Search results for: inflammatory indexes
202 Development of a Novel Antibacterial to Block Growth of Pseudomonas Aeruginosa and Prevent Biofilm Formation
Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur
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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa
Procedia PDF Downloads 281201 Yellow Necklacepod and Shih-Balady: Possible Promising Sources Against Human Coronaviruses
Authors: Howaida I. Abd-Alla, Omnia Kutkat, Yassmin Moatasim, Magda T. Ibrahim, Marwa A. Mostafa, Mohamed GabAllah, Mounir M. El-Safty
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Artemisia judaica (known shih-balady), Azadirachta indica and Sophora tomentosa (known yellow necklace pod) are members of available medicinal plants well-known for their traditional medical use in Egypt which suggests that they probably harbor broad-spectrum antiviral, immunostimulatory and anti-inflammatory functions. Their ethyl acetate-dichloromethane (1:1, v/v) extracts were evaluated for the potential anti-Middle East respiratory syndrome-related coronavirus (anti-MERS-CoV) activity. Their cytotoxic activity was tested in Vero-E6 cells using 3-(4,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with minor modification. The plot of percentage cytotoxicity for each extract concentration has calculated the concentration which exhibited 50% cytotoxic concentration (TC50). A plaque reduction assay was employed using safe dose of extract to evaluate its effect on virus propagation. The highest inhibition percentage was recorded for the yellow necklace pod, followed by Shih-balady. The possible mode of action of virus inhibition was studied at three different levels viral replication, viral adsorption and virucidal activity. The necklace pod leaves have induced virucidal effects and direct effects on the replication of virus. Phytochemical investigation of the promising necklace pod led to the isolation and structure determination of nine compounds. The structure of each compound was determined by a variety of spectroscopic methods. Compounds 4-O-methyl sorbitol 1, 8-methoxy daidzin 6 and 6-methoxy apigenin-7-O-β-D-glucopyranoside 8 were isolated for the first time from the Sophora genus and the other six compounds were the first time that they were isolated from this species according to available works of literature. Generally, the highest anti-CoV 2 activity of S. tomentosa was associated with the crude ethanolic extract, indicating the possibility of synergy among the antiviral phytochemical constituents (1-9).Keywords: coronavirus, MERS-CoV, mode of action, necklace pod, shih-balady
Procedia PDF Downloads 203200 Cytotoxicity of 13 South African Macrofungal Species and Mechanism/s of Action against Cancer Cell Lines
Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender
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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action
Procedia PDF Downloads 239199 Electrochemical Bioassay for Haptoglobin Quantification: Application in Bovine Mastitis Diagnosis
Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo
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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine
Procedia PDF Downloads 163198 A Quality Index Optimization Method for Non-Invasive Fetal ECG Extraction
Authors: Lucia Billeci, Gennaro Tartarisco, Maurizio Varanini
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Fetal cardiac monitoring by fetal electrocardiogram (fECG) can provide significant clinical information about the healthy condition of the fetus. Despite this potentiality till now the use of fECG in clinical practice has been quite limited due to the difficulties in its measuring. The recovery of fECG from the signals acquired non-invasively by using electrodes placed on the maternal abdomen is a challenging task because abdominal signals are a mixture of several components and the fetal one is very weak. This paper presents an approach for fECG extraction from abdominal maternal recordings, which exploits the characteristics of pseudo-periodicity of fetal ECG. It consists of devising a quality index (fQI) for fECG and of finding the linear combinations of preprocessed abdominal signals, which maximize these fQI (quality index optimization - QIO). It aims at improving the performances of the most commonly adopted methods for fECG extraction, usually based on maternal ECG (mECG) estimating and canceling. The procedure for the fECG extraction and fetal QRS (fQRS) detection is completely unsupervised and based on the following steps: signal pre-processing; maternal ECG (mECG) extraction and maternal QRS detection; mECG component approximation and canceling by weighted principal component analysis; fECG extraction by fQI maximization and fetal QRS detection. The proposed method was compared with our previously developed procedure, which obtained the highest at the Physionet/Computing in Cardiology Challenge 2013. That procedure was based on removing the mECG from abdominal signals estimated by a principal component analysis (PCA) and applying the Independent component Analysis (ICA) on the residual signals. Both methods were developed and tuned using 69, 1 min long, abdominal measurements with fetal QRS annotation of the dataset