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10 años de experiencia con el uso de tratamiento biológico en pacientes con artritis idiopática juvenil en el Hospital Nacional de Niños “Dr. Carlos Sáenz Herrera”
(2024) Chacón González, Constanza; Ivankovich Escoto, Gabriela
La artritis idiopática juvenil (AIJ) es la enfermedad reumática crónica más común en la edad pediátrica, caracterizada por inflamación articular durante más de seis semanas en menores de 16 años, y cuando no se ha logrado identificar otra causa para la artritis. Sin tratamiento, puede llevar a secuelas que comprometen la calidad de vida de los pacientes. Su abordaje se basa en disminuir la inflamación, con el fin de permitirle al paciente el mayor tiempo libre de síntomas y sin complicaciones a largo plazo. Los tratamientos biológicos se han convertido en un pilar terapéutico para esta población. En Costa Rica no existen estudios que caractericen la evolución de los pacientes con AIJ, particularmente de aquellos que han recibido terapia biológica. Este es el primer estudio donde se analizarán las características de los pacientes con diagnóstico de AIJ entre los años 2014 y 2024 que han recibido tratamiento biológico en el Hospital Nacional de Niños, Dr. Carlos Sáenz Herrera, de la Caja Costarricense del Seguro Social, con el fin de justificar el uso de este tratamiento.
12-HETE is a regulator of PGE2 production via COX-2 expression induced by a snake venom group IIA phospholipase A2 in isolated peritoneal macrophages
(2020) Moreira, Vanessa; Gutiérrez, José María; Lomonte, Bruno; Ramirez Vinolo, Marco Aurélio; Curi, Rui; Lambeau, Gérard; Teixeira, Catarina de Fátima
The snake venom myotoxin (MT)-III is a group IIA secreted phospholipase A2 (sPLA2) with pro-inflammatory activities. Previous studies have demonstrated that MT-III has the ability to stimulate macrophages to release inflammatory lipid mediators derived from arachidonic acid metabolism. Among them, we highlight prostaglandin (PG)E2 produced by the cyclooxygenase (COX)-2 pathway, through activation of nuclear factor (NF)-κB. However, the mechanisms coordinating this process are not fully understood. This study investigates the regulatory mechanisms exerted by other groups of bioactive eicosanoids derived from 12-lipoxygenase (12-LO), in particular 12-hydroxyeicosatetraenoic (12-HETE), on group IIA sPLA2-induced (i) PGE2 release, (ii) COX-2 expression, and (iii) activation of signaling pathways p38 mitogen-activated protein kinases(p38MAPK), protein C kinase (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and NF-κB. Stimulation of macrophages with group IIA sPLA2 resulted in release of 12-HETE without modification of 12-LO protein levels. Pre-treatment of these cells with baicalein, a 12-LO inhibitor, decreased the sPLA2-induced PGE2 production, significantly reduced COX-2 expression, and inhibited sPLA2-induced ERK; however, it did not affect p38MAPK or PKC phosphorylation. In turn, sPLA2-induced PGE2 release and COX-2 expression, but not NF-κB activation, was attenuated by pre-treating macrophages with PD98059 an inhibitor of ERK1/2. These results suggest that, in macrophages, group IIA sPLA2-induced PGE2 release and COX-2 protein expression are distinctly mediated through 12-HETE followed by ERK1/2 pathway activation, independently of NF-κB activation. These findings highlight an as yet undescribed mechanism by which 12-HETE regulates one of the distinct signaling pathways for snake venom group IIA sPLA2-induced PGE2 release and COX-2 expression in macrophages.
Un 4,5% de casos positivos en Pavas no descarta transmisión comunitaria
(2020-07-02) Rosero Bixby, Luis
El 4,5% de positividad significa 4.000 habitantes del distrito infectados, número que indica una catastrófica transmisión comunitaria y, lo más grave, transmisión asintomática rampante.
