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Objetivo: Determinar los valores de referencia de espirometría y formular una ecuación de predicción de valores espirométricos en población económicamente activa (PEA) de regiones con altitud 0-100 m.s.n.m. Métodos: Se seleccionaron a los participantes del estudio considerando los criterios de selección del estudio. Se recogió la información sobre las variables consideradas en el estudio: Capacidad Vital Forzada (CVF) y Volumen Espiratorio Forzado en el primer Segundo (VEF1), datos sociodemográficos y medidas antropométricas. Se dividió a la muestra en dos grupos para poder formular la ecuación de referencia y para evaluar su confiabilidad en un subgrupo de validación mediante las pruebas de correlación intraclase, T de Student para muestras pareadas y los gráficos de Bland-Altman. Resultados: Se seleccionaron 1052 participantes varones. Los rangos normales de CVF y VEF1 calculados fueron de CVF de 3.48 -5.47 y VEF1 de 2.83 - 4.41. Mediante una regresión lineal múltiple, se obtuvieron las siguientes fórmulas: CVF = 2.206 - 0.131 (Altitud Geográfica) - 0.014 (Edad) + 0.045 (Talla) y VEF1 = 1.589 - 0.08 (Altitud Geográfica) - 0.015 (Edad) + 0.033 (Talla). En los análisis de confiabilidad, se encontró una diferencia estadísticamente significativa en las medias entre los valores predichos por la ecuación y los valores reales, aunque en los gráficos de Bland-Altman no se evidenció un sesgo significativo y los coeficientes de correlación intraclase (CVF-ICC: 0.69; VEF1-ICC: 0.70) se encontraban dentro de un rango adecuado. Conclusiones: Las ecuaciones de CVF y VEF1 desarrolladas permiten predecir adecuadamente los valores espirométricos en PEA masculina de las regiones incluidas en el estudio.
Objective: Determine the spirometry reference values and formulate an equation to predict spirometric values in the economically active population (EAP) in regions with an altitude of 0-100 m.a.s.l. Materials and Methods: Study participants were selected considering the study selection criteria. Information was collected on the variables considered in the study: Forced Vital Capacity (FVC) and Forced Expiratory Volume in the first second (FEV1), sociodemographic data and anthropometric measurements. The sample was divided into 2 groups to be able to formulate the reference equation and to assess its reliability in a validation subgroup using intraclass correlation tests, Student's t-test for paired samples, and Bland-Altman plots. Results: 1052 male participants were selected. The normal ranges for FVC and FEV1 calculated were FVC 3.48 - 5.47 and FEV1 2.83 - 4.41. Using multiple linear regression, the following formulas were obtained: FVC = 2.206 - 0.131 (Geographic Altitude) - 0.014 (Age) + 0.045 (Height) and FEV1 = 1.589 - 0.08 (Geographic Altitude) - 0.015 (Age) + 0.033 (Height). In the reliability analyses, a statistically significant difference was found in the means between the values predicted by the equation and the real values, although the Bland-Altman plots did not show a significant bias and the intraclass correlation coefficients (FVC- ICC: 0.69; FEV1-ICC: 0.70) were within an adequate range. Conclusions: The developed FVC and FEV1 equations allow adequate prediction of spirometric values in male PEA of the regions included in the study.
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BACKGROUND: Tilapia (Oreochromis spp.) in the form of frozen fillets is one of the fishes with the highest commercial production levels worldwide. However, protein denaturation, membrane rupture, and lipid oxidation are commonly observed in fillets when stored at standard commercial freezing temperatures for long periods. This study proposes, for the first time, the use of maltodextrin and state diagrams to define processing strategies and suitable storage temperatures for fresh and dehydrated tilapia fillets. Differential scanning calorimetry (DSC) was used to study the effect of maltodextrin weight fractions ( W MD ) of 0, 0.4, and 0.8 on the thermal transitions of tilapia fillets as a function of solid mass fractions ( W s ). RESULTS: The glass transition temperature curve ( T g vs . W s ) and characteristic parameters of maximal freeze concentration ( T g ' , T m ' , W s ' ) of tilapia increased significantly with the addition of maltodextrin. Using developed state diagrams, freezing and storage temperatures of -22 °C, -15 °C, and -10 °C (P < 0.05) for long-term preservation were defined for tilapia fillets produced with W MD of 0, 0.4, and 0.8. CONCLUSION: Maltodextrin is an excellent alternative as a cryoprotectant and drying aid to increase the thermal parameters of tilapia fillets by achieving frozen storage temperatures above the standard commercial freezing temperature of -18 °C. © 2023 Society of Chemical Industry.