A provided by PhysioNet/Computing in Cardiology Challenge 2013. The QIO-based and the ICA-based methods were compared in analyzing two databases of abdominal maternal ECG available on the Physionet site. The first is the Abdominal and Direct Fetal Electrocardiogram Database (ADdb) which contains the fetal QRS annotations thus allowing a quantitative performance comparison, the second is the Non-Invasive Fetal Electrocardiogram Database (NIdb), which does not contain the fetal QRS annotations so that the comparison between the two methods can be only qualitative. In particular, the comparison on NIdb was performed defining an index of quality for the fetal RR series. On the annotated database ADdb the QIO method, provided the performance indexes Sens=0.9988, PPA=0.9991, F1=0.9989 overcoming the ICA-based one, which provided Sens=0.9966, PPA=0.9972, F1=0.9969. The comparison on NIdb was performed defining an index of quality for the fetal RR series. The index of quality resulted higher for the QIO-based method compared to the ICA-based one in 35 records out 55 cases of the NIdb. The QIO-based method gave very high performances with both the databases. The results of this study foresees the application of the algorithm in a fully unsupervised way for the implementation in wearable devices for self-monitoring of fetal health.Keywords: fetal electrocardiography, fetal QRS detection, independent component analysis (ICA), optimization, wearable
Procedia PDF Downloads 273197 Methylglyoxal Induced Glycoxidation of Human Low Density Lipoprotein: A Biophysical Perspective and Its Role in Diabetes and Periodontitis
Authors: Minhal Abidi, Moinuddin
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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis
Procedia PDF Downloads 187196 Influence of Cobalt Incorporation on the Structure and Properties of SOL-Gel Derived Mesoporous Bioglass Nanoparticles
Authors: Ahmed El-Fiqi, Hae-Won Kim
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Incorporation of therapeutic elements such as Sr, Cu and Co into bioglass structure and their release as ions is considered as one of the promising approaches to enhance cellular responses, e.g., osteogenesis and angiogenesis. Here, cobalt as angiogenesis promoter has been incorporated (at 0, 1 and 4 mol%) into sol-gel derived calcium silicate mesoporous bioglass nanoparticles. The composition and structure of cobalt-free (CFN) and cobalt-doped (CDN) mesoporous bioglass nanoparticles have been analyzed by X-ray fluorescence (XRF), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier-Transform Infra-red spectroscopy (FT-IR). The physicochemical properties of CFN and CDN have been investigated using high-resolution transmission electron microscopy (HR-TEM), Selected area electron diffraction (SAED), and Energy-dispersive X-ray (EDX). Furthermore, the textural properties, including specific surface area, pore-volume, and pore size, have been analyzed from N²⁻sorption analyses. Surface charges of CFN and CDN were also determined from surface zeta potential measurements. The release of ions, including Co²⁺, Ca²⁺, and SiO₄⁴⁻ has been analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Loading and release of diclofenac as an anti-inflammatory drug model were explored in vitro using Ultraviolet-visible spectroscopy (UV-Vis). XRD results ensured the amorphous state of CFN and CDN whereas, XRF further confirmed that their chemical compositions are very close to the designed compositions. HR-TEM analyses unveiled nanoparticles with spherical morphologies, highly mesoporous textures, and sizes in the range of 90 - 100 nm. Moreover, N²⁻ sorption analyses revealed that the nanoparticles have pores with sizes of 3.2 - 2.6 nm, pore volumes of 0.41 - 0.35 cc/g and highly surface areas in the range of 716 - 830 m²/g. High-resolution XPS analysis of Co 2p core level provided structural information about Co atomic environment and it confirmed the electronic state of Co in the glass matrix. ICP-AES analysis showed the release of therapeutic doses of Co²⁺ ions from 4% CDN up to 100 ppm within 14 days. Finally, diclofenac loading and release have ensured the drug/ion co-delivery capability of 4% CDN.Keywords: mesoporous bioactive glass, nanoparticles, cobalt ions, release
Procedia PDF Downloads 100195 Investigating Anti-Tumourigenic and Anti-Angiogenic Effects of Resveratrol in Breast Carcinogenesis Using in-Silico Algorithms
Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin
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Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol
Procedia PDF Downloads 319194 Nanoparticles Made from PNIPAM-G-PEO Double Hydrophilic Copolymers for Temperature-Controlled Drug Delivery
Authors: Victoria I. Michailova, Denitsa B. Momekova, Hristiana A. Velichkova, Evgeni H. Ivanov