A biocomputational platform for the automated construction of large-scale mathematical models of miRNA-transcription factor networks for studies on gene dosage compensation
(2016-11-09) Acón, Man Sai; Siles Canales, Francisco; Mora Rodríguez, Rodrigo Antonio
Cancer complexity and resistance is mediated by cell-to-cell heterogeneity, which is the consequence of the enormous instability of its genetic material. It is unknown how cancer cells are able to withstand the effects of these alterations, while normal cells are typically very sensitive. We hypothesize that cancer requires specific type of stability to survive the enormous chromosomal alterations. This stability may be mediated by a group of genes, whose expression is tightly regulated to maintain viability through a process called gene dosage compensation. This mechanism could be mediated by systems-level properties of complex networks of microRNAs (miRNA) and transcription factors (TF), regulating gene expression despite changes in copy number. Therefore, we designed a biocomputational platform to automatically construct large-scale mathematical models regulating the expression of several candidate genes under dosage compensation. This platform has a broader potential application to other scientific questions involving miRNA and TF networks.
A brief account of the history of family planning in Costa Rica
(2009) Carranza Maxera, María
Costa Rica has been a focus of demographic attention for at least two reasons: its startling rate of natural population growth, which peaked at 3.8% during 1955 and 1960 and which was considered one of the highest in the world3; and the astounding decline in the total fertility rate, from 7.3 to 3.7 children, that took place between 1960 and 1975, and which has rarely been recorded elsewhere (Gómez, 1968: 3; Reynolds, 1973: 312; Rosero-Bixby, 1979: 4). This sharp reduction in the fertility rate, which occurred in all strata of the population, albeit with varying intensity and chronology4, has been attributed in large measure to the use of modern contraceptive methods (Rosero-Bixby, 1979:13; 1986: 70-71). Their provision by state health institutions played a fundamental role in accelerating the phenomenon and spreading it from urban and educated women (among whom it started) to rural and less educated women (Rosero-Bixby, 1986: 70-71).
A bright future for integrative venomics
(2015-10) Calvete Chornet, Juan José; Lomonte, Bruno
Venomous secretions are produced by a myriad of animal species, from invertebrates to vertebrates. As a general rule, peptides and proteins represent the most abundant and functionally relevant components of these dangerous “cocktails”. It may be argued that the first and indispensable requirement to understand a particular venom is to know its composition, and, to this end, the combination of -omics technologies have emerged as the most powerful tools available to date
A Call for Incorporating Social Research in the Global Struggle against Snakebite
(2015-09-17) Gutiérrez, José María; Burnouf, Thierry; Harrison, Robert A.; Calvete Chornet, Juan José; Brown, Nicholas I.; Jensen, Simon D.; Warrell, David A.; Williams, David J.
In Africa, Asia, Latin America, and parts of Oceania, envenoming after snakebite is a serious public health problem. Conservative data suggest that between 1.2 and 5.5 million people suffer snakebites every year, resulting in 25,000 to 125,000 deaths and leaving approximately 400,000 victims with permanent sequelae. Despite its significant impact on human health, this disease remains largely neglected by national and international health authorities, funding agencies, pharmaceutical companies, patients’ organizations, and health advocacy groups
A case-control study of breast cancer and hormonal contraception in Costa Rica
(1987) Rosero Bixby, Luis; Grimaldo Vásquez, Carmen; Rovira, Elizabeth; Lee, Nancy C.; Oberle, Mark W.; Watley, Anne S.
