BETTERMENT OF DICLOFENAC-INDUCED NEPHROTOXICITY BY PENTOXIFYLLINE THROUGH MODULATION OF INFLAMMATORY BIOMARKERS

Objectives: Diclofenac-induced nephrotoxicity is caused by oxidative stress which leads to lipid peroxidation and formation of free radicals. Pentoxifylline can ameliorates renal tissue injury by its anti-inflammatory, antifibrotic, and antioxidant effects, so it mitigates the progression of renal diseases. Therefore, the aim of this study was to evaluate the nephroprotective effects of pentoxifylline on diclofenac-induced nephrotoxicity in rats. Methods: A total of 30 male Sprague-Dawley rats were allocated into three groups, Group 1 (n=10): Rats treated with distilled water 5 ml/kg plus normal saline 5 ml/kg for 12 days, Group 2 (n=10): Rats treated with distilled water 5 ml/kg plus diclofenac 15 mg/kg for 12 days, and Group 3 (n=10): Rats treated with pentoxifylline 100 mg/kg plus diclofenac 15 mg/kg for 12 days. Blood urea, creatinine, malondialdehyde (MDA), superoxide dismutase (SOD-1), glutathione reductase (GSH), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecules (KIM-1) vitronectin (VTN), integrin (ITG) , interleukin-18 (IL-18) and cystatin-C were used to measure the severity of nephrotoxicity. Results: Diclofenac-induced nephrotoxicity led to significant elevation in blood urea, serum creatinine, MDA, IL-18, KIM-1, NGAL, serum ITG, and VTN with decrease of SOD-1 and GSH sera levels p<0.05. Treatment with pentoxifylline showed no significant effect on all biomarker levels compared to diclofenac group except on serum level KIM-1 and serum VTN, p<0.05. Conclusion: Pentoxifylline produced significant nephroprotective effect on diclofenac-induced nephrotoxicity through modulation of inflammatory biomarkers

Impurity effects on the melting of Ni clusters

We demonstrate that the addition of a single carbon impurity leads to significant changes in the thermodynamic properties of Ni clusters consisting of more than a hundred atoms. The magnitude of the change induced is dependent upon the parameters of the Ni-C interaction. Hence, thermodynamic properties of Ni clusters can be effectively tuned by the addition of an impurity of a particular type. We also show that the presence of a carbon impurity considerably changes the mobility and diffusion of atoms in the Ni cluster at temperatures close to its melting point. The calculated diffusion coefficients of the carbon impurity in the Ni cluster can be used for a reliable estimate of the growth rate of carbon nanotubes.Comment: 27 pages, 13 figure

Therapeutic Properties of Vanadium Complexes

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology

Impact of laptop dealer firm’s service quality on customers’ loyalty in Jordan

This study aims to investigate how various aspects of service quality in laptop dealer companies affect customers’ loyalty in Jordan. Data were collected from 341 Jordanian clients of dealer firms selling laptops in Jordan (HP, LG, Toshiba, Apple, Samsung, Sony, and Dell). Collected data were then analyzed; the hypotheses were assessed with the help of SPSS and structural equation modeling. The findings showed that customers’ loyalty is significantly impacted by reliability, accessibility to service, and safety. Furthermore, the value of beta represents relative importance. The dimension of safety showed the highest level in size of the impact on customers’ loyalty, and its value was 0.446 of the total impact. Next, the access to service dimension was the second factor in the impact size (0.239), and the reliability dimension demonstrated the smallest impact size with 0.146. Additionally, the findings revealed that reliability, access to service, and safety explain 52% of the variance in customers’ loyalty to purchase a laptop in Jordan. As a result, the study recommends that Jordanian laptop dealer firms consider all three service quality characteristics, particularly safety, to maintain the loyalty of their customers

Attenuating the DNA damage response to double strand breaks restores function in models of CNS neurodegeneration

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system

Analysis of Optimal Motion Performance for Underactuated Gantry Crane System using MOPSO with Linear Weight Summation Approach

This paper present the development of Multi-Objective Particle Swarm Optimization (MOPSO) with Linear Weight Summation (LWS) approach to enhance the effectiveness and efficiency of Gantry Crane System (GCS). The purpose of using LWS is to control the desired trolley position and payload oscillation according to the Settling Time (Ts), Steady State Error (SSE) and Overshoot (OS). The effectiveness of variation in weight summation is observed to find the optimal motion performances of the system. It demonstrated that GCS is able to achieve the goals while able to move the trolley as fast as possible to the desired position with low payload oscillation. Through this approach, the best optimal motion performances can be achieved by setting similar value of weightage for OS and Ts and reduce the priority for SSE

Lactate Dehydrogenase-B Is Silenced by Promoter Methylation in a High Frequency of Human Breast Cancers

Objective: Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. Experimental design: Lactate Dehydrogenase (LDH) isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. Results: Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/ 25 cases of breast cancer tissues, but not in 5/ 5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained), was seen in 23/ 26 (88%) breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O2), for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002), and T-47D cells (2.9 fold, p = 0.009), but not in MDA-MB-436 (-0.9 fold, p = 0.229), or MCF10AT (1.2 fold, p = 0.09) cells. Conclusions: Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia