Mechanism of action of liver growth induced by peroxisome proliferators

Humans are ubiquitously exposed to peroxisome proliferators including hypolipidemic agents, industrial solvents and atural products. Because of this and the fact that peroxisome proliferators cause non-genotoxic hepatocarcinogenesis in rodents, it is of importance to elucidate the mechanism of action of the peroxisome proliferators in order to provide an assessment of the hazard, if any, of these compounds to humans. It is also known that the peroxisome proliferators begin their actions by inducing hepatic DNA synthesis. Thus, the aim of this thesis was to find genes that could be responsible for triggering the induction of hepatic DNA synthesis caused by peroxisome proliferators, specifically ciprofibrate. First, it was important to indicate when the induction of hepatic DNA synthesis actually happens. This was done with BrdU immunohistochemical procedures. The induction of hepatic DNA synthesis with ciprofibrate in mice was observable only after 4 days making it difficult to specify when the induction actually happened. In rats the induction of hepatic DNA synthesis was found to peak at 24 hours and this system gave the better opportunity to find the genes responsible. The difference in the timing of induced hepatic DNA synthesis betweenmice and rats implied that there could be a species difference in the mechanism of each species’ response to PPAR. With immunohistochemistry it was noticed that there was a difference in the lobular localization of hepatic DNA synthesis in the liver tissues of rats and mice dosed with different inducers, with the rat livers exhibiting periportal distribution while hepatic DNA synthesis in the mice seemed to be distributed throughout the liver tissue. The effects of ciprofibrate or cyproterone acetate on liver gene expression in rats were studied, using cDNA microarrays, transcriptome sequencing and quantitative real- time PCR. A 1- 5 hour treatment period was chosen to detect the immediate early gene response, while a 24 hour time point was chosen to elucidate the confounding effects from the hepatic DNA synthesis seen during the 24 hour stimulation. The results showed that ciprofibrate altered the expression of numerous genes including previously known PPARa agonist-responsive genes involved in processes such as PPAR signalling pathways, fatty acid metabolic pathway, cell cycle, palmitoyl-CoA hydrolase activity, lipid metabolism, inflammatory responses, and stress responses, in addition to a large number of novel candidate genes. Three novel induced genes G0s2, Ccnd1 and Scd1, (and two marker genes CYP4A1 and CYP3A1) were confirmed with quantitative real- time PCR. The G0s2, Ccnd1 and Scd1 were found to be up-regulated at the hours 1 and 3 after dosing and not 24 hours, and the G0s2 and Scd1 were specific for the ciprofibrate suggesting they were involved in a distinct PPARa pathway responsible for the hepatic DNA synthesis. The complete database of the transcriptional response provided here opens doors of opportunity for further research to identify genes responsible for the liver growth induced by peroxisome proliferators

Mechanism of action of liver growth induced by peroxisome proliferators

Humans are ubiquitously exposed to peroxisome proliferators including hypolipidemic agents, industrial solvents and atural products. Because of this and the fact that peroxisome proliferators cause non-genotoxic hepatocarcinogenesis in rodents, it is of importance to elucidate the mechanism of action of the peroxisome proliferators in order to provide an assessment of the hazard, if any, of these compounds to humans. It is also known that the peroxisome proliferators begin their actions by inducing hepatic DNA synthesis. Thus, the aim of this thesis was to find genes that could be responsible for triggering the induction of hepatic DNA synthesis caused by peroxisome proliferators, specifically ciprofibrate. First, it was important to indicate when the induction of hepatic DNA synthesis actually happens. This was done with BrdU immunohistochemical procedures. The induction of hepatic DNA synthesis with ciprofibrate in mice was observable only after 4 days making it difficult to specify when the induction actually happened. In rats the induction of hepatic DNA synthesis was found to peak at 24 hours and this system gave the better opportunity to find the genes responsible. The difference in the timing of induced hepatic DNA synthesis betweenmice and rats implied that there could be a species difference in the mechanism of each species’ response to PPAR. With immunohistochemistry it was noticed that there was a difference in the lobular localization of hepatic DNA synthesis in the liver tissues of rats and mice dosed with different inducers, with the rat livers exhibiting periportal distribution while hepatic DNA synthesis in the mice seemed to be distributed throughout the liver tissue. The effects of ciprofibrate or cyproterone acetate on liver gene expression in rats were studied, using cDNA microarrays, transcriptome sequencing and quantitative real- time PCR. A 1- 5 hour treatment period was chosen to detect the immediate early gene response, while a 24 hour time point was chosen to elucidate the confounding effects from the hepatic DNA synthesis seen during the 24 hour stimulation. The results showed that ciprofibrate altered the expression of numerous genes including previously known PPARa agonist-responsive genes involved in processes such as PPAR signalling pathways, fatty acid metabolic pathway, cell cycle, palmitoyl-CoA hydrolase activity, lipid metabolism, inflammatory responses, and stress responses, in addition to a large number of novel candidate genes. Three novel induced genes G0s2, Ccnd1 and Scd1, (and two marker genes CYP4A1 and CYP3A1) were confirmed with quantitative real- time PCR. The G0s2, Ccnd1 and Scd1 were found to be up-regulated at the hours 1 and 3 after dosing and not 24 hours, and the G0s2 and Scd1 were specific for the ciprofibrate suggesting they were involved in a distinct PPARa pathway responsible for the hepatic DNA synthesis. The complete database of the transcriptional response provided here opens doors of opportunity for further research to identify genes responsible for the liver growth induced by peroxisome proliferators