By 1981, 11% of married women in Costa Rica ages 20-49 years had used depot-medroxyprogesterone acetate (DMPA) and 58% had used oral contraceptives (OCs). Since 1977, the Costa Rican Ministry of Health has maintained a nationwide cancer registry. These circumstances provided an opportunity for a population-based, case-control study of DMPA, OCs, and breast cancer in Costa Rica. Cases were 171 women ages 25-58 years with breast cancer diagnosed between 1982 and 1984; controls were 826 women randomly chosen during a nationwide household survey. Cases and controls were interviewed with the use of a standard questionnaire covering their reproductive and contraceptive histories. Logistic regression methods were used to adjust for confounding factors. While few cases or controls had ever used DMPA, DMPA users had an elevated relative risk (RR) estimate of breast cancer of 2.6 (95% confidence limits=1.4-4.7) compared with never users. However, no dose-response relationship was found; even the group of women who had used DMPA for less than 1 year had an elevated RR estimate (RR =2.3; 95% confidence limits=1.0-5.1). In contrast, OC users had no elevation in RR compared with never users (RR=1.2; 95% confidence limits= 0.8-1.8). The results of the DMPA analysis are inconclusive. Before decisions are made on whether to continue providing this effective contraceptive method, other ongoing studies will need to confirm of refute these findings.
A catalytically-inactive snake venom Lys49 phospholipase A2 homolog induces expression of cyclooxygenase-2 and production of prostaglandins through selected signaling pathways in macrophages
(2013-05-15) Moreira, Vanessa; de Castro Souto, Pollyana Cristina Maggio; Ramirez Vinolo, Marco Aurélio; Lomonte, Bruno; Gutiérrez, José María; Curi, Rui; Teixeira, Catarina de Fátima
The effects of a snakevenom Lys-49phospholipaseA2 (PLA2) homolog named MT-II,devoid of enzymatic activity, on the biosynthesis of prostaglandins and protein expression of cyclooxygenase-2(COX-2) and signaling pathways involved were evaluated in mouse macrophages in culture and in peritoneal cells ex vivo. Stimulation of macrophages wit hMT-II leads to production of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) and protein expression of COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1). Inhibition of cytosolic PLA2 (cPLA2), but not Ca2+ independent PLA2 (iPLA2) reduced release of PGD2 and PGE2 and expression of COX-2induced by MT-II. Inhibition of nuclear factor kB (NF-kB) significantly reduced MT-II-induced PGE2, but not PGD2 production and COX-2 expression. Inhibitors of either proteinkinase C (PKC), proteintyrosinekinase (PTK),or extracellular signal-regulated kinase(ERK) pathways abrogated MT-II-induced NF-kB activation and reduced COX-2 expression and PGE2 release, whereas the p38 mitogen-activated protein kinase (MAPK) inhibit or reduced MT-II-induced COX-2 expression and PGD2 production.Inhibition of phosphatidylinositol-3-kinase (PI3K) pathway abrogated MT-II-induced NF-kB activation,but affected neither prostaglandins production nor COX-2expression.MT-II-induced production of PGD2 and PGE2 and COX-2 expression were also observed in vivo after intraperitoneal injection into mice. Collectively,our data demonstrate that a catalytically-inactivePLA2 homolog is capable of inducing prostaglandins biosynthesis and COX-2expression in macrophages in both in vitro and in vivo models,indicating that the enzymatic activity of PLA2 is not necessary to trigger these effects. MT-II-activated NF-kB, cPLA2 and distinct protein kinases are the principal steps involved in these cellular events.
A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C
(2005-07-22) Flores Díaz, Marietta; Alape Girón, Alberto; Clark, Graeme; Catimel, Bruno; Hirabayashi, Yoshio; Nice, Ed; Gutiérrez, José María; Titball, Richard; Thelestam, Mónica
Clostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. Previously, a cellular UDP-Glc deficiency was related with a hypersensitivity to the cytotoxic effect of Cp-PLC. Because UDP-Glc is required in the synthesis of proteoglycans, N-linked glycoproteins, and glycosphingolipids, the role of these gly-coconjugates in the cellular sensitivity to Cp-PLC was studied. The cellular sensitivity to Cp-PLC was significantly enhanced by glycosphingolipid synthesis inhibitors, and a mutant cell line deficient in gangliosides was found to be hypersensitive to Cp-PLC. Gangliosides protected hypersensitive cells from the cytotoxic effect of Cp-PLC and prevented its membrane-disrupting effect on artificial membranes. Removal of sialic acids by C. perfringens sialidase increases the sensitivity of cultured cells to Cp-PLC and intramuscular co-injection of C. perfringens sialidase, and Cp-PLC in mice potentiates the myotoxic effect of the latter. This work demonstrated that a reduction in gangliosides renders cells more susceptible to the membrane damage caused by Cp-PLC and revealed a previously unrecognized synergism between Cp-PLC and C. perfringens sialidase, providing new insights toward understanding the pathogenesis of clostridial myonecrosis.