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The aim of this work is to design and develop thermo-responsive nanosized drug delivery systems based on poly(N-isopropylacrylamide)-g-poly(ethylene oxide) (PNIPAM-g-PEO) double hydrophilic graft copolymers. The PNIPAM-g-PEO copolymers are able to self-assemble in water into nanoparticles above the LCST of the thermo-responsive PNIPAM backbone and to disassemble and rapidly release the entrapped drugs upon cooling. However, their drug delivery applications are often hindered by their low loading capacity as the drugs to be encapsulated do not dissolve in water. In order to overcome this limitation, here we applied a low-temperature procedure with ethanol as an alternative route to the formation and loading a model hydrophobic drug, Indomethacin (IMC), into PNIPAM-g-PEO nanoparticles. The rationale for this approach was that ethanol dissolves both IMC and the copolymer and its mixing with water may induce micellization of PNIPAM-g-PEO at temperatures lower than the LCST. The influence of the volume fraction of ethanol and the temperature on the aggregation characteristics of PNIPAM-g-PEO copolymers (2.7 mol% PEO) was investigated by means of DLS, TEM and rheological dynamic oscillatory tests. The studies showed rich phase behavior at T < LCST, incl. the formation of highly solvated 500-1000 nm complex structures, 30-70 nm micelles and polymersomes as well as giant polymersomes, as the fraction of added ethanol increased. We believe that the PNIPAM-g-PEO self-assembly is favored due to the different solvation of its constituting blocks in ethanol-water mixtures. The incorporation of IMC led to alteration of the physicochemical and morphological characteristics of the blank nanoparticles. In this case, only monodisperse polymersomes and micelles were observed in the solutions with an average diameter less than 65 nm and substantial drug loading (DLC ~117 – 146 wt%). Indomethacin release from the nanoparticles was responsive to temperature changes, being much faster at a temperature of 42oC compared to that of 37oC under otherwise the same conditions. The results obtained suggest that these PNIPAM-g-PEO nanoparticles could be potential in mild hyper-thermic delivery of nonsteroidal anti-inflammatory drugs.Keywords: drug delivery, nanoparticles, poly(N-isopropylacryl amide)-g-poly(ethylene oxide), thermo-responsive
Procedia PDF Downloads 282193 Identification of the Expression of Top Deregulated MiRNAs in Rheumatoid Arthritis and Osteoarthritis
Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr
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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis
Procedia PDF Downloads 73192 History of Pediatric Renal Pathology
Authors: Mostafa Elbaba
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Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.Keywords: history, medicine, nephrology, pediatrics, pathology
Procedia PDF Downloads 52191 The Effect of Emotional Intelligence on Physiological Stress of Managers
Authors: Mikko Salminen, Simo Järvelä, Niklas Ravaja
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One of the central models of emotional intelligence (EI) is that of Mayer and Salovey’s, which includes ability to monitor own feelings and emotions and those of others, ability to discriminate different emotions, and to use this information to guide thinking and actions. There is vast amount of previous research where positive links between EI and, for example, leadership successfulness, work outcomes, work wellbeing and organizational climate have been reported. EI has also a role in the effectiveness of work teams, and the effects of EI are especially prominent in jobs requiring emotional labor. Thus, also the organizational context must be taken into account when considering the effects of EI on work outcomes. Based on previous research, it is suggested that EI can also protect managers from the negative consequences of stress. Stress may have many detrimental effects on the manager’s performance in essential work tasks. Previous studies have highlighted the effects of stress on, not only health, but also, for example, on cognitive tasks such as decision-making, which is important in managerial work. The motivation for the current study came from the notion that, unfortunately, many stressed individuals may not be aware of the circumstance; periods of stress-induced physiological arousal may be prolonged if there is not enough time for recovery. To tackle this problem, physiological stress levels of managers were collected using recording of heart rate variability (HRV). The goal was to use this data to provide the managers with feedback on their stress levels. The managers could access this feedback using a www-based learning environment. In the learning environment, in addition to the feedback on stress level and other collected data, also developmental tasks were provided. For example, those with high stress levels were sent instructions for mindfulness exercises. The current study focuses on the relation between the measured physiological stress levels and EI of the managers. In a pilot study, 33 managers from various fields wore the Firstbeat Bodyguard HRV measurement devices for three consecutive days and nights. From the collected HRV data periods (minutes) of stress and recovery were detected using dedicated software. The effects of EI on HRV-calculated stress indexes were studied using Linear Mixed Models procedure in SPSS. There was a statistically significant effect of total EI, defined as an average score of Schutte’s emotional intelligence test, on the percentage of stress minutes during the whole measurement period (p=.025). More stress minutes were detected on those managers who had lower emotional intelligence. It is suggested, that high EI provided managers with better tools to cope with stress. Managing of own emotions helps the manager in controlling possible negative emotions evoked by, e.g., critical feedback or increasing workload. High EI managers may also be more competent in detecting emotions of others, which would lead to smoother interactions and less conflicts. Given the recent trend to different quantified-self applications, it is suggested that monitoring of bio-signals would prove to be a fruitful direction to further develop new tools for managerial and leadership coaching.Keywords: emotional intelligence, leadership, heart rate variability, personality, stress