Evaluation of shear behavior of prepared recycled concrete aggregate concrete deep beam

In this article, the shear behavior of a deep beam made of Recycled Aggregate Concrete (RAC) was analyzed. Rapid urbanization has presented a massive new activity that is necessary to meet the needs of the influx of people. Developments of all types, from housing to infrastructure, necessitate considerable input from both natural and monetary resources. The purpose of this study is to compare the strength and loading capacity of RAC to that of Naturally Aggregate Concrete (NAC). The samples were evaluated at a controlled deformation rate of 2mm/minute in the "Material Testing Laboratory of the Department of Civil Engineering," where this investigation was conducted. The researcher has chosen two different sizes of coarse totals to use throughout this study: those measuring 5mm to 15mm (60.2%) and those measuring 15mm to 25mm (40.3%). In support of her claims, the researcher presents a variety of charts and datasets in the following research. There is an overall drop in strength in the recycled aggregate concrete samples. The load-deflection curves and the techniques are depicted by which the specimens failed. Shear required beams' experimental data and predicted values. This study reveals that compared to natural aggregate concrete, recycled aggregate concrete has weaker compressive, flexural, and breaking tensile strengths. The maximum load-bearing strength of longitudinally supported beams built of "recycled and natural aggregate concrete" is also not significantly different

Vitamin D deficiency and low hemoglobin level as risk factors for severity of acute lower respiratory tract infections in Egyptian children: A case-control study

AbstractObjectiveAcute lower respiratory tract infection (ALRTI) is an important cause of morbidity in the developed world, and both morbidity and mortality in the developing world. Vitamin D has a major role in both acquired and innate immunity. Anemic children have less oxygen carrying capacity of blood. This study was done to determine the relation between vitamin D deficiency, anemia and the severity of ALRTIs in hospitalized children.MethodsThis study included 96 hospitalized infants with ALRTI, 48 diagnosed with pneumonia and 48 with bronchiolitis. Mean age was 10.67±3.143months. Matched age and sex infants with no respiratory illness were included. Serum 25 hydroxy vitamin D was measured in all cases and controls by Radio-immune assay. Hemoglobin level was measured by Coulter.ResultsVitamin D deficiency and low hemoglobin level were positively correlated with the severity of ALRTIs (r=0.798 and P=0.001) and (r=0.708, P=0.028), respectively. Low vitamin D level was significantly correlated with low hemoglobin level (r=0.708, P=0.028).ConclusionVitamin D deficiency was associated with severity of ALRTIs. Low hemoglobin level was more prevalent in those children. Improving the nutritional status in children by preventing vitamin D deficiency and low hemoglobin might influence the outcome of children with ALRTI

Characterization of blue green algae isolated from Egyptian rice field with potential anti-hepatitis C active components

