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Author

Jorge Rodríguez

Other affiliations: Metropolitan University
Bio: Jorge Rodríguez is an academic researcher from University of Chile. The author has contributed to research in topics: Trypanosoma cruzi & Xenodiagnosis. The author has an hindex of 18, co-authored 66 publications receiving 929 citations. Previous affiliations of Jorge Rodríguez include Metropolitan University.


Papers
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Journal ArticleDOI
TL;DR: The data strongly suggest that trypanocidal action of the complexes could mainly rely on the inhibition of the parasite-specific enzyme NADH-fumarate reductase.
Abstract: In the search for new therapeutic tools against Chagas disease (American trypanosomiasis) palladium and platinum complexes of the bioactive ligand pyridine-2-thiol N-oxide were exhaustively characterized and evaluated in vitro. Both complexes showed high in vitro growth inhibition activity (IC(50) values in the nanomolar range) against Trypanosoma cruzi, the causative agent of the disease. They were 39-115 times more active than the antitrypanosomal drug Nifurtimox. The palladium complex showed an approximately threefold enhancement of the activity compared with the parent compound. In addition, owing to their low unspecific cytotoxicity on mammalian cells, the complexes showed a highly selective antiparasite activity. To get an insight into the mechanism of action of these compounds, DNA, redox metabolism (intraparasite free-radical production) and two parasite-specific enzymes absent in the host, namely, trypanothione reductase and NADH-fumarate reductase, were evaluated as potential parasite targets. Additionally, the effect of metal coordination on the free radical scavenger capacity previously reported for the free ligand was studied. All the data strongly suggest that trypanocidal action of the complexes could mainly rely on the inhibition of the parasite-specific enzyme NADH-fumarate reductase.

57 citations

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TL;DR: The free radical-scavenging activities and k(2) values discriminate well between hydroxynaphthalenones and dihydroxyanthracenones, showing that the latter have better antioxidant properties.

51 citations

Journal ArticleDOI
TL;DR: Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.
Abstract: Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2-14 yr) who received decreasing steroid doses stopping at day 7 post-Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid-based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student's t-test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid-based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid-based group. Patient and graft survival was 98% in both groups at one-yr post-transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.

48 citations

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TL;DR: Electrochemical studies, parasite respiration studies and ESR experiment showed that 5-nitroindazole derivatives not be able to yield a redox cycling with molecular oxygen such as occurs with nifurtimox (Nfx).

39 citations

Journal ArticleDOI
TL;DR: The electrochemical studies showed that the trypanocidal 5-nitroindazole derivatives yielded nitro-anion radical via one-electron process at physiological pH in the parasite according to ESR experiment with the T. cruzi microsomal fraction showing that 5-Nitroindrazole derivatives suffer bio-reduction without reactive oxygen species generation.

39 citations


Cited by
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Journal ArticleDOI
TL;DR: Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation and can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
Abstract: Rationale: Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways.Objectives: We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery.Methods: In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 ± 11.4% predicted) inhaled technetium-99m–labeled monodisperse albuterol aerosols (30-μg dose) of 1.5-, 3-, and 6-μm mass median aerodynamic diameter, at slow (30–60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar γ-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-μg dose) and 200 μg metered-dose inhaler (MDI) albuterol.Results: Smaller particles achieved greater total lung deposition (1.5 μm [56%], 3 μm [50%], and 6 μm [46%]), farther d...

503 citations

Journal ArticleDOI
TL;DR: This review highlights various hypoxia-targeted and activated design strategies for the formulation of drugs or prodrugs and their mechanism of action for tumour diagnosis and treatment.
Abstract: Hypoxia is a state of low oxygen tension found in numerous solid tumours. It is typically associated with abnormal vasculature, which results in a reduced supply of oxygen and nutrients, as well as impaired delivery of drugs. The hypoxic nature of tumours often leads to the development of localized heterogeneous environments characterized by variable oxygen concentrations, relatively low pH, and increased levels of reactive oxygen species (ROS). The hypoxic heterogeneity promotes tumour invasiveness, metastasis, angiogenesis, and an increase in multidrug-resistant proteins. These factors decrease the therapeutic efficacy of anticancer drugs and can provide a barrier to advancing drug leads beyond the early stages of preclinical development. This review highlights various hypoxia-targeted and activated design strategies for the formulation of drugs or prodrugs and their mechanism of action for tumour diagnosis and treatment.

294 citations

Journal ArticleDOI
TL;DR: The current Perspective covers various aspects of agents that contain nitro groups, their bioreductive activation mechanisms, their toxicities, and approaches to combat their toxicity issues.
Abstract: The nitro group is considered to be a versatile and unique functional group in medicinal chemistry. Despite a long history of use in therapeutics, the nitro group has toxicity issues and is often categorized as a structural alert or a toxicophore, and evidence related to drugs containing nitro groups is rather contradictory. In general, drugs containing nitro groups have been extensively associated with mutagenicity and genotoxicity. In this context, efforts toward the structure–mutagenicity or structure–genotoxicity relationships have been undertaken. The current Perspective covers various aspects of agents that contain nitro groups, their bioreductive activation mechanisms, their toxicities, and approaches to combat their toxicity issues. In addition, recent advances in the field of anticancer, antitubercular and antiparasitic agents containing nitro groups, along with a patent survey on hypoxia-activated prodrugs containing nitro groups, are also covered.

285 citations

Journal ArticleDOI
01 Mar 1937
TL;DR: Metacyclic trypomastigotes (hemoflagellates) are intermittently found in the peripheral blood and are the stage that transmits the infection to vectors or blood recipients.
Abstract: • Protozoan, 16-20 mm (trypomastigotes) 1.5 ¥ 4.0 mm (amastigotes) • Order: Kinetoplastida • Family: Trypanosomatidae • Metacyclic trypomastigotes and amastigote life-cycle stages found in human hosts. Metacyclic trypomastigotes (hemoflagellates) are intermittently found in the peripheral blood and are the stage that transmits the infection to vectors or blood recipients. Amastigotes are intracellular, tissue-dwelling forms, often associated with cardiac tissue.

280 citations