61 research outputs found
Antimicrobiens naturels d'origine bactérienne : contribution à l'étude de leur activité biologique, leur stabilité gastrointestinale et leur toxicité
Au cours des dernières décennies, les antimicrobiens naturels d'origine bactérienne, telles que les bactériocines et la reutérine, ont reçu une attention considérable entant que conservateurs alimentaires ou comme alternatives aux antibiotiques pour les secteurs humain et animal. L'approbation des bactériocines et de la reutérine entant que bio-conservateurs ou assainisseurs par les organismes réglementaires repose non seulement sur les preuves d'efficacité mais également sur des données crédibles de cytotoxicité et de comportement dans l'environnement gastro-intestinal. Bien que les activités antimicrobiennes des bactériocines et de la reutérine soient largement documentées dans la littérature, très peu de données sont disponibles sur leur biodisponibilité dans les matrices biologiques et sur leur toxicité pour les différentes applications. Par conséquent, l'objectif général de cette thèse est d'évaluer, à travers différents modèles in vitro, la stabilité gastro-intestinale, l'activité biologique et la toxicité des bactériocines et de la reutérine en vue de leur utilisation dans différentes applications alimentaire, médicale et vétérinaire. Le premier objectif spécifique était de produire, purifier et évaluer l'activité antimicrobienne des bactériocines et de la reutérine seules et en combinaison contre un large panel de organismes pathogènes et d'altération d'intérêt pour les différents secteurs. Cinq consortia synergiques différents ont été identifiés, dont trois -microcine J25 + l'acide citrique + l'acide lactique, microcine J25 + reutérine + acide citrique, et microcine J25 + reutérine + acide lactique- ont montré une activité significative contre Salmonella enterica subsp. enterica serovar Newport ATCC6962 (indice FIC = 0,5). Deux autres combinaisons- pédiocine PA-1 + acide citrique+ acide lactique, et reutérine + acide citrique + acide lactique- ont montré des effets partiellement synergiques contre Listeria ivanovii HPB28 (indice FIC = 0,75). Le deuxième objectif spécifique était d'évaluer la stabilité gastro-intestinale de la reutérine à l'aide d'un modèl simulant des conditions digestives chez l'humain ainsi que l'activité hémolytique et la cytotoxicité in vitro de la reutérine par dosage au rouge neutre et dosage colorimétrique à la lactate déshydrogénase (LDH) en utilisant la lignée cellulaire Caco-2. La reutérine s'est révélée biologiquement très stable los du transit gastro-intestinal. L'exposition des cellules Caco-2 à différentes concentrations de réutérine n'a montré aucun effet négatif sur la viabilité ni sur l'intégrité des cellules à des concentrations allant jusqu'à 1080 mM. De plus, aucune hémolyse n'a été observée sur les cellules sanguines exposées à des concentrations allant jusqu'à 270 mM de reutérine. En conséquence, cette étude nous a permis de démontrer que la réutérine peut être utilisée de façon très sécuritaire à des concentrations n'excédant pas 270 mM, dans différentes applications. Le troisième objectif était d'évaluer la stabilité gastro-intestinale et l'activité de la microcine J25, de la pédiocine PA-1, de la bactofencine A et de la nisine à l'aide de modèles in vitro. De plus, la cytotoxicité et l'activité hémolytique de ces bactériocine sont été étudiées sur des cellules Caco-2 et des érythrocytes de rat, respectivement. Nos résultats ont montré que la pédiocine PA-1, la bactofencine A et la nisine sont dégradées à différents niveaux lors du transit gastro-intestinal, tandis que la microcine J25 n'est que partiellement dégradée. D'autre part, les études réalisées sur les cellules Caco-2 n'ont montré aucun effet cytotoxique jusqu'à des concentrations de 400 µg/mL. L'étude sur les érythrocytes de rat a montré un effet, hémolytique significatif lorsque la pédiocine PA-1, la bactofencine A et la nisine sont utilisées à des concentrations supérieures à 50 µg/mL, tandis que la microcine J25 n'a montré aucun effet hémolytique Dans le quatrième objectif, la toxicité cutanée de la reutérine, de la microcine J25, de la pédiocine PA-1, de la bactofencine A et de la nisine Z a été étudiée in vitro en utilisant des tests de libération de rouge neutre et de LDH sur des cellules NHEK. Les potentiels de sensibilisation et d'irritation cutanée de ces mêmes bactériocine sont également été déterminés en utilisant respectivement le test h-CLAT et le modèle épidermique humain EpiDerm™. Les essais réalisés sur les cellules NHEK ont montré que l'exposition de ces