402 results on '"M. Kratz"'
Search Results
2. Invited commentary on 'Green HEMS in mountain and remote areas: reduction of carbon footprint through drones?'
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E. ter Avest, M. Kratz, T. Dill, and M. Palmer
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Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Published
- 2023
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Catalog
3. Synthesis and Anti-Trypanosoma cruzi Activity of 3‑Cyanopyridine Derivatives
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Brian W. Slafer, Marco A. Dessoy, Ramon G. de Oliveira, Maria C. Mollo, Eun Lee, An Matheeussen, Louis Maes, Guy Caljon, Leonardo L. G. Ferreira, Renata Krogh, Adriano D. Andricopulo, Luiza R. Cruz, Charles E. Mowbray, Jadel M. Kratz, and Luiz C. Dias more...
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Chemistry ,QD1-999 - Published
- 2024
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4. Variability of serum IgG sialylation and galactosylation degree in women with advanced endometriosis
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Katarzyna Sołkiewicz, Hubert Krotkiewski, Marcin Jędryka, and Ewa M. Kratz
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Medicine ,Science - Abstract
Abstract Endometriosis is an inflammatory disease which diagnostics is difficult and often invasive, therefore non-invasive diagnostics methods and parameters are needed for endometriosis detection. The aim of our study was to analyse the glycosylation of native serum IgG and IgG isolated from sera of women classified as: with endometriosis, without endometriosis but with some benign ginecological disease, and control group of healthy women, in context of its utility for differentiation of advanced endometriosis from the group of healthy women. IgG sialylation and galactosylation/agalactosylation degree was determined using specific lectins: MAA and SNA detecting sialic acid α2,3- and α2,6-linked, respectively, RCA-I and GSL-II specific to terminal Gal and terminal GlcNAc, respectively. The results of ROC and cluster analysis showed that the serum IgG MAA-reactivity, sialylation and agalactosylation factor may be used as supplementary parameters for endometriosis diagnostics and could be taken into account as a useful clinical tool to elucidate women with high risk of endometriosis development. Additionally, we have shown that the analysis of native serum IgG glycosylation, without the prior time-consuming and expensive isolation of the protein, is sufficient to differentiation endometriosis from a group of healthy women. more...
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- 2021
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5. Chagas Disease Drug Discovery in Latin America—A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021
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Ramon G. de Oliveira, Luiza R. Cruz, María C. Mollo, Luiz C. Dias, and Jadel M. Kratz
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Trypanosoma cruzi ,screening ,hit identification ,hit to lead ,lead optimization ,medicinal chemistry ,Chemistry ,QD1-999 - Abstract
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing. more...
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- 2021
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6. 2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling.
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Rafael Augusto Alves Ferreira, Celso de Oliveira Rezende Junior, Pablo David Grigol Martinez, Paul John Koovits, Bruna Miranda Soares, Leonardo L G Ferreira, Simone Michelan-Duarte, Rafael Consolin Chelucci, Adriano D Andricopulo, Mariana K Galuppo, Silvia R B Uliana, An Matheeussen, Guy Caljon, Louis Maes, Simon Campbell, Jadel M Kratz, Charles E Mowbray, and Luiz Carlos Dias more...
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro properties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency. more...
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- 2021
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7. Glycoprotein fucosylation is increased in seminal plasma of subfertile men
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Beata Olejnik, Ewa M Kratz, Mariusz Zimmer, and Mirosława Ferens-Sieczkowska
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fucose ,glycosylation ,infertility ,seminal plasma ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Fucose, the monosaccharide frequent in N- and O-glycans, is a part of Lewis-type antigens that are known to mediate direct sperm binding to the zona pellucida. Such interaction was found to be inhibited in vitroby fucose-containing oligo- and polysaccharides, as well as neoglycoproteins. The objective of this study was to screen seminal plasma proteins of infertile/subfertile men for the content and density of fucosylated glycoepitopes, and compare them to samples of fertile normozoospermic subjects. Seminal proteins were separated in polyacrylamide gel electrophoresis and blotted onto nitrocellulose membrane and probed with fucose-specific Aleuria aurantia lectin (AAL). Twelve electrophoretic bands were selected for quantitative densitometric analysis. It was found that the content, and especially the density of fucosylated glycans, were higher in glycoproteins present in seminal plasma of subfertile men. No profound differences in fucosylation density were found among the groups of normozoospermic, oligozoospermic, asthenozoospermic, and oligoasthenozoospermic subfertile men. According to the antibody probing, AAL-reactive bands can be attributed to male reproductive tract glycoproteins, including prostate-specific antigen, prostatic acid phosphatase, glycodelin and chorionic gonadotropin. Fibronectin, α1 -acid glycoprotein, α1 -antitrypsin, immunoglobulin G and antithrombin III may also contribute to this high fucosylation. It is suggested that the abundant fucosylated glycans in the sperm environment could interfere with the sperm surface and disturb the normal course of the fertilization cascade. more...
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- 2015
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8. Experimentally Validated hERG Pharmacophore Models as Cardiotoxicity Prediction Tools.
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Jadel M. Kratz, Daniela Schuster 0001, Michael Edtbauer, Priyanka Saxena, Christina E. Mair, Julia Kirchebner, Barbara Matuszczak, Igor Baburin, Steffen Hering, and Judith M. Rollinger
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- 2014
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9. Safety and Efficacy of Arterial Closure Devices Following Antegrade Femoral Access: A Case–Control Study
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Ansar Z Vance, Mark P. Mantell, Timothy Clark, J. Redmond, Louis-Xavier Barrette, and Kathleen M. Kratz
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Male ,endocrine system ,medicine.medical_specialty ,Time Factors ,Closure (topology) ,Hemorrhage ,Punctures ,Walking ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Femoral access ,Catheterization, Peripheral ,Humans ,Medicine ,Vascular closure device ,Aged ,Retrospective Studies ,Aged, 80 and over ,Hemostatic Techniques ,business.industry ,Equipment Design ,Recovery of Function ,General Medicine ,Middle Aged ,Surgery ,Femoral Artery ,Treatment Outcome ,Female ,Cardiology and Cardiovascular Medicine ,business ,Vascular Closure Devices - Abstract
Purpose: Vascular closure device (VCD) use following antegrade femoral access may present unique challenges relative to retrograde access. We retrospectively compared safety and efficacy of these devices between antegrade and retrograde patient cohorts undergoing percutaneous intervention. Materials and Methods: Over a 5-year period, a consecutive series of 107 limbs in 84 patients underwent VCD arteriotomy closure following percutaneous revascularization using an antegrade approach (VCD-A). Device deployment success rates, time to ambulation, and complication rates were compared to a contemporaneous control group of 401 limbs in 305 patients who underwent closure following retrograde access (VCD-R) during revascularization or embolization procedures. Results: Closure was attempted in VCD-A using 53 StarClose, 35 Perclose, and 19 Angio-Seal devices. Hemostasis (without supplemental manual compression) was achieved in 86/107 (80.4%) limbs. Closure was attempted in VCD-R using 215 StarClose, 119 Perclose, and 67 Angio-Seal devices with hemostasis in 357/401 (89.0%) limbs. Device deployment failure occurred in 7/107 (6.5%) of VCD-A and 20/401 (5.0%) of VCD-R ( P = .52), independent of specific device type. Femoral pseudoaneurysm developed in 1/107 and 1/401 of VCD-A and VCD-R ( P = .31), and minor hematoma developed in 3/107 and 8/401 of the VCD-A and VCD-R ( P = .61). Mean time to ambulation was 204.1 minutes in VCD-A and 204.8 minutes in VCD-R ( P = .97). Conclusion: Antegrade femoral closure was associated with high rates of technical success and low complications, similar to retrograde closure. Time to ambulation was the same in both groups despite higher heparin doses in the antegrade patients. more...
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- 2020
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10. The translational challenge in Chagas disease drug development
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Jadel M Kratz, Karolina R Gonçalves, Lavínia MD Romera, Carolina Borsoi Moraes, Paula Bittencourt-Cunha, Sergio Schenkman, Eric Chatelain, and Sergio Sosa-Estani
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Microbiology (medical) ,pharmacokinetic pharmacodynamic (PK/PD) relationship ,dormancy ,Drug Development ,Trypanosoma cruzi ,animal model ,Drug Discovery ,Humans ,Neglected Diseases ,Chagas Disease ,persisters ,Trypanocidal Agents ,in vitro assay - Abstract
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease. more...
- Published
- 2022
11. Nitrogen cycling in biological soil crusts; microbial transformation processes and atmospheric nitrous acid and nitric oxide emissions
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Bettina Weber, Stefanie Maier, Alexandra M. Kratz, Jens Weber, Minsu Kim, Diego Leiva, Maria Prass, Fobang Liu, Adam T. Clark, Raeid M.M. Abed, Hang Su, Yafang Cheng, Thilo Eickhorst, Sabine Fiedler, and Ulrich Pöschl more...