A Clostridium difficile Lineage Endemic to Costa Rican Hospitals Is Multidrug Resistant by Acquisition of Chromosomal Mutations and Novel Mobile Genetic Elements
(2017-01) Ramírez Vargas, Gabriel; Quesada Gómez, Carlos; Acuña Amador, Luis Alberto; López Ureña, Diana; Murillo Corrales, Tatiana; Gamboa Coronado, María del Mar; Chaves Olarte, Esteban; Thomson, Nicholas R.; Rodríguez Cavallini, Evelyn; Rodríguez Sánchez, César
The antimicrobial resistance (AMR) rates and levels recorded for Clostridium difficile are on the rise. This study reports the nature, levels, diversity, and genomic context of the antimicrobial resistance of human C. difficile isolates of the NAPCR1/RT012/ST54 genotype, which caused an outbreak in 2009 and is endemic in Costa Rican hospitals. To this end, we determined the susceptibilities of 38 NAPCR1 isolates to 10 antibiotics from seven classes using Etests or macrodilution tests and examined 31NAPCR1 whole-genome sequences to identify single nucleotide polymorphisms (SNPs) and genes that could explain the resistance phenotypes observed. The NAPCR1 isolates were multidrug resistant (MDR) and commonly exhibited very high resistance levels. By sequencing their genomes, we showed that they possessed resistance-associated SNPs in gyrA and rpoB and carried eight to nine acquired antimicrobial resistance (AMR) genes. Most of these genes were located on known or novel mobile genetic elements shared by isolates recovered at different hospitals and at different time points. Metronidazole and vancomycin remain the first-line treatment options for these isolates. Overall, the NAPCR1 lineage showed an enhanced ability to acquire AMR genes through lateral gene transfer. On the basis of this finding, we recommend further vigilance and the adoption of improved control measures to limit the dissemination of this lineage and the emergence of more C. difficile MDR strains.
A Comparison of Associations Between Self-Reported and Device-Based Sedentary Behavoir and Obesity Markers in Adults: A Multi-National Cross-Sectional Study
(2021-05-28) Ferrari, Gerson Luis de Moraes; Herrera Cuenca, Marianella; Zalcman Zimberg, Ioná; Guajardo, Viviana; Gómez Salas, Georgina; Rigotti, Attilio; Cortés Sanabria, Lilia Yadira; Yépez García, Martha Cecilia; Pareja Torres, Rossina Gabriella; Peralta, Miguel; Marques, Adilson; Leme, Ana Carolina Barco; Kovalskys, Irina; Scott, Rollo; Fisberg, Mauro
The purpose of this study was to examine the associations between self-reported and device-based measures of sedentary behavior (SB) with obesity markers in adults from Latin American countries. Sitting time and total time spent in different SBs were self-reported using two different questionnaires. Accelerometers were used to assess total sedentary time. Body mass index, waist, and neck circumferences were assessed. The highest self-reported sitting time was in Argentina, the highest total time spent in different SBs was in Brazil and Costa Rica, and the highest device-based sedentary time was observed in Peru. Neither self-reported sitting time, total time spent in different SBs or device-based sedentary time were associated with body mass index. Device-based sedentary time was positively associated with waist circumference and self-reported sitting time was positively associated with neck circumference. Caution is warranted when comparing the associations of self-reported and device-based assessments of SB with anthropometric variables.