cellules aux bactériocines et à la reutérine à des concentrations allant à 400 µg/mL et 80 mg/mL respectivement, n'a entrainé aucun effet cytoxique. De plus, la microcine J25 et la reutérine n'ont montré aucune sensibilisation cutanée à des concentrations allant à 100 µg/mL et 40 mg/mL, respectivement, tandis que la pédiocine PA-1, la bactofencine A et la nisine Z ontprovoqué une sensibilisation à des concentrations supérieures à 100 µg/mL. La viabilité des tissus n'a pas été affectée en présence de bactériocines et de reutérine à des concentrations allant jusqu'à 200 µg/mL et 40 mg/mL, respectivement. L'ensemble de ces résultats montre que certaines bactériocines et la reutérine pourraient être incorporées en toute sécurité comme ingrédient antimicrobien dans différentes préparations topiques destinées à des applications humaines et animales Finalement, le dernier chapitre de la thèse a été consacré au développement et à la caractérisation de différents hydrogels à activité antimicrobienne et ayant comme principe actif des bactériocines ou de la réutérine. La reutérine, la pédiocine PA-1 et la microcine J25 ont été incorporées dans des formules d'hydrogel développées à partir de biopolymères à base de chitosan (1,5% , 2,5%) ou de carboxymethle cellulose (CMC 3% , 5%). Les hydrogels développés ont été caractérisés en termes d'aspect général, de viscosité, d'activité antimicrobienne et de stabilité pendant lors de l'entreposage à température ambiante. Les résultats obtenus ont montré que le chitosane à 1,5 % et 2,5 % contenant de la microcine J25 ou de la pédiocine PA-1demontré une activité inhibitrice significative durant toute la période d'entreposage. L'effet inhibiteur de la microcine J25 et de la reutérine dans les hydrogels CMC 3% et 5% est resté inchangé tandis que la pédiocine ajouté aux hydrogels de CMC 3% et 5% a perdu son activité dès la première semaine. En termes de viscosité, l'ajout d'antimicrobiens aux hydrogels n'a pas affecté leur viscosité et toutes les formules sont restées stables pendant les quatre semaines d'entreposage. Les résultats obtenus montrent que les formules développées présentent un fort potentiel d'application dans les secteurs alimentaire, médical et vétérinaire. En conclusion, le travail décrit dans cette thèse a permis de générer des résultats uniques sur le comportement, l'activité biologique, la stabilité et la toxicité de plusieurs composés antimicrobiens d'origine bactérienne incluant différentes bactériocines et la reutérine. Différents modèles in vitro récents et protocoles expérimentaux ont alors été utilisés et adoptés pour notre étude. Les résultats obtenus sont très pertinents et sont indispensable dans les démarches d'homologation de ces composés naturels par les différents organismes règlementaires pour différentes applications que ce soit pour le secteur alimentaire, médicale et/ou vétérinaire. En conclusion, le travail décrit dans cette these a permis de générer des résultats uniques sur le comportement, l'activité biologique, la stabilité et la toxicité de plusieurs composés antimicrobiens d'origine bactérienne incluant différentes bactériocines et la reutérine. Différents modèles in vitro récents et protocoles expérimentaux ont alors été utilisés et adoptés pour notre étude. Les résultats obtenus sont très pertinents et sont indispensable dans les démarches d'homologation de ces composés naturels par les différents organismes règlementaires pour différentes applications que ce soit pour le secteur alimentaire, médicale et/ou vétérinaire.In recent decades, natural antimicrobials produced by bacteria, such as bacteriocins and reuterin, have received considerable attention as food preservatives or as alternatives to antibiotics for the human and animal sectors. Approval of bacteriocins and reuterin as bio-preservatives or sanitizers by regulatory agencies is based not only on evidence of efficacy but also on sufficient data on cytotoxicity and behavior in the gastrointestinal conditions. Although the antimicrobial activities of bacteriocins and reuterin have been widely studied, very little data is available on their behavior in biological matrices and their toxicity for different applications. Therefore, the general objective of this thesis was to evaluate the gastrointestinal stability, the biological activity, and the toxicity of bacteriocins and reuterin using different in vitro models for their intended use in food, medical, and veterinary applications. The first specific objective was to produce, purify and evaluate the antimicrobial activity of bacteriocins and reuterin alone and in combination