- Abstract
Biological soil crusts (abbreviated as biocrusts) are composed of photoautotrophic cyanobacteria, algae, lichens, and bryophytes, growing together with heterotrophic bacteria, archaea and fungi and forming an intimate association with soil particles in the uppermost millimeters of the substrate. They occur globally in drylands, where they cover about 1/3 of the soil surface, corresponding to an area of about 18 x 106 km2. Biocrusts fix atmospheric nitrogen (N), which is needed for physiological processes and the formation of biomass. However, it recently was also shown that similar to bulk soil, N is cycled within biocrusts and major fractions of it are released as nitrous acid (HONO) and nitric oxide (NO) to the atmosphere.Based on these initial results, we investigated the biologically mediated N-cycling processes in biocrusts as related to wetting and drying events. We investigated the microbial activity at different drying stages by means of transcriptome analysis and related these results to soil nitrite and nitrate concentrations over time. In addition, we utilized catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) to quantify the number of bacteria, archaea, and nitrite oxidizing bacteria in different strata over time.Our results revealed that within less than 30 minutes after wetting, genes encoding for all relevant N cycling processes, including N fixation, ammonification, nitrification, denitrification, and assimilatory and dissimilatory N reduction were expressed. The most abundant transcriptionally active N-transforming microorganisms belonged to the Rhodobacteraceae, Enterobacteriaceae and Pseudomonadaceae within the Alpha- and Gammaproteobacteria. The soil nitrite contents increased significantly during the desiccation process, likely serving as a precursor for NO and HONO emissions, which peaked at relatively low water contents of ~20% water holding capacity. This nitrite accumulation was likely caused by a differential expression of nitrite as compared to nitrate reductase encoding genes over the course of desiccation. Additionally, our data suggest that ammonia-oxidizing organisms may have responded to changing local oxygen conditions during drying. These mechanisms are also supported by process-based modelling, which has been conducted by us. Thus, our results show that the activity of N-cycling microorganisms, as related to the water and oxygen conditions within the substrate, determines the process rates and overall quantity of reactive nitrogen emissions. more...
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- 2022
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12. Chagas Disease Drug Discovery in Latin America-A Mini Review of Antiparasitic Agents Explored Between 2010 and 2021
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Luiza R. Cruz, Jadel M. Kratz, Luiz C. Dias, María C. Mollo, and Ramon G. de Oliveira
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Chagas disease ,medicine.medical_specialty ,Mini Review ,Trypanosoma cruzi ,hit identification ,Disease ,lead optimization ,medicinal chemistry ,medicine ,Nifurtimox ,Intensive care medicine ,neglected tropical diseases ,QD1-999 ,business.industry ,screening ,Tropical disease ,General Chemistry ,Hit to lead ,medicine.disease ,Antiparasitic agent ,Chemistry ,hit to lead ,Benznidazole ,Neglected tropical diseases ,business ,medicine.drug - Abstract
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing. more...
- Published
- 2021
13. Investigation of seminal plasma chitotriosidase-1 and leukocyte elastase as potential markers for 'silent' inflammation of the reproductive tract of the infertile male - a pilot study
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E M, Kratz, E, Zurawska-Plaksej, K, Solkiewicz, I, Kokot, R, Faundez, and A, Piwowar
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Adult ,Inflammation ,Male ,Pilot Projects ,Oligospermia ,Middle Aged ,Hexosaminidases ,Predictive Value of Tests ,Semen ,Case-Control Studies ,Humans ,Inflammation Mediators ,Leukocyte Elastase ,Biomarkers - Abstract
Inflammatory mediators - chitotriosidase-1 (CHIT1) and leukocyte elastase (LE) - were analyzed in human seminal plasma in relation to total antioxidative status (TAS) and pro-inflammatory markers IL-1β and IL-6. Samples collected from 34 males who were part of infertile couples were divided into normozoospermic (N; n = 12, without symptoms of inflammation), oligozoospermic (O; n = 11) and teratozoospermic (T; n = 11) groups. significant differences were observed only in CHIT1 concentration between N and O samples. However, a higher mean LE concentration was also observed in O and T patients (3.7-times and 900-times, respectively) compared with the N group. in IL-1β and IL-6 concentrations, an upward trend was observed from N, through O, up to the T group. The positive correlation between the concentration of IL-1β and the activity and specific activity of CHIT11 as well as the moderate negative correlation between concentrations of IL-1β and CHIT1 may suggest that elevated CHIT11 levels appeared in early stages of inflammation before the increase in IL-1β concentrations, or remained stable even after the levels of cytokine decreased. The above seem to confirm the role of CHIT1 in the manifestation of 'silent' inflammation at a very early stage. To conclude, CHIT1 concentration appears to be an interesting biomarker that signals the presence of possible 'silent' inflammation accompanying oligozoospermia. We cannot draw such conclusions regarding LE concentration, because, although we observed differences in the mean values and medians between analyzed groups, they were not significant. The utility of CHIT1 in the follow-up of oligozoospermia-associated 'silent' subclinical inflammation is promising, but further studies on a larger patient test set are required. more...
- Published
- 2020
14. Clinical and pharmacological profile of benznidazole for treatment of Chagas disease
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Jadel M. Kratz, Colin Forsyth, Facundo García Bournissen, and Sergio Sosa-Estani
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0301 basic medicine ,Chagas disease ,medicine.medical_specialty ,BENZNIDAZOLE ,030106 microbiology ,030231 tropical medicine ,Drug Resistance ,law.invention ,purl.org/becyt/ford/3.3 [https] ,03 medical and health sciences ,0302 clinical medicine ,law ,ANTIPARASITIC TREATMENT ,medicine ,Animals ,Humans ,Chagas Disease ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,Intensive care medicine ,Adverse effect ,Nifurtimox ,Clinical pharmacology ,business.industry ,CHAGAS DISEASE ,Public health ,Neglected Diseases ,TRYPANOSOMA CRUZI ,General Medicine ,medicine.disease ,Trypanocidal Agents ,Regimen ,Clinical research ,Nitroimidazoles ,Benznidazole ,purl.org/becyt/ford/3 [https] ,Public Health ,business ,medicine.drug - Abstract
Introduction: Chagas disease (CD) is one of the most neglected public health problems in the Americas, where
- Published
- 2018
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15. Community-Based Outbreak of Neisseria meningitidis Serogroup C Infection in Men who Have Sex with Men, New York City, New York, USA, 2010−2013
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Molly M. Kratz, Don Weiss, Alison Ridpath, Jane R. Zucker, Anita Geevarughese, Jennifer L. Rakeman, and Jay K. Varma
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Neisseria meningitides ,bacteria ,disease outbreaks ,meningococcal meningitis ,serogroup C ,men who have sex with men ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
In September 2012, the New York City Department of Health and Mental Hygiene identified an outbreak of Neisseria meningitidis serogroup C invasive meningococcal disease among men who have sex with men (MSM). Twenty-two case-patients and 7 deaths were identified during August 2010−February 2013. During this period, 7 cases in non-MSM were diagnosed. The slow-moving outbreak was linked to the use of websites and mobile phone applications that connect men with male sexual partners, which complicated the epidemiologic investigation and prevention efforts. We describe the outbreak and steps taken to interrupt transmission, including an innovative and wide-ranging outreach campaign that involved direct, internet-based, and media-based communications; free vaccination events; and engagement of community and government partners. We conclude by discussing the challenges of managing an outbreak affecting a discrete community of MSM and the benefits of using social networking technology to reach this at-risk population. more...
- Published
- 2015
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16. Reviews of Books
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Robert T. Tally, Hugh Charles O’Connell, Jerome Winter, Greg Conley, Dominick Grace, Sandor Klapcsik, Steven Holmes, D. Harlan Wilson, Jason P. Vest, Cait Coker, Dennis M. Kratz, Susan A. George, Rafeeq O. McGiveron, Jason W. Ellis, and Holger Briel more...
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Cultural Studies ,Literature and Literary Theory - Published
- 2017
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17. Structure-activity relationship of 4-azaindole-2-piperidine derivatives as agents against Trypanosoma cruzi
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Paul J. Koovits, Guy Caljon, Charles E. Mowbray, Luiz C. Dias, Louis Maes, Jadel M. Kratz, Marco A. Dessoy, and An Matheeussen
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Chagas disease ,Trypanosoma cruzi ,Clinical Biochemistry ,Pharmaceutical Science ,Moderate activity ,Pharmacology ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,In vivo ,Drug Discovery ,parasitic diseases ,medicine ,Structure–activity relationship ,Animals ,Humans ,Chagas Disease ,Molecular Biology ,Biology ,biology ,010405 organic chemistry ,Drug discovery ,Pharmacology. Therapy ,Organic Chemistry ,biology.organism_classification ,medicine.disease ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Chemistry ,chemistry ,Molecular Medicine ,Piperidine ,Human medicine - Abstract
The structure-activity relationship of a 4-Azaindole-2-piperidine compound selected from GlaxoSmithKline’s recently disclosed open-resource “Chagas box” and possessing moderate activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, is presented. Despite considerable medicinal chemistry efforts, a suitably potent and metabolically stable compound could not be identified to advance the series into in vivo studies. This research should be of interest to those in the area of neglected diseases and in particular anti-kinetoplastid drug discovery. more...
