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Role of quorum sensing in bacterial infections

World Journal of Clinical Cases 2015年第7期3卷 575-598页

作者： Israel Castillo-Juárez Toshinari Maeda Edna Ayerim Mandujano-Tinoco María Tomás Berenice Pérez-Eretza silvia julieta garcía-contreras Thomas K Wood Rodolfo garcía-contreras Colegio de Postgraduados Campus Montecillo Department of Biological Functions and Engineering Kyushu Institute of Technology Epigenetics of Cancer Laboratory Division of Basic ResearchNational Institute of Genomic Medicine Department of Microbiology Instituto de Investigación Biomédica de A Coruña(INIBIC)Complexo Hospitalario Universitario de A Coruña(CHUAC)SergasUniversidade da Coruña(UDC)15006 A CoruñaSpain Departamento de Microbiología y Parasitología Facultad de MedicinaUniversidad Nacional Autónoma de México Centro Médico Coyoacán Department of Chemical Engineering Pennsylvania State UniversityUniversity Park Department of Biochemistry and Molecular Biology Pennsylvania State UniversityUniversity Park

Quorum sensing(QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed.

关键词： Quorum sensing Virulence Infections Pseudomonas aeruginosa Staphylococcus aureus Animal models

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Lipid-Polymer Membranes as Carriers for L-Tryptophan: Molecular and Metabolic Properties

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Open Journal of Medicinal Chemistry 2013年第1期3卷 31-39页

作者： Fernández Ruocco María julieta Siri Macarena Igartúa Daniela Prieto María Jimena Alonso silvia Del Valle Chiaramoni Nadia silvia Instituto Multidisciplinario de Biología Celular Consejo Nacional de Investigaciones Científicas y Técnicas Buenos Aires Argentina Laboratory of Biomembranes Department of Science and Technology Universidad Nacional de Quilmes Buenos Aires Argentina

Polymerized liposomes encapsulating L-tryptophan were studied with the aim to characterize them as drug delivery systems for the treatment of several metabolic diseases that need an increased systemic L-tryptophan concentration. polymerized liposomes were obtained by UV irradiation of vesicles containing 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a 1:1 molar ratio, in the presence of 10 and 50 mol% of L-tryptophan (respect to total lipid concentration). Polymerization efficiency was studied spectrophotometrically. Also, bilayer packing at the polar head region was followed with the Merocyanine 540 (MC540) and specific interactions in the lipopolymers were studied by FTIR. High L-tryptophan concentrations (50 mol% respect to total lipid concentration) induced a higher amount of six- and nine-unit polymers. This phenomenon was induced because the L-tryptophan located outside the lipid membrane was included in it during the polymerization process and was thus responsible for the better accommodate of the polar head region. This was not possible with the lower amount of L-tryptophan (10 mol%). The stability of lipopolymers with different amounts of L-tryptophan was studied through release profiles. Polymerized liposomes with 50 mol% of L-tryptophan were able to retain around 80% of the amino acid after 24 hours, whereas those with 10 mol % of the amino acid were able to retain 20%. The metabolic activity of the Caco-2 cell line was also studied. Cytotoxic effects were low in the presence of polymerized liposomes, rendering a maximum percentage of cell death of 30%. In summary, this work stresses the relevance of nonspecific drug-polymerized membrane binding on L-tryptophan pharmacological interaction with possible pharmaceutical applications in liposomal drug delivery. Moreover, the absence of significant cytotoxic effects allows the system proposed to be applied in human health.

关键词： Lipopolymers L-Tryptophan Drug Delivery

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Pre-treatment prediction of response to peginterferon plus ribavirin in chronic hepatitis C genotype 3

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World Journal of Hepatology 2015年第4期7卷 703-709页

作者： Sebastian Marciano silvia M Borzi Melisa Dirchwolf Ezequiel Ridruejo Manuel Mendizabal Fernando Bessone Maria E Sirotinsky Diego H Giunta julieta Trinks Pablo A Olivera Omar A Galdame Marcelo O Silva Hugo A Fainboim Adrian C Gadano Liver Unit Hospital Italiano de Buenos Aires Hepatology Section Hospital R. Rossi La Plata Buenos Aires Argentina Liver Infectious Disease Unit Hospital F.J Muniz Uspallata 2272 Buenos Aires Argentina Hepatology Section Department of Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Avenida Galvan 4102 Buenos Aires Argentina Hepatology and Liver Transplant Unit Hospital Universitario Austral Hepatology Unit Sanatorio del Parque Rosario Argentina HEPATOSUR group Comodoro Rivadavia Chubut Argentina Internal Medicine Research Unit Hospital Italiano de Buenos Aires Buenos Aires Argentina Basic Science and Experimental Medicine Institute Hospital Italiano de Buenos Aires Internal Medicine Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno "CEMIC" Buenos Aires Argentina