against a wide range of pathogenic and spoilage organisms of interest to different sectors. Five different synergistic consortia were identified, of which three of them (microcin J25 + citric acid + lactic acid, microcin J25 + reuterin + citric acid, and microcine J25 + reuterin + lactic acid) showed significant activity against Salmonella enterica subsp. enterica serovar Newport ATCC 6962 (FIC index = 0.5). Two other combinations (pediocin PA-1 + citric acid + lactic acid, and reuterin + citric acid + lactic acid) showed partially synergistic effect against Listeria ivanovii HPB28 (FIC index = 0.75). The second specific objective was to evaluate the gastrointestinal stability of reuterin using an in vitro simulated digestion conditions in humans. Furthermore, the hemolytic activity, and in vitro cytotoxicity of reuterin using neutral red assay and lactate dehydrogenase (LDH) release assays were determined on assay on the Caco-2 cell line. Reuterin was observed to be very stable biologically during gastrointestinal transit. Moreover, exposure of Caco-2 cells to different concentrations of reuterin showed no negative effect on cell viability or membrane integrity at concentrations up to 1080 mM. In addition, no hemolysis was observed on erythrocytes exposed to concentrations up to 270 mM of reuterin. As a result, this study demonstrated that reuterin can be safely used at concentrations up to 270 mM, in various applications. The third objective was to assess the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using in vitro models. In addition, the cytotoxicity and hemolytic activity of these bacteriocins were studied on Caco-2 cells and rat erythrocytes, respectively. According to the results, pediocin PA-1, bactofencin A and nisin were degraded at different levels during gastrointestinal transit, while microcin J25 was only partially degraded. Moreover, bacteriocins did not show cytotoxic effects on Caco-2 cells at concentrations up to 400 µg/mL. Finally, pediocin PA-1, bactofencin A, and nisin at concentrations higher than 50 µg/mL showed hemolytic potential, while microcin J25 did not cause hemolysis. In the fourth objective, the dermal toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A and nisin Z was studied in vitro using neutral red and LDH release assays on NHEK cells. The skin sensitization and irritation potentials of these bacteriocins and reuterin were also determined using the h-CLAT test and the human epidermal model EpiDerm ™, respectively. The results demonstrated that exposure of NHEK cells to these bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively, did not induce any cytotoxic effect. Inaddition, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was not affected in the presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/mL, respectively. Taken together, these results showed that certain bacteriocins and reuterin could be safely incorporated as an antimicrobial ingredient in various topical preparations intended for human and animal applications. Finally, the last chapter of the thesis was devoted to the development and characterization of different antimicrobial hydrogels based on bacteriocins or reuterin. Reuterin, pediocin PA-1, microcin J25 were incorporated into hydrogel formulations developed from biopolymers; chitosan (1.5%, 2.5%) or carboxymethyl cellulose (CMC, 3, 5%). The developed hydrogels were characterized in terms of general appearance, viscosity, antimicrobial activity, and stability during storage at room temperature. The results showed that the 1.5% and 2.5% chitosan containing microcin J25 or pediocin PA-1 have significant inhibitory activity throughout the storage period. The inhibitory effect of microcin J25 and reuterin in the 3% and 5% CMC hydrogels remained unchanged while the pediocin PA-1 added to the 3% and 5% CMC hydrogels totally lost its activity after one week. In terms of viscosity, the addition of antimicrobials to the hydrogels did not affect their viscosity and all formulations remained stable during the four weeks of storage. The results suggested that the formulas developed have great potential for application as sanitizer in the food, medical and veterinary sectors. In conclusion, this thesis has generated unique results on the gastrointestinal behavior, biological activity, stability, and toxicity of several bacterial drived antimicrobials including different bacteriocins and reuterin. Different in vitro models were adopted for this study. The results obtained are very relevant and are essential for the approval process of these natural compounds by the various regulatory agencies for different applications in food, medical or veterinary sector