- Published
- 2019
18. The impact of metalloestrogens on the physiology of male reproductive health as a current problem of the XXI century
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K, Jurkowska, E M, Kratz, E, Sawicka, and A, Piwowar
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Male ,Reproductive Health ,Metals ,Reproduction ,Animals ,Humans ,Estrogens ,History, 21st Century ,Spermatozoa ,Infertility, Male - Abstract
In the XXI
- Published
- 2019
19. Waltharius and Ruodlieb
- Author
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Dennis M. Kratz
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Literature ,History ,Expression (architecture) ,business.industry ,Medieval Latin ,Narrative ,EPIC ,business - Abstract
Published in 1984: The Waltharius and Ruodlieb are considered by many scholars to be among the finest works of medieval Latin literature. Both the Waltharius, composed by an anonymous eleventh-century poet from Southern Germany, are heroic narratives that provide examples of the creative transformation of the Latin epic tradition into a vehicle for expression of Christian values. more...
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- 2019
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20. Pick your poison: hERG-blocking alkaloids in the emetic herbal drug ipecac
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Judith M. Rollinger, Sarah K. Oettl, Steffen Hering, Christina E. Mair, Daniela Schuster, Jadel M. Kratz, Olaf Scheel, and Priyanka Saxena
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Pharmacology ,Drug ,biology ,Chemistry ,Blocking (radio) ,media_common.quotation_subject ,Organic Chemistry ,hERG ,Pharmaceutical Science ,Analytical Chemistry ,Complementary and alternative medicine ,Drug Discovery ,biology.protein ,Molecular Medicine ,media_common - Published
- 2016
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21. Enzymatic synthesis of ascorbyl ester derived from linoleic acid
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Gabriela Rotta Gomes, Jadel M. Kratz, Débora de Oliveira, Alexsandra Valério, Cláudia Maria Oliveira Simões, and Manuela Balen
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0106 biological sciences ,Radical ,Linoleic acid ,Bioengineering ,Ascorbic Acid ,Molecular sieve ,Shelf life ,01 natural sciences ,Catalysis ,Fungal Proteins ,chemistry.chemical_compound ,010608 biotechnology ,Organic chemistry ,Lipase ,Chromatography ,biology ,010405 organic chemistry ,General Medicine ,Enzymes, Immobilized ,0104 chemical sciences ,Ascorbyl linoleate ,Linoleic Acids ,chemistry ,biology.protein ,Industrial and production engineering ,Biotechnology - Abstract
Antioxidants are substances that defend cells against damage, kidnapping and destroying free radicals. They have been largely used in the food industry due the possibility to control the oxidation process, aimed to increase shelf life. Thus, esterification reaction to obtain ascorbyl linoleate catalyzed by Novozym 435 lipase assisted by ultrasound bath was investigated. In this work, molecular sieve (4 Å) was added to the reaction medium to remove the water formed during the esterification reaction to improve the process performance. According to the results, ascorbyl linoleate production up to 90 % was reached after 1 h of reaction time carried out using ultrasound bath, 1:9 molar ratio of substrates L-ascorbic acid to linoleic acid, 20 mL of tert-butanol as organic solvent, 5 wt% of Novozym 435 lipase, 10 wt% of molecular sieve at 70 °C. more...
- Published
- 2016
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22. Pharmacokinetics of hERG Channel Blocking Voacangine in Wistar Rats Applying a Validated LC-ESI-MS/MS Method
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Bibiana Verlindo de Araújo, Ulrike Grienke, Jadel M. Kratz, Carolina de Miranda Silva, Christina E. Mair, Judith M. Rollinger, Teresa Dalla Costa, Estevan Sonego Zimmermann, and Fernando Carreño
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Male ,0301 basic medicine ,hERG ,Pharmaceutical Science ,Pharmacology ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacokinetics ,Tandem Mass Spectrometry ,Drug Discovery ,Animals ,Humans ,Medicine ,Rats, Wistar ,Voacanga ,Voacangine ,Molecular Structure ,biology ,business.industry ,Alkaloid ,Organic Chemistry ,Ibogaine ,biology.organism_classification ,Ether-A-Go-Go Potassium Channels ,Rats ,Bioavailability ,030104 developmental biology ,Voacanga africana ,Complementary and alternative medicine ,chemistry ,biology.protein ,Molecular Medicine ,business ,medicine.drug - Abstract
Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-a-go-go-related gene channel blocker in vitro . Blockage of this channel might imply possible cardiotoxicity. Therefore, the aim of this study was to characterise voacangine in vivo to assess its pharmacokinetics and to estimate if further studies to investigate its cardiotoxic risk are required. Male Wistar rats received different doses of voacangine as a pure compound and as a hydro-ethanolic extract of V. africana root bark with a quantified amount of 9.71 % voacangine. For the obtained data, a simultaneous population pharmacokinetics model was successfully developed, comprising a two-compartment model for i. v. dosing and a one-compartmental model with two first-order absorption rates for oral dosing. The absolute bioavailability of voacangine was determined to be 11–13 %. Model analysis showed significant differences in the first absorption rate constant for voacangine administered as a pure compound and voacangine from the extract of V. africana . Taking into account the obtained low bioavailability of voacangine, its cardiotoxic risk might be neglectable in healthy consumers, but may have a serious impact in light of drug/drug interactions and impaired health conditions. more...
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- 2016
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23. The Silk Road: Traveled, Imagined, Transformed
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Dennis M. Kratz
- Subjects
Cultural exchange ,060103 classics ,Aesthetics ,General Engineering ,Lens (geology) ,0601 history and archaeology ,Ocean Engineering ,06 humanities and the arts ,Sociology - Abstract
Western artists, philosophers and politicians have inevitably viewed China and its actions through a distorting lens – often seeking to confirm assumptions rather than to gain new understanding. This paper examines Western and specifically American responses to three manifestations of the Silk Road: the historical Silk Road that enabled the transport of goods, people and ideas from China through Central Asia as far as Europe; the “Silk Road of the Western Imagination;” and the modern transformation of the Silk Road into China’s Belt and Road Initiative. It explores reasons for the American idealized fascination for the first two and hostility toward the BRI. The tendency to interpret history and China from a “heroic” perspective serves as an obstacle to fostering a modern era of cultural exchange and cooperation that both Americans and Chinese believe the Silk Road symbolizes. more...
- Published
- 2020
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24. Chemical Constituents and Pharmacology properties of Aristolochia triangularis: a south brazilian highly-consumed botanical with multiple bioactivities
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Sérgio Augusto de Loreto Bordignon, Argyro Vontzalidou, Flávio Henrique Reginatto, Tatiana da Rosa Guimarães, Cesar Paulo Simionato, Jadel M. Kratz, Cláudia Maria Oliveira Simões, Mário Steindel, Danielle T.M. Costa, Eloir Paulo Schenkel, Vitor Clasen Chaves, Simone Quintana de Oliveira, and Sapfo Dimitrakoudi more...
- Subjects
Antifungal Agents ,medicine.drug_class ,medicine.medical_treatment ,Phytochemicals ,Antiprotozoal Agents ,Fractionation ,Chemical Fractionation ,Antiviral Agents ,01 natural sciences ,Aristolochia ,chemistry.chemical_compound ,antiproliferative ,medicine ,Humans ,lcsh:Science ,Antidote ,Chromatography, High Pressure Liquid ,Lignan ,Multidisciplinary ,Ethanol ,Chloroform ,biology ,Traditional medicine ,Plant Extracts ,010405 organic chemistry ,Aristolochia triangularis ,Antimicrobial ,biology.organism_classification ,Anti-Bacterial Agents ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry ,antiprotozoal ,Antiprotozoal ,antimicrobial ,lcsh:Q ,aristolochic acids ,Brazil ,antiherpes - Abstract
Aristolochia triangularis Cham., is one of the most frequently used medicinal plant in Southern Brazil. Preparations containing the leaves and/or stems are traditionally used as anti-inflammatory, diuretic, as well as antidote against snakebites. This study screened A. triangularis extracts, fractions and isolated compounds for different bioactivities. A weak antiproliferative activity against human lung cancer cell line (A549) was observed only for chloroform fraction obtained from stems (CFstems - CC50: 2.93 µg/mL). Also, a moderate antimicrobial activity against Staphylococcus aureus was detected just for chloroform fraction obtained from leaves (CFleaves -13-16 mm inhibition zone). Additionally, two semi-purified fractions (CFstems-4 and CFleaves-4) selectively inhibited HSV-1 replication (IC50 values of 0.40 and 2.61 µg/mL, respectively), while only CFleaves showed promising results against Leishmania amazonensis. Fractionation of extracts resulted in the isolation of one neolignan (-) cubebin and one lignan (+) galbacin. However, these compounds are not responsible for the in vitro bioactivities herein detected. The presence of aristolochic acid I and aristolochic acid II in the crude ethanol extract of stems (CEEstems) and leaves (CEEleaves) was also investigated. The HPLC analysis of these extracts did not display any peak with retention time or UV spectra comparable to aristolochic acids I and II. more...
