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1.
Pharmaceutics ; 16(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39065617

RESUMO

In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53-4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82-10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28-30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52-2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72-3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan-Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure-Activity Relationship analysis revealed that furosemide's sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.

2.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674152

RESUMO

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.


Assuntos
Benzimidazóis , Trichomonas vaginalis , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/genética , Trichomonas vaginalis/metabolismo , Benzimidazóis/farmacologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Antiprotozoários/farmacologia , Antitricômonas/farmacologia
3.
Lett Appl Microbiol ; 77(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38211976

RESUMO

Acinetobacter baumannii is a relevant bacterium due to its high-resistance profile. It is well known that antimicrobial resistance is primarily linked to mutations and the acquisition of external genomic material, such as plasmids or phages, to which the Clustered Regularly Interspaced Short Palindromic Repeats associated with Cas proteins, or CRISPR-Cas, system is related. It is known that the system can influence the acquisition of foreign genetic material and play a role in various physiological pathways. In this study, we conducted an in-silico analysis using 91 fully assembled genomes of clinical strains obtained from the NCBI database. Among the analyzed genomes, the I-F1 subtype of the CRISPR-Cas system was detected showcasing variations in architecture and phylogeny. Using bioinformatic tools, we determined the presence, distribution, and specific characteristics of the CRISPR-Cas system. We found a possible association of the system with resistance genes but not with virulence determinants. Analysis of the system's components, including spacer sequences, suggests its potential role in protecting against phage infections, highlighting its protective function.


Assuntos
Acinetobacter baumannii , Bacteriófagos , Acinetobacter baumannii/genética , Sistemas CRISPR-Cas , Plasmídeos/genética , Genômica , Filogenia , Bacteriófagos/genética
4.
Environ Pollut ; 341: 122936, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37979648

RESUMO

Water pollution via natural and anthropogenic activities has become a global problem, which can lead to short and long-term impacts on humans' health and the ecosystems. Substantial amounts of individual or mixtures of organic pollutants move into the surface water via point and non-point source contamination. Some of these compounds are known to be toxic and difficult to remove from water sources, thus affecting their quality. Moreover, environmental regulations in high-income countries have become very strict for drinking water treatment over the past decades, especially regarding pesticides. This study aimed to evaluate the efficiency of different residential water treatments to remove 13 pesticides with distinct physicochemical characteristics from the drinking water. Nine water treatments were used: four membrane filters, an activated carbon filter, ultraviolet radiation, reverse osmosis, ion exchange resins, and ozonation. The trial was performed with tap water contaminated with an environmental concentration of 13 pesticides. According to the results, activated carbon and reverse osmosis were 100% efficient for pesticide removal, followed by ion exchange resins and ultraviolet radiation. Membrane filters, in general, showed low efficiency and should, therefore, not be used for this purpose.


Assuntos
Água Potável , Praguicidas , Poluentes Químicos da Água , Purificação da Água , Humanos , Carvão Vegetal , Ecossistema , Raios Ultravioleta , Purificação da Água/métodos , Resinas de Troca Iônica
5.
Salud UNINORTE ; 39(3): 1239-1270, dic. 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1576807

RESUMO

resumen está disponible en el texto completo


ABSTRACT Background: Urinary tract infection (UTI) is a common disease in childhood and one of the most common causes of consultation in the pediatric emergency department. Its incidence ranges between 5% and 10% in children under 2 years old. Objective: To generate recommendations on the diagnosis, treatment, and follow-up of UTI in pediatric patients in Colombia. Methods: 15 questions of clinical interest in the diagnosis, treatment, and follow-up of UTI in pediatric patients were formulated. A systematic review of the literature was carried out to identify the clinical practice guidelines (CPG) available in UTI, in order to use this evidence to answer the proposed questions and articulate the recommendations. Local and international tools were used to select and evaluate the CPGs. Information was retrieved from the selected guidelines, preliminary recommendations were compiled, and final recommendations were approved by expert consensus. Finally, the strength and direction of each recommendation was assessed. Results: A total of 4 CPGs were selected: American Academy of Pediatrics, Spanish Ministry of Health, McTaggart, and National Institute for Health and Care Excellence. Final recommendations for the diagnosis, treatment, and follow-up of UTI are presented in this paper. Conclusions: These recommendations will guide the teams to make clinical decisions regarding health care of pediatric patients with UTI in Colombia. This will help to improve health care and to generate policies for timely diagnosis, treatment, and follow-up in these patients.

