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1.
Microbiol Spectr ; 12(6): e0410523, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38700337

RESUMO

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted. IMPORTANCE: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Colômbia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico
2.
Antimicrob Agents Chemother ; 68(5): e0147423, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38602418

RESUMO

Pseudomonas aeruginosa harboring Verona Integron-encoded metallo-ß-lactamase enzymes (VIM-CRPA) have been associated with infection outbreaks in several parts of the world. In the US, however, VIM-CRPA remain rare. Starting in December 2018, we identified a cluster of cases in our institution. Herein, we present our epidemiological investigation and strategies to control/manage these challenging infections. This study was conducted in a large academic healthcare system in Miami, FL, between December 2018 and January 2022. Patients were prospectively identified via rapid molecular diagnostics when cultures revealed carbapenem-resistant P. aeruginosa. Alerts were received in real time by the antimicrobial stewardship program and infection prevention teams. Upon alert recognition, a series of interventions were performed as a coordinated effort. A retrospective chart review was conducted to collect patient demographics, antimicrobial therapy, and clinical outcomes. Thirty-nine VIM-CRPA isolates led to infection in 21 patients. The majority were male (76.2%); the median age was 52 years. The majority were mechanically ventilated (n = 15/21; 71.4%); 47.6% (n = 10/21) received renal replacement therapy at the time of index culture. Respiratory (n = 20/39; 51.3%) or bloodstream (n = 13/39; 33.3%) were the most common sources. Most infections (n = 23/37; 62.2%) were treated with an aztreonam-avibactam regimen. Six patients (28.6%) expired within 30 days of index VIM-CRPA infection. Fourteen isolates were selected for whole genome sequencing. Most of them belonged to ST111 (12/14), and they all carried blaVIM-2 chromosomally. This report describes the clinical experience treating serious VIM-CRPA infections with either aztreonam-ceftazidime/avibactam or cefiderocol in combination with other agents. The importance of implementing infection prevention strategies to curb VIM-CRPA outbreaks is also demonstrated.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , beta-Lactamases , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Gestão de Antimicrobianos , Compostos Azabicíclicos/uso terapêutico , Aztreonam/uso terapêutico , Aztreonam/farmacologia , beta-Lactamases/genética , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Ceftazidima/uso terapêutico , Ceftazidima/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Integrons/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Estudos Retrospectivos
4.
Int J Mol Sci ; 24(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38069022

RESUMO

Natural products obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been used for cancer treatment, but the mechanisms by which they exert their antitumor activity appear to be different. In the present work, we show that the Anamu-SC extract reduces tumor growth in the 4T1 murine mammary carcinoma model but not in the B16-F10 melanoma model, unlike the standardized P2Et extract. Both extracts decreased the levels of interleukin-10 (IL-10) in the B16-F10 model, but only P2Et increased the levels of tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). Likewise, co-treatment of P2Et and doxorubicin (Dox) significantly reduced tumor size by 70% compared to the control group, but co-treatment of Anamu-SC with Dox had no additive effect. Analysis of intratumoral immune infiltrates showed that Anamu-SC decreased CD4+ T cell frequency more than P2Et but increased CD8+ T cell frequency more significantly. Both extracts reduced intratumoral monocytic myeloid-derived suppressor-like cell (M-MDSC-LC) migration, but the effect was lost when co-treated with doxorubicin. The use of P2Et alone or in co-treatment with Anamu-SC reduced the frequency of regulatory T cells and increased the CD8+/Treg ratio. In addition, Anamu-SC reduced glucose consumption in tumor cells, but this apparently has no effect on IFNγ- and TNFα-producing T cells, although it did reduce the frequency of IL-2-producing T cells. The efficacy of these herbal preparations is increasingly clear, as is the specificity conditioned by tumor heterogeneity as well as the different chemical complexity of each preparation. Although these results contribute to the understanding of specificity and its future benefits, they also underline the fact that the development of each of these standardized extracts called polymolecular drugs must follow a rigorous path to elucidate their biological activity.


Assuntos
Produtos Biológicos , Carcinoma , Melanoma Experimental , Camundongos , Animais , Produtos Biológicos/uso terapêutico , Modelos Animais de Doenças , Fator de Necrose Tumoral alfa/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Melanoma Experimental/patologia , Interferon gama/uso terapêutico , Imunidade , Camundongos Endogâmicos C57BL
5.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139247

RESUMO

Previously, studies have shown that leukemic cells exhibit elevated glycolytic metabolism and oxidative phosphorylation in comparison to hematopoietic stem cells. These metabolic processes play a crucial role in the growth and survival of leukemic cells. Due to the metabolic plasticity of tumor cells, the use of natural products has been proposed as a therapeutic alternative due to their ability to attack several targets in tumor cells, including those that could modulate metabolism. In this study, the potential of Petiveria alliacea to modulate the metabolism of K562 cell lysates was evaluated by non-targeted metabolomics. Initially, in vitro findings showed that P. alliacea reduces K562 cell proliferation; subsequently, alterations were observed in the endometabolome of cell lysates treated with the extract, mainly in glycolytic, phosphorylative, lipid, and amino acid metabolism. Finally, in vitro assays were performed, confirming that P. Alliacea extract decreased the oxygen consumption rate and intracellular ATP. These results suggest that the anti-tumor activity of the aqueous extract on the K562 cell line is attributed to the decrease in metabolites related to cell proliferation and/or growth, such as nucleotides and nucleosides, leading to cell cycle arrest. Our results provide a preliminary part of the mechanism for the anti-tumor and antiproliferative effects of P. alliacea on cancer.


