Publications by authors named "Ronald Sánchez"

14 Publications

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Development and characterization of two equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19.

Sci Rep 2021 05 10;11(1):9825. Epub 2021 May 10.

Facultad de Microbiología, Instituto Clodomiro Picado, Universidad de Costa Rica, San José, Costa Rica.

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
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http://dx.doi.org/10.1038/s41598-021-89242-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110969PMC
May 2021

A Nonsense N -Terminus NFKB2 Mutation Leading to Haploinsufficiency in a Patient with a Predominantly Antibody Deficiency.

J Clin Immunol 2020 11 19;40(8):1093-1101. Epub 2020 Aug 19.

Immunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Building 10, Room 2C306, 10 Center Drive, MSC1508, Bethesda, MD, USA.

The noncanonical NF-κB pathway is implicated in diverse biological and immunological processes. Monoallelic C-terminus loss-of-function and gain-of-function mutations of NFKB2 have been recently identified as a cause of immunodeficiency manifesting with common variable immunodeficiency (CVID) or combined immunodeficiency (CID) phenotypes. Herein we report a family carrying a heterozygous nonsense mutation in NFKB2 (c.809G > A, p.W270*). This variant is associated with increased mRNA decay and no mutant NFKB2 protein expression, leading to NFKB2 haploinsufficiency. Our findings demonstrate that bona fide NFKB2 haploinsufficiency, likely caused by mutant mRNA decay and protein instability leading to the transcription and expression of only the wild-type allele, is associated with clinical immunodeficiency, although with incomplete clinical penetrance. Abnormal B cell development, hypogammaglobulinemia, poor antibody response, and abnormal noncanonical (but normal canonical) NF-κB pathway signaling are the immunologic hallmarks of this disease. This adds a third allelic variant to the pathophysiology of NFKB2-mediated immunodeficiency disorders.
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http://dx.doi.org/10.1007/s10875-020-00842-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567683PMC
November 2020

New molecular target for the phylogenetic identification of Leptospira species directly from clinical samples: an alternative gene to 16S rRNA.

Rev Soc Bras Med Trop 2020 16;53:e20190333. Epub 2020 Mar 16.

Basic Science Research Group, Graduates School - CES University. Medellín, Antioquia, Colombia.

Introduction: Phylogenetic analysis of the 16S ribosomal gene initial region is used to identify Leptospira isolates at the species level from clinical samples. Unfortunately, this method cannot differentiate between some intermediates and saprophytic species.

Methods: We used comparative genomic analysis between 35 Leptospira species to find new molecular targets for Leptospira species identification.

Results: We proposed the use of the rpoC gene, encoding the DNA-directed RNA polymerase β-subunit, for identifying 35 Leptospira species.

Conclusions: The rpoC gene can be a molecular target to identify the main species of the Leptospira genus directly from clinical samples.
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http://dx.doi.org/10.1590/0037-8682-0333-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094048PMC
April 2020

Feasibility and Outcomes of an Electronic Health Record Intervention to Improve Hypertension Management in Immigrant-serving Primary Care Practices.

Med Care 2019 06;57 Suppl 6 Suppl 2:S164-S171

Department of Population Health, NYU School of Medicine.

Background: South Asians experience a disproportionate burden of high blood pressure (BP) in the United States, arguably the most preventable risk factor for cardiovascular disease.

Objective: We report 12-month results of an electronic health record (EHR)-based intervention, as a component of a larger project, "Implementing Million Hearts for Provider and Community Transformation." The EHR intervention included launching hypertension patient registries and implementing culturally tailored alerts and order sets to improve hypertension control among patients treated in 14 New York City practices located in predominantly South Asian immigrant neighborhoods.

Design: Using a modified stepped-wedge quasi-experimental study design, practice-level EHR data were extracted, and individual-level data were obtained on a subset of patients insured by a Medicaid insurer via their data warehouse. The primary aggregate outcome was change in proportion of hypertensive patients with controlled BP; individual-level outcomes included average systolic BP (SBP) and diastolic BP (DBP) at last clinic visit. Qualitative interviews were conducted to assess intervention feasibility.

