of the virus on DNA repair was most prominent 24h after infection, suggesting that this time point is crucial for the viral establishment in B cells. Our results suggest that during an early infection EBV virus dampens crucial cellular responses to DNA double-strand breaks which facilitate successful viral infection, but at the same time might provide the mechanism for tumor development.

Keywords: EBV, ATM, DNA damage, germinal center cells

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45 A New Cytoprotective Drug on the Basis of Cytisine: Phase I Clinical Trial Results

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

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44 Broccoli Sprouts Powder Could Improve Metabolic and Liver Disorder-Induced by High-Fructose Corn Syrup

Authors: Zahra Bahadoran, Parvin Mirmiran, Hanieh-Sadat Ejtahed, Maryam Tohidi, Fereidoun Azizi

Abstract:

Background and Aim: Broccoli sprouts, rich source of bioactive compounds specially sulforaphane (SFN), have unique functional properties. This study was conducted to investigate the possible treatment effects of high-SFN broccoli sprouts powder on metabolic and liver disorders in rats fed with high-fructose corn syrup. Methods: Thirty-two male wistar rats, pretreated with an eight-week high-fructose diet (water containing 30% fructose), were randomly allocated into three groups: Baseline control (BC), control (C) (normal diet), and BSP-diet (normal diet+5% BSP). The duration of the study was 6 weeks. Biochemical measurements, liver weight and triglyceride content were evaluated and histopathological examination of liver was performed. Results: After 6-weeks, the liver weight was significantly lower in BSP group compared to controls (13.4 g vs. 11.4 g, P<0.05). After 6 weeks, a significant decrease was observed in fasting serum glucose, total cholesterol and triglyceride levels in both experimental groups (P<0.05). Compared to controls, serum levels of HDL-C were significantly higher in BSP group. The liver TG content in BSP compared to control group was lower (14.6 vs. 16.4 mg/mg tissue). The hepatic levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase had not considerable changes in the groups after the intervention period but the level of alkaline phosphatase significantly decreased in BSP group (P<0.05). The histopathological examination of liver confirmed a decrease lobular and portal inflammation and ballooning in BSP group compared to control. Conclusion: High-SFN broccoli sprouts powder has beneficials effect on metabolic and liver changes-induced by high fructose corn syrup.

Keywords: broccoli sprouts, metabolic disorders, fatty liver, food science

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