Assuntos
Tilápia , Animais , Tilápia/metabolismo , Temperatura , Temperatura Baixa , Polissacarídeos/metabolismoRESUMO
Currently, demand for functional foods is increasing in the public interest in order to improve life expectations and general health. Food matrices containing probiotic microorganisms and active compounds encapsulated into carrier agents are essential in this context. Encapsulation via the lyophilisation method is widely used because oxidation reactions that affect physicochemical and nutritional food properties are usually avoided. Encapsulated functional ingredients, such as quercetin and Bacillus clausii, using two carrier agents' matrices-I [inulin (IN), lactose (L) and maltodextrin (MX)] and II [arabic (A), guar (G), and xanthan (X) gums)]-are presented in this work. A D-optimal procedure involving 59 experiments was designed to evaluate each matrix's yield, viability, and antioxidant activity (AA). Matrix I (33.3 IN:33.3 L:33.3 MX) and matrix II (33.3 A:33.3 G:33.3 X) exhibited the best yield; viability of 9.7 log10 CFU/g and 9.73 log10 CFU/g was found in matrix I (using a ratio of 33.3 IN:33.3 L:33.3 MX) and matrix II (50 G:50 X), respectively. Results for the antioxidant capacity of matrix I (100 IN:0 L:0M X) and matrix II (0 A:50 G:50 X) were 58.75 and 55.54 (DPPH* scavenging activity (10 µg/mL)), respectively. Synergy between matrices I and II with use of 100IN:0L:OMX and 0A:50G:50X resulted in 55.4 log10 CFU/g viability values; the antioxidant capacity was 9. 52 (DPPH* scavenging activity (10 µg/mL). The present work proposes use of a carrier agent mixture to produce a functional ingredient with antioxidant and probiotic properties that exceed the minimum viability, 6.0 log10 CFU/g, recommended by the FAO/WHO (2002) to be probiotic, and that contributes to the recommended daily quercetin intake of 10-16 mg/day or inulin intake of 10-20 g/day and dietary fibre intake of 25-38 g per day.
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The effect that the fructans of Cichorium intybus and Agave salmiana have on health, as well as on the growth of some Lactobacillus species, has been demonstrated. The aim of this work was to evaluate the effect of linear and branched fructans on the growth of seven strains and some probiotic characteristics. The molecular identification of seven strains was performed. Moreover, the growth, resistance to antibiotics and simulated gastrointestinal conditions were also evaluated when these microorganisms were grown in a culture medium containing agave and chicory fructans. The strains were identified as Lactiplantibacillus plantarum, Lactiplantibacillus pentosus, Lactiplantibacillus fabifermentans and Lactiplantibacillus paraplantarum. The results suggest that the seven Lactobacillus strains were able to grow using agave (branched) and chicory (linear) fructans. The linear and branched fructans statistically influenced the kinetic parameters. The specific growth rate varied between 0.270 and 0.573 h-1 and the generation time between 1.21 and 2.45 h for all strains and culture media. All strains showed a growth of 9 Log CFU/mL in all the culture media. Production of lactic, acetic, propionic, butyric, formic and succinic acid was influenced by linear and branched fructans (p < 0.05). All the strains survived simulated gastrointestinal conditions greater than 83%. The resistance of Lactobacillus against ciprofloxacin and rifaximin was significantly affected by linear and branched fructans, but survival to gastrointestinal conditions was not affected by the type of substrate. These results highlight the use of the seven strains, which have probiotic potential; therefore, these could be applied in several biotechnological products.
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Agave , Probióticos , Agave/química , Bebidas , Meios de Cultura , Frutanos/química , Lactobacillus , MéxicoRESUMO
The beneficial health of evaluating prebiotic effect by the consumption of Agave salmiana fructans (A. salmiana fructans) was assessed in the epithelium of the cecum and proximal colon of Wistar rats fed at different doses for 35 days with regards to mucus production, morphological cell changes, and the serum concentration of tumor necrosis factor-α (TNF-α). Results showed a significant increase in mucus-secreting cells (P < 0.05) and a normal structure with preserved crypts, without morphological damage to colonic cells for a dose of 12.5% (w/w) with respect to the control and the other doses evaluated. The concentration of pro-inflammatory cytokine TNF-α was decreased significantly (P < 0.05) in the groups with doses of 10 and 12.5% (w/w) at 7 and 35 days, respectively. This effect was positively correlated with the reduction of inflammation in epithelial cells. This study provides direct evidence of the effects of the A. salmiana fructans on the colonic epithelium, demonstrating that a diet supplemented with 12.5% of fructans for 35 days exerts health benefits through the strengthening of the mucosa layer, which favors the adherence of the bacterial population and suppresses inflammation.