Procedia PDF Downloads 219190 Investigation of The Effects of Hydroxytyrosol on Cytotoxicity, Apoptosis, PI3K/Akt, and ERK 1/2 Pathways in Ovarian Cancer Cell Cultures
Authors: Latife Merve Oktay, Berrin Tugrul
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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer
Procedia PDF Downloads 352189 Effect of Psychological Stress to the Mucosal IL-6 and Helicobacter pylori Activity in Functional Dyspepsia and Myocytes
Authors: Eryati Darwin, Arina Widya Murni, Adnil Edwin Nurdin
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Background: Functional dyspepsia (FD) is a highly prevalent and heterogeneous disorder. Most patients with FD complain of symptoms related to the intake of meals. Psychological stress may promote peptic ulcer and had an effect on ulcers associated Hp, and may also trigger worsen symptoms in inflammatory disorders of the gastrointestinal. Cells in mucosal gastric stimulate the production of several cytokines, which might associated with Helicobacter pylori infection. The cascade of biological events leading to stress-induced FD remains poorly understood. Aim of Study: To determine the prion-flammatory cytokine IL-6, and Helicobacter pylori activity on mucosal gastric of FD and their association with psychological stress. Methods: The subjects of this study were dyspeptic patients who visited M. Djamil General Hospital and in two Community Health Centers in Padang. On the basis of the stress index scale to identify psychological stress by using Depression Anxiety and Stress Scale (DASS 42), subjects were divided into two groups of 20 each, stress groups and non-stress groups. All diagnoses were confirmed by review of cortisol and esophagogastroduodenoscopy reports. Gastric biopsy samples and peripheral blood were taken during diagnostic procedures. Immunohistochemistry methods were used to determine the expression of IL-6 and Hp in gastric mucosal. The data were statistically analyzed by univariate and bivariate analysis. All procedures of this study were approved by Research Ethics Committee of Medical Faculty Andalas University. Results: In this study, we enrolled 40 FD patients (26 woman and 14 men) in range between 35-56 years old. Cortisol level of blood FD patients as parameter of stress hormone which taken in the morning was significantly higher in stress group than non-stress group. The expression of IL-6 in gastric mucosa was significantly higher in stress group in compared to non-stress group (p<0,05). Helicobacter pylori activity in gastric mucosal in stress group were significantly higher than non-stress group. Conclusion: The present study showed that psychological stress can induce gastric mucosal inflammation and increase of Helicobacter pylori activity.Keywords: functional dyspepsia, Helicobacter pylori, interleukin-6, psychological stress
Procedia PDF Downloads 275188 Allylation of Active Methylene Compounds with Cyclic Baylis-Hillman Alcohols: Why Is It Direct and Not Conjugate?
Authors: Karim Hrratha, Khaled Essalahb, Christophe Morellc, Henry Chermettec, Salima Boughdiria
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Among the carbon-carbon bond formation types, allylation of active methylene compounds with cyclic Baylis-Hillman (BH) alcohols is a reliable and widely used method. This reaction is a very attractive tool in organic synthesis of biological and biodiesel compounds. Thus, in view of an insistent and peremptory request for an efficient and straightly method for synthesizing the desired product, a thorough analysis of various aspects of the reaction processes is an important task. The product afforded by the reaction of active methylene with BH alcohols depends largely on the experimental conditions, notably on the catalyst properties. All experiments reported that catalysis is needed for this reaction type because of the poor ability of alcohol hydroxyl group to be as a suitable leaving group. Within the catalysts, several transition- metal based have been used such as palladium in the presence of acid or base and have been considered as reliable methods. Furthemore, acid catalysts such as BF3.OEt2, BiX3 (X= Cl, Br, I, (OTf)3), InCl3, Yb(OTf)3, FeCl3, p-TsOH and H-montmorillonite have been employed to activate the C-C bond formation through the alkylation of active methylene compounds. Interestingly a report of a smoothly process for the ability of 4-imethyaminopyridine(DMAP) to catalyze the allylation reaction of active methylene compounds with cyclic Baylis-Hillman (BH) alcohol appeared recently. However, the