6.
Plants (Basel) ; 12(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37687380

RESUMO

BACKGROUND: Crop yields have been affected by many different biotic and abiotic factors. Generally, plants experience more than one stress during their life cycle, and plants can tolerate multiple stresses and develop cross-tolerance. The expected rise in atmospheric CO2 concentration ([CO2]) can contribute to cross-tolerance. Priming is a strategy to increase yield or to maintain yield under stress conditions. Thus, our objective was to evaluate if priming the rice plants with water deficit during the vegetative stage can induce tolerance to heat stress at anthesis and to evaluate the contribution of e[CO2]. METHODS: The experiment was arranged in a completely randomized design in a factorial arrangement. Factor A consisted of the following treatments: water deficit at four-leaf stage (no-stress, and drought stress), heat at anthesis (normal temperature, high temperature), and priming with water deficit at four-leaf stage and heat stress at anthesis; and Factor B was two [CO2] treatments: a[CO2] = 400 ± 40 µmol mol-1 and e[CO2] = 700 ± 40 µmol mol-1. We assessed the effect of the treatments on plant growth, yield, biochemical, and transcriptome alterations. RESULTS: Although e[CO2] affected rice growth parameters, it did not affect the priming effect. Primed plants showed an increase in yield and number of panicles per plant. Primed plants showed upregulation of OsHSP16.9A, OsHSP70.1, and OsHSP70.6. These results showed induced cross-tolerance. CONCLUSIONS: Water deficit at the rice vegetative stage reduces the effect of heat stress at the reproductive stage. Water deficit at the vegetative stage can be used, after further testing in field conditions, to reduce the effect of heat stress during flowering in rice.

7.
Int J Mol Sci ; 24(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628871

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting an estimated 500 million people worldwide, is a genetic disorder that causes human enzymopathies. Biochemical and genetic studies have identified several variants that produce different ranges of phenotypes; thus, depending on its severity, this enzymopathy is classified from the mildest (Class IV) to the most severe (Class I). Therefore, understanding the correlation between the mutation sites of G6PD and the resulting phenotype greatly enhances the current knowledge of enzymopathies' phenotypic and genotypic heterogeneity, which will assist both clinical diagnoses and personalized treatments for patients with G6PD deficiency. In this review, we analyzed and compared the structural and functional data from 21 characterized G6PD variants found in the Mexican population that we previously characterized. In order to contribute to the knowledge regarding the function and structure of the variants associated with G6PD deficiency, this review aimed to determine the molecular basis of G6PD and identify how these mutations could impact the structure, stability, and function of the enzyme and its relation with the clinical manifestations of this disease.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Glucosefosfato Desidrogenase , Humanos , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Genótipo , Mutação , Fenótipo
8.
Pathogens ; 12(5)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37242413

RESUMO

The ESKAPE group constitute a threat to public health, since these microorganisms are associated with severe infections in hospitals and have a direct relationship with high mortality rates. The presence of these bacteria in hospitals had a direct impact on the incidence of healthcare-associated coinfections in the SARS-CoV-2 pandemic. In recent years, these pathogens have shown resistance to multiple antibiotic families. The presence of high-risk clones within this group of bacteria contributes to the spread of resistance mechanisms worldwide. In the pandemic, these pathogens were implicated in coinfections in severely ill COVID-19 patients. The aim of this review is to describe the main microorganisms of the ESKAPE group involved in coinfections in COVID-19 patients, addressing mainly antimicrobial resistance mechanisms, epidemiology, and high-risk clones.