Several species of cyanobacteria has been recognized for its therapeutic value that can be used for treatment of malnutrition, cancer and viral infection. Many natural occurring cyanobacteria are known to produce toxins, for example, species of the genera Microcystis, Nodularia, Nostoc, Anabaena, Aphanizomenon, Cylindrospermopsis, and Planktothrix (Oscillatoria). Cyanotoxins are classified according to their mode of action in vertebrates as hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritants. Microcystin is a hepatotoxin which commonly found in Microcystis and it was found to be produced by other genera, including Anabaena, Nostoc, Nodularia, and Planktothrix. In the present study cyanobacteria strain isolated from Egyptian soil was purified, characterized and identified as Nostoc sp. and named Nostoc EGY. PCR-based techniques targeting the toxin biosynthesis genes were used verifying absence of toxic genes in the newly purified cyanobacteria. Cell lysate was prepared from the purified strain; the efficacy of this lysate to prevent hepatitis C virus (HCV) replication in vitro was proved qualitatively and quantitatively. Lysate prepared from isolated cyanobacteria after 10 and 25 days of cultivation was able to prevent replication of in vitro cultivated HCV.Keywords: Hepatitis C, green algae, cyanobacteria, polymerase chain reactionAfrican Journal of Biotechnology, Vol. 13(9), pp. 1086-1096, 26 February, 201

Anatomical Variations in Palmar Creases and Their Correlation to The Intelligence Capacity of Libyan Medical and Dental Students of Omar Al-Mukhtar University.

Background: For centuries, clinicians, anthropologists, and palmists have found the creases in the palm interesting. However, only in the last fifty years that research's started to examine the variations in these creases. Based on the three main palmar creases, thenar, proximal, and distal transverse creases, four patterns of palmar creases are identified; nonvariant, Sydney, Suwon, and simian. Previous studies of palmar creases revealed that familial components, race, sex, and age are factors that influence the expression of palmar crease patterns. Simian patterns of palmar creases are linked to various congenital diseases, some characterized by low level of intelligence. Aim: This paper aims to investigate the variations in palmar crease patterns among medical and dental students of Omar Al-Mukhtar University and to study the range of intelligence capacity associated with each pattern. Materials and methods: The study was conducted on 183 students. A paper-based IQ test was performed and photos were taken from both palms of all participants. Results: Out of 183 participants, the nonvariant pattern of palmar creases was found in 92%, in which, 100 students have bilateral 2 points of origin palmar creases and 48 students have bilateral 3 points of origin palmar creases, whereas 18 participants have one palm of 2 points and the other palm of 3 points of origin. Unilateral simian was the dominant type in the aberrant palmar creases, followed by bilateral Sydney, then unilateral Sydney, and Suwon. Conclusion: The students with unilateral simian have the highest average score of 47.166 followed by bilateral nonvariant and unilateral nonvariant. Students with unilateral Sydney have the lowest average score of 41

Species-specific kinetics and zonation of hepatic DNA synthesis induced by ligands of PPAR?

PPAR? ligands evoke a profound mitogenic response in rodent liver, and the aim of this studywas to characterise the kinetics of induction of DNA synthesis. The CAR ligand, 1,4-bis[2-(3,5-dichoropyridyloxy)]benzene, caused induction of hepatocyte DNA synthesis within 48 hours in129S4/SvJae mice, but the potent PPAR? ligand, ciprofibrate, induced hepatocyte DNA synthesisonly after 3 or 4 days dosing; higher or lower doses did not hasten the DNA synthesisresponse. This contrasted with the rapid induction (24 hours) reported by Styles et al. (Carcinogenesis9:1647-1655). C57BL/6 and DBA/2J mice showed significant induction of DNA synthesisafter 4, but not 2, days ciprofibrate treatment. Alderley Park and 129S4/SvJae mice dosedwith methylclofenapate induced hepatocyte DNA synthesis at 4, but not 2, days after dosing,and proved that inconsistency with prior work was not due to a difference in mouse strain orPPAR? ligand. Ciprofibrate-induced liver DNA synthesis and growth was absent in PPAR?-null mice, and are PPAR?-dependent. In the Fisher344 rat, hepatocyte DNA synthesis was inducedat 24 hours after dosing, with a second peak at 48 hours. Lobular localisation of hepatocyteDNA synthesis showed preferential periportal induction of DNA synthesis in rat, butpanlobular zonation of hepatocyte DNA synthesis in mouse. These results characterise a markedlylater hepatic induction of panlobular DNA synthesis by PPAR? ligands in mouse, comparedto rapid induction of periportal DNA synthesis in rat

