Person: Zaruma Torres, Fausto Leonardo
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1969-09-19
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0000-0003-1229-8257
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56826115800
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Universidad de Cuenca, Facultad de Ciencias Químicas, Cuenca, Ecuador
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Ecuador
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Zaruma Torres
First Name
Fausto Leonardo
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Publication Association of ABCB1, ABCC5 and xanthine oxidase genetic polymorphisms with methotrexate adverse reactions in Mexican pediatric patients with ALL(2015) Zaruma Torres, Fausto Leonardo; Lares Asseff, Ismael; Reyes Espinoza, Aarón; Loera Castañeda, Verónica; Chairez Hernández, Isaías; Sosa Macías, Martha; Galaviz Hernández, Carlos; Almanza Reyes, HoracioBackground: Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase (XO) polymorphisms, 1936A>G and 2107A>G, as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, ABCB1 and ABCC5, of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. Methods: A total of 35 Mexican children from Centro Estatal de Cancerología-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. Results: The ABCB11936A>G and 2107A>G and ABCC5 3414+434A>C polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of ABCB1 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p[removed]C (OR 0.12, 95% CI: 0.027-0.58, p[removed]T of ABCB1 and ABCC5 3933+313T>C are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population. © 2015 by De Gruyter 2015.Publication Corrigendum to: “venomics of the poorly studied hognosed pitvipers porthidium arcosae and porthidium volcanicum”(2019) Ruiz Campos, Marco; Sanz, Libia; Bonilla Murillo, Fabián; Mahmood M., Sasa; Lomonte Vigliotti, Bruno; Zaruma Torres, Fausto Leonardo; Teran Zavala, Maria Del carmen; Fernandez Ulate, Julian; Calvete Chornet, Juan José; Caldeira, Cleópatra Alves da Silva; Da Silva, Saulo LuisWe report the first proteomics analyses of the venoms of two poorly studied snakes, the Manabi hognosed pitviper Porthidium arcosae endemic to the western coastal province of Manabí (Ecuador), and the Costa Rican hognosed pitviper P. volcanicum with distribution restricted to South Pacific Costa Rica and western Panamá. These venom proteomes share a conserved compositional pattern reported in four other congeneric species within the clade of South American Porthidium species, P. nasutum, P. lansbergii, P. ophryomegas, and P. porrasi. The paraspecific immunorecognition profile of antivenoms produced in Costa Rica (ICP polyvalent), Perú (Instituto Nacional de Salud) and Brazil (soro antibotrópico pentavalente, SAB, from Instituto Butantan) against the venom of P. arcosae was investigated through a third-generation antivenomics approach. The maximal venom-binding capacities of the investigated antivenoms were 97.1 mg, 21.8 mg, and 25.7 mg of P. arcosae venom proteins per gram of SAB, ICP, and INS-PERU antibody molecules, respectively, which translate into 28.4 mg, 13.1 mg, and 15.2 mg of total venom proteins bound per vial of SAB, ICP, and INS-PERU AV. The antivenomics results suggest that 21.8%, 7.8% and 6.1% of the SAB, ICP, and INS-PERU antibody molecules recognized P. arcosae venom toxins. The SAB antivenom neutralized P. arcosae venom's lethality in mice with an ED50 of 31.3 mgV/g SAB AV. This preclinical neutralization paraspecificity points to Brazilian SAB as a promising candidate for the treatment of envenomings by Ecuadorian P. arcosae. BIOLOGICAL SIGNIFICANCE: Assessing the preclinical efficacy profile of antivenoms against homologous and heterologous medically relevant snake venoms represents an important goal towards defining the biogeographic range of their clinical utility. This is particularly relevant in regions, such as Mesoamerica, where a small number of pharmaceutical companies produce antivenoms against the venoms of a small number of species of maximum medical relevance among the local rich herpetofauna, leaving a wide range of snakes of secondary medical relevance, but also causing life-threatening human envenomings without nominal clinical coverage. This work is part of a larger project aiming at mapping the immunological characteristics of antivenoms generated in Latin American countries towards venoms of such poorly studied snakes of the local and neighboring countries' herpetofauna. Here we report the proteomics characterization of the Manabi hognosed pitviper Porthidium arcosae endemic to the western coastal province of Manabí (Ecuador), and the Costa Rican hognosed pitviper P. volcanicum with distribution restricted to southwestern Costa Rica, the antivenomics assessment of three bothropoid commercial antivenoms produced in Costa Rica, Perú, and Brazil against the venom components of P. arcosae, and the in vivo capacity of the Brazilian soro antibotrópico pentavalente (SAB) from Instituto Butantan to neutralize the murine lethality of P. arcosae venom. The preclinical paraspecific ED50 of 31.3 mg of P. arcosae venom per gram of antivenom points to Brazilian SAB as a promising candidate for the treatment of envenomings by the Manabi hognosed pitviper P. arcosae.Publication Assessing the stability of historical and desiccated snake venoms from a medically important ecuadorian collection(2020) De Almeida, José Rafael; Mendes, Bruno; Palma Patiño, Ricardo Sebastian; Pico Zerna, Jose Manuel; Laines Aguilar, Johanna Rosaly; Teran Zavala, Maria Del carmen; Salazar Mogollón, Noroska Gabriela; Zaruma Torres, Fausto Leonardo; Da Silva, Saulo Luis; Alves da Silva Caldeira, CleópatraBothrops asper and Bothrops atrox are important venomous snakes from Ecuador responsible for the most of ophidic accidents, which in the past were treated with a national polyvant antivenom. For years, the venom pools were collected and stored at room temperature in a laboratory. Taking into account the controversial ability of desiccated samples to retain their biological effects and enzymatic activities, we investigated the biochemical and toxicological properties of venoms after