EMPIRICAL ANALYSIS OF THE FINANCIAL BEHAVIOR OF INVESTORS WITH BRAND APPROACH (CASE STUDY: TEHRAN STOCK EXCHANGE)
Behavioral science in the field of finance and investment is among new topics raised in recent years. The relationship between financial sciences and other fields of social sciences such as financial psychology has caused researchers to do many researches regarding the behavior of investors in the financial markets and their reactions to different situations. Based on the theories of financial behavior, shareholders' decision to buy and sell stocks is under the influence of internal and external psychological factors. Through designing and experimental testing of the model of investors' financial behavior in the Tehran Stock Exchange with an emphasis on brand, this study was an attempt to investigate the influence of these factors. To this end, financial, psychological and social factors were considered as the most important external factors influencing the behavior of investors and, considering the mediating role of brand awareness, their impact on perceived risk and perceived return as well as investment intention was tested. The research population consisted of all individual investors in the Tehran Stock Exchange. In order to determine the sample size, considering unlimited population, Cochran formula was used and hence the sample size was determined to be 145. For data collection, standard questionnaire was used. Confirmatory factor analysis was used to test the reliability of the questionnaire and the research hypotheses were tested using path analysis. The results showed that psychological factors have a positive impact on perceived risk and returns. Financial factors had a positive impact on perceived risk but no impact on perceived return. The impact of social factors on perceived risk and perceived return was not confirmed. Moreover, the results showed that brand awareness has a moderating role in the relationship between social factors and perceived risk and return. However, its moderating role was not confirmed in the relationship between the psychological and financial factors and perceived risk and return. Perceived risk had a positive effect on attitude toward the brand. However, the impact of perceived return on attitude toward the brand was not significant. Finally, the attitude toward the brand had a positive effect on shareholders' investment intention.JEL Codes - G0
Spike Protein Mutations and the Effects on SARS-CoV-2 Pathogenesis
The severe acute respiratory syndrome coronavirus 2 spike (S) glycoprotein facilitates receptor binding to initiate cell entry that is the critical initial step in the infection cycle. Due to S glycoprotein's pivotal role, in this review, we pointed to show potential functional and structural consequences of S glycoprotein and its variants, which has been related with increased viral load in humans with SARS-CoV-2 infection
Bacteriocin-based synergetic consortia : a promising strategy to enhance antimicrobial activity and broaden the spectrum of inhibition
Bacteria-derived natural antimicrobial compounds such as bacteriocins,
reruterin, and organic acids have recently received substantial attention as food
preservatives or therapeutic alternatives in human or animal sectors. This study
aimed to evaluate the antimicrobial activity of different bacteria-derived antimicrobials, alone or in combination, against a large panel of Gram-negative and Grampositive bacteria. Bacteriocins, including microcin J25, pediocin PA-1, nisin Z, and
reuterin, were investigated alone or in combination with lactic acid and citric acid,
using a checkerboard assay. Concentrations were selected based on predetermined
MICs against Salmonella enterica subsp. enterica serovar Newport ATCC 6962 and
Listeria ivanovii HPB28 as Gram-negative and Gram-positive indicator strains, respectively. The results demonstrated that the combination of microcin J25 1 citric acid 1
lactic acid; microcin J25 1 reuterin 1 citric acid; and microcin J25 1 reuterin 1
lactic acid tested against S. Newport ATCC 6962 showed synergistic effects (FIC
index = 0.5). Moreover, a combination of pediocin PA-1 1 citric acid 1 lactic acid;
and reuterin 1 citric acid 1 lactic acid against L. ivanovii HPB28 showed a partially
synergistic interactions (FIC index = 0.75). Nisin Z exerted a partially synergistic effect
in combination with acids (FIC index = 0.625 -0.75), whereas when it was combined
with reuterin or pediocin PA-1, it showed additive effects (FIC index = 1) against L.
