Modulation of Antioxidant Enzyme Expression and Activity by Paraquat in Renal Epithelial NRK-52E Cells

Renal toxicity produced by paraquat involves the generation of reactive oxygen species (ROS) which can overwhelm antioxidant defences, leading to oxidant injury. However, there are conflicting reports regarding the activity and/or expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) during oxidative stress injury. This study investigated the activity and expression of these enzymes in a renal epithelial cell line following exposure to paraquat. Confluent NRK-52E cells were incubated with increasing concentrations of paraquat (1-100mM) for up to 24 hours. Renal cell death was determined by measurement of lactate dehydrogenase release. Oxidant damage was determined via measurement of malondialdehyde formation and DNA strand breaks. The effects of paraquat on DNA and de novo protein synthesis were determined using radio-labelled thymidine and leucine respectively. ROS generation (superoxide anion and hydroxyl radical formation) was measured using nitro-bluetetrazolium and deoxyribose assays. Antioxidant enzyme activities and expression were measured using established biochemical assays and Western blot analysis. Exposure of confluent NRK-52E cells to paraquat resulted in significant cell death involving increased lipid peroxidation, DNA damage and inhibition of DNA and de novo protein synthesis. Renal cell injury and death were secondary to increased ROS generation. Incubation with paraquat reduced SOD and CAT activities; in contrast, GSH-Px activity increased significantly. Although SOD expression was significantly reduced, catalase expression was unaffected. These results indicate that paraquat mediates renal toxicity via oxidative stress involving both an increase in ROS generation and reductions in SOD and CAT activities with a concomitant reduction in SOD expression

Novel Superoxide Dismutase Mimetics for Protection against Paraquat-induced Acute Renal Injury

Paraquat-induced nephrotoxicity involves severe renal damage caused by reactive oxygen species (ROS), specifically by increasing superoxide (O2●-) generation in the kidney. While proven to be of benefit in animal models of organ injury involving O2●-, superoxide dismutase (SOD) and superoxide dismutase mimetics (SODm) can suffer problems regarding their bioavailability and toxicity. Since ROS has been incriminated in the pathogenesis of several disease conditions including acute kidney injury, the search for ideal SODm therefore continues unabated. Thus, the current study aims at investigating the therapeutic potential of Manganese (II) complexes of ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) and ethylenebis hydroxyphenylglycine (EHPG), novel SODm, against paraquat-induced nephrotoxicity using an in vivo rodent model. Administration of a single intraperitoneal dose of 10-50 or 100 mg/kg paraquat to male Wistar rats (200-250g) produced acute kidney injury within 48 and 24 hours respectively; as evidenced by a significant increase in serum creatinine, fractional excretion of sodium and a reduction in creatinine clearance. Unlike Mn (II)-EGTA (2mg/kg), Mn (II)-EHPG (4mg/kg) was able to significantly attenuate the acute kidney injury induced by 10-50 mg/kg paraquat. These complexes were not toxic at the doses examined unlike SOD or conventional SODm which can display pro-oxidant actions at higher concentrations. Since the clinical toxicity profiles of EGTA and EHPG are already known, these novel SODm particularly Mn (II)-EHPG could be beneficial in attenuating disease conditions involving ROS generation. Keywords: Acute kidney injury, Oxidative stress, Paraquat, Superoxide anion, Superoxide dismutase mimetic

A Petrographic Analysis of the Microbial Thrombolite Buildup in the Oxfordian Smackover Formation, Little Cedar Creek Field, Alabama

The Jurassic (Oxfordian) Smackover Formation in Little Cedar Creek Field, Alabama is composed of microbial thrombolitic buildups. Core description, petrography, SEM, and isotopic analysis were used to identify the succession of organisms, microbial carbonate deposition, and diagenesis that contributed to formation of these thrombolitic buildups. The microbial thrombolite reef facies in this study accounts for 38.5% of the total Smackover Formation. This facies was deposited 0.5 to 6.75 miles from the paleo-coastline. Today it is located 10,225 to 11,750 feet in the subsurface and contains buildups 26 to 50 feet thick. Four microfacies were defined: A- Black Renalcis-like layers, B- Digitate, C- Chaotic and D- Brown laminated centimeter-scale cycles. In most of the buildup, distinct layers of microbially precipitated micrite forms in succession. Microfacies A (Black Renalcis-like Layer) is the relatively least porous and permeable, acting as a potential barrier to flow in contrast to the other more porous microfacies