9.
J Diabetes Res ; 2023: 8898958, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36846513

RESUMO

Diabetes mellitus is a disease with no cure that can cause complications and even death. Moreover, over time, it will lead to chronic complications. Predictive models have been used to identify people with a tendency to develop diabetes mellitus. At the same time, there is limited information regarding the chronic complications of patients with diabetes. Our study is aimed at creating a machine-learning model that will be able to identify the risk factors of a diabetic patient developing chronic complications such as amputations, myocardial infarction, stroke, nephropathy, and retinopathy. The design is a national nested case-control study with 63,776 patients and 215 predictors with four years of data. Using an XGBoost model, the prediction of chronic complications has an AUC of 84%, and the model has identified the risk factors for chronic complications in patients with diabetes. According to the analysis, the most crucial risk factors based on SHAP values (Shapley additive explanations) are continued management, metformin treatment, age between 68 and 104 years, nutrition consultation, and treatment adherence. But we highlight two exciting findings. The first is a reaffirmation that high blood pressure figures across patients with diabetes without hypertension become a significant risk factor at diastolic > 70 mmHg (OR: 1.095, 95% CI: 1.078-1.113) or systolic > 120 mmHg (OR: 1.147, 95% CI: 1.124-1.171). Furthermore, people with diabetes with a BMI > 32 (overall obesity) (OR: 0.816, 95% CI: 0.8-0.833) have a statistically significant protective factor, which the paradox of obesity may explain. In conclusion, the results we have obtained show that artificial intelligence is a powerful and feasible tool to use for this type of study. However, we suggest that more studies be conducted to verify and elaborate upon our findings.


Assuntos
Diabetes Mellitus , Hipertensão , Metformina , Humanos , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Metformina/uso terapêutico , Estudos de Casos e Controles , Inteligência Artificial , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Fatores de Risco , Obesidade/complicações , Aprendizado de Máquina
10.
Ciênc. rural (Online) ; 53(4): e20210671, 2023. tab, graf
Artigo em Inglês | LILACS-Express | VETINDEX | ID: biblio-1384599

RESUMO

ABSTRACT: Rice yield in Southern Brazil has increased linearly over the years. Early season sowing is the primary contributor to rice yield increase in Southern Brazil. However, that practice might expose rice seedlings to the risk of low-temperature stress, which can enhance herbicide injury and reduce rice yield. This research evaluated the effect of sowing dates on herbicide selectivity and agronomical rice traits. We conducted field experiments during the 2010/11 and 2011/12 growing seasons in Capão do Leão, RS, Brazil. The experimental design was a complete randomized block with a factorial arrangement. Factor A was early-sowed (in September) and late-sowed (in November); factor B was herbicide treatment (bispyribac-sodium, cyhalofop-butyl penoxsulam, metsulfuron-methyl, and nontreated check). Rice response to herbicide treatments differed between years. In 2010/11, bispyribac-sodium, penoxsulam, and metsulfuron-methyl injured rice only on early-sowed. In both years, early sowing rice promoted higher yield potential despite herbicide injury. The injury caused by the herbicides bispyribac-sodium, penoxsulam and metsulfurom-methyl was transient did not lead to yield losses. Cold temperature close the application increases the injury of ALS herbicides.


RESUMO: A produtividade do arroz no Sul do Brasil aumentou linearmente ao longo dos anos. A semeadura no início da janela é o principal contribuinte para o aumento da produtividade do arroz no sul do Brasil. No entanto, essa prática pode expor as plântulas de arroz ao estresse por baixa temperatura, aumentando os danos do herbicida e reduzindo a produtividade do arroz. Este trabalho teve como objetivo avaliar o efeito de épocas de semeadura na seletividade de herbicidas em caracteres agronômicos do arroz. Conduzimos experimentos de campo durante as safras 2010/11 e 2011/12 em Capão do Leão, RS, Brasil. O delineamento experimental foi em blocos casualizados completos com arranjo fatorial. O fator A foram a semeadura-precoce (em setembro) e a semeadura-tardia (em novembro); o fator B foram os tratamentos com herbicidas (bispyribac-sodium, cyhalofop-butyl, penoxsulam, metsulfuron-methyl e controle - sem herbicida). A resposta do arroz aos tratamentos com herbicidas diferiu entre os anos. Em 2010/11, o bispyribac-sodium, o penoxsulam e o metsulfuron-methyl prejudicaram o arroz apenas na semeadura-precoce. Em ambos os anos, a semeadura precoce do arroz promoveu maior potencial de rendimento, apesar dos danos dos herbicidas. As injúrias causadas pelos herbicidas bispyribac-sodium, penoxsulam e metsulfuron-methyl foram transitórias, não acarretando em perdas de produtividade. A temperatura fria próxima a aplicação aumenta a injúria dos herbicidas ALS.