A comparison of in vitro methods for assessing the potency of therapeutic antisera against the venom of the coral snake Micrurus nigrocinctus
(1997-04) Alape Girón, Alberto; Miranda Arrieta, Keyna; Cortés Bratti, Ximena; Stiles, Bradley G.; Gutiérrez, José María
Therapeutic antisera against Micrurus nigrocinctus venom were tested for protection against lethality, as well as for inhibition of the nicotinic acetylcholine receptor (AchR)-binding and neutralization of phospholipase A2 (PLA2) activities of the homologous venom. Protection against venom lethality did not correlate with inhibition of AchR-binding activity, whereas there was a significant correlation between antisera potency and inhibition of PLA2 activity (r = 0.82, n = 10, P < 0.02). Inhibition of PLA2 activity could be useful in assessing the protective efficacy of M. nigrocinctus antisera during antivenom production. Micrurus nigrocinctus nigrocinctus venom proteins were fractionated by cation-exchange chromatography on Mono S FPLC and fractions assayed for lethality, AchR-binding and PLA2 activities. Antisera were titrated by enzyme-linked immunoassay (ELISA) against a crude M. n. nigrocinctus venom, two FPLC lethal fractions containing AchR-binding activity, and two toxins purified from M. n. nigrocinctus venom. No correlation was found between protective efficacy and the ELISA titer against any of these antigens. Compared to other elapid venoms that contain few toxins as major components, M. n. nigrocinctus venom appears to be more complex and its lethal effect is likely to be due to the combined effect of several neurotoxins.
A constant area monolayer method to assess optimal lipid packing for lipolysis tested with several secreted phospholipases A2
(2015-10) Yunes Quartino, Pablo J.; Portela, Madelón; Lima, Analía; Durán, Rosario; Lomonte, Bruno; Fidelio, Gerardo Daniel
We present an analysis of lipid monolayer hydrolysis at a constant area to assess the optimal lateral surface pressure value (Πopt) and thus, the surface packing density of the lipid, at which the activity of a given lipolytic enzyme is maximal. This isochoric method consists of a measurement of the decrease down to zero of theΠopt of phospholipid substrate monolayer due to continuous hydrolysis using only one reaction compartment. We performed the comparison of both approaches using several commercially available and literature-evaluated sPLA2s. Also, we characterized for the first time the profile of hydrolysis of DLPC monolayers catalyzed by a sPLA2 from Streptomyces violaceoruber and isoenzymes purified from Bothrops diporus venom. One of these viper venomenzymes is a newisoenzyme, partially sequenced by amass spectrometry approach.We also included the basicmyotoxin sPLA2-III fromBothrops asper. Results obtained with the isochoricmethod and the standard isobaric one produced quite similar values of Πopt, validating the proposal. In addition, we propose a new classification parameter, a lipolytic ratio of hydrolysis at two lateral pressures, 20 mN·m−1 and 10 mN·m−1, termed here as LR20/10 index. This index differentiates quite well “high surface pressure” from “low surface pressure” sPLA2s and, by extension; it can be used as a functional criterion for the quality of a certain enzyme. Also, this index could be added to the grouping systematic criteria for the superfamily proposed for phospholipase A2.
A cross-national comparison of 12 biomarkers finds no universal biomarkers of aging among individuals aged 60 and older
(2016) Rehkopf, David H.; Rosero Bixby, Luis; Dow, William H.
There is uncertainty about whether biological and anthropometric measures that are clinical risk factors for disease are universally associated with chronological age, or whether these correlations vary depending on the social and economic context. The answer to this question has implications for the malleability of biological aging. To examine this issue, we use population-based data on individuals aged 60 and older from the Costa Rican Study on Longevity and Healthy Aging, and temporally consistent data from the United States National Health and Nutrition Examination Survey and the United States Health and Retirement Study. Our analysis focuses on 12 biomarkers that have been shown in the literature to have an association with age, and that occur prior to the clinical manifestation of disease. We find that there are few consistent patterns of association with age when these biomarkers are stratified by gender, country, and level of education. This result suggests that these measures of biological aging are highly context-dependent, and that none of the 12 biomarkers we examined are universal biomarkers of aging. Future research that investigates composite measures of biological age should test newly proposed measures across gender, social class, and country.