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- 2019
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25. Associations between Post-treatment Inflammatory Biomarkers and Survival among Stage II-III Colorectal Cancer Patients
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PA Newcomb, M Kratz, and Xinwei Hua
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Oncology ,education.field_of_study ,medicine.medical_specialty ,Epidemiology ,business.industry ,Colorectal cancer ,Population ,Hazard ratio ,medicine.disease ,National Death Index ,Quartile ,Internal medicine ,Medicine ,Biomarker (medicine) ,business ,education ,Body mass index ,Cause of death - Abstract
We aimed to evaluate post-treatment inflammatory biomarkers, namely C-reactive protein (CRP), interleukin-6 (IL6), monocytes chemoattractant protein-1 (MCP1), leptin and adiponectin, in relation to overall survival (OS) in stage II-III colorectal cancer (CRC) patients. Methods: Participants were incident, invasive CRC cases who were 22–74 years of age, diagnosed between 1997–2008 from the population-based Seattle Colon Cancer Family Registry. We included stage II-III cases who were at the greatest risk for disease progression. Further restriction to 308 participants with a blood draw 1–3 years after diagnosis was made to preclude acute treatment effects. We measured concentrations of all five markers in EDTA-plasma samples using the Meso Scale Discovery immunoassays. Biomarker levels were log-transformed to ensure normality. We also divided patients into sex-specific quartiles for each marker to test for a dose-effect of a biomarker on disease progression. Mortality and cause of death were assessed through linkage to the National Death Index. We used Cox proportional hazard regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of post-treatment inflammatory markers with OS. HRs were adjusted for potential confounders selected a priori, including age at blood draw, sex, body mass index, plasma storage time, the time between diagnosis and blood draw, and stage at diagnosis. Results: Elevated CRP levels were associated with poorer OS (HR = 1.32 per unit increase of log-CRP, 95% CI = 1.13–1.55). For circulating IL6, a dose-response relationship with survival was evident: compared with the lowest quartile of IL6, the 2nd, 3rd and 4th quartiles were significantly associated with OS, with HRs (95% CIs) of 2.72 (1.42–5.21), 4.23 (2.24–7.99), and 6.80 (3.56–12.96) respectively (p for trend < 0.0001). For MCP1, we observed a 2-fold increase in the risk of overall mortality per unit increase in log-MCP1 (HR = 2.17, 95% CI = 1.39–3.39). Circulating levels of leptin and adiponectin were not significantly associated with OS. Conclusions: Circulating inflammatory markers, specifically CRP, IL6, and MCP1, are prognostic markers in stage II/III CRC patients and should be considered for incorporation into studies of CRC outcomes. more...
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- 2020
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26. 4:21 PM Abstract No. 51 Safety and efficacy of arterial closure devices following antegrade femoral access: a case-control study
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Timothy Clark, Mark P. Mantell, Louis-Xavier Barrette, Ansar Z Vance, J. Redmond, and Kathleen M. Kratz
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medicine.medical_specialty ,business.industry ,Femoral access ,Closure (topology) ,Medicine ,Radiology, Nuclear Medicine and imaging ,Cardiology and Cardiovascular Medicine ,business ,Surgery - Published
- 2020
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27. Pharmacokinetics of Saquinavir Mesylate from Oral Self-Emulsifying Lipid-Based Delivery Systems
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Cláudia Maria Oliveira Simões, Thiago Caon, Bibiana Verlindo de Araújo, Letícia Scherer Koester, Gislaine Kuminek, Gustavo Amadeu Micke, Melina Heller, and Jadel M. Kratz
- Subjects
Male ,Drug ,media_common.quotation_subject ,Administration, Oral ,Biological Availability ,02 engineering and technology ,Absorption (skin) ,Pharmacology ,Models, Biological ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Dogs ,Drug Delivery Systems ,0302 clinical medicine ,Pharmacokinetics ,Oral administration ,Animals ,Medicine ,Distribution (pharmacology) ,Pharmacology (medical) ,Saquinavir ,media_common ,business.industry ,021001 nanoscience & nanotechnology ,Lipids ,Bioavailability ,Saquinavir mesylate ,Drug delivery ,Administration, Intravenous ,Emulsions ,0210 nano-technology ,business - Abstract
Although lipid-based drug delivery systems have gained much importance in recent years due to their ability to improve the solubility and bioavailability of poorly soluble drugs, compartmental pharmacokinetic analyses have not been extensively explored. The oral pharmacokinetics of commercial liquid formulation and a developed semisolid system containing saquinavir mesylate (SQVM) were compared in Beagle dogs. A compartmental analysis after intravenous bolus administration of this drug (1 mg/kg) was also performed. Pharmacokinetic profiles were analyzed using both non-compartmental and compartmental approaches. Plasma concentration of the drug was determined by high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS). The disposition curve of SQVM given intravenously was better described by a three-compartment model. In contrast, plasma profiles obtained following the oral administration were fitted to a two-compartment model with lag time due to the fact that the distribution phase was masked by the absorption phase in these formulations. The proposed semisolid lipid system was found to be a promising formulation for commercial purposes given the similarity of SQVM absorption rate to that from the commercial liquid formulation. more...
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- 2016
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28. Inclusion complexes of hydrochlorothiazide and β-cyclodextrin: Physicochemical characteristics, in vitro and in vivo studies
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Marcos Antonio Segatto Silva, Patricia de Oliveira Benedet, Paulo R. Oliveira, Jéssica Henriques Kruger, Aline Buttchevitz, Cassiana Mendes, Jadel M. Kratz, and Cláudia Maria Oliveira Simões
- Subjects
Drug ,Hot Temperature ,Chemistry, Pharmaceutical ,media_common.quotation_subject ,Pharmaceutical Science ,Beta-Cyclodextrins ,02 engineering and technology ,030226 pharmacology & pharmacy ,Intestinal absorption ,03 medical and health sciences ,0302 clinical medicine ,Hydrochlorothiazide ,Drug Stability ,X-Ray Diffraction ,In vivo ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Rats, Wistar ,Solubility ,Diuretics ,Chromatography, High Pressure Liquid ,media_common ,chemistry.chemical_classification ,Chromatography ,Calorimetry, Differential Scanning ,Cyclodextrin ,Chemistry ,beta-Cyclodextrins ,021001 nanoscience & nanotechnology ,Freeze Drying ,Biopharmaceutical ,Intestinal Absorption ,Female ,Caco-2 Cells ,0210 nano-technology ,Powder Diffraction ,medicine.drug - Abstract
Hydrochlorothiazide is a thiazide diuretic widely used in clinics to treat arterial hypertension. It is a class IV drug according to the Biopharmaceutical Classification System, that is, it presents low solubility and low permeability and, consequently, low absorption in the gastrointestinal tract. As a strategy to improve stability and biopharmaceutical properties of hydrochlorothiazide, the use of cyclodextrins to produce inclusion complexes, applying different methods, was investigated. In the phase solubility studies, β-cyclodextrin was identified as the cyclodextrin which provided the most promising results in terms of the solubilization of the drug. The thermal analysis verified the interaction between hydrochlorothiazide and β-cyclodextrin, indicating the formation of inclusion complexes, and the thermal stability varied according to the preparation technique. The physicochemical characterization showed that in the inclusion complexes obtained by co-evaporation, kneading followed by freeze-drying and kneading followed by spray-drying the hydrochlorothiazide complexation mostly occurred with different degrees of amorphization and the drug solubility was improved. These three inclusion complexes presented better in vitro characteristics and the inclusion complex obtained by kneading followed by freeze-drying increased the in vivo diuretic activity of the drug accompanied by significant effects on natriuresis, kaliuresis and chloriuresis. The inclusion complex formation was effective in improving the biopharmaceutical properties of hydrochlorothiazide and protecting the drug from hydrolysis. This paper describes an important alternative approach to the development of liquid pharmaceutical formulations to pediatric administration, a real need of the current pharmaceutical market. more...
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- 2016
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29. Discovery of a Novel 2,6-Disubstituted Glucosamine Series of Potent and Selective Hexokinase 2 Inhibitors
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Mary Ann Hardwicke, Hong Lin, Karl F. Erhard, John D. Martin, Ren Xie, Kaushik Raha, Rosanna Tedesco, Jin Zeng, Yanqiu Qian, Patricia M. Kratz, Yong Jiang, Ted Cecconie, Stan F. Martens, Angela Smallwood, Patrick McDevitt, James F. Mack, Baoguang Zhao, Stephenie B. Chen, Anthony J. Jurewicz, Juan I. Luengo, Mark J. Schulz, Nino Campobasso, Catherine A. Oleykowski, Lawrence M. Szewczuk, Alan R. Rendina, Cynthia M. Rominger, Benjamin J. Schwartz, Leng Nickels, Junya Qu, and Jacques Briand more...
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Stereochemistry ,Organic Chemistry ,Biology ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,Hexokinase-2 ,Enzyme ,chemistry ,Cell culture ,Glucosamine ,030220 oncology & carcinogenesis ,Drug Discovery ,Bladder tumor ,Glycolysis ,Selectivity - Abstract
A novel series of potent and selective hexokinase 2 (HK2) inhibitors, 2,6-disubstituted glucosamines, has been identified based on HTS hits, exemplified by compound 1. Inhibitor-bound crystal structures revealed that the HK2 enzyme could adopt an "induced-fit" conformation. The SAR study led to the identification of potent HK2 inhibitors, such as compound 34 with greater than 100-fold selectivity over HK1. Compound 25 inhibits in situ glycolysis in a UM-UC-3 bladder tumor cell line via (13)CNMR measurement of [3-(13)C]lactate produced from [1,6-(13)C2]glucose added to the cell culture. more...