reaction mechanism remains ambiguous, since the C- allylation process leads to an unexpected product (noted P1), corresponding to a direct allylation instead of conjugate allylation, which involves the most electrophilic center according to the electron withdrawing group CO effect. The main objective of the present theoretical study is to better understand the role of the DMAP catalytic activity as well as the process leading to the end- product (P1) for the catalytic reaction of a cyclic BH alcohol with active methylene compounds. For that purpose, we have carried out computations of a set of active methylene compounds varying by R1 and R2 toward the same alcohol, and we have attempted to rationalize the mechanisms thanks to the acid–base approach, and conceptual DFT tools such as chemical potential, hardness, Fukui functions, electrophilicity index and dual descriptor, as these approaches have shown a good prediction of reactions products.The present work is then organized as follows: In a first part some computational details will be given, introducing the reactivity indexes used in the present work, then Section 3 is dedicated to the discussion of the prediction of the selectivity and regioselectivity. The paper ends with some concluding remarks. In this work, we have shown, through DFT method at the B3LYP/6-311++G(d,p) level of theory that: The allylation of active methylene compounds with cyclic BH alcohol is governed by orbital control character. Hence the end- product denoted P1 is generated by direct allylation.Keywords: DFT calculation, gas phase pKa, theoretical mechanism, orbital control, charge control, Fukui function, transition state
Procedia PDF Downloads 296187 Epigenetic Modifying Potential of Dietary Spices: Link to Cure Complex Diseases
Authors: Jeena Gupta
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In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.Keywords: epigenetics, spices, phytochemicals, fenchone
Procedia PDF Downloads 150186 Long-Term Conservation Tillage Impact on Soil Properties and Crop Productivity
Authors: Danute Karcauskiene, Dalia Ambrazaitiene, Regina Skuodiene, Monika Vilkiene, Regina Repsiene, Ieva Jokubauskaite
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The main ambition for nowadays agriculture is to get the economically effective yield and to secure the soil ecological sustainability. According to the effect on the main soil quality indexes, tillage systems may be separated into two types, conventional and conservation tillage. The goal of this study was to determine the impact of conservation and conventional primary soil tillage methods and soil fertility improvement measures on soil properties and crop productivity. Methods: The soil of the experimental site is Dystric Glossic Retisol (WRB 2014) with texture of sandy loam. The trial was established in 2003 in the experimental field of crop rotation of Vėžaičiai Branch of Lithuanian Research Centre for Agriculture and Forestry. Trial factors and treatments: factor A- primary soil tillage in (autumn): deep ploughing (20-25cm), shallow ploughing (10-12cm), shallow ploughless tillage (8-10cm); factor B – soil fertility improvement measures: plant residues, plant residues + straw, green manure 1st cut + straw, farmyard manure 40tha-1 + straw. The four - course crop rotation consisted of red clover, winter wheat, spring rape and spring barley with undersown. Results: The tillage had no statistically significant effect on topsoil (0-10 cm) pHKCl level, it was 5.5 - 5.7. During all experiment period, the highest soil pHKCl level (5.65) was in the shallow ploughless tillage. The organic fertilizers particularly the biomass of grass and farmyard manure had tendency to increase the soil pHKCl. The content of plant - available phosphorus and potassium significantly increase in the shallow ploughing compared with others tillage systems. The farmyard manure increases those elements in whole arable layer. The dissolved organic carbon concentration was significantly higher in the 0 - 10 cm soil layer in the shallow ploughless tillage compared with deep ploughing. After the incorporation of clover biomass and farmyard manure the concentration of dissolved organic carbon increased in the top soil layer. During all experiment period the largest amount of water stable aggregates was determined in the soil where the shallow ploughless tillage was applied. It was by 12% higher compared with deep ploughing. During all experiment time, the soil moisture was higher in the shallow ploughing and shallow ploughless tillage (9-27%) compared to deep ploughing. The lowest emission of CO2 was determined in the deep ploughing soil. The highest rate of CO2 emission was in shallow ploughless tillage. The addition of organic fertilisers had a tendency to increase the CO2 emission, but there was no statistically significant effect between the different types of organic fertilisers. The crop yield was larger in the deep ploughing soil compared to the shallow and shallow ploughless tillage.Keywords: reduced tillage, soil structure, soil pH, biological activity, crop productivity
Procedia PDF Downloads 260185 A Case-Series Analysis of Tuberculosis in Patients at Internal Medicine Department
Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.