11.
Ciênc. rural (Online) ; 53(4): e20210671, 2023. ilus, tab
Artigo em Inglês | VETINDEX | ID: biblio-1412137

RESUMO

Rice yield in Southern Brazil has increased linearly over the years. Early season sowing is the primary contributor to rice yield increase in Southern Brazil. However, that practice might expose rice seedlings to the risk of low-temperature stress, which can enhance herbicide injury and reduce rice yield. This research evaluated the effect of sowing dates on herbicide selectivity and agronomical rice traits. We conducted field experiments during the 2010/11 and 2011/12 growing seasons in Capão do Leão, RS, Brazil. The experimental design was a complete randomized block with a factorial arrangement. Factor A was early-sowed (in September) and late-sowed (in November); factor B was herbicide treatment (bispyribac-sodium, cyhalofop-butyl penoxsulam, metsulfuron-methyl, and nontreated check). Rice response to herbicide treatments differed between years. In 2010/11, bispyribac-sodium, penoxsulam, and metsulfuron-methyl injured rice only on early-sowed. In both years, early sowing rice promoted higher yield potential despite herbicide injury. The injury caused by the herbicides bispyribac-sodium, penoxsulam and metsulfurom-methyl was transient did not lead to yield losses. Cold temperature close the application increases the injury of ALS herbicides.


A produtividade do arroz no Sul do Brasil aumentou linearmente ao longo dos anos. A semeadura no início da janela é o principal contribuinte para o aumento da produtividade do arroz no sul do Brasil. No entanto, essa prática pode expor as plântulas de arroz ao estresse por baixa temperatura, aumentando os danos do herbicida e reduzindo a produtividade do arroz. Este trabalho teve como objetivo avaliar o efeito de épocas de semeadura na seletividade de herbicidas em caracteres agronômicos do arroz. Conduzimos experimentos de campo durante as safras 2010/11 e 2011/12 em Capão do Leão, RS, Brasil. O delineamento experimental foi em blocos casualizados completos com arranjo fatorial. O fator A foram a semeadura-precoce (em setembro) e a semeadura-tardia (em novembro); o fator B foram os tratamentos com herbicidas (bispyribac-sodium, cyhalofop-butyl, penoxsulam, metsulfuron-methyl e controle - sem herbicida). A resposta do arroz aos tratamentos com herbicidas diferiu entre os anos. Em 2010/11, o bispyribac-sodium, o penoxsulam e o metsulfuron-methyl prejudicaram o arroz apenas na semeadura-precoce. Em ambos os anos, a semeadura precoce do arroz promoveu maior potencial de rendimento, apesar dos danos dos herbicidas. As injúrias causadas pelos herbicidas bispyribac-sodium, penoxsulam e metsulfuron-methyl foram transitórias, não acarretando em perdas de produtividade. A temperatura fria próxima a aplicação aumenta a injúria dos herbicidas ALS.


Assuntos
Oryza , Irrigação Agrícola , Herbicidas
12.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430836

RESUMO

Treatments to combat giardiasis have been reported to have several drawbacks, partly due to the drug resistance and toxicity of current antiparasitic agents. These constraints have prompted many researchers to investigate new drugs that act against protozoan parasites. Enzyme inhibition is an important means of regulating pathogen metabolism and has recently been identified as a significant alternative target in the search for new treatments. Glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase (G6PD::6PGL) is a bifunctional enzyme involved in the pentose phosphate pathway (PPP) in Giardia lamblia (G. lamblia). The G. lamblia enzyme is unusual since, unlike the human enzyme, it is a fused enzyme. Here, we show, through inhibition assays, that an in-house chemical library of 120 compounds and four target compounds, named CNZ-7, CNZ-8, CMC-1, and FLP-2, are potent inhibitors of the G. lamblia G6PD::6PGL fused enzyme. With a constant (k2) of 2.3, 3.2, and 2.8 M−1 s−1, respectively, they provoke alterations in the secondary and tertiary protein structure and global stability. As a novel approach, target compounds show antigiardial activity, with IC50 values of 8.7, 15.2, 15.3, and 24.1 µM in trophozoites from G. lamblia. Moreover, these compounds show selectivity against G. lamblia, since, through counter-screening in Caco-2 and HT29 human cells, they were found to have low toxicity. This finding positions these compounds as a potential and attractive starting point for new antigiardial drugs.