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- 2016
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30. Novozym® 435-catalyzed production of ascorbyl oleate in organic solvent ultrasound-assisted system
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Marco Di Luccio, Leandro G. Nandi, Jadel M. Kratz, Débora de Oliveira, Manuela Balen, Camila Silveira, Cláudia Maria Oliveira Simões, Alexsandra Valério, and Jorge Luiz Ninow
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Chromatography ,biology ,Chemistry ,Bioengineering ,Molecular sieve ,Ascorbic acid ,Applied Microbiology and Biotechnology ,Chemical synthesis ,Catalysis ,Solvent ,Oleic acid ,chemistry.chemical_compound ,biology.protein ,Lipase ,Solubility ,Agronomy and Crop Science ,Food Science ,Biotechnology - Abstract
Ultrasound-assisted system is promising for chemical synthesis. This study aimed the production of ascorbyl oleate catalyzed by lipase Novozym® 435 in organic solvent using ultrasound-assisted system. Different organic solvents and solvent concentration were tested at 70 °C using 1:9 M ratio ascorbic acid:oleic acid. The solubility was evaluated by visual analysis after 40 min of stirring substrates and solvent. By this procedure, 20 mL of tert-butanol was defined as the best solvent for the reaction. The maximized conditions for ascorbyl oleate production in the ultrasound-assisted system were determined by evaluating the temperature, enzyme concentration and molecular sieves influence in the kinetics reaction. At the end of reaction the best conditions obtained for the maximal ascorbyl oleate conversion was molar ratio ascorbic acid:oleic acid, 1:9, 20 mL tert-butanol, 70 °C, 5 wt% Novozym® 435, 20 wt% molecular sieve, 100% ultrasound power and 12 h reaction, resulting in 87% of ascorbyl oleate conversion. Without the use of molecular sieve, the kinetic study pointed the maximized experimental condition conversions of 66% after 3 h of reaction. more...
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- 2015
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31. Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549
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Miguel S. B. Caro, Karen Luise Lang, Eloir Paulo Schenkel, Lucas Lourenço Marostica, Izabella Thaís Silva, Cláudia Maria Oliveira Simões, Fernando Javier Duran, F. Geller, Jadel M. Kratz, and Lara Persich more...
- Subjects
Lung Neoplasms ,Paclitaxel ,Survivin ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Irinotecan ,Toxicology ,Inhibitor of Apoptosis Proteins ,chemistry.chemical_compound ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Clonogenic assay ,Lung cancer ,Cell Proliferation ,Cisplatin ,Cell growth ,Drug Synergism ,General Medicine ,medicine.disease ,Actins ,Triterpenes ,G2 Phase Cell Cycle Checkpoints ,chemistry ,Mechanism of action ,M Phase Cell Cycle Checkpoints ,Camptothecin ,Tumor Suppressor Protein p53 ,medicine.symptom ,Reactive Oxygen Species ,medicine.drug - Abstract
Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer. more...
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- 2015
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32. Oral saquinavir mesylate solid dispersions: In vitro dissolution, Caco-2 cell model permeability and in vivo absorption studies
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Gislaine Kuminek, Thiago Caon, Melina Heller, Letícia Scherer Koester, Jadel M. Kratz, Cláudia Maria Oliveira Simões, Ricardo Augusto Konig, and Gustavo Amadeu Micke
- Subjects
Drug ,Chromatography ,Chemistry ,General Chemical Engineering ,media_common.quotation_subject ,Intestinal absorption ,Bioavailability ,Saquinavir mesylate ,Oleic acid ,chemistry.chemical_compound ,Castor oil ,PEG ratio ,medicine ,Particle size ,media_common ,medicine.drug - Abstract
The aim of this study was to investigate the effects of solid dispersions (SDs) containing a mixture of PVP K30 and different carriers (PEG 4000 or Gelucire® 44/14) on in vitro dissolution and intestinal permeability of saquinavir mesylate (SQVM), and to evaluate their impact on the oral bioavailability of SQVM in a dog model by comparing with Svir® (commercial formulation). Although hydrophilic carriers such as PEG may provide advantages in terms of drug release, their limited solubilization capacity led to precipitation of drug and therefore to a reduced and variable oral bioavailability, as observed for SQVM from this carrier. On the other hand, self-emulsifying systems composed of Gelucire® 44/14 or oleic acid/Castor oil mixture (Svir®) were more effective at improving oral bioavailability of SQVM (approximately 5-fold higher than PEG-based formulations), probably due to the improved solubility of SQVM in GI tract, reduced particle size and inhibitory effects on P-gp (a 2.3-fold reduction of efflux ratio). The selection of carriers and other excipients which display a solubilizing effect and inhibitory effect on P-gp seems to be key factors for increasing the oral bioavailability of SQVM. Gelucire might be considered as a promising carrier for the development of a SQVM commercial formulation. more...
- Published
- 2015
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33. hERG channel blockers in medicinal plants: Hysteria or serious problem?
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Judith M. Rollinger, Jadel M. Kratz, Christina E. Mair, and Ulrike Grienke
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biology ,Traditional medicine ,business.industry ,hERG ,biology.protein ,Medicine ,Channel blocker ,Hysteria ,Medicinal plants ,business ,medicine.disease - Published
- 2017
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34. Exploration and Pharmacokinetic Profiling of Phenylalanine Based Carbamates as Novel Substance P 1–7 Analogues
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Per Artursson, Anna Carlsson-Jonsson, Jadel M. Kratz, Gunnar Nordvall, Richard Svensson, Anja Sandström, Mathias Hallberg, Rebecca Fransson, and Johan Bylund
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Hydroxamic acid ,Peptidomimetic ,Stereochemistry ,Organic Chemistry ,Phenylalanine ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Amide ,Drug Discovery ,Cyanamide ,Bioisostere ,Pharmacophore ,Lead compound - Abstract
The bioactive metabolite of Substance P, the heptapeptide SP1-7 (H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-OH), has been shown to attenuate signs of hyperalgesia in diabetic mice, which indicate a possible use of compounds targeting the SP1-7 binding site as analgesics for neuropathic pain. Aiming at the development of drug-like SP1-7 peptidomimetics we have previously reported on the discovery of H-Phe-Phe-NH2 as a high affinity lead compound. Unfortunately, the pharmacophore of this compound was accompanied by a poor pharmacokinetic (PK) profile. Herein, further lead optimization of H-Phe-Phe-NH2 by substituting the N-terminal phenylalanine for a benzylcarbamate group giving a new type of SP1-7 analogues with good binding affinities is reported. Extensive in vitro as well as in vivo PK characterization is presented for this compound. Evaluation of different C-terminal functional groups, i.e., hydroxamic acid, acyl sulfonamide, acyl cyanamide, acyl hydrazine, and oxadiazole, suggested hydroxamic acid as a bioisosteric replacement for the original primary amide. more...
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- 2014
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35. Drug discovery for chagas disease: A viewpoint
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Jadel M. Kratz
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0301 basic medicine ,Chagas disease ,medicine.medical_specialty ,Trypanosoma cruzi ,Veterinary (miscellaneous) ,030231 tropical medicine ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Humans ,Chagas Disease ,Nifurtimox ,Intensive care medicine ,business.industry ,Public health ,Tropical disease ,030108 mycology & parasitology ,medicine.disease ,Trypanocidal Agents ,Infectious Diseases ,Nitroimidazoles ,Benznidazole ,Insect Science ,Neglected tropical diseases ,Parasitology ,business ,Trypanosomiasis ,medicine.drug - Abstract
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It is a significant public health problem, affecting millions of people worldwide. And although it was described 110 years ago, only two old nitroheterocyclic drugs, benznidazole and nifurtimox, are currently available for the treatment of Chagas disease and both have several limitations. Besides the clear unmet medical need, many challenges preclude the development of new treatments, some of them related to a lack of understanding of the pathophysiology of the disease and parasite-host interactions. New knowledge and tools are becoming available, but the number of new chemical entities progressing through the preclinical pipeline is inadequate. Therefore, it is still uncertain whether safe, effective and accessible new drugs will be available in the near future. The Chagas disease research community must commit to even greater collaboration to ensure that patients eventually benefit from better treatments. more...
- Published
- 2019
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36. Polyacetylenes from the leaves of Vernonia scorpioides (Asteraceae) and their antiproliferative and antiherpetic activities
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Daniel F. Coimbra, Andersson Barison, Luiz A.E. Pollo, Jadel M. Kratz, Caroline Rigotto, Andrea S. Leite, Giovanni F. Caramori, Maique W. Biavatti, Cristiane F. Bosi, Cláudia Maria Oliveira Simões, Francinete Ramos Campos, Angelita Nepel, and David E. P. Fonseca more...
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food.ingredient ,Human cell line ,Plant Science ,Horticulture ,Antiviral Agents ,Biochemistry ,food ,Cell Line, Tumor ,Botany ,Humans ,Simplexvirus ,Molecular Biology ,Inhibitory effect ,chemistry.chemical_classification ,Apiaceae ,Molecular Structure ,biology ,Plant Extracts ,Polyynes ,Glycoside ,General Medicine ,Asteraceae ,biology.organism_classification ,Small Cell Lung Carcinoma ,Plant Leaves ,chemistry ,Herb ,Araliaceae ,Medicine, Traditional ,Vernonia ,Two-dimensional nuclear magnetic resonance spectroscopy - Abstract
Polyacetylenes constitute an underexplored and unstable class of compounds that are found mainly in the Apiaceae, Araliaceae and Asteraceae families. Vernonia scorpioides (Lam.) Pers., Asteraceae is a lianous neotropical herb that usually grows in soils that have been deforested and are of poor quality. It is used in folk medicine for the treatment of several skin conditions. This study addresses the characterisation of eight polyacetylenes isolated from the leaves of V. scorpioides. Their structures were established on the basis of 1D and 2D NMR spectroscopy and MS analysis. Ab initio calculations including solvent effects were employed to aid the elucidation of the absolute configurations of the compounds. The in vitro antiproliferative and anti-herpetic activities of the polyacetylenes were determined. The isolated compounds presented no inhibitory effect against a human cell line of non-small cell lung cancer, but presented a mild non-selective in vitro antiviral activity, although their corresponding glycosides were inactive. more...