Measures: Hypertension was defined as having at least 1 hypertension ICD-9/10 code. Well-controlled hypertension was defined as SBP<140 and DBP<90 mm Hg.

Results: Postintervention, we observed a significant improvement in hypertension control at the practice level, adjusting for age and sex patient composition (adjusted relative risk, 1.09; 95% confidence interval, 1.04-1.14). Among the subset of Medicaid patients, we observed a significant reduction in average SBP and DBP adjusting for time, age, and sex, by 1.71 and 1.13 mm Hg, respectively (P<0.05). Providers reported feeling supported and satisfied with EHR components.

Conclusions: EHR initiatives in practices serving immigrants and minorities may enhance practice capabilities to improve hypertension control.
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http://dx.doi.org/10.1097/MLR.0000000000000994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527132PMC
June 2019

Intestinal Life Cycle of Eimeria caliginosa (Apicomplexa: Eimeriidae) From the Dusky Rice Rat, Melanomys caliginosus (Rodentia: Cricetidae: Sigmodontinae), In Costa Rica.

J Parasitol 2018 08 8;104(4):347-352. Epub 2018 May 8.

3   Department of Biology, University of New Mexico, Albuquerque, New Mexico 87131.

The endogenous life cycle of Eimeria caliginosa was studied in experimentally infected dusky rice rats, Melanomys caliginosus. All endogenous stages were located in the epithelial cells of villi in the small intestine. Both Giemsa-stained mucosal scrapings and histological sections were studied for the diagnosis of all the life-cycle stages. Eimeria caliginosa has 3 generations of meronts (M) that differ by size, shape, and number of merozoites (m), which also differ in their size, shape, and location of their nuclei within the cytoplasm of the meronts. The 3 meront types, M-M, respectively, had 20-33 (m), 5-9 (m), and 13-16 (m) merozoites. Macrogametocytes and microgametocytes, as well as macrogametes and microgametes, completed the sexual cycle, which concludes with the formation of unsporulated oocysts. This parasite's endogenous development produced severe intestinal lesions in the experimentally infected dusky rice rats. In our ongoing work to understand the biodiversity present in plants and animals of the protected Reserva Biológica Alberto Manuel Brenes (ReBAMB) field station in Costa Rica, we now have discovered 3 new Eimeria species, and this is the second complete life cycle in which we document both the asexual and sexual stages.
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http://dx.doi.org/10.1645/17-153DOI Listing
August 2018

Endogenous Life Cycle of Eimeria melanomytis (Apicomplexa: Eimeriidae) from the Dusky Rice Rat, Melanomys caliginosus (Rodentia: Cricetidae: Sigmodontinae) in Costa Rica.

J Parasitol 2017 02 27;103(1):56-62. Epub 2016 Oct 27.

Research Department, Universidad de Ciencias Médicas (UCIMED), San José, Costa Rica, del MAG 400 metros al Oeste carretera a Escazú, Código postal 638-1007 Centro Colón.

Endogenous stages of the life cycle of Eimeria melanomytis, infecting the peripheral epithelial cells of villi of the small intestine of experimentally infected young dusky rice rats, Melanomys caliginosus , were studied. Giemsa-stained mucosal scrapings and histological sections were examined for all the stages. Eimeria melanomytis has 3 generations of meronts (M), different in size, shape, and number of merozoites (m); and in size, shape, and location of the nuclei within the cytoplasm of the meronts. The 3 meront types, M-M, respectively, had 11-14 (m), 7-10 (m), and 20-30 (m) merozoites. Macrogametocytes and microgametocytes, as well as macrogametes and microgametes, complete the sexual cycle forming the unsporulated oocysts. This parasite's endogenous development produced severe intestinal lesions in experimentally infected dusky rice rats.
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http://dx.doi.org/10.1645/16-98DOI Listing
February 2017

Autologous Plasma Rich in Growth Factors Eyedrops in Refractory Cases of Ocular Surface Disorders.