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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.Keywords: tuberculosis, infection, autoimmune disease, granulomatosis
Procedia PDF Downloads 181184 Effect of Nigella sativa on Blood Pressure, Vascular Reactivity, Inflammatory Biomarkers and Nitric Oxide in L-Name-Induced Hypertensive Rats
Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das
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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity
Procedia PDF Downloads 414183 The h3r Antagonist E159 Alleviates Neuroinflammation and Autistic-Like Phenotypes in BTBR T+ tf/J Mouse Model of Autism
Authors: Shilu Deepa Thomas, P. Jayaprakash, Dorota Łazewska, Katarzyna Kieć-Kononowicz, B. Sadek
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A large body of evidence suggests the involvement of cognitive impairment, increased levels of inflammation and oxidative stress in the pathogenesis of autism spectrum disorder (ASD). ASD commonly coexists with psychiatric conditions like anxiety and cognitive challenges, and individuals with ASD exhibit significant levels of inflammation and immune system dysregulation. Previous Studies have identified elevated levels of pro-inflammatory markers such as IL-1β, IL-6, IL-2 and TNF-α, particularly in young children with ASD. The current therapeutic options for ASD show limited effectiveness, signifying the importance of exploring an efficient drugs to address the core symptoms. The role of histamine H3 receptors (H3Rs) in memory and the prospective role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., ASD, is well-accepted. Hence, the effects of chronic systemic administration of H3R antagonist E159 on autistic-like repetitive behaviors, social deficits, memory and anxiety parameters, as well as neuroinflammation in Black and Tan BRachyury (BTBR) mice, were evaluated using Y maze, Barnes maze, self-grooming, open field and three chamber social test. E159 (2.5, 5 and 10 mg/kg, i.p.) dose-dependently ameliorated repetitive and compulsive behaviors by reducing the increased time spent in self-grooming and improved reduced spontaneous alternation in BTBR mice. Moreover, treatment with E159 attenuated disturbed anxiety levels and social deficits in tested male BTBR mice. Furthermore, E159 attenuated oxidative stress by significantly increasing GSH, CAT, and SOD and decreasing the increased levels of MDA in the cerebellum as well as the hippocampus. In addition, E159 decreased the elevated levels of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6). The observed results show that H3R antagonists like E159 may represent a promising novel pharmacological strategy for the future treatment of ASD.Keywords: histamine H3 receptors, antagonist E159, autism, behaviors, mice
Procedia PDF Downloads 50182 Evaluating Antimicrobial Activity of Selenium Nanoparticles Against Food-Borne Bacteria
Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao
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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium
Procedia PDF Downloads 89181 Changes in the fecal Microbiome of Periparturient Dairy Cattle and Associations with the Onset of Salmonella Shedding
Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing
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Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.Keywords: dairy cattle, microbiome, periparturient, Salmonella
Procedia PDF Downloads 165180 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity
Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna
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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib
Procedia PDF Downloads 56179 Immune Modulation and Cytomegalovirus Reactivation in Sepsis-Induced Immunosuppression
Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia
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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load
Procedia PDF Downloads 144178 Size and Content of the Doped Silver Affected the Pulmonary Toxicity of Silver-Doped Nano-Titanium Dioxide Photocatalysts and the Optimization of These Two Parameters
Authors: Xiaoquan Huang, Congcong Li, Tingting Wei, Changcun Bai, Na Liu, Meng Tang
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Silver is often doped on nano-titanium dioxide photocatalysts (Ag-TiO₂) by photodeposition method to improve their utilization of visible-light while increasing the toxicity of TiO₂。 However, it is not known what factors influence this toxicity and how to reduce toxicity while maintaining the maximum catalytic activity. In this study, Ag-TiO₂ photocatalysts were synthesized by the photodeposition method with different silver content (AgC) and photodeposition time (PDT). Characterization and catalytic experiments demonstrated that silver was well assembled on TiO₂ with excellent visible-light catalytic activity, and the size of silver increased with PDT. In vitro, the cell viability of lung epithelial cells A549 and BEAS-2B showed that the higher content and smaller size of silver doping caused higher toxicity. In vivo, Ag-TiO₂ catalysts with lower AgC or larger silver particle size obviously caused less pulmonary pro-inflammatory and pro-fibrosis responses. However, the visible light catalytic activity decreased with the increase in silver size. Therefore, in order to optimize the Ag-TiO₂ photocatalyst with the lowest pulmonary toxicity and highest catalytic performance, response surface methodology (RSM) was further performed to optimize the two independent variables of AgC and PDT. Visible-light catalytic activity was evaluated by the degradation rate of Rhodamine B, the antibacterial property was evaluated by killing log value for Escherichia coli, and cytotoxicity was evaluated by IC50 to BEAS-2B cells. As a result, the RSM model showed that AgC and PDT exhibited an interaction effect on catalytic activity in the quadratic model. AgC was positively correlated with antibacterial activity. Cytotoxicity was proportional to AgC while inversely proportional to PDT. Finally, the optimization values were AgC 3.08 w/w% and PDT 28 min. Under this optimal condition, the relatively high silver proportion ensured the visible-light catalytic and antibacterial activity, while the longer PDT effectively reduced the cytotoxicity. This study is of significance for the safe and efficient application of silver-doped TiO₂ photocatalysts.Keywords: Ag-doped TiO₂, cytotoxicity, inflammtion, fibrosis, response surface methodology