Genetic polymorphism of cytochrome p450 (2C19) enzyme in Iranian Turkman ethnic group

Objective: Different findings indicate that CYP2C plays a clinical role in determining interindividual and interethnic differences in drug effectiveness. The ethnic differences in the frequency of CYP2C19 mutant alleles continue to be a significant study topic. The aim of the present study was to assess the frequency of allelic variants of CYP2C19 in Turkman ethnic groups and compare them with the frequencies in other ethnic populations. Methods: The study group included 140 unrelated healthy ethnic Turkman subject referred to the Health Center. Genotyping of CYP2C19 alleles (CYP2C19*1, CYP2C19*2, and CYP2C19*3 alleles) was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique Results: The allele frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 56.43%, 23.57% and 20%, respectively. The result also showed that 39.7% of subjects expressed the CYP2C19*1/*1 genotype. While 42.1%, 9.3%, 9.3% and 1.4% expressed CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2 and CYP2C19*3/*3 genotypes, respectively. The genotype CYP2C19*2/*3 was not expressed in this study population. The findings suggested that 10% of subjects were poor metabolizers by expressing CYP2C19*2/*2 and CYP2C19*3/*3 genotypes. Fifty one percent of subjects were intermediate metabolizers having CYP2C19*1/*2, CYP2C19*2/*3 and CYP2C19*1/*3 genotypes and 37.86% were found to be extensive metabolizers expressing CYP2C19*1/*1 genotype. The frequency of intermediate metabolizers genotype was high (51%) in Turkman ethnic groups. Conclusion: This study showed that the determined allelic variants of CYP2C19 (CYP2C19*2 and CYP2C19*3 mutations) in Turkman ethnic group are comparable to other populations. These findings could be useful for the clinicians in different country to determine optimal dosage and effectiveness of drugs metabolized by this polymorphic enzyme. © OMSB, 2013

Succeed or succumb?

The case study primarily deals with the analysis of two different, rather opposing styles of leadership and their resultant effects on the personality, attitude and performance of the subordinate employees. This case details the characteristics of a bossy, authoritative, prejudiced, close-minded, and destructive critical leader whose approach to dealing with subordinate staff lowers an employee’s morale, leads to lower productivity and even forces one to quit the job; whereas on the other hand, it shows a participative, open-minded, supportive, amicable, and friendly leader who is able to boost employee morale and enhance motivation to work harder, while being committed to the organisation. This case study also provides an illustration of the fact that sometimes, in order to succeed and get promoted in an organisation, we may have to put aside our personal relationships in the workplace, or even walk over them to climb the ladder of success

Tematika ljubavi u različitim pedagoškim konceptima

The theme of love throughout history appears in many pedagogical concepts, where it has been researched in detail by various pedagogical theorists and practitioners, and many have also included it in their educational concepts. It is important from the point of view of the child and his involvement in the educational process itself and for proper introduction into the process itself, it requires an empathetic and professionally trained teacher and educator. Through a review of numerous scientific and professional works, the authors investigated the occurrence of the theme of love and found that it appears in many pedagogical concepts. These were presented in detail, critically evaluated and professionally analyzed and compared. They also found that the role of the teacher and educator and their example, which students and children follow, is crucial for the introduction of the theme of love.Tema ljubavi se kroz povijest nalazi u mnogim pedagoškim konceptima gdje su je detaljno istraživali razni pedagoški teoretičari i praktičari, a mnogi su je također uključili u svoje odgojno-obrazovne koncepte. Važna je s gledišta djeteta i njegove uključenosti u sam odgojno-obrazovni proces, a za pravilno uvođenje ljubavi u sam proces potreban je empatičan i stručno osposobljen učitelj i odgajatelj. Pregledom brojnih znanstvenih i stručnih radova autorice su istražile uključenost teme ljubavi i utvrdile da se ona pojavljuje u brojnim pedagoškim konceptima. Ti su koncepti detaljno predstavljeni, kritički su vrednovani te stručno analizirani i uspoređeni. Autorice su također utvrdile da je za uvođenje teme ljubavi presudna uloga učitelja i odgajatelja i njihov primjer kojeg učenici i djeca slijede