Ophthalmic Res 2015 17;55(2):53-61. Epub 2015 Nov 17.

Instituto Universitario Fernx00E1;ndez-Vega, Fundacix00F3;n de Investigacix00F3;n Oftalmolx00F3;gica, Universidad de Oviedo, Oviedo, Spain.

Purpose: Preliminary information about the safety and efficacy of plasma rich in growth factors (PRGF) eyedrops in the treatment of refractory cases of diverse ocular surface disorders (OSDs) is presented here.

Material And Methods: This retrospective cohort study included cases with OSDs refractory to previous treatment with conventional treatments or autologous serum or cyclosporine, and treated with PRGF eyedrops. The signs and symptoms of ocular surface disorders [using the ocular surface disease index (OSDI), best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency and VAS severity] were evaluated before and after treatment with PRGF. A safety assessment was also performed reporting all adverse events or complications.

Results: Forty-one patients with a total of 80 treated eyes were evaluated. Statistically significant reductions in the OSDI scale (39.27%), VAS frequency (38.9%) and VAS severity (40.3%), and a significant improvement in BCVA (54.86%) were all observed (p < 0.05). The results were stratified according to the identified potential effect modifiers. There were only two adverse events (eye redness and eyelid inflammation), which were reported as mild and resolved in a few days.

Conclusions: PRGF eyedrops could be a safe and effective treatment option for refractory cases of OSDs. When treating patients the possible influence on the results of some clinical variables must be taken into account.
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http://dx.doi.org/10.1159/000439280DOI Listing
July 2016

A new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from the dusky rice rat Melanomys caliginosus (Tomes) (Mammalia: Rodentia) in Costa Rica.

Syst Parasitol 2014 Jun 16;88(2):181-4. Epub 2014 May 16.

Research Department, Universidad de Ciencias Médicas (UCIMED), San José, Costa Rica.

We collected faecal samples from 24 dusky rice rats, Melanomys caliginosus (Tomes) (Rodentia: Cricetidae: Sigmodontinae), in a Biological Reserve in Costa Rica, and found three (12.5%) to be infected with a species of Eimeria Schneider, 1875, which we describe here as new. Sporulated oöcysts of Eimeria caliginosa n. sp. are almost spheroidal and measure 16-21 × 17-20 (mean 19.6 × 18.2) μm; micropyle, oöcyst residuum and polar granule are absent. Sporocysts are ovoidal, 9-13 × 6-8 (mean 11.2 × 6.7) μm, with small Stieda and sub-Stieda bodies present, but a para-Stieda body is absent; the sporocyst residuum is a compact mass of c.11-15 granules, c.5 μm wide. Sporozoites are crescent-shaped, 5-8 × 2-3 (mean 6.8 × 2.4) μm. This is the third species of Eimeria described from the genus Melanomys Thomas.
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http://dx.doi.org/10.1007/s11230-014-9489-0DOI Listing
June 2014

In vitro antimalarial activity of extracts of some plants from a biological reserve in Costa Rica.

Rev Biol Trop 2012 Jun;60(2):881-91

Laboratorio de Investigación Universidad de Ciencias Medicas "Dr. Andrds Vesalio Guzmin" (UCIMED), San JosC, Costa Rica, Amdrica Central.