- Published
- 2013
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37. Latino subgroup as a moderator of the relationship between language usage and alcohol use in a national sample of Latino emerging adults
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Ellen L. Vaughan, Oscar S. Escobar, Lisa M. Kratz, and Katharine G. Middendorf
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Cultural Studies ,Gerontology ,Longitudinal study ,Social Psychology ,Cuban American ,common ,Binge drinking ,Alcohol ,Sample (statistics) ,Moderation ,Article ,Clinical Psychology ,chemistry.chemical_compound ,Increased risk ,chemistry ,Anthropology ,common.group ,Psychology ,Applied Psychology ,Demography ,Adolescent health - Abstract
Emerging adulthood represents a period of increased risk for alcohol use. For Latino emerging adults, less is known regarding the role cultural variables play in alcohol use behaviors. Research in this area has primarily been conducted using Latino college student samples and/or a single Latino subgroup. This study investigates Latino subgroup as a moderator of the relationship between language usage and alcohol use variables, using a nationally-representative sample of Latino emerging adults from the National Longitudinal Study of Adolescent Health (Add Health). Participants (N=2,477) identified as Mexican/ Mexican American, Cuban/ Cuban American, Puerto Rican, or Central/South American/Other Hispanic. Results of regression analyses indicated that gender, education, and language usage have a differential impact on alcohol use and binge drinking behaviors among individuals from different Latino subgroups. Implications for future research and alcohol prevention are discussed. more...
- Published
- 2013
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38. In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats
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Luis Fernando Ospina, Marcela Aragón, Aura Rocio Hernández, Cláudia Maria Oliveira Simões, Jadel M. Kratz, Alvaro F. Jimenez-Kairuz, Paola Andrea Cárdenas, Yolima Baena, and Geison M. Costa
- Subjects
0301 basic medicine ,CIENCIAS MÉDICAS Y DE LA SALUD ,Inmunología ,Cmax ,lcsh:RS1-441 ,Intestinal permeability/study/In vitro ,Pharmacology ,6-Methylcoumarin/Pharmacokinetics/rats ,030226 pharmacology & pharmacy ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,0302 clinical medicine ,Elimination rate constant ,Pharmacokinetics ,In vivo ,Oral administration ,medicine ,Distribution (pharmacology) ,General Pharmacology, Toxicology and Pharmaceutics ,Intestinal permeability ,Chemistry ,purl.org/becyt/ford/3.1 [https] ,medicine.disease ,Medicina Básica ,030104 developmental biology ,Intestinal permeability/study ,purl.org/becyt/ford/3 [https] ,6-Methylcoumarin/distribution ,Half time - Abstract
6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke) 0.0070 min-1 and a short life half time of (T1/2) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated. Fil: Cárdenas, Paola Andrea. Universidad Nacional de Colombia. Departamento de Farmacia. Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas; Colombia Fil: Kratz, Jadel Müller. Universidade Federal de Santa Catarina. Departamento de Ciências Farmacêuticas. Grupo de Análise e Desenvolvimento de Fármacos de Origem Natural; Brasil Fil: Hernández, Aura. Universidad Nacional de Colombia. Departamento de Farmacia.Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas; Colombia Fil: Costa, Geison Modesti. Universidad Nacional de Colombia. Departamento de Química. Grupo de Estudio y Aprovechamiento de Productos Naturales Marinos y Frutas de Colombia ; Colombia Fil: Ospina, Luis Fernando. Universidad Nacional de Colombia. Departamento de Farmacia.Grupo de Principios Bioactivos de Plantas Medicinales; Colombia Fil: Baena, Yolima. Universidad Nacional de Colombia. Departamento de Farmacia.Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas; Colombia Fil: Simões, Cláudia Maria Oliveira. Universidade Federal de Santa Catarina. Departamento de Ciências Farmacêuticas. Grupo de Análise e Desenvolvimento de Fármacos de Origem Natural; Brasil Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Ciencias Farmacéuticas; Argentina Fil: Aragón, Marcela. Universidad Nacional de Colombia. Departamento de Farmacia. Grupo Sistemas de Liberación Modificada de Moléculas Biológicamente Activas; Colombia more...
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- 2017
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39. Natural products modulating the hERG channel: heartaches and hope
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Ulrike Grienke, Stefan A. Mann, Olaf Scheel, Judith M. Rollinger, and Jadel M. Kratz
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0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Cardiotoxicity ,biology ,Drug discovery ,Chemistry ,Organic Chemistry ,hERG ,Pharmacology ,Biochemistry ,Potassium channel ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Antitarget ,030220 oncology & carcinogenesis ,Drug Discovery ,biology.protein ,Repolarization ,Channel blocker ,cardiovascular diseases ,Ion channel - Abstract
Covering: 1996–December 2016 The human Ether-a-go-go Related Gene (hERG) channel is a voltage-gated potassium channel playing an essential role in the normal electrical activity in the heart. It is involved in the repolarization and termination of action potentials in excitable cardiac cells. Mutations in the hERG gene and hERG channel blockage by small molecules are associated with increased risk of fatal arrhythmias. Several drugs have been withdrawn from the market due to hERG channel-related cardiotoxicity. Moreover, as a result of its notorious ligand promiscuity, this ion channel has emerged as an important antitarget in early drug discovery and development. Surprisingly, the hERG channel blocking profile of natural compounds present in frequently consumed botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is not routinely assessed. This comprehensive review will address these issues and provide a critical compilation of hERG channel data for isolated natural products and extracts over the past two decades (1996–2016). In addition, the review will provide (i) a solid basis for the molecular understanding of the physiological functions of the hERG channel, (ii) the translational potential of in vitro/in vivo results to cardiotoxicity in humans, (iii) approaches for the identification of hERG channel blockers from natural sources, (iv) future perspectives for cardiac safety guidelines and their applications within phytopharmaceuticals and dietary supplements, and (v) novel applications of hERG channel modulation (e.g. as a drug target). more...
- Published
- 2017
40. hERG Channel Blocking Ipecac Alkaloids Identified by Combined In Silico - In Vitro Screening
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Steffen Hering, Olaf Scheel, Daniela Schuster, Christina E. Mair, Priyanka Saxena, Judith M. Rollinger, Sarah K. Oettl, and Jadel M. Kratz
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0301 basic medicine ,Voltage clamp ,hERG ,Pharmaceutical Science ,Emetine ,Pharmacology ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Xenopus laevis ,Alkaloids ,Ipecac ,Drug Discovery ,Ipecacuanha ,medicine ,Animals ,Humans ,Channel blocker ,Computer Simulation ,biology ,Molecular Structure ,Cephaelis ,Organic Chemistry ,biology.organism_classification ,Ether-A-Go-Go Potassium Channels ,030104 developmental biology ,Complementary and alternative medicine ,chemistry ,biology.protein ,Molecular Medicine ,Carapichea ipecacuanha ,Cephaeline ,Pharmacophore ,medicine.drug - Abstract
Human ether-a-go-go-related gene channel blocking is associated with QT interval prolongation and increased risk of potentially fatal arrhythmias. As natural products keep increasing in popularity, there is an urgent need for studies assessing human ether-a-go-go-related gene channel-related cardiotoxic risks. We selected 49 plant species based on the results of a pharmacophore-based virtual screening campaign, in parallel with a literature data survey concerning highly consumed herbal medicines with reported cardiac liabilities. Lead-like enhanced extracts were prepared, an initial in vitro screening was performed at 100 µg/mL by voltage clamp on Xenopus oocytes, and five human ether-a-go-go-related gene channel blocking extracts were identified. In accordance to the six virtually predicted alkaloids, the root extract of Carapichea ipecacuanha inhibited human ether-a-go-go-related gene channel currents by 32.5 %. A phytochemical workflow resulted in the isolation and identification of five out of the six virtually predicted alkaloids. All isolates blocked human ether-a-go-go-related gene channel currents to different extents. The major ipecac constituents emetine (1) and cephaeline (2) showed IC50 values of 21.4 and 5.3 µM, respectively, measured by whole-cell patch clamp in HEK293 cells. This is the first report on human ether-a-go-go-related gene channel blockers from C. ipecacuanha. Its roots and rhizomes are used to produce different pharmacopeial ipecac preparations that are mainly used as emetics for poisoning treatment. Our findings raise further questions regarding the safety and over-the-counter appropriateness of these herbal products. more...