AIM: To evaluate pre-treatment factors associated with sustained virological response(SVR) in patients with hepatitis C virus(HCV) genotype 3 treated with peginterferon and ribavirin(RBV). METHODS: We retrospectively analyzed treatment naive, mono-infected HCV genotype 3 patients treated with peginterferon and RBV. Exclusion criteria included presence of other liver disease, alcohol consumption and African American or Asian ethnicity. The variables collected and compared between patients who achieved an SVR and patients who did not were as follows: gender, age, fibrosis stage, diabetes, body mass index,steatosis, INFL3 polymorphism, pre-treatment HCVRNA, type of peginterferon, RBV dose and adherence. RESULTS: A total of 107 patients treated between June, 2004 and March, 2013 were included. Mean treatment duration was 25.1(± 1.8) wk. Overall, 58%(62/107) of the patients achieved an SVR and 42%(45/107) did not. In the multivariate logistic regression analysis, pre-treatment HCV-RNA ≥ 600000 UI/m L(OR = 0.375, 95%CI: 0.153-0.919, P = 0.032) and advanced fibrosis(OR = 0.278, 95%CI: 0.113-0.684,P = 0.005) were significantly associated with low SVR rates. In patients with pre-treatment HCV-RNA ≥600000 UI/m L and advanced fibrosis, the probability of achieving an SVR was 29%(95%CI: 13.1-45.2).In patients with pre-treatment HCV-RNA < 600000UI/m L and mild to moderate fibrosis, the probability of achieving an SVR was 81%(95%CI: 68.8-93.4).CONCLUSION: In patients with HCV genotype 3infections the presence of advance fibrosis and high pre-treatment viral load might be associated with poor response to peginterferon plus RBV. These patients could benefit the most from new direct antiviral agentsbased regimes.

关键词： Sustained virological response Direct antiviral agents Sofosbuvir Cirrhosis Viral load

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Hippocampal High-Frequency Stimulation Inhibites the Progression of Rapid Kindling-Induced Seizure in Rats

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Neuroscience & Medicine 2013年第2期4卷 71-76页

作者： Belen Gori Magdalena Pereyra Lucas Toibaro Carola Brescacin Gerardo Battaglia julieta Pastorino Ariela Smigliani Milagros Galardi silvia Kochen Center of Clinical and Experimental Neuroscience Epilepsy Cognition and Behavior Institute of Cellular Biology and Neuroscience “Prof. E. De Robertis” (IBCN)-National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina Center of Clinical and Experimental Neuroscience Epilepsy Cognition and Behavior Institute of Cellular Biology and Neuroscience “Prof. E. De Robertis” (IBCN)-National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina Laboratory of Biomedical Technology Department of Electronics Buenos Aires Faculty National Technological University (UTN) Buenos Aires Argentina.

Epilepsy is one of the most common serious neurological disorders. Pharmacoresistant epilepsy patients are poorly controlled or their seizures are refractory to drug treatment. Resective surgery is frequently a promising therapy in this population, however, not all the patients meet the eligibility criteria for the surgical treatment. Deep brain stimulation has been investigated in clinical studies and animal studies as an alternative treatment, but the optimal stimulation parameters remain an issue. The present study was designed to investigate the effect of unilateral high-frequency stimulation (HFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats, and compared the results with those of low-frequency stimulation previously published by our group. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 7) received only RK stimulus, while the treated group (HFS-hRK;n = 9) received also HFS (biphasic square wave pulses, 130 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing 78% (p 0.01) of the animals receiving HFS treatment were still not fully kindled staying in stages 0 -III (p 0.01). HFS group needed a higher number of stimulations to achieve stage III (p 0.05) with respect to control group. However, no significant differences in the cumulative daily afterdischarge duration were observed. HFS did not present significant differences compared with LFS in any of studied parameters. The findings suggest that unilateral HFS applied on hippocampus effectively inhibited the epileptogenic process induced by hippocampal rapid kindling. According to the comparative results about hippocampal rapid kindled animals stimulated with HFS and LFS (5 Hz), we found no conclusive inf

关键词： Hippocampal Rapid Kindling Epilepsy Electrical Stimulation High-Frequency Stimulation Low-Frequency Stimulation

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Effect of Unilateral Low-Frequency Stimulation of Hippocampus on Rapid Kindling—Induced Seizure Development in Rats

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Neuroscience & Medicine 2012年第2期3卷 174-180页

作者： Lucas Toibaro Magdalena Pereyra julieta Pastorino Ariela Smigliani Florencia Ocariz Germán Ortmann María Milagros Galardi María Belén Gori silvia Kochen Epilepsy Laboratory Institute of Cellular Biology and Neuroscience—National Council for Scientific and Technical Research (CONICET) School of Medicine University of Buenos Aires Buenos Aires Argentina

Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical procedure. However, the optimal stimulation parameters remain undetermined and active research in humans and animals is necessary. The present study was designed to investigate the effect of unilateral Low Frequency Stimulation (LFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 6) received only RK stimulus, while the treated group (LFS-hRK;n = 8) received also LFS (biphasic square wave pulses, 1 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing on day 3, 62% (P < 0.05) of the animals receiving LFS treatment were still not fully kindled staying in stages 0-III (P < 0.01). The number of stimulations needed to achieve generalized seizures (stage IV-V of Racine scale) was significantly higher (P < 0.05) in the LFS group with respect to control group. No significant differences in the cumulative daily afterdischarge duration were observed between both groups. These findings suggest that preemptive LFS can significantly decrease the incidence of hippocampus-kindled seizures and delay the progression and secondary generalization of focal seizures.

关键词： Hippocampal Rapid Kindling Epilepsy Electrical Stimulation Low-Frequency Stimulation Electrical Stimulation Protective Effect

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