Procedia PDF Downloads 64177 Fine Needle Aspiration Biopsy of Thyroid Nodules
Authors: Ilirian Laçi, Alketa Spahiu
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Big strums of thyroid glandule observed by a simple viewing can be witnessed in everyday life. Medical cabinets evidence patients withpalpablenodes of thyroid glandule, mainly nodes of the size of 10 millimeters. Further, more cases which have resulted in negative under palpation have resulted in positive at ultrasound examination. Therefore, the use of ultrasound for diagnosing has increased the number of patients with nodes of thyroid glandule in the last couple of decades in all countries, Albania included. Thus, there has been evidence of an increased number of patients affected by this pathology, where female patients dominate. Demographically, the capital shows high numbers due to the high population, but of interest is the high incidence of those areas distanced from the sea. While regarding related pathologies, no significant link was evidenced, an element of ancestry was evident in the nodes of the thyroid glandule. When we talk of nodes of the thyroid glandule, we should consider hyperplasia, neoplasia, and inflammatory diseases that cause nodes of the thyroid glandule. This increase parallels the world’s increase of the incidence of thyroid glandule, with malign cases, which are at about 5% and are not depended on size. Given the numbers, with most thyroid glandule nodes being benign, the main objective of the examination of the nodes was the determination of benign and malign cases to avoid undue surgery. Subject of this study were 212 patients that underwent fine-needle aspiration (FNA) under ultrasound guidance at the Medical University Center of Tirana. All the patients came to the Mother Teresa University Hospital from public and private hospitals and other polyclinics. These patients had an ultrasound examination before visiting the Center of Nuclear Medicine for a scintigraph of thyroid glandule in the period September 2016 and September 2017. To correlate, all patients had been examined via ultrasound of the thyroid glandule prior to the scintigraph. The ultrasound included evaluation of the number of nodes, their size, their solid, cystic, or solid-cystic structure, echogenicity according to the gray scale, the presence of calcification, the presence of lymph nodes, the presence of adenopathy, and the correlation of the cytology results from the Laboratory of Pathological Anatomy of Medical University Center of Tirana.Keywords: thyroid nodes, fine needle aspiration, ultrasound, scintigraphy
Procedia PDF Downloads 96176 Economic Impacts of Nitrogen Fertilizer Use into Tropical Pastures for Beef Cattle in Brazil
Authors: Elieder P. Romanzini, Lutti M. Delevatti, Rhaony G. Leite, Ricardo A. Reis, Euclides B. Malheiros
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Brazilian beef cattle production systems are an important profitability source for the national gross domestic product. The main characteristic of these systems is forage utilization as the exclusive feed source. Forage utilization had been causing on owners the false feeling of low production costs. However, this low cost is followed to low profit causing a lot times worst animal index what can result in activities changes or until land sold. Aiming to evaluate economic impacts into Brazilian beef cattle systems were evaluated four nitrogen fertilizer (N) application levels (0, 90, 180 and 270 kg per hectare [kg.ha-1]). Research was developed during 2015 into Forage Crops and Grasslands section of São Paulo State University, “Júlio de Mesquita Filho” (Unesp) (Jaboticabal, São Paulo, Brazil). Pastures were seeded with Brachiaria brizantha Stapf. ‘Marandu’ (Palisade grass) handled using continuous grazing system, with variable stocking rate, sward height maintained at 25 cm. The economic evaluation was developed in rearing e finishing phases. We evaluated the cash flows inside each phase on different N levels. Economic valuations were considering: cost-effective operating (CEO), cost-total operating (CTO), gross revenue (GR), operating profit (OP) and net income (NI), every measured in US$. Complementary analyses were developed, profitability was calculated by [OP/GR]. Pay back (measured in years) was calculated considering average capital stocktaking pondered by area in use (ACS) divided by [GR-CEO]. And the internal rate of return (IRR) was calculated by 100/(pay back). Input prices were prices during 2015 and were obtained from Anuário Brasileiro da Pecuária, Centro de Estudos Avançados em Economia Aplicada and quotation in the same region of animal production (northeast São Paulo State) during the period above mentioned. Values were calculated in US$ according exchange rate US$1.00 equal R$3.34. The CEO, CTO, GR, OP and NI per hectare for each N level were respectively US$1,919.66; US$2,048.47; US$2,905.72; US$857.25 and US$986.06 to 0 kg.ha-1; US$2,403.20; US$2,551.80; US$3,530.19; US$978.39 and US$1,126.99 to 90 kg.ha-1; US$3,180.42; US$3,364.81; US$4,985.03; US$1,620.23 and US$1,804.62 to 180 kg.ha-1andUS$3,709.14; US$3,915.15; US$5,554.95; US$1,639.80 and US$1,845.81 to 270 kg.ha-1. Relationship to another economic indexes, profitability, pay back and IRR, the results were respectively 29.50%, 6.44 and 15.54% to 0 kg.ha-1; 27.72%, 6.88 and 14.54% to 90 kg.ha-1; 32.50%, 4.08 and 24.50% to 180 kg.ha-1 and 29.52%, 3.42 and 29.27% to 270 kg.ha-1. Values previously presented in this evaluation allowing to affirm that the best result was obtained to N level 270 kg.ha-1. These results among all N levels evaluated could be explained by improve occurred on stocking rate caused by increase on N level. However, a crucial information about high N level application into pastures is the efficiency of N utilization (associated to environmental impacts) that normally decrease with the increase on N level. Hence, considering all situations (efficiency of N utilization and economic results) into tropical pastures used to beef cattle production could be recommended N level equal to 180kg.ha-1, which had better profitability and cause lesser environmental impacts, proved by other studies developed in the same area.Keywords: Brachiaria brizantha, cost-total operating, gross revenue, profitability