Determination of Reinforced Concrete Rectangular Sections Having Plastic Moments Equal to all IPE Profiles

The comparison between steel structures and reinforced concrete structures has always been governed by economy and response to earthquake. Steel structures being lighter and are thus more efficient to resist earthquake. On the other hand, they are more expensive (4 to 5 times). Theoretically, two structural elements having the same plastic moment have an equal failure or collapse load. Different profiles of IPE are realized in industry and all their characteristics are determined with a great precision (weight, geometrical characteristics and thus their plastic moment). Determining equivalent rectangular singly reinforced concrete cross-sections is not easy and seems impossible to be solved analytically. To a given profile it may be found a multitude of equivalent rectangular reinforced concrete cross-section (singly and doubly reinforced with different yield strengths and compositions of concrete). To take into consideration all these factors, it is absolutely necessary to construct three axis design charts with an appropriate choice of system of coordinates in order to cover all possible ranges of different parameters. The choice of all these possible rectangular reinforced concrete sections is governed by the plastic performance of these later. They must be under reinforced, allowing plastification of steel before failure in order to permit the redistribution phenomenon in plastic analysis. The exploitation of these different charts has revealed that the absolute majority of these rectangular reinforced concrete cross-section are reasonably well designed and are in conformity with the dimensions used in practice. The results of the present characterization using Eurocode 2 characteristics are compared to those of CP110. The impact does not seem to be very relevant. Doi: 10.28991/cej-2021-03091677 Full Text: PD

Prevalence of Tobacco Use and Physical Activity among Adult Sierra Leonean Population

The current burden of non-communicable diseases (NCDs) and their risk factors such as tobacco use and physical inactivity remain largely unknown in Sierra Leone. Thus, this study was conducted to document the prevalence of tobacco use and physical activity among the adult Sierra Leonean population with a specific objective of determining the sex and age prevalence. A cross sectional population based survey utilising the multi-stage cluster sampling strategy was used. A total of 5,483 individuals aged 25-64 years of both sexes were recruited into the survey. The World Health Organisation (WHO) STEPwise approach to surveillance instrument was adapted and questionnaire was administered to one individual in selected household. The data was analysed and graphed using Epi-Info software version 3.4.3 and graph pad prism version 5.1 respectively. The analyses showed that 34% of the respondents use tobacco products with 26% engaged in smoking tobacco products and 8% were smokeless tobacco users at the time of this study. The average age of commencing tobacco smoking was 21 years; with 92% and 96% of the male and female daily smokers smoking at least six manufactured tobacco respectively. Seventy four percent (74%) and 69% of the non-smoking respondents were exposed to environmental tobacco smoke (ETS) at home and workplace respectively. The study further revealed that 15%, 23% and 87% of the total respondents reported no work-, transport- or recreational- related physical activity respectively; and were therefore classified as physically inactive. The lowest level of physical activity was reported in the recreation domain. Even those who reported moderate physical activity at work or from travel, their median metabolic equivalent (MET) was not sufficient to achieve a level of physical activity that is beneficial to their health. In conclusion, a significant proportion of the population is exposed either directly or indirectly to tobacco smoke, and a large proportion of the adult population is physically inactivity. Thus, NCD prevention policy addressing lifestyle changes such as no smoking should not be limited to work places but should be population based. Keywords: Non-communicable diseases, Physical activity, Risk factors, Sierra Leone, Tobacc