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The general aim of this study was to evaluate physicochemical properties, prebiotic activity and anticancer potential of jackfruit (Artocarpus heterophyllus) seed flour. The drying processes of jackfruit seeds were performed at 50, 60 and 70 °C in order to choose the optimal temperature for obtaining the flour based on drying time, polyphenol content and antioxidant capacity. The experimental values of the moisture ratio during jackfruit seed drying at different temperatures were obtained using Page's equation to establish the drying time for the required moisture between 5 and 7% in the flour. The temperature of 60 °C was considered adequate for obtaining good flour and for performing its characterization. The chemical composition, total dietary fiber, functional properties and antioxidant capacity were then examined in the flour. The seed flour contains carbohydrates (73.87 g/100 g), dietary fiber (31 g/100 g), protein (14 g/100 g) and lipids (1 g/100 g). The lipid profile showed that the flour contained monounsaturated (4 g/100 g) and polyunsaturated (46 g/100 g) fatty acids. Sucrose, glucose, and fructose were found to be the predominant soluble sugars, and non-digestible oligosaccharides like 1-kestose were also found. The total polyphenol content was 2.42 mg of gallic acid/g of the sample; furthermore, the antioxidant capacity obtained by ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) was 901.45 µmol Trolox/100 g and 1607.87 µmol Trolox/100 g, respectively. The obtained flour exhibited good functional properties, such as water and oil absorption capacity, swelling power and emulsifier capacity. Additionally, this flour had a protective and preventive effect which is associated with the potential prebiotic activity in Lactobacillus casei and Bifidobacterium longum. These results demonstrate that jackfruit seed flour has good nutritional value and antioxidant and prebiotic activity, as well as potential protective effects and functional properties, making it an attractive food or ingredient in developing innovative functional products.
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Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Artocarpus/química , Fenômenos Químicos , Farinha/análise , Prebióticos , Sementes/química , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Dessecação , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Umidade , Cinética , Lipídeos/análise , Extratos Vegetais/farmacologia , Polifenóis/análise , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Superóxido Dismutase/metabolismo , Viscosidade , Água/químicaRESUMO
In this work is presented the complete thermal analysis of polyols by direct methods such as simultaneous thermogravimetric and differential thermal analyzer (TGA-DTA), differential scanning calorimetry (DSC), modulated DSC (MDSC), and supercooling MDSC. The different thermal events in the temperature range of 113â»553 K were identified for glycerol (GL), ethylene glycol (EG), and propylene glycol (PG). Boiling temperature (TB) decreased as GL > EG > PG, but increased with the heating rate. GL showed a complex thermal event at 191â»199 K, identified as the glass transition temperature (Tg) and devitrification temperature (Tdv), and a liquidâ»liquid transition (TL-L) at 215â»221 K was identified as the supercooling temperature. EG showed several thermal events such as Tg and Tdv at 154 K, crystallization temperature (Tc) at 175 K, and melting temperature (Tm) at 255 K. PG also showed a complex thermal event (Tg and Tdv) at 167 K, a second devitrification at 193 K, and TL-L at 245 K. For PG, crystallization was not observed, indicating that, during the cooling, the liquid remained as an amorphous solid.
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Currently, bacterial diseases cause a death toll around 2 million people a year encouraging the search for new antimicrobial agents. DNA gyrase is a well-established antibacterial target consisting of two subunits, GyrA and GyrB, in a heterodimer A(2)B(2). GyrA is involved in DNA breakage and reunion and GyrB catalyzes the hydrolysis of ATP. The GyrB subunit from Escherichia coli has been investigated, namely the ATP binding pocket both considering the protein without ligands and bound with the inhibitors clorobiocin, novobiocin and 5'-adenylyl-ß-γ-imidodiphosphate. The stability of the systems was studied by molecular dynamics simulation with the further analysis of the time dependent root-mean-square coordinate deviation (RMSD) from the initial structure, and temperature factors. Moreover, exploration of the conformational space of the systems during the MD simulation was carried out by a clustering data mining technique using the average-linkage algorithm. Recognizing the key residues in the binding site of the enzyme that are involved in the binding mode with the aforementioned inhibitors was investigated by using two techniques: free energy decomposition and computational alanine scanning. The results from these simulations highlight the important residues in the ATP binding site and can be useful in the design process of potential new inhibitors.