Assuntos
Leucemia Mieloide , Phytolaccaceae , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células K562 , Leucemia Mieloide/tratamento farmacológico , Phytolaccaceae/química
6.
Front Mol Biosci ; 10: 1235160, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028534

RESUMO

Acute leukemias (AL) are aggressive neoplasms with high mortality rates. Metabolomics and oxidative status have emerged as important tools to identify new biomarkers with clinical utility. To identify the metabolic differences between healthy individuals (HI) and patients with AL, a multiplatform untargeted metabolomic and lipidomic approach was conducted using liquid and gas chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS or GC-QTOF-MS). Additionally, the total antioxidant capacity (TAC) was measured. A total of 20 peripheral blood plasma samples were obtained from patients with AL and 18 samples from HI. Our analysis revealed 135 differentially altered metabolites in the patients belonging to 12 chemical classes; likewise, the metabolic pathways of glycerolipids and sphingolipids were the most affected in the patients. A decrease in the TAC of the patients with respect to the HI was evident. This study conducted with a cohort of Colombian patients is consistent with observations from other research studies that suggest dysregulation of lipid compounds. Furthermore, metabolic differences between patients and HI appear to be independent of lifestyle, race, or geographic location, providing valuable information for future advancements in understanding the disease and developing more global therapies.

7.
Life (Basel) ; 13(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38004281

RESUMO

This study presents a polymeric scaffold designed and manufactured to mimic the structure and mechanical compressive characteristics of trabecular bone. The morphological parameters and mechanical behavior of the scaffold were studied and compared with trabecular bone from bovine iliac crest. Its mechanical properties, such as modulus of elasticity and yield strength, were studied under a three-step monotonic compressive test. Results showed that the elastic modulus of the scaffold was 329 MPa, and the one for trabecular bone reached 336 MPa. A stepwise dynamic compressive test was used to assess the behavior of samples under various loading regimes. With microcomputed tomography (µCT), a three-dimensional reconstruction of the samples was obtained, and their porosity was estimated as 80% for the polymeric scaffold and 88% for trabecular bone. The full-field strain distribution of the samples was measured using in situ µCT mechanics and digital volume correlation (DVC). This provided information on the local microdeformation mechanism of the scaffolds when compared to that of the tissue. The comprehensive results illustrate the potential of the fabricated scaffolds as biomechanical templates for in vitro studies. Furthermore, there is potential for extending this structure and fabrication methodology to incorporate suitable biocompatible materials for both in vitro and in vivo clinical applications.

8.
Antimicrob Agents Chemother ; 67(11): e0057823, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37855639

RESUMO

Biofilm-producing Pseudomonas aeruginosa infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat P. aeruginosa infections. Ten MDR/XDR P. aeruginosa strains and five P. aeruginosa-specific phages were genetically characterized and evaluated based upon their antibiotic susceptibilities and phage sensitivities. Two selected strains, AR351 (XDR) and I0003-1 (MDR), were treated singly and in combination with either a broad-spectrum or narrow-spectrum phage, phage EM-T3762627-2_AH (EM), or 14207, respectively, and bactericidal antibiotics of five classes in biofilm time-kill analyses. Synergy and/or bactericidal activity was demonstrated with all PACs against one or both drug-resistant P. aeruginosa strains (average reduction: -Δ3.32 log10 CFU/cm2). Slightly improved ciprofloxacin susceptibility was observed in both strains after exposure to phages (EM and 14207) in combination with ciprofloxacin and colistin. Based on phage cocktail optimization with four phages (EM, 14207, E20050-C (EC), and 109), we identified several effective phage-antibiotic cocktails for further analysis in a 4-day pharmacokinetic/pharmacodynamic in vitro biofilm model. Three-phage cocktail, EM + EC + 109, in combination with ciprofloxacin demonstrated the greatest biofilm reduction against AR351 (-Δ4.70 log10 CFU/cm2 from baseline). Of remarkable interest, the addition of phage 109 prevented phage resistance development to EM and EC in the biofilm model. PACs can demonstrate synergy and offer enhanced eradication of biofilm against drug-resistant P. aeruginosa while preventing the emergence of resistance.