A cryptic palm-pitviper species (Squamata: Viperidae: Bothriechis) from the Costa Rican highlands, with notes on the variation within B. nigroviridis
(2016-07-15) Doan, Tiffany M.; Mason, Andrew J.; Castoe, Todd A.; Sasa Marín, Mahmood; Parkinson, Christopher L.
Middle America is one of the most biodiverse regions in the world, harboring an exceptional number of rare and endemic species. This is especially true of Middle American cloud forests, where montane specialists occupy restricted, high-elevation ranges making them attractive candidates for investigating historical biogeography and speciation. One such highland- restricted species, the black speckled palm-pitviper (Bothriechis nigroviridis), occupies the Central, Tilarán, and Talamanca Cordilleras in Costa Rica and Panama. In this study, we investigate the genetic and morphological variation among populations of B. nigroviridis by inferring a multilocus phylogeny (21 individuals) and analyzing meristic scale characters with a principal component analysis (64 individuals). We find B. nigroviridis sensu stricto to be composed of two deeply divergent lineages, one with a restricted range in the northern and central Cordillera Talamanca and the other ranging throughout the Central, Tilarán, and Talamanca Cordilleras. Furthermore, these two lineages are morphologically distinct, with previously unrecognized differences in several characters allowing us to name and diagnose a new species B. nubestris sp. nov. We also examine the genetic and morphological variation within B. nigroviridis and discuss biogeographic hypotheses that may have led to the diversification of Bothriechis lineages.
A detailed analysis of open-field habituation and behavioral and neurochemical antidepressant-like effects in postweaning enriched rats
(2009-01-30) Brenes Sáenz, Juan Carlos; Padilla Mora, Michael; Fornaguera Trías, Jaime
Our previous work has shown that male Sprague–Dawley rats reared in social isolation, standard housing and environmental enrichment differ in their spontaneous open-field activity and in some neurobehavioral depressive-like parameters. Here, we extended this evidence by using a shorter postweaning rearing period (1 month) and including additional evaluations. First, in order to obtain a better characterization of the exploratory strategies among rearing conditions we analyzed in detail the spontaneous activity at the first minute and during the 10-min session. Second, we asked whether the changes in open-field activity were related with basal anxiety levels in the elevated plus-maze. Third, behavior in the forced-swimming test was analyzed and afterward, the tissue levels of hippocampal norepinephrine and serotonin were assessed. The possible relationship between neurotransmitters and forced-swimming behavior were explored through correlation analyses. We found that rearing conditions (i) differed on locomotor habituation and on sensory-motor exploration at the first minute and during the 10-min session without modifying the plus-maze behavior; (ii) affected differentially the grooming time, its sequential components, and the relationship between grooming and locomotor parameters; (iii) modified forced-swimming behavior and the hippocampal concentration of norepinephrine, serotonin, and its turnover; and (iv) produced different correlation patterns between both neurotransmitters and forced-swimming behaviors. Overall, environmental enrichment accelerated open-field habituation and led to behavioral and neurochemical antidepressant-like effects. In contract, isolation rearing strongly impaired habituation and simple information processing, but showed marginal effects on depressive-like behavior and on hippocampal neurochemistry. The current results suggest that differential rearing is not only a useful procedure to study behavioral plasticity or rigidity in response to early experience, but also to modeling some developmental protective or risk factors underlying depressive disorders.