Assuntos
DNA Girase/química , DNA Girase/metabolismo , Escherichia coli/enzimologia , Estrutura Terciária de Proteína , Inibidores da Topoisomerase II , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Alanina/genética , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Análise por Conglomerados , DNA Girase/genética , Humanos , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Quaternária de ProteínaRESUMO
The egg and larval stages of Gnathostoma turgidum were examined using light microscopy. Fertilized uterine eggs are 65.97 long and 32.28 wide, oval, brownish, with two cap-like thickenings. The eggshell surface is covered with numerous irregularly shaped pits of various sizes and depths. A sheathed second-stage larva emerges from the egg, measures 178 x 9; the sheath measures 243 x 21. Development to early third-stage larva in the coelomic cavity of cyclopoid copepods is similar to that described for other gnathostome species. After 10 days at 27 degrees C, the larvae undergo a molt (the second for gnathostomes) and develop to early third stage. The body of this stage measures 412.3 x 40.1, with evident hemispherical cephalic bulbs. Cephalic bulbs measure 25 x 40, armed with four transverse rows of sharp hooklets. The average number of hooklets in each row is 31, 34, 37, and 42, respectively. The whole body is covered with 193 transverse rows of small single-pointed cuticular spines. One pair of cervical papillae and an excretory pore are present on the anterior part of the body. On the other hand, potential species-specific features regarding the latter larval stage are discussed. Finally, some G. turgidum life cycle considerations are portrayed.
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Gnathostoma/crescimento & desenvolvimento , Estágios do Ciclo de Vida , Animais , Gnathostoma/anatomia & histologia , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , MicroscopiaRESUMO
Two female advanced third-stage larvae of Gnathostoma turgidum recovered from the liver of one naturally infected four-eyed opossum Philander opossum pallidus collected in Oaxaca, Mexico, were morphologically examined. Because of some characteristics, the larvae do not fit into the typical advanced third-stage. The body shows a size at least three times larger than expected and rows of spines only in the anterior part of the body surface. Consequently, in this research, we document for the first time the precocity in third-stage larvae of G. turgidum, and we also highlight some facts about the fourth larval stage occurring in spirurins.
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Gnathostoma/isolamento & purificação , Gambás/parasitologia , Infecções por Spirurida/veterinária , Animais , Feminino , Gnathostoma/anatomia & histologia , Gnathostoma/crescimento & desenvolvimento , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Fígado/parasitologia , MéxicoRESUMO
BACKGROUND: the periventricular leukomalacia (PLM) is considered a lesion of the central nervous system secondary to a hypoxic-ischemic insult, and affects more to premature than term neonates. However, the reported rates in the literature are between 2 % to 25 % in premature neonates. The objective was to determine the prevalence of PLM in premature neonates. METHODS: a two year prospective screening program with transfontanel ultrasound in premature neonates weighing < 2000 g was carried out at 4 weeks of age. RESULTS: from 38 355 consecutive deliveries 562 were premature neonates weighted = 2000 g who fulfilled inclusion criteria and all were studied with transfontanel ultrasonography; we found 36 (6.34 %) premature neonates with PLM. Of the 346 neonates weighing = 1500 g, 26 (7.5 %) had a positive examination for PLM. In the 1501 g to 2000 g group, 10 of 216 (4.6 %) had PLM. The PLM prevalence was higher in male (2:1). Neurological exam was normal at the time of study. CONCLUSIONS: the PLM was present in 6.3 % of premature neonates weighing < 2000 g with 2 affected males for each female.
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Recém-Nascido Prematuro , Leucomalácia Periventricular/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Prevalência , Estudos ProspectivosRESUMO
In order to clarify the role of Gnathostoma turgidum as an etiological agent involved in human gnathostomiasis in Mexico, establish the taxonomic identity of the advanced third-stage larvae (AdvL(3)), and contribute to the knowledge of its life cycle, experimental host infections, examination of potential natural hosts, and morphological comparisons were carried out. Examination of ten species of potential hosts at San Pedro las Playas and Tres Palos Lagoon in Guerrero state, Mexico revealed that two (Kinosternon integrum and Rana zweifeli) were infected by 15 AdvL(3) of G. turgidum. A specific identity was obtained comparing these larvae with those recovered from hosts experimentally infected. The AdvL(3) measured 1.6 mm in length, with two cervical papillae (both in 12th row) and an excretory pore on the 19th row. The average of cephalic hooklets, from first to fourth row, was 30.8, 34.0, 36.7, and 39.6, respectively. This is the first record of AdvL(3) of G. turgidum in America, and it represents a significant contribution for the understanding of the life cycle of this species.