Assuntos
Giardia lamblia , Giardíase , Animais , Humanos , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Trofozoítos/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Células CACO-2
13.
Cells ; 11(19)2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36231114

RESUMO

Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation. It is noteworthy that TFEB activation is context-dependent; therefore, its regulation is subjected to coordinated mechanisms that respond not only to nutrient fluctuations but also to stress cell programs to ensure proper cell homeostasis and organismal health. In this review, we provide updated insights into novel post-translational modifications that regulate TFEB activity and give an overview of TFEB beyond its widely known role in autophagy and the lysosomal pathway, thus opening the possibility of considering TFEB as a potential therapeutic target.


Assuntos
Autofagia , Lisossomos , Autofagia/genética , Carboidratos , Regulação da Expressão Gênica , Lisossomos/metabolismo , Fosforilação
14.
Plants (Basel) ; 11(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36079650

RESUMO

The differential growth and yield response of plant species to rising carbon dioxide concentrations and climatic change may alter species diversity within biomes. The Pampa Biome in South America is an important grassland biome of agronomic and environmental importance. Acanthostyles buniifolius (Chirca) is one of the most important weeds in natural pasture areas widely distributed in southern South America and can adversely affect livestock production. The current study was designed to identify possible responses of Chirca to CO2 concentration ([CO2]) and drought that would indicate higher adaptation and potential proliferation within the Pampa Biome. Chirca plants were cultivated at two CO2 concentrations (400 (a[CO2]) and 700 (e[CO2]) µmol mol-1) and two water conditions (under water restriction-15% of the pot capacity; and plants without water restriction-pot capacity). Besides growth parameters, we also determined water potential (ѱw), relative water contents (RWC), proline, glycine betaine, total soluble sugars, hydrogen peroxide, lipid peroxidation, superoxide dismutase (SOD), ascorbate peroxidase (APX) activity, chlorophyll A and B, carotenoids and root dry mass (RDM). Plants exposed to e[CO2] are more efficient in water use and have a greater increase in root dry mass, enabling greater adaptation to climate-induced droughts. Among the biochemical changes observed in the plants under drought stress, the accumulation of proline, glycine betaine, and total soluble sugars were the most evident mechanisms allowing plants to tolerate drought stress by osmotic adjustment.

15.
Microorganisms ; 10(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35889079

RESUMO

Helicobacter pylori (H. pylori) has been proposed as the foremost risk factor for the development of gastric cancer. We found that H. pylori express the enzyme glucose-6-phosphate dehydrogenase (HpG6PD), which participates in glucose metabolism via the pentose phosphate pathway. Thus, we hypothesized that if the biochemical and physicochemical characteristics of HpG6PD contrast with the host G6PD (human G6PD, HsG6PD), HpG6PD becomes a potential target for novel drugs against H. pylori. In this work, we characterized the biochemical properties of the HpG6PD from the H.pylori strain 29CaP and expressed the active recombinant protein, to analyze its steady-state kinetics, thermostability, and biophysical aspects. In addition, we analyzed the HpG6PD in silico structural properties to compare them with those of the HsG6PD. The optimal pH for enzyme activity was 7.5, with a T1/2 of 46.6 °C, at an optimum stability temperature of 37 °C. The apparent Km values calculated for G6P and NADP+ were 75.0 and 12.8 µM, respectively. G6P does not protect HpG6PD from trypsin digestion, but NADP+ does protect the enzyme from trypsin and guanidine hydrochloride (Gdn-HCl). The biochemical characterization of HpG6PD contributes to knowledge regarding H. pylori metabolism and opens up the possibility of using this enzyme as a potential target for specific and efficient treatment against this pathogen; structural alignment indicates that the three-dimensional (3D) homodimer model of the G6PD protein from H. pylori is different from the 3D G6PD of Homo sapiens.

16.
Int J Mol Sci ; 23(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35743027

RESUMO

Acinetobacter baumannii is a Gram-negative bacillus that causes multiple infections that can become severe, mainly in hospitalized patients. Its high ability to persist on abiotic surfaces and to resist stressors, together with its high genomic plasticity, make it a remarkable pathogen. Currently, the isolation of strains with high antimicrobial resistance profiles has gained relevance, which complicates patient treatment and prognosis. This resistance capacity is generated by various mechanisms, including the modification of the target site where antimicrobial action is directed. This mechanism is mainly generated by genetic mutations and contributes to resistance against a wide variety of antimicrobials, such as ß-lactams, macrolides, fluoroquinolones, aminoglycosides, among others, including polymyxin resistance, which includes colistin, a rescue antimicrobial used in the treatment of multidrug-resistant strains of A. baumannii and other Gram-negative bacteria. Therefore, the aim of this review is to provide a detailed and up-to-date description of antimicrobial resistance mediated by the target site modification in A. baumannii, as well as to detail the therapeutic options available to fight infections caused by this bacterium.


