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The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re-N-acetylated, a chemically modified heparin (mHep).In vitro assays (cell tube formation, viability, proliferation, and migration) with endothelial cells were performed after 24 h of treatment with mHep at 10, 100, and 1000 ng/mL or saline. In vivo tests were performed after laser-induced choroidal neovascularization (CNV) in rats, followed by an intravitreal injection (5 µL) of mHep (10, 100, 1000 ng/mL) or balanced salt solution. Immunofluorescence analysis of the CNV was performed after 14 days.mHep produced a statistically significant reduction in cell proliferation, tube formation, and migration, without cell viability changes when compared to saline. Mean measures of CNV area were 54.84 × 10These results suggest that mHep N-DRN is a potent anti-angiogenic, anti-proliferative, and anti-migratory compound with negligible anticoagulant or hemorrhagic action and no cytotoxicity for retina cells. This compound may serve as a candidate for treating choroidal neovascularization.

Made available in DSpace on 2022-04-29T08:38:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-23 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Background: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. Methods and analysis: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load). Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8. Department of Surgery and Orthopedics São Paulo State University – UNESP Botucatu Medical School, SP Applied Biotechnology Laboratory Research Nucleus of Clinical Hospital São Paulo State University – UNESP Botucatu Medical School, SP Department of Bioprocess and Biotechnology São Paulo State University – UNESP School of Pharmaceutical Sciences, SP Internal Medicine Division São Paulo State University – UNESP Botucatu Medical School, SP Department of Microbiology Institute of Biomedical Sciences University of São Paulo – USP, SP Scientific Platform Pasteur University of São Paulo – USP, SP Bioprocessing and Biotechnology Department São Paulo State University – UNESP School of Agriculture, SP Molecular & Structural Biosciences School of Life Sciences Keele University, Newcastle-Under-Lyme Department of Biochemistry Federal University of São Paulo – UNIFESP, SP Institute of Science and Technology Federal University of São Paulo – UNIFESP, SP Department of Infectious Diseases São Paulo State University – UNESP Botucatu Medical School, SP Clinical Research Unit São Paulo State University – UNESP Botucatu Medical School, SP Biosciences Institute São Paulo State University UNESP, SP Quality Control Laboratory Cellavita Scientific Research, SP Department of Orthopedics and Traumatology University of Campinas – UNICAMP School of Medical Sciences, SP Department of Surgery and Orthopedics São Paulo State University – UNESP Botucatu Medical School, SP Applied Biotechnology Laboratory Research Nucleus of Clinical Hospital São Paulo State University – UNESP Botucatu Medical School, SP Department of Bioprocess and Biotechnology São Paulo State University – UNESP School of Pharmaceutical Sciences, SP Internal Medicine Division São Paulo State University – UNESP Botucatu Medical School, SP Bioprocessing and Biotechnology Department São Paulo State University – UNESP School of Agriculture, SP Department of Infectious Diseases São Paulo State University – UNESP Botucatu Medical School, SP Clinical Research Unit São Paulo State University – UNESP Botucatu Medical School, SP Biosciences Institute São Paulo State University UNESP, SP FAPESP: 2020/12165-8

Quinolones and fluoroquinolones are widely used to treat uropathogenic Escherichia coli infections. Bacterial resistance to these antimicrobials primarily involves mutations in gyrA and parC genes. To date, no studies have examined the potential relationship between biochemical characteristics and quinolone resistance in uropathogenic E. coli strains. The present work analyzed the quinolone sensitivity and biochemical activities of fifty-eight lactose-negative uropathogenic E. coli strains. A high percentage of the isolates (48.3%) was found to be resistant to at least one of the tested quinolones, and DNA sequencing revealed quinolone resistant determining region gyrA and parC mutations in the multi-resistant isolates. Statistical analyses suggested that the lack of ornithine decarboxylase (ODC) activity is correlated with quinolone resistance. Despite the low number of isolates examined, this is the first study correlating these characteristics in lactose-negative E. coli isolates.