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Gnathostoma/isolamento & purificação , Gnathostoma/fisiologia , Estágios do Ciclo de Vida , Infecções por Spirurida/veterinária , Estruturas Animais/anatomia & histologia , Animais , Gnathostoma/anatomia & histologia , México , Microscopia , Infecções por Spirurida/parasitologiaRESUMO
Morphological abnormalities were observed on the cephalic bulb hooklets of advanced third-stage larvae (AdvL(3)) of genus Gnathostoma. The larvae were obtained from the fish "Mexican rivulus" Millerichthys robustus collected from a seasonal pond near Tlacotalpan, Veracruz, Mexico. The abnormalities involved (1) extra rudimentary hooklets, located between the four rows and after the fourth row, (2) branched or lobulated hooklets, and (3) fragmented hooklets not uniformly disposed in rows. The alterations observed on the cephalic bulb hooklets do not represent intraspecific variations, and they may be considered as a potential tool for assessing the presence of pollutants or stressors located within the ecosystem.
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Ciprinodontiformes/parasitologia , Gnathostoma/anatomia & histologia , Animais , Gnathostoma/isolamento & purificação , Cabeça/anormalidades , Humanos , Larva/anatomia & histologia , MéxicoRESUMO
BACKGROUND: Retinopathy of prematurity (ROP) is a serious complication of treatment and extension of survival in premature infants and leads to blindness unless recognized and treated early. An ROP prospective screening survey was performed, enrolling all premature newborns weighing <2000 g at delivery. METHODS: A total of 2014 infants had a retinal evaluation by indirect ophthalmoscopy at 4-6 weeks of age. If any ROP stage was detected, the patient was followed periodically to assess treatment. All premature infants with threshold retinopathy were treated by transscleral cryotherapy at the time of detection. RESULTS: We found 449 infants (22.2%) with ROP in any stage, and 230 (11.42%) with threshold retinopathy who underwent cryotherapy. In the 500-1000 g group (n = 334), 48.2% had ROP in any stage and 92 (27.5%) had threshold retinopathy. In the 1001-1500 g group (n = 1374), 257 (18.7%) had any ROP stage and 122 (8.8%) had stage 3. In the 1501-2000 g group, 306 neonates were evaluated, 31 (10%) had any ROP stage and 16 (5.2%) underwent cryotherapy. A total of 198/230 infants (86%) with threshold retinopathy who received cryotherapy had complete recovery, but 5% developed unilateral and 9% bilateral retinal detachment. There were no complications related to anesthesia. CONCLUSIONS: Overall ROP rate was 2.68/1000 deliveries and 22.2% of premature infants <2000 g had any ROP stage, 11.42% with retinal detachment risk received cryotherapy with 86% successful results.