Procedia PDF Downloads 162175 Hypoglycaemic and Hypolipidemic Activity of Cassia occidentalis Linn. Stem Bark Extract in Streptozotocin Induced Diabetes
Authors: Manjusha Choudhary
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Objective: Cassia occidentalis Linn. belongs to Family Caesalpiniaceae is a common weed scattered from the foothills of Himalayas to West Bengal, South India, Burma, and Sri Lanka. It is used widely in folklore medicine in India as laxative, expectorant, analgesic, anti-malarial, hepatoprotective, relaxant, anti-inflammatory and antidiabetic. The present study was carried out to investigate the hypoglycaemic and hypolipidemic activities of ethanolic extract of Cassia occidentalis stem bark. Methods: Stem bark extract of Cassia occidentalis (SBCO) was administered orally at 250 and 500 mg/kg doses to normal and streptozotocin (STZ) induced type-2 diabetic mice. Various parameters like fasting blood glucose (FBG) level, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake were performed for the evaluation of antidiabetic effects. Results: Both the doses of extract caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. Administration of SBCO led to the decrease in the blood glucose, food intake, water intake, organ weight, SGOT, SGPT levels with significant value and increased the levels of TG, HDL cholesterol, creatinine, cholesterol, total protein with a significant value (p < 0.05-0.01). The decrease in body weight induced by STZ was restored to normal with a significant value (p < 0.01) at both doses. Conclusion: Present study reveals that SBCO possess potent hypoglycaemic and hypolipidemic activities and supports the folklore use of the stem bark of plant as antidiabetic agent.Keywords: Cassia occidentalis, diabetes, folklore, herbs, hypoglycemia, streptozotocin
Procedia PDF Downloads 398174 The Efficacy of Government Strategies to Control COVID 19: Evidence from 22 High Covid Fatality Rated Countries
Authors: Imalka Wasana Rathnayaka, Rasheda Khanam, Mohammad Mafizur Rahman
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TheCOVID-19 pandemic has created unprecedented challenges to both the health and economic states in countries around the world. This study aims to evaluate the effectiveness of governments' decisions to mitigate the risks of COVID-19 through proposing policy directions to reduce its magnitude. The study is motivated by the ongoing coronavirus outbreaks and comprehensive policy responses taken by countries to mitigate the spread of COVID-19 and reduce death rates. This study contributes to filling the knowledge by exploiting the long-term efficacy of extensive plans of governments. This study employs a Panel autoregressive distributed lag (ARDL) framework. The panels incorporate both a significant number of variables and fortnightly observations from22 countries. The dependent variables adopted in this study are the fortnightly death rates and the rates of the spread of COVID-19. Mortality rate and the rate of infection data were computed based on the number of deaths and the number of new cases per 10000 people.The explanatory variables are fortnightly values of indexes taken to investigate the efficacy of government interventions to control COVID-19. Overall government response index, Stringency index, Containment and health index, and Economic support index were selected as explanatory variables. The study relies on the Oxford COVID-19 Government Measure Tracker (OxCGRT). According to the procedures of ARDL, the study employs (i) the unit root test to check stationarity, (ii) panel cointegration, and (iii) PMG and ARDL estimation techniques. The study shows that the COVID-19 pandemic forced immediate responses from policymakers across the world to mitigate the risks of COVID-19. Of the four types of government policy interventions: (i) Stringency and (ii) Economic Support have been most effective and reveal that facilitating Stringency and financial measures has resulted in a reduction in infection and fatality rates, while (iii) Government responses are positively associated with deaths but negatively with infected cases. Even though this positive relationship is unexpected to some extent in the long run, social distancing norms of the governments have been broken by the public in some countries, and population age demographics would be a possible reason for that result. (iv) Containment and healthcare improvements reduce death rates but increase the infection rates, although the effect has been lower (in absolute value). The model implies that implementation of containment health practices without association with tracing and individual-level quarantine does not work well. The policy implication based on containment health measures must be applied together with targeted, aggressive, and rapid containment to extensively reduce the number of people infected with COVID 19. Furthermore, the results demonstrate that economic support for income and debt relief has been the key to suppressing the rate of COVID-19 infections and fatality rates.Keywords: COVID-19, infection rate, deaths rate, government response, panel data
Procedia PDF Downloads 71173 Association between a Serotonin Re-Uptake Transporter Gene Polymorphism and Mucosal Serotonin Level in Women Patients with Irritable Bowel Syndrome and Healthy Control: A Pilot Study from Northern India
Authors: Sunil Kumar, Uday C. Ghoshal
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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism
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