Treatment with the usual antimalarial drugs, have induced parasite resistance, reinforcing the need to finding natural antimalarial components that would be found on plants from the forest. Therefore, we decided to look for these components in Costa Rican plants from a protected forest area. Fresh and dry extracts of roots, bark, leaves, flowers and fruits of 25 plants from a biological reserve in Costa Rica, Reserva Biol6gica Alberto Manuel Brenes (REBAMB), were studied in vitro for the presence of substances with antimalarial activity. By studying the inhibition of P berghei schizogony, we assessed the antimalarial activity of several plant extracts: Aphelandra aurantiaca, A. tridentata (Acanthaceae); Xanthosoma undipes (Araceae); Iriartea deltoidea (Arecaceae); Neurolaena lobata (Asteraceae); Senna papillosa, Pterocarpus hayessi, Lonchocarpus pentaphyllus (Fabaceae); Nectandra membranacea, Persea povedae, Cinamomum chavarrianum (Lauraceae); Hampea appendiculata (Malvaceae); Ruagea glabra, Guarea glabra (Meliaceae); Psidium guajava (Myrtaceae); Bocconia frutescens (Papaveraceae); Piper friedrichsthalii (Piperaceae); Clematis dioica (Ranunculaceae); Prunus annularis (Rosaceae); Siparuna thecaphora (Siparunaceae); Solanum arboreum, Witheringia solanacea (Solanaceae); Ticodendrum incognitum (Ticodendraceae); Heliocarpus appendiculatus (Tiliaceae) and Myriocarpa longipes (Urticaceae). We used different parts of the plants as well as fresh and dried extracts for testing IC50. The solid content of the extracts ranged from 1-71.9 microg/mL. The fresh extracts showed stronger activity than the dry ones. Since the plants showing the strongest antimalarial activity are very common in Central America, and some similar genera of these plants have shown positives results in South America, we considered important to present these findings for discussion. On the other hand, this is the first systematic study of this kind ever realized in a circumscribed and protected area of Costa Rica.
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http://dx.doi.org/10.15517/rbt.v60i2.4024DOI Listing
June 2012

Two new Eimeria spp. (Apicomplexa: Eimeriidae) from the dusky rice rat, Melanomys caliginosus, Tome 1860, in Costa Rica.

J Parasitol 2013 Feb 27;99(1):82-4. Epub 2012 Aug 27.

Research Department and Department of Medical Parasitology, Universidad de Ciencias Médicas (UCIMED), Apartado 638-1007, San José, Costa Rica, Central América.

We collected fecal samples from 9 dusky rice rats, Melanomys caliginosus (Rodentia, Cricetidae, Sigmodontinae), in a Biological Reserve in Costa Rica and found 8 (89%) to be infected with 2 Eimeria species which we describe here as new. Sporulated oocysts (n = 20) of the first, Eimeria melanomytis n. sp., are cylindroidal and measure 20.1 × 13.3 μm (18-23 × 13-15); micropyle and oocyst residuum are both absent, but a bilobular polar granule is present. Its sporocysts are ovoidal, 10.5 × 7.4 μm (10-13 × 6-8) with a small Stieda body, but both substieda and parastieda bodies are absent; a spheroidal sporocyst residuum is present, ≈ 5 μm wide. Sporulated oocysts (n = 20) of the second, Eimeria rebambensis n. sp., are subspheroidal, 21.2 × 17.0 μm (19-23 × 14-18); micropyle and oocyst residuum are both absent, but with a polar granule ≈ 2 μm wide. Sporocysts are elongate-ovoidal, 12.4 × 7.0 μm (11-14 × 6-9) with a distinct knob-like Stieda body, and a substieda body directly beneath it which is about twice as wide, but no parastieda body is present; the sporocyst residuum is an irregular mass composed of 8-10 globules scattered among the sporozoites, which are ≈ 10 × 5 μm, and have 1 refractile body at their wider end and a central nucleus. These are the first eimerians described from this rodent genus.
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http://dx.doi.org/10.1645/GE-3144.1DOI Listing
February 2013

Molecular systematics and phylogeography of Cebus capucinus (Cebidae, Primates) in Colombia and Costa Rica by means of the mitochondrial COII gene.

Am J Primatol 2012 Apr 31;74(4):366-80. Epub 2011 Mar 31.

Laboratorio de Genética de Poblaciones Molecular y Biología Evolutiva, Departamento de Biología, Pontificia Universidad Javeriana, Bogotá, DC, Colombia.