Assuntos
Acinetobacter baumannii , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla , Fluoroquinolonas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamas/farmacologia
17.
Rev. Univ. Ind. Santander, Salud ; 54(1): e317, Enero 2, 2022. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1407016

RESUMO

Resumen Introducción: La pandemia por COVID-19 ha requerido de la respuesta institucional de las diferentes organizaciones para mitigar sus efectos. Objetivo: Describir el proceso de respuesta institucional dirigida a la comunidad universitaria de la Universidad Industrial de Santander (UIS) frente la epidemia por COVID-19 y analizar los resultados de los procesos implementados durante 2020 y 2021. Metodología: Estudio descriptivo de tipo mixto con un componente cualitativo descriptivo de la organización y desarrollo de la respuesta institucional y un componente cuantitativo descriptivo del análisis de los casos sospechosos y confirmados de COVID-19 en la comunidad universitaria UIS. Resultados: La respuesta institucional UIS comenzó desde marzo de 2020 y comprendió lineamientos y adaptaciones de tipo académico y laboral y un plan de respuesta que incluyó 6 componentes de acción y un retorno gradual a la presencialidad. Durante 2021 se confirmaron 272 casos en funcionarios y docentes y 208 casos en estudiantes, con una tendencia que reflejó la dinámica de transmisión local, pero con menor letalidad. Conclusiones: La respuesta institucional UIS frente a la epidemia por COVID-19 inició tempranamente e incluyó diferentes componentes que permitieron un retorno progresivo con baja transmisión en las sedes. Los aspectos por mejorar estuvieron relacionados con la cobertura, calidad y continuidad del diagnóstico y atención oportunos, conexas a las competencias y fragmentación propias del sistema de salud, y con la visibilidad del plan y sus resultados dentro de la comunidad universitaria.


Abstract Introduction: The COVID-19 pandemic has required the institutional response of different organizations to mitigate its effects. Objective: To describe the institutional response process for the COVID-19 pandemic at the Universidad Industrial de Santander (UIS) and analyze the results of the processes implemented during 2020 and 2021. Methodology: Descriptive mixed study with a qualitative component of the organization and development of the institutional response, and a descriptive quantitative component of the analysis of suspected and confirmed cases of COVID-19. Results: The UIS institutional response began in March 2020. The plan included academic and employment guidelines and adaptations, a response plan that included 6 action components and a gradual return to attendance. During 2021, 272 cases were confirmed in employees and professors, and 208 cases in students with a trend that reflected the dynamics of local transmission, but with lower lethality. Conclusions: The UIS institutional response to the COVID-19 epidemic began early and included different components that allowed for a progressive return with low transmission. The aspects to improve were related to the coverage, quality and continuity of timely diagnosis and care related to competencies and fragmentation of the health system, and the visibility of the plan and its results within the university community.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Universidades , COVID-19 , Viroses , Saúde Pública , Colômbia , Educação , Pandemias
18.
Ciênc. rural (Online) ; 52(12): e20210350, 2022. tab, graf, ilus
Artigo em Inglês | VETINDEX | ID: biblio-1384536

RESUMO

An increase in 2,4-D use is expected as tolerant crops have been approved to use in Brazil, which may negatively affect important crops such as tobacco. Our objective was to determine safe distances between 2,4-D applications and tobacco fields considering herbicide contamination to the harvested product. A field experiment was conducted, consisting of a 2,4-D application done perpendicularly to the wind direction, using a tractor sprayer. Drifted herbicide was collected using tobacco plants placed at various points (-50 up to 400 meters from application zone), following three schemes: a) 0 to 0.5 hours after application (HAT); b) 0 to 24 HAT; and c) 0.5 to 24 HAT. Environmental conditions were recorded. Herbicide in tobacco leaves was quantified. Drift was detected up to 200 m in both years. Vapor movement of 2,4-D was detected up to 400 m from the application strip in 2016, on plants taken to the field after herbicide application. Environmental conditions in 2015 favored off-target movement (higher wind speed and air temperature and lower humidity); although, in 2016 the herbicide traveled further due to wet deposition. These results indicated that a 100-meter buffer zone is enough to significantly decrease chances of tobacco contamination above the tolerated threshold, and highlighted the importance of environmental conditions in the transport processes for 2,4-D under field conditions.