ivanovii HPB28. The inhibitory activity of synergetic consortia were tested against a
large panel of Gram-positive and Gram-negative bacteria. According to our results,
combining different antimicrobials with different mechanisms of action led to
higher potency and a broad spectrum of inhibition, including multidrug-resistance
pathogens
In vitro assessment of skin sensitization, irritability and toxicity of bacteriocins and reuterin for possible topical applications
Bacteriocins and reuterin are promising antimicrobials for application in food, veterinary, and medical sectors. In the light of their high potential for application in hand sanitizer, we investigated the skin toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A, and nisin Z in vitro using neutral red and LDH release assays on NHEK cells. We determined their skin sensitization potential using the human cell line activation test (h-CLAT). Their skin irritation potential was measured on human epidermal model EpiDerm™. We showed that the viability and membrane integrity of NHEK cells remained unaltered after exposure to bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively. Furthermore, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A, and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was unafected in presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/ mL, respectively, which was confrmed by measuring cytokine IL-1α and IL-8 levels and by histological analysis. In conclusion, the current study provides scientifc evidence that some bacteriocins and reuterin, could be safely applied topically as sanitizers at recommended concentration
A practical approach to the guideline-directed pharmacological treatment of heart failure with reduced ejection fraction
Over the last 15–20 years, remarkable developments of heart failure (HF) pharmacotherapies have been achieved. However,
HF remains a global healthcare challenge with more than 64 million patients worldwide. Optimization of guideline-directed
chronic HF medical therapy is highly recommended with every patient visit to improve outcomes in patients with HF with reduced ejection fraction. However, the majority of patients in real-world settings are treated with doses that are lower than
those with proven efficacy in clinical trials, which might be due to concerns of adverse effects and inertia of physicians. Likewise, a significant proportion of patients still do not receive all drug classes that could improve their prognosis. The recent
European Society of Cardiology guidelines do not provide detailed recommendations on how these drug classes should be implemented in the treatment of inpatients to allow for both safety and a high likelihood of efficacy. We therefore propose a
practical approach algorithm to support physicians to treat HF patients in their daily practice
Investigating the Effect of Variations in Irrigation Water Price on Cropping Pattern and Gross Margin under Uncertainty (Case Study: Khorasan Razavi)
Water shortage crisis is an issue that has led to drastic
changes in different agricultural policies, especially in
arid and semi-arid areas. Uncertainty in the amount of resources,
e.g. water, used for agricultural production entails risk for
farmers' income and cropping pattern changes. In the present
study, the robust optimization model was used for optimal allocation
of arable lands of Khorasan Razavi Province under
uncertainty. During the allocation, the effect of water input
price variations on total gross margin and cropping pattern
was considered. It was found that under certain data, both parameters
of total gross margin and total acreage are more than
uncertain data. Given that water price variations resulted in
tangible changes in wheat acreage, it is recommended to adopt
appropriate policies to reduce its production risk
Bacteriocins as a new generation of antimicrobials : toxicity aspects and regulations
In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins
have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical
antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been
declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their
broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural
alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food
preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more
widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the
application of bacteriocins, their toxicity and impacts
Design sensitive model reference controller with application to medical technology
The past two decades have seen the incorporation of robotics into medical applications. From a manufacturing perspective, robots have been used in pharmaceuticals, preparing medications. But on more novel levels, robots have been used in service roles, surgery, and prosthetics. The capability of high-precision operation in manufacturing settings gave the medical industry high hopes that robots could be used to assist in surgery. Not only are robots capable of much higher precision than a human, they are not susceptible to human factors, such as trembling and sneezing, that are undesirable in the surgery room. Another advantage to robots in medicine is the ability to perform surgery with very small incisions, which results in minimal scar tissue, and dramatically reduced recovery times. The popularity of these minimally invasive surgical (MIS) procedures has enabled the incorporation of robots in surgeries. In this paper, model reference computed torque controller is recommended for four degrees of freedom serial links robot manipulator, which modeled in SIMSCAPE. To design stable controller conventional computed torque controller is recommended. It is a nonlinear, stable, and reliable controller. The proposed approach effectively combines of design methods from nonlinear controller, and linear Proportional-Derivative (PD) control to improve the performance and stability. This paper has two important objectives: a) study on modeling of 4 degrees of freedom (DOF) based on Simscape software and b) design PD model reference computed torque controller to improve the sensitivity of surgical robot manipulator
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