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- 2016
41. Apicoaortic Conduits
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John W. Nance, U. Joseph Schoepf, J. Michael Barraza, Thomas Henzler, John M. Kratz, and William G. McMaster
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Diagnostic Imaging ,Pulmonary and Respiratory Medicine ,Cardiac Catheterization ,medicine.medical_specialty ,medicine.medical_treatment ,Ventricular outflow tract obstruction ,Aorta, Thoracic ,Ventricular Outflow Obstruction ,Blood Vessel Prosthesis Implantation ,Postoperative Complications ,Aortic valve replacement ,medicine.artery ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Cardiac Surgical Procedures ,Cardiac catheterization ,Apicoaortic Conduit ,Aorta ,Cardiopulmonary Bypass ,business.industry ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Cardiothoracic surgery ,Descending aorta ,cardiovascular system ,medicine.symptom ,business ,Artery - Abstract
Left ventricular apex to descending aorta conduits may be used as a last resort treatment of severe left ventricular outflow tract obstruction in cases in which alternative therapies are contraindicated. Although this technique is rarely used in current practice for congenital cases, its use in the elderly population is increasing, largely due to the expansion of this patient cohort and associated comorbidities precluding aortic valve replacement, the most common of which are a severely calcified "porcelain" aorta and/or previous coronary artery bypass grafts preventing aortic root manipulation. Diagnostic imaging is essential in the presurgical workup and subsequent follow-up of these patients, as complications of the procedure are potentially life threatening and are not rare. Several imaging modalities may be used, each with advantages and disadvantages. Both anatomic and functional assessments play a role in the comprehensive evaluation of both presurgical and postsurgical patients. more...
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- 2012
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42. Combined Carotid Endarterectomy and Coronary Artery Bypass Grafting Versus Coronary Artery Bypass Grafting Alone: A Retrospective Review of Outcomes at Our Institution
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Amanda M. Dick, Thomas Brothers, Jacob G. Robison, Bruce M. Elliott, John M. Kratz, J. Matthew Toole, Arthur J. Crumbley, and Fred A. Crawford
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Male ,medicine.medical_specialty ,Time Factors ,South Carolina ,medicine.medical_treatment ,Myocardial Infarction ,Coronary Artery Disease ,Carotid endarterectomy ,Risk Assessment ,Severity of Illness Index ,Risk Factors ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Carotid Stenosis ,cardiovascular diseases ,Myocardial infarction ,Coronary Artery Bypass ,Propensity Score ,Stroke ,Aged ,Retrospective Studies ,Endarterectomy, Carotid ,business.industry ,General Medicine ,Odds ratio ,Perioperative ,Middle Aged ,medicine.disease ,Confidence interval ,Treatment Outcome ,medicine.anatomical_structure ,Concomitant ,Cardiology ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Artery - Abstract
Background: It remains controversial whether patients with concomitant carotid and coronary disease should undergo operative repair separately or in combination. Methods: Patients with documented cerebrovascular disease undergoing coronary artery bypass grafting (CABG) alone were matched by propensity scoring with patients undergoing combined carotid endarterectomy (CEA)/CABG procedures and compared for the occurrence of stroke, myocardial infarction (MI), and mortality. Results: Of the 4943 patients undergoing CABG, 908 had known cerebrovascular disease. Among these, 134 underwent concomitant CEA, and these were propensity matched with 134 patients undergoing CABG only. No differences were observed in the perioperative risks of stroke (4% vs 3%, odds ratio [OR] 1.5, 95% confidence interval [CI] 0.4-5.5), MI (0.7% vs 0.7%, not significant [NS]), or combined cardiovascular events (6% vs 10%, OR 0.5, 95% CI [0.2-1.3]), although mortality (1% vs 8%, OR 0.2, 95% CI [0.04-0.8] was higher with CABG only. Discussion: Addition of CEA to CABG did not significantly alter the risk of perioperative stroke relative to propensity-matched patients undergoing CABG alone. more...
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- 2011
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43. Fucose and Sialic Acid Expressions in Human Seminal Fibronectin andα1-Acid Glycoprotein Associated with Leukocytospermia of Infertile Men
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Ewa M. Kratz, Ricardo Faundez, and Iwona Kątnik-Prastowska
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Biochemistry (medical) ,Clinical Biochemistry ,Genetics ,General Medicine ,Molecular Biology - Abstract
Introduction: The aim of this study was to compare fucose and sialic acid residue expression on fibronectin andα1-acid glycoprotein in the seminal plasma of men suspected of infertility and suffering from leukocytospermia.Subjects and methods: Seminal ejaculates were collected from 27 leukocytospermic and 18 healthy, normozoospermic men. The relative degree of fucosylation and sialylation of fibronectin andα1-acid glycoprotein was estimated by ELISA using fucose and sialic acid specific lectins fromAleuria aurantia, Lotus tetragonolobus, andUlex europaeusas well asMaackia amurensisandSambucus nigra, respectively.Results: Leukocytospermic seminal fibronectin, in comparison with fibronectin of normal fertile group, showed lower relative reactivity with AAL, LTA and UEA, and higher reactivity with MAA and SNA, while the AGP of the leukocytospermic group was less reactive with AAL, and the relative reactivity with LTA and MAA was significantly higher. Fibronectin andα1-acid glycoprotein reactivity with UEA and MAA showed high positive correlations.Discussion: Leukocytospermia was associated with the alterations of terminal monosaccharide expression in human seminal fibronectin andα1-acid glycoprotein. The increase of sialyl-Lewisxantigen inα1-acid glycoprotein can be used as a marker of genital tract inflammation manifested by leukocytospermia. more...
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- 2011
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44. Pacemaker and Internal Cardioverter Defibrillator Lead Extraction: A Safe and Effective Surgical Approach
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John M. Kratz and John M. Toole
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Thorax ,Pacemaker, Artificial ,medicine.medical_specialty ,Adolescent ,Defibrillation ,medicine.medical_treatment ,Cardioversion ,medicine ,Humans ,Child ,Lead (electronics) ,Device Removal ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Extraction (chemistry) ,Retrospective cohort study ,Bacterial Infections ,Middle Aged ,Defibrillators, Implantable ,Surgery ,Child, Preschool ,Anesthesia ,Arterial line ,Female ,Hemodialysis ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Need for pacemaker or internal cardioverter defibrillator lead removal is increasing. Removal can be dangerous, difficult, or unsuccessful. Methods We retrospectively reviewed our results and the techniques we used in 365 patients from 1992 through 2009 for successful complete removal of leads and complications. Various techniques of extraction were analyzed for effectiveness and complications. The eras before (1992 to 1999) and after the availability of laser sheath extraction (2000 to 2009) are compared. Results Of 365 patients who underwent transvenous lead extraction, of which 235 were infected, and 130 had lead removal for noninfectious indication. Staphylococcus aureus was the infecting organism in 40%, and coagulase-negative Staphylococcus occurred in 33%. One-half of the organisms were methicillin resistant. Preimplant risk factors for infection included more than one device implant procedure in 105 (47%), preimplant Coumadin therapy (Bristol-Myers Squibb, Princeton, NJ) in 74 (31%), and hemodialysis in 9 (4%). Laser extraction became available in 2000. The era with the availability of laser extraction was associated with a better complete extraction rate (93% vs 89.55%) a lower bleeding rate (1.9% vs 3.1%), and complete extraction without the additional use of femoral workstation extraction tools. Mortality was 1.1%. No death was due to device removal. All deaths were the result of severe preoperative and continuing postextraction sepsis. Conclusions A lead extraction protocol that included procedures done in an operating room environment allowing rapid, open intervention for bleeding, a varied choice of extraction tools, arterial line monitoring, transesophageal echocardiography, general anesthesia, and an experienced team yielded complete extraction in more than 90% of patients, with a low complication rate and no procedurally related deaths. more...
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- 2010
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45. Twenty-Five Year Experience With the St. Jude Medical Mechanical Valve Prosthesis
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Scott M. Bradley, John S. Ikonomidis, Arthur J. Crumbley, John M. Kratz, Fred A. Crawford, Martha R. Stroud, and J. Matthew Toole
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Aortic valve ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Heart Valve Diseases ,Prosthesis Design ,Risk Assessment ,Prosthesis ,Mechanical valve ,Cohort Studies ,Young Adult ,Postoperative Complications ,Mitral valve ,Confidence Intervals ,Odds Ratio ,medicine ,Humans ,Endocarditis ,Prospective Studies ,Prospective cohort study ,Aged ,Probability ,Proportional Hazards Models ,Aged, 80 and over ,Bioprosthesis ,Heart Valve Prosthesis Implantation ,business.industry ,Mitral valve replacement ,Middle Aged ,medicine.disease ,Survival Analysis ,Prosthesis Failure ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Aortic Valve ,Heart Valve Prosthesis ,Multivariate Analysis ,Mitral Valve ,Female ,Implant ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background We evaluated all adult St. Jude mechanical valve recipients at our institution since the initial implant in January 1979 and now present our 25-year experience. Methods Nine hundred forty-five valve recipients were followed prospectively at 12-month intervals from January 1979 to December 2007. Results Operative mortality was 3% in the aortic valve recipients and 5% in the mitral valve recipients. Follow-up was 95% complete. Among aortic valve recipients, late actuarial survival was 81% ± 2%, 59% ± 2%, 41% ± 3%, 28% ± 3%, and 17% ± 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five–year freedom from reoperation, thromboembolism, bleeding, and endocarditis was 90% ± 2%, 69% ± 5%, 67% ± 3%, and 9% 3 ± 2% respectively. Among mitral valve recipients late actuarial survival was 84% ± 2%, 63% ± 3%, 44% ± 3%, 31% ± 3%, and 23% ± 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five–year freedom from reoperation, thromboembolism, bleeding and endocarditis was 81% ± 10%, 52% ± 8%, 64% ± 6%, and 97% ± 1%. Freedom from valve-related mortality and morbidity at 25 years was 26% ± 7% and 29% ± 6% for aortic and mitral valve replacement, respectively. Freedom from valve-related mortality was 66% ± 8% and 87% ± 3% for aortic and mitral valve replacement, respectively. Conclusions These results compare favorably with those for other mechanical prostheses. After two and a half decades of observation with close follow-up, the St. Jude mechanical valve continues to be a reliable prosthesis. more...