We propose the first molecular systematic hypothesis for the origin and evolution of Cebus capucinus based on an analysis of 710 base pairs (bp) of the cytochrome c oxidase subunit II (COII) mitochondrial gene in 121 C. capucinus specimens sampled in the wild. The animals came from the borders of Guatemala and Belize, Costa Rica, and eight different departments of Colombia (Antioquia, Chocó, Sucre, Bolivar, Córdoba, Magdalena, Cauca, and Valle del Cauca). Three different and significant haplotype lineages were found in Colombia living sympatrically in the same departments. They all presented high levels of gene diversity but the third Colombian gene pool was determined likely to be the most ancestral lineage. The second Colombian mitochondrial (mt) haplogroup is likely the source of origin of the unique Central America mt haplogroup that was detected. Our molecular population genetics data do not agree with the existence of two well-defined subspecies in Central America (limitaneus and imitator). This Central America mt haplogroup showed significantly less genetic diversity than the Colombian mt haplogroups. All the C. capucinus analyzed showed evidence of historical population expansions. The temporal splits among these four C. capucinus lineages were related to the completion of the Panamanian land bridge as well as to climatic changes during the Quaternary Period.
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http://dx.doi.org/10.1002/ajp.20940DOI Listing
April 2012

Prevalence of fur mites (Acari: Atopomelidae) in non-human primates of Costa Rica.

Rev Biol Trop 2009 Mar-Jun;57(1-2):353-60

Centro de Investigación en Enfermedades Tropicales, Departamento de Parasitología, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.

Parasites have been investigated for some New World primates; however, very little is known about ectoparasites and specifically fur mites. In this study, Alouatta palliata, Cebus capucinus, Saimiri oerstedii, and Ateles geoffroyi monkeys from different areas of Costa Rica were searched for fur mites. A total of 276 monkeys were evaluated, and 51 of them were positive for mites of the family Atopomelidae. Listrocarpus alouattae was identified on 22.3% of A. palliata; Listrocarpus capucinus on 12.8% of C. capucinus; and Listrocarpus costaricensis on 36.8% of S. oerstedii; No fur mites were found on A. geoffroyi. Sex was not considered a determinant of mite infestation, but prevalence was significantly higher in the Central Volcanic Mountain Range Conservation Area for L. alouattae (p=0.01) and in the Central Pacific Conservation Area for L. capucinus (p=0.002). These primate fur mites are highly host-specific. Differences in the geographical distribution may be due to monkey behavior and history, as well as to environmental conditions.
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http://dx.doi.org/10.15517/rbt.v57i1-2.11326DOI Listing
November 2009

Distribution, ecology, life history, genetic variation, and risk of extinction of nonhuman primates from Costa Rica.

Rev Biol Trop 2004 Sep;52(3):679-93

Universidad de Costa Rica, Escuela de Biología, Ciudad Universitaria Rodrigo Facio, San José, Costa Rica.

We examined the association between geographic distribution, ecological traits, life history, genetic diversity, and risk of extinction in nonhuman primate species from Costa Rica. All of the current nonhuman primate species from Costa Rica are included in the study; spider monkeys (Ateles geoffroyi), howling monkeys (Alouatta palliata), capuchins (Cebus capucinus), and squirrel monkeys (Saimiri oerstedii). Geographic distribution was characterized accessing existing databases. Data on ecology and life history traits were obtained through a literature review. Genetic diversity was characterized using isozyme electrophoresis. Risk of extinction was assessed from the literature. We found that species differed in all these traits. Using these data, we conducted a Pearson correlation between risk of extinction and ecological and life history traits, and genetic variation, for widely distributed species. We found a negative association between risk of extinction and population birth and growth rates; indicating that slower reproducing species had a greater risk of extinction. We found a positive association between genetic variation and risk of extinction; i.e., species showing higher genetic variation had a greater risk of extinction. The relevance of these traits for conservation efforts is discussed.
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http://dx.doi.org/10.15517/rbt.v1i2.15355DOI Listing
September 2004