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Possible protective effects of two different doses of cyanocobalamin against methotrexate nephrotoxicity in rats
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Abstract

   Nephrotoxicity is defined as rapid deterioration in kidney functions. It arises from direct exposure to drugs or their metabolites. Methotrexate is a famous chemotherapeutic drug with anti-inflammatory and immunosuppressive properties. A high-dose methotrexate-induced renal dysfunction can be life threatening. Cyanocobalamin, one of the forms of vitamin B12, acts as a coenzyme in the conversion of homocysteine to methionine in the cytosol, and the conversion of methylmalonyl-CoA to succinyl-CoA in the mitochondrion. This study is designed to examine the effect of cyanocobalamin in two different doses each co-administered with methotrexate at 20 mg/kg induced nephrotoxicity in rats through the involvement of Nrf2/keap1 molecular mechanism in this respect. Rats utilized in this study were randomized into 4 groups (ten rats per each group); Group 1- (Control) rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days. Group 2- Rats intraperitoneally injected with 0.5ml normal saline once daily for 7 consecutive days; and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg) is to be injected. Group 3- Rats intraperitoneally injected with a 0.5mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Group 4- Rats intraperitoneally injected with a 2mg/kg cyanocobalamin once daily for 7 consecutive days, and at day 2, a single intraperitoneal dose of methotrexate (20mg/kg). Co-administration of cyanocobalamin at doses cyanocobalamin 0.5mg/kg and 2mg/kg with methotrexate showed significant  reduction  (P<0.05) in malondialdehyde, significant elevation (P<0.05)  in reduced glutathione level, significant upregulation in  renal Nrf2 expression and significant down regulation in renal keap1 expression each compared to corresponding levels in methotrexate-only treated group. In conclusion this study demonstrated that co-administration of cyanocobalamin at two different doses with MTX resulted in attenuation of its nephrotoxicity by the utilization of selected parameters.

Keywords: Nephrotoxicity, methotrexate, cyanocobalamin, malondialdehyde, glutathione, Nrf2, Keap1.

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Publication Date
Mon Jan 01 2024
Journal Name
Aims Energy
The impact of different compression ratios on emissions, and combustion characteristics of a biodiesel engine
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<p>The current work investigated the combustion efficiency of biodiesel engines under diverse ratios of compression (15.5, 16.5, 17.5, and 18.5) and different biodiesel fuels produced from apricot oil, papaya oil, sunflower oil, and tomato seed oil. The combustion process of the biodiesel fuel inside the engine was simulated utilizing ANSYS Fluent v16 (CFD). On AV1 diesel engines (Kirloskar), numerical simulations were conducted at 1500 rpm. The outcomes of the simulation demonstrated that increasing the compression ratio (CR) led to increased peak temperature and pressures in the combustion chamber, as well as elevated levels of CO<sub>2</sub> and NO mass fractions and decreased CO emission values un

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Publication Date
Sun Dec 01 2019
Journal Name
Engineering, Technology &amp; Applied Science Research
Experimental and Numerical Comparison of Reinforced Concrete Gable Roof Beams with Openings of Different Configurations
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This paper demonstrates an experimental and numerical study aimed at comparing the influence of openings of different configurations on the flexural behavior of reinforced concrete gable roof beams. The experimental program consisted of testing six simply supported gable beams subjected to mid-point concentrated load. The variable which has been investigated in this work was opening's configuration (quadrilateral or circular) with the same upper and lower chords depth. The results indicate improvement in the beams’ flexural behavior when circular openings were used compared with that of quadrilateral openings, represented by an increase in ultimate load capacity and a decrease in deflection at the service limit. Also, there was an

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Publication Date
Wed Sep 15 2010
Journal Name
Journal Of Baghdad College Of Dentistry
Computerized measurement of bite forces for edentulous subjects with denture bases of different impression techniques
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Background: Complete denture wearers show lower levels of bite force than dentate subjects. This has a significant influence on their chewing efficiency. In this study an attempt was made to investigate the effect of the impression technique on the maximum bite force in complete denture wearers. Materials and methods: The patients selected for this research were 12 edentulous patients. Three different techniques for registering the final impression were made; the mucostatic, mucofunctional, and the selective pressure impression technique. Two sets of upper and lower denture bases and one set of upper and lower dentures were constructed for each subject. Intraoral and extraoral instruments and devices, as well as a computer program were used

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Publication Date
Fri Dec 15 2023
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of different curing distances on the microhardness of flowable bulk-fill composite materials
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Background: The microhardness of a composite resin is a vital parameter that is used to determine its clinical behavior. Measuring the microhardness of a composite resin has been used as an indirect method to assess its degree of conversion and extent of polymerization. The purpose of this in vitro study was to evaluate the effect of three curing distances (0, 2, and 4 mm) on the microhardness of the top and bottom surfaces of three types of flowable bulk-fill composite resins (smart dentin replacement, Opus bulk fill flow, and Tetric N). Material and method: Sixty-three specimens from the three types of composite resins (n=21) were fabricated using Teflon mold with a 4mm depth and a 5 mm internal diameter and cured for 20 seconds. For e

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Publication Date
Tue Feb 01 2022
Journal Name
Externally Bonded Cfrp For Flexural Strengthening Of Rc Beams With Different Levels Of Soffit Curvature
Externally Bonded CFRP for Flexural Strengthening of RC Beams with Different Levels of Soffit Curvature
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This paper reports a comprehensive study on the behavior of concavely curved soffit reinforced concrete (RC) beams strengthened in flexure with carbon fiber-reinforced polymer (CFRP) composites under static loading. The main objective of this paper is to explore the effect of surface concavity on the bond performance of externally bonded wet layup CFRP sheets and laminates. An experimental program consisting of flexural strengthening of 24 RC beams with concavely curved soffits was carried out. All specimens were simply supported RC beams tested under three-point bending. Of the 24 beams, 6 beams were flat soffit RC beams, and the remainder were fabricated with concavely curved soffits with a degree of curvature that is ranging from 5 mm/m

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Publication Date
Tue Nov 01 2022
Journal Name
Journal Of Cleaner Production
Modeling of biogas production and biodegradability of date palm fruit wastes with different moisture contents
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Publication Date
Tue Nov 01 2022
Journal Name
Journal Of Cleaner Production
Modeling of biogas production and biodegradability of date palm fruit wastes with different moisture contents
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Publication Date
Fri Dec 06 2019
Journal Name
Mechanics Of Advanced Materials And Structures
Finite element modeling of RC gable roof beams with openings of different sizes and configurations
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Publication Date
Sun Feb 03 2019
Journal Name
Journal Of The College Of Education For Women
The concept of suspense and mystery with some references to dickens s Novels ; A tale of two cities and Great expectations
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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Structure dependence of gamma ray irradiation effects on polyurethane and epoxy resin studied by PAL technique
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Positron annihilation lifetime (PAL) technique has been employed to
study the microstructural changes of polyurethane (PU), EUXIT 101
and epoxy risen (EP), EUXIT 60 by Gamma-ray irradiation with the
dose range (95.76 - 957.6) kGy. The size of the free volume hole and
their fraction in PU and EP were determined from ortho-positronium
lifetime component and its intensity in the measured lifetime spectra.
The results show that the irradiation causes significant changes in the
free volume hole size (Vh) and the fractional free volume (Fh), and
thereby the microstructure of PU and EP. The results indicate that
the γ-dose increases the crystallinity in the amorphous regions of PU
and increas

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