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- 2010
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46. Power System Flicker Analysis by RMS Voltage Values and Numeric Flicker Meter Emulation
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Xavier Yang and M. Kratz
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Engineering ,business.industry ,Flicker ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,Energy Engineering and Power Technology ,computer.software_genre ,Dynamic load testing ,law.invention ,Simulation software ,Electric power system ,law ,Electrical network ,Power electronics ,Hardware_INTEGRATEDCIRCUITS ,Electronic engineering ,Waveform ,Electrical and Electronic Engineering ,business ,computer ,ComputingMethodologies_COMPUTERGRAPHICS ,Voltage - Abstract
This paper introduces a new methodology of flicker analysis by using root-mean-square (rms) voltage values. The main objective is to simplify flicker assessment in a large-scale grid and propose adequate methods in order to carry out flicker analysis with general power system software. The basis of this paper is that the common flicker frequency of industrial loads is lower than 25 Hz; this makes it possible to use rms values instead of waveform samples to perform flicker computation. The researches are focused on the following three key points in flicker analysis: (1) fast voltage change-dependent distribution load model used for flicker propagation study, (2) IEC 61000-4-15 flicker meter emulators, and (3) simplified dynamic flicker load models. The studied load models and flicker meter emulators have been integrated in power-quality simulation software with the electromechanical transient analysis module. Field measurements have been used to verify and support the proposed methodology. Different case studies show that this approach gives satisfied results in flicker assessment and flicker mitigation. It is also used by utilities to perform flicker assessment prior to the connection of a disturbance load. more...
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- 2009
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47. Use of Recombinant Activated Factor VII Concentrate to Control Postoperative Hemorrhage in Complex Cardiovascular Surgery
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Lyndsey J. Bowman, John S. Ikonomidis, Martha R. Stroud, John M. Toole, Arthur J. Crumbley, Lydia R. Christiansen, John M. Kratz, Walter E. Uber, Fred A. Crawford, and John Lazarchick
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Adult ,Male ,Reoperation ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Heart Diseases ,Aortic Diseases ,Factor VIIa ,Postoperative Hemorrhage ,Cohort Studies ,chemistry.chemical_compound ,Refractory ,Risk Factors ,Blood product ,Edema ,medicine ,Coagulopathy ,Humans ,Hospital Mortality ,Aged ,Retrospective Studies ,Dose-Response Relationship, Drug ,Factor VII ,business.industry ,Thrombosis ,Pneumonia ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Surgery ,Intensive Care Units ,chemistry ,Anesthesia ,Cohort ,Heart Transplantation ,Female ,Blood Coagulation Tests ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Complex cardiovascular surgery often results in postoperative hemorrhage. Excessive blood product use may cause systemic thrombosis, end-organ dysfunction, and edema preventing chest closure. Recombinant activated factor VII (rFVIIa) concentrate may decrease hemorrhage where other treatment measures failed. We reviewed our experience with rFVIIa after complex cardiovascular surgery.A retrospective review evaluating 846 complex cardiovascular surgery patients of whom 36 received rFVIIa between January 1, 2001, and December 31, 2006, was performed. Efficacy and safety data were collected for the entire cohort in addition to delayed sternal closure requirements, reoperation, and operative mortality in the patient cohort temporally separated into two groups (pre-rFVIIa era, 2001 to 2003, 1 patient received rFVIIa; rFVIIa era, 2004 to 2006, 35 patients received rFVIIa).A total of 36 patients received 41 rFVIIa doses with an in-hospital survival of 91.7%. Hemorrhage was controlled in 83.3% of patients, with 1 dose sufficient in 75.0%. There was a significant decrease (p0.005) in all blood product requirements post-rFVIIa compared with pre-rFVIIa administration. In the intensive care unit (n = 6), rFVIIa significantly reduced chest tube output (p = 0.028) and prevented reexploration for bleeding in 5 patients. The requirement for delayed sternal closure was significantly higher in the pre-rFVIIa era versus the rFVIIa era (p = 0.011). The incidence of thrombosis in all patients receiving rFVIIa was 11.1%. In the rFVIIa era, a higher incidence of postoperative renal failure (p = 0.005) and pneumonia (p0.002) was detected in patients receiving rFVIIa.Recombinant activated factor VII appears to be effective in patients with refractory coagulopathy undergoing high-risk cardiovascular surgery. more...
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- 2008
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48. Rosmarinic Acid--Pharmaceutical and Clinical Aspects
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Jadel M. Kratz, Solomon K.S. Amoah, Maique W. Biavatti, and Louis P. Sandjo
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0301 basic medicine ,Pharmacology ,Web of science ,business.industry ,Rosmarinic acid ,Organic Chemistry ,Pharmaceutical Science ,Computational biology ,Depsides ,Analytical Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Complementary and alternative medicine ,Biochemistry ,chemistry ,Cinnamates ,Drug Discovery ,Molecular Medicine ,Medicine ,Animals ,Humans ,business - Abstract
The biosynthesis and biotechnological production of Rosmarinic acid, a phenolic ester that is widespread in the plant kingdom, has been widely investigated. This compound has shown many remarkable biological and pharmacological activities, which have led to its pharmaceutical and analytical development, as well as clinical studies, which are summarized and analyzed here for the first time. This review compiles data from the Pubmed, Scopus, Scifinder, Web Of Science, and Science Direct databases published between 1990 and 2015, restricting the search to works with the keywords “Rosmarinic acid” in the title. The initial search identified more than 800 articles; after an initial screening and removal of duplicate works, the search was further refined, resulting in approximately 300 articles that were scrutinized and comprise this review. The articles were organized to describe extraction and isolation, analytical methods, pharmaceutical development, and biological and pharmacological activities [divided into nonclinical (in vitro, in vivo) and clinical studies], pharmacokinetic studies, and stability studies. more...
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- 2016
49. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide
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Vitor Clasen Chaves, Silvana A. Barea, Letícia Scherer Koester, Ariadne Cristiane Cabral da Cruz, Rafael Nicolay Pereira, Cláudia Maria Oliveira Simões, Cristiane Bastos de Mattos, and Jadel M. Kratz
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Chemistry, Pharmaceutical ,Pharmaceutical Science ,Infrared spectroscopy ,02 engineering and technology ,Polyethylene glycol ,030226 pharmacology & pharmacy ,Permeability ,03 medical and health sciences ,chemistry.chemical_compound ,Crystallinity ,0302 clinical medicine ,X-Ray Diffraction ,Drug Discovery ,medicine ,Solubility ,Dissolution ,Pharmacology ,Drug Carriers ,Chromatography ,Polyvinylpyrrolidone ,Organic Chemistry ,Membranes, Artificial ,021001 nanoscience & nanotechnology ,Thalidomide ,Solvent ,chemistry ,Polymorphism (materials science) ,0210 nano-technology ,Nuclear chemistry ,medicine.drug - Abstract
Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2–3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported. more...
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- 2016
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50. In vitro antiviral activity of antimicrobial peptides against herpes simplex virus 1, adenovirus, and rotavirus
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Margherita Anna Barracco, Cláudia Maria Oliveira Simões, Evelyne Bachère, Márcia Cristina Carriel-Gomes, Célia Regina Monte Barardi, and Jadel M. Kratz
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Microbiology (medical) ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Antimicrobial peptides ,Drug Evaluation, Preclinical ,lcsh:QR1-502 ,Peptide ,Herpesvirus 1, Human ,Biology ,Virus Replication ,medicine.disease_cause ,Antiviral Agents ,lcsh:Microbiology ,Adenoviridae ,Cell Line ,Microbiology ,Structure-Activity Relationship ,antimicrobial peptides ,herpesvirus ,Rotavirus ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Cytotoxicity ,chemistry.chemical_classification ,adenovirus ,Antimicrobial ,Virology ,In vitro ,Herpes simplex virus ,rotavirus ,chemistry ,antiviral activity ,Antimicrobial Cationic Peptides - Abstract
Peptides with broad-spectrum antimicrobial activity, known as antimicrobial peptides, have been isolated from distinct organisms. This paper describes the in vitro evaluation of the cytotoxicity and antiviral activity of nine peptides with different structures and origins against herpes simplex virus type 1, human adenovirus respiratory strain, and rotavirus SA11. Most of the evaluated peptides presented antiviral activity but they were only active near cytotoxic concentrations. Nevertheless, these results seem promising, and further modifications on the peptide's structures may improve their selectivity and reduce their cytotoxicity. more...
- Published
- 2007
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