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Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Retinopatia da Prematuridade/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Programas de Rastreamento , México/epidemiologia , Oftalmoscopia , PrevalênciaRESUMO
A topological substructural molecular design approach (TOPS-MODE) has been used to predict whether a given compound is a P-glycoprotein (P-gp) substrate or not. A linear discriminant model was developed to classify a data set of 163 compounds as substrates or nonsubstrates (91 substrates and 72 nonsubstrates). The final model fit the data with sensitivity of 82.42% and specificity of 79.17%, for a final accuracy of 80.98%. The model was validated through the use of an external validation set (40 compounds, 22 substrates and 18 nonsubstrates) with a 77.50% of prediction accuracy; fivefold full cross-validation (removing 40 compounds in each cycle, 80.50% of good prediction) and the prediction of an external test set of marketed drugs (35 compounds, 71.43% of good prediction). This methodology evidenced that the standard bond distance, the polarizability and the Gasteiger-Marsilli atomic charge affect the interaction with the P-gp; suggesting the capacity of the TOPS-MODE descriptors to estimate the P-gp substrates for new drug candidates. The potentiality of the TOPS-MODE approach was assessed with a family of compounds not covered by the original training set (6-fluoroquinolones), and the final prediction had a 77.7% of accuracy. Finally, the positive and negative substructural contributions to the classification of 6-fluoroquinolones, as P-gp substrates, were identified; evidencing the possibilities of the present approach in the lead generation and optimization processes.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Modelos Biológicos , Preparações Farmacêuticas/metabolismo , Simulação por Computador , Fluoroquinolonas/classificação , Fluoroquinolonas/metabolismo , Modelos Lineares , Preparações Farmacêuticas/classificação , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-AtividadeRESUMO
The paper describes an introductory characterization of antigenic stimulation of excretion-secretion products (ESP) of Gnathostoma binucleatum advanced third-stage larvae cultured in vitro and proteinases present in this products. Excretory and secretory proteins were obtained after 10 larvae were maintained in 5% CO(2) RPMI medium. The supernatant was collected each week for two months. The proteins were dialyzed, concentrated, and separated in 10% SDS-PAGE gels under reducing conditions and transferred to nitrocellulose paper for immunoblot analyses. G. binucleatum immunized mice serum was used to determine protein antigenicity. Four proteins of 40, 80, 120, and 208 kDa persisted for two months and three proteins, 80, 120, and 208 kDa were recognized for antibodies of mice. In SDS-PAGE gelatin substrate gels ESP resolved as two proteins with molecular weight of 80 and 208 kDa that were sensitive to a metalloproteinase inhibitor, and thus it may be inferred that they might be used for diagnosis of gnathostomiasis.
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Antígenos de Helmintos/análise , Gnathostoma/imunologia , Peptídeo Hidrolases/análise , Infecções por Spirurida/parasitologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/química , Antígenos de Helmintos/imunologia , Western Blotting , Cães , Eletroforese em Gel de Poliacrilamida , Feminino , Gnathostoma/enzimologia , Humanos , Soros Imunes/imunologia , Larva/enzimologia , Larva/imunologia , Camundongos , Peso Molecular , Peptídeo Hidrolases/química , Infecções por Spirurida/imunologiaRESUMO
TOPological Sub-structural MOlecular DEsign (TOPS-MODE) was used to assess acute aquatic toxicity of a series of 69 benzene derivatives. The obtained model was able to explain more than 88% of data variance, stressing the importance of molecule hydrophobicity and its dipolar moment, as well as the distance between their bonds to describe the property under study. On the other hand, this model was better than those obtained with Dragon software (Constitutional, Galvez topological charges indices and BCUT) using the same number of variables. This approach proved to be a very good method to assess acute aquatic toxicity of these king of compounds, which could be applied to other series of substances.
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Derivados de Benzeno/toxicidade , Animais , Análise por Conglomerados , Cyprinidae , Relação Quantitativa Estrutura-AtividadeRESUMO
The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentration ratio. The final model explained the 70% of the variance and it was validated through the use of an external validation set (33 compounds of the 119, MAE = 0.33), a leave-one-out crossvalidation (q(2) = 0.65, S(press) = 0.43), fivefold full crossvalidation (removing 28 compounds in each cycle, MAE = 33, RMSE = 0.43) and the prediction of +/- values for an external test set (85.7% of good prediction). This methodology evidenced that the hydrophobicity increase the blood-brain barrier permeation, while the polar surface and its interaction with the atomic mass of compounds decrease it; suggesting the capacity of the TOPS-MODE descriptors to estimate brain penetration potential of new drug candidates. Finally, by the present approach, positive and negative substructural contributions to the brain permeation were identified, and their possibilities in the lead generation and optimization processes were evaluated.
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Barreira Hematoencefálica/metabolismo , Modelos Biológicos , Permeabilidade Capilar/fisiologia , Simulação por Computador , Modelos Lineares , Valor Preditivo dos TestesRESUMO
The TOPological Substructural MOlecular DEsign (TOPS-MODE) has been successfully used in order to explain the toxicity in the Tetrahymena pyriformis on a large data set. The obtained models for the training set had good statistical parameters (R(2)=0.72-0.81, p<0.05) an also the prediction power of the models found was adequate (Q(2)=0.70-0.80). A detailed study of the influence of variable numbers in the equation and the statistical outliers was carried out; leading to a good final model with a better physicochemical interpretation than the rest of the published models. Only two molecular descriptors codifying dipolar and hydrophobic features were introduced. Finally, the fragment contributions to the toxicity prediction evidenced the powerful of this topological approach.