The Effects of Wheat Flour and Barley Flour on the Quality and Properties of Biscuits Colored with Synthetic and Natural Colorants

Biscuit is one of the most popular processed ready to eat snacks that have possesses several attractive features including wide consumer base, relatively less expensive, more convenient with long shelf-life and have ability to serve as vehicles for important nutrients. It’s usually available in different sizes, tastes and shapes.  It can also be enriched or fortified with other ingredients in order to meet specific nutritional or therapeutic needs of consumers. In recent years, numerous studies have shown the potential of utilizing natural plant such as green leafy vegetable in cookies and biscuit production; the potential of amaranthus leaves used as a source of iron and β-carotene inpakora, vada, namakpal, kurmure, biscuit and cake. The present research was carried out to throw the light on the effect of wheat flour and barley flour with natural and synthetic colors to improve chemical composition, the nutritional value and quality characteristics of producing biscuits. The results indicate that that treatment 100% barley flour 72% with turmeric and cocoa as a natural colors recorded a significant increase in the content of protein, ash, minerals such as iron, zinc, potassium, magnesium and some physical analysis like weight, volume, density as well as sensory evaluation. As compared with wheat flour 72% and synthetic color tartrazine ADI 7.5 mg/kg.bw and chocolate brown ADI 0.15 mg/kg.bw. In conclusion, results showed that barley flour improved nutritional quality, physical characteristics and sensory characteristics of produce biscuit with mixture natural and natural color

Assessment of Albumin Usage Patterns and Appropriateness in a Comprehensive Cancer Centre: A retrospective study in Jordan

Objectives: Albumin is commonly used for various indications; however, there is conflicting data regarding its appropriate use in different clinical cases. This study aimed to determine the pattern and appropriateness of albumin use among cancer patients at the King Hussein Cancer Center in Jordan. Methods: A retrospective analysis was conducted on adult cancer patients who were prescribed albumin between January 2019 and July 2020 in both outpatient and inpatient settings. Data collected included demographics, prescribing services, indications and dosing regimens. A literature review was performed using PubMed to assess the appropriateness of albumin indications and dosing regimens against current guidelines, drug information resources and the package insert. Results: Albumin was prescribed to 1,361 patients during the study period. Each patient received an average of 74.4 ± 89 g of albumin for an average of 2.6 ± 1.8 days. Albumin use was deemed appropriate in 69% of the patients. The critical care service accounted for the highest albumin consumption, with 37% of prescriptions for septic shock. Inappropriate use of albumin was most prevalent in the medical solid tumour services (40.8% of prescriptions), primarily for edema (28%). Conclusion: To the best of the author’s knowledge, this study is the first to evaluate albumin use in a large cohort of oncology patients. Approximately one-third of the albumin prescriptions were considered inappropriate. Continuous education on appropriate usage and regular evaluations of guideline adherence are essential to ensure proper utilisation of albumin in cancer care

Overview on Blood Transfusion-Transmitted Diseases

As it is important for the Blood transfusion to be extremely safe, some measures have to be taken long safeguarded the blood supply from the major transfusion transmissible diseases (TTIs).  The risk of transfusion-transmitted infection (TTI) rises with the number of donors exposed, and the effects of TTI are frequently more severe in immune compromised people. TTIs (hepatitis B virus [HBV], HIV, and hepatitis C virus [HCV]) are examples of typical transfusion-transmitted infectious agents. As a result of the gradual application of nucleic acid-amplification technology (NAT) screening for HIV, HCV, and HBV, the residual risk of infected window-period donations has been minimized. Nonetheless, infections emerge far more frequently than is commonly acknowledged, needing ongoing surveillance and individual assessment of transfusion-associated risk. Although there is a constant need to monitor present dangers owing to established TTI, the ongoing issues in blood safety are mostly related to surveillance for developing agents, as well as the creation of quick reaction systems when such agents are detected