A DNA pooling based system to detect Escherichia coli virulence factors in fecal and wastewater samples
(2012) Cortés Bratti, Ximena; Chacón Jiménez, Luz María; Taylor Castillo, Mayra Lizeth; Valiente Álvarez, Carmen Isabel; Alvarado Pérez, Irene
The availability of a useful tool for simple and timely detection of the most important virulent varieties of Escherichia coli is indispensable. To this end, bacterial DNA pools which had previously been categorized were obtained from isolated colonies as well as selected in terms of utilized phenotype; the pools were assessed by two PCR Multiplex for the detection of virulent E. coli eaeA, bfpA, stx1, stx2, ipaH, ST, LT, and aatA genes, with the 16S gene used as DNA control. The system was validated with 66 fecal samples and 44 wastewater samples. At least one positive isolate was detected by a virulent gene among the 20 that were screened. The analysis of fecal samples from children younger than 6 years of age detected frequencies of 25% LT positive strains, 8.3% eae, 8.3% bfpA, 16.7% ipaH, as well as 12.5 % aatA and ST. On the other hand, wastewater samples revealed frequencies of 25.7% eaeA positive, 30.3% stx1, 15.1% LT and 19.7% aatA. This study is an initial step toward carrying out epidemiological field research that will reveal the presence of these bacterial varieties.
A eficácia do antiveneno botrópico-crotálico na neutralização das principais atividades do veneno de Bothrops jararacussu
(1992) Dos Santos, María Cristina; Gonçalves, Luís Roberto de Camargo; Fortes Dias, Consuelo L.; Cury, Yara; Gutiérrez, José María; Furtado, María de Fátima
Myonecrosis is one of the effects of Bothrops jararacussu venom, from which a myotoxin was isolated showing structural homology to phospholipase A2 (PLA2), but without enzimatic activity. Such myotoxic activity is also present in the Crotalus durissus terrificus venom, and is atributed to crotoxin and to PLA2 (crotoxin B), the basic component of the crotoxin complex. The Bothrops jararacussu venom showed three proteins with immunologic identity to PLA2 from crotoxin. The bothropic (AB) and the bothropic/crotalic (AB/C) antivenoms, two commercial polyvalent antivenoms produced at Instituto Butantan, were compared in order to assess their capacity for neutralization of the lethal, hemorrhagic, coagulant and myotoxic activities of Bothrops jararacussu venom. Both antivenoms showed the same level of hemorrhagic activity neutralization. However, AB/C was about three times more efficient than AB in neutralizing the myotoxic activity, and two times more potent for neutralization of lethality and coagulant activity of Bothrops jararacussu venom. These data suggest that the use of AB/C could be of value in the treatment of patients bitten by snakes of this species
A first perturbome of Pseudomonas aeruginosa: Identification of core genes related to multiple perturbations by a machine learning approach
(2021) Molina Mora, José Arturo; Montero Manso, Pablo; García Batan, Raquel; Campos Sánchez, Rebeca; Vilar Fernández, José; García Santamaría, Fernando
Tolerance to stress conditions is vital for organismal survival, including bacteria under specific environmental conditions, antibiotics, and other perturbations. Some studies have described common modulation and shared genes during stress response to different types of disturbances (termed as perturbome), leading to the idea of central control at the molecular level. We implemented a robust machine learning approach to identify and describe genes associated with multiple perturbations or perturbome in a Pseudomonas aeruginosa PAO1 model. Using microarray datasets from the Gene Expression Omnibus (GEO), we evaluated six approaches to rank and select genes: using two methodologies, data single partition (SP method) or multiple partitions (MP method) for training and testing datasets, we evaluated three classification algorithms (SVM Support Vector Machine, KNN KNearest neighbor and RF Random Forest). Gene expression patterns and topological features at the systems level were included to describe the perturbome elements. We were able to select and describe 46 core response genes associated with multiple perturbations in P. aeruginosa PAO1 and it can be considered a first report of the P. aeruginosa perturbome. Molecular annotations, patterns in expression levels, and topological features in molecular networks revealed biological functions of biosynthesis, binding, and metabolism, many of them related to DNA damage repair and aerobic respiration in the context of tolerance to stress. We also discuss different issues related to implemented and assessed algorithms, including data partitioning, classification approaches, and metrics. Altogether, this work offers a different and robust framework to select genes using a machine learning approach.

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