O aumento no uso do 2,4-D é esperado, uma vez que as culturas tolerantes foram aprovadas para uso no Brasil, o que pode afetar negativamente culturas importantes, como o tabaco. Nosso objetivo foi determinar a distância segura entre aplicações de 2,4-D e lavouras de tabaco, considerando a contaminação do herbicida no produto colhido. Um experimento de campo foi realizado, utilizando aplicação de 2,4-D perpendicularmente à direção do vento, com pulverizador tratorizado. A deriva do herbicida foi coletada plantas de tabaco colocadas em vários pontos (-50 até 400 metros da zona de aplicação), seguindo três esquemas: a) 0 a 0,5 horas após a aplicação (HAT); b) 0 a 24 HAT; e c) 0,5 a 24 HAT. As condições ambientais foram registradas. Foi quantificado o herbicida em folhas de tabaco. A deriva foi detectada até 200 m em 2015 e até 150 m em 2016. A volatilização ocorreu em ambos os anos, pois o 2,4-D foi detectado em plantas transportadas para o campo após a aplicação. As condições ambientais em 2015 favoreceram o movimento fora do alvo (maior velocidade do vento e temperatura do ar e menor umidade). Esses resultados indicam que uma zona de exclusão de 100 metros é suficiente para diminuir significativamente as chances de contaminação do tabaco acima do limite tolerado e, destaca a importância das condições ambientais nos processos de transporte do 2,4-D em condições de campo.


Assuntos
Nicotiana , Resíduos de Praguicidas/análise , Resíduos Voláteis , Herbicidas/administração & dosagem , Ácidos Indolacéticos/administração & dosagem , 24444
19.
Microorganisms ; 9(8)2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34442758

RESUMO

Giardia lamblia is a single-celled eukaryotic parasite with a small genome and is considered an early divergent eukaryote. The pentose phosphate pathway (PPP) plays an essential role in the oxidative stress defense of the parasite and the production of ribose-5-phosphate. In this parasite, the glucose-6-phosphate dehydrogenase (G6PD) is fused with the 6-phosphogluconolactonase (6PGL) enzyme, generating the enzyme named G6PD::6PGL that catalyzes the first two steps of the PPP. Here, we report that the G6PD::6PGL is a bifunctional enzyme with two catalytically active sites. We performed the kinetic characterization of both domains in the fused G6PD::6PGL enzyme, as well as the individual cloned G6PD. The results suggest that the catalytic activity of G6PD and 6PGL domains in the G6PD::6PGL enzyme are more efficient than the individual proteins. Additionally, using enzymatic and mass spectrometry assays, we found that the final metabolites of the catalytic reaction of the G6PD::6PGL are 6-phosphoglucono-δ-lactone and 6-phosphogluconate. Finally, we propose the reaction mechanism in which the G6PD domain performs the catalysis, releasing 6-phosphoglucono-δ-lactone to the reaction medium. Then, this metabolite binds to the 6PGL domain catalyzing the hydrolysis reaction and generating 6-phosphogluconate. The structural difference between the G. lamblia fused enzyme G6PD::6PGL with the human G6PD indicate that the G6PD::6PGL is a potential drug target for the rational synthesis of novels anti-Giardia drugs.

20.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205867

RESUMO

The increase in the use of antimicrobials such as colistin for the treatment of infectious diseases has led to the appearance of Aeromonas strains resistant to this drug. However, resistance to colistin not only occurs in the clinical area but has also been determined in Aeromonas isolates from the environment or animals, which has been determined by the detection of mcr genes that confer a resistance mechanism to colistin. The variants mcr-1, mcr-3, and mcr-5 have been detected in the genus Aeromonas in animal, environmental, and human fluids samples. In this article, an overview of the resistance to colistin in Aeromonas is shown, as well as the generalities of this molecule and the recommended methods to determine colistin resistance to be used in some of the genus Aeromonas.


Assuntos
Aeromonas/genética , Antibacterianos/química , Colistina/química , Farmacorresistência Bacteriana/genética , Aeromonas/efeitos dos fármacos , Aeromonas/patogenicidade , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Colistina/uso terapêutico , Humanos , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética
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