years of storage. The proteomic profiles of historical venoms analyzed by high-performance liquid chromatography and electrophoresis are very similar. The fresh batches of venom were more lethal than those stored for years, just as the initial and current LD50 values of these samples changed. Significant differences were showed in the myotoxic and hemorrhagic activity of some venom pools, while no significant statistical differences were found for the edema activity. The enzymatic assays revealed a variation in proteolytic activity on azocasein and phospholipase A2 activity, and low differences were reported for thrombin-like serine protease activity. The maintenance of the proteomic profile and certain toxicological activities convert this venom library in a valuable source for research purposes. Nonetheless, the significative reduction of toxicological activities, such as hemorrhagic activity not feasible using these samples for the antivenom production.Publication Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children(2016) Zaruma Torres, Fausto LeonardoAcute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL18A1 (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, CI 95% 1.11–5.83, p = 0.0001) and TT genotype (OR = 21.05, CI 95% 5.62–78.87, p < 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, CI 95% 10.42–191.63, p = 0.0001); in ABCB1 rs1045642 TT carriers (OR = 13.76, CI 95% 5.94–31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, CI 95% 1.05–6.48, p < 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, CI 95% 3.19–31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children.Publication Viperidae snakebites in Ecuador: a review of epidemiological and ecological aspects(2020) Arias Peláez, María Cristina; Da Silva, Saulo Luis; Celorio Carvajal, Cristopher Andrew; Zaruma Torres, Fausto Leonardo; Soares, Andreimar M.; Alves da Silva Caldeira, Cleópatra; Ochoa Avilés, Angélica María; Heredia Andino, Odalys Stefania; Escandón Dután, Samuel AdriánSnakebite envenoming is a neglected disease of public health concern. Most snakebite accidents occur in developing countries. In Ecuador, 17 viper species are responsible for 99% of official accidents, and ten species are in critical conservation states. This report analyzes the snakebite incident cases and mortality rates in Ecuador between 2014 and 2019. The data obtained from the national surveillance system suggests that the incidence and mortality rates remained constant. The geographic region with the highest incidence rates is the Amazonian region. National policies are urgently needed to prevent snakebite accidents and to protect snakes in danger of extinction.Publication Impacto de polimorfismos genéticos de la vía metabólica del metotrexato sobre la sobrevida de niños mexicanos con leucemia linfoblástica aguda (LLA)(2015) ; Zaruma Torres, Fausto LeonardoAcute lymphoblastic leukemia (ALL) is a major cancer disease in Mexican pediatric population, were the genotype could affect the effectiveness of chemotherapy in which the methotrexate (MTX) is involved and consequently the time of disease free survival and overall survival. Objective: Determine the association of 10 genetic polymorphisms of the folate pathway: in cellular carriers (CO-L18A1, SLC19A1, ABCB1 and ABCC5) and in enzymes such as folylpolyglutamate synthetase (FPGS) and xanthine oxidase (XO), with survival of children with acute lymphoblastic leukemia. Methods: Thirty-nine children with acute lymphoblastic leukemia from the State Cancer Center in Durango (Mexico) treated with MTX and 102 healthy controls, were qPCR analyzed for 10 polymorphisms in the folate pathway. During 5 years of follow up, the disease-free survival and overall survival rates were investiga-ted in relation with their genotypes. Results: Four polymorphisms were not found in Hardy-Weinberg Equilibrium COL18A1 (rs2274808), ABCC5 (rs9838667 and rs3792585) and XO (rs1701136 85). Only XO (rs170113685) was associated with risk of being present in patients with ALL whose odds ratio was 9.771 (95% 4.974-19.196, p=0.001). The polymorphism rs1544105 for FPGS affected disease free survival and overall survival (Log Rank test p<0.05). Conclusion: Polymorphism (rs17011368)of XO showed risk association for acute lymphoblastic leukemia; likewise, an important association was found between carriers of the FPGS (rs154 4105) and increased survival times of patients treated with methotrexate.Publication Acute oral toxicity of a novel functional drink based on Ilex guayusa, Vernonanthura patens, and cocoa husk(2021) Iñiga Alvarado, Elsy Catalina; Sarmiento Tomalá, Glenda Marcela; Orellana Manzano, Andrea Katherine; Paladines Santacruz, Geovanna Lissette; Pilozo Muentes, Glenda Margarita; Berghe, Wim Vanden; Manzano Santana, Patricia Isabel; Villacres Cevallos, María del Carmen; Orellana Manzano, Silvia Gabriela; DI GRUMO, DAVIDE; Quijano Aviles, Maria Fernanda; Ortiz Ulloa, Silvia Johana; ; Zaruma Torres, Fausto LeonardoA novel functional drink with nutraceutical properties was formulated from the aqueous extracts of Ilex guayusa, and Vernonanthura patens leaves, and cocoa husks. This juice contains various bioactive compounds, such as phenolic compounds and methylxanthines, with antioxidant and stimulant properties of pharmacological interest. However, it is known whether herbal extracts' interaction may have adverse toxic effects on human health. To evaluate this functional drink's innocuity, we estimated the acute oral toxicity (AOT) in experimental mice. This paper presents the AOT evaluation of two formulations of a functional drink (pre-formulation and microencapsulation) at a single dose of 2000 mg/kg of body weight (b.w.). No signs of adverse toxicity and mortality were observed after a single oral dose of 2000 mg/kg b.w. Likewise, no significant body and organ weight changes, food and water consumption behavior, and no histopathological changes were observed in the main organs evaluated. In conclusion, this functional drink can be categorized as low toxicity " according to the Globally Harmonized Classification System (GHS), making it a potential beverage with high nutritional and pharmacological value.