Assuntos
Bacteriófagos , Infecções por Pseudomonas , Humanos , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Biofilmes
9.
Psychoneuroendocrinology ; 158: 106380, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37696229

RESUMO

OBJECTIVE: Stress is common among pregnant individuals and is associated with an altered gut microbiota composition in infants. It is unknown if these compositional changes persist into the preschool years when the gut microbiota reaches an adult-like composition. This study aimed to investigate if indicators of prenatal stress (i.e., psychological distress and stress-related physiology) are associated with children's gut microbiota composition and metabolites at 3-4 years of age. METHODS: Maternal-child pairs (n = 131) were from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Each trimester, psychological distress was measured as symptoms of anxiety (Symptom Checklist-90-R) and depressed mood (Edinburgh Postnatal Depression Scale), whereas salivary cortisol was quantified as a measure of stress-related physiology. Child stool samples were collected at 3-4 years to evaluate gut microbiota composition using 16S rRNA gene sequencing and fecal metabolome using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Associations between prenatal distress and cortisol with the gut microbiota were determined using Pearson and Spearman correlations and corrected for multiple testing. Associations between prenatal distress and cortisol with the fecal metabolome were assessed using Metaboanalyst. RESULTS: Symptoms of depressed mood during the 2nd and 3rd trimesters and anxiety during the 2nd trimester of pregnancy were associated with increased alpha diversity of the child's gut microbiota. Cortisol levels during the 1st trimester were also associated with increased Faith PD diversity (r = 0.32), whereas cortisol levels during the 2nd trimester were associated with reduced Shannon diversity (r = -0.27). Depression scores during the 2nd and 3rd trimesters were associated with reductions in the relative abundances of Eggerthella, Parasutterella, and increases in Ruminococcaceae (rs = -0.28, rs = -0.32, rs = 0.32, respectively), as well as the fecal metabolome (e.g., branched-chain amino acid metabolism). Cortisol levels during the 2nd trimester correlated with 7 bacterial taxa, whereas 1st-trimester cortisol levels were associated with the child's fecal metabolome. CONCLUSIONS: Prenatal distress and cortisol were associated with both child gut microbiota composition and fecal metabolome at preschool age. Understanding these associations may allow for the identification of microbiota-targeted interventions to support child developmental outcomes affected by prenatal stress.


Assuntos
Depressão , Microbioma Gastrointestinal , Feminino , Gravidez , Adulto , Lactente , Humanos , Pré-Escolar , Depressão/metabolismo , Hidrocortisona/análise , Cromatografia Líquida , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S , Espectrometria de Massas em Tandem
10.
Biology (Basel) ; 12(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37759596

RESUMO

Nutritional phosphate deficiency is a major limitation to plant growth. Here, we monitored fluxes in pathways supporting respiratory metabolism in potato (Solanum tuberosum) cell cultures growing in control or limiting phosphate conditions. Sugar uptake was quantified using [U-14C]sucrose as precursor. Carbohydrate degradation through glycolysis and respiratory pathways was estimated using the catabolism of [U-14C]sucrose to 14CO2. Anaplerotic carbon flux was assessed by labeling with NaH14CO3. The data showed that these metabolic fluxes displayed distinct patterns over culture time. However, phosphate depletion had relatively little impact on the various fluxes. Sucrose uptake was higher during the first six days of culture, followed by a decline, which was steeper in Pi-sufficient cells. Anaplerotic pathway flux was more important at day three and decreased thereafter. In contrast, the flux between sucrose and CO2 was at a maximum in the mid-log phase of the culture, with a peak at Day 6. Metabolization of [U-14C]sucrose into neutral, basic and acidic fractions was also unaffected by phosphate nutrition. Hence, the well-documented changes in central metabolism enzymes activities in response to Pi deficiency do not drastically modify metabolic fluxes, but rather result in the maintenance of the carbon fluxes that support respiration.

11.
Int J Mol Sci ; 24(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37629156

RESUMO

The poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.


Assuntos
Leucemia Mieloide , Phytolaccaceae , Animais , Camundongos , Carga Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
12.
Cancer Immunol Immunother ; 72(10): 3279-3292, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37464192

RESUMO

Although the antitumor effect of P. nigrum has been widely studied, research related to its possible immunomodulatory effects is relatively scarce. Here, the antitumor and immunomodulatory activity of an ethanolic extract of P. nigrum were evaluated in the murine models of 4T1 breast cancer and B16-F10 melanoma. In vitro evaluations showed that the P. nigrum extract has cytotoxic activity, induces apoptotic cell death, and has a pro-oxidant effect in both cell lines, but it regulates glucose uptake differently in both lines, decreasing it in 4T1 but not in B16-F10. P. nigrum extract significantly reduced tumor size in both models and decreased the occurrence of macrometastases in 4T1 model. Evaluation of immune subpopulations by flow cytometry revealed that the P. nigrum extract significantly increases the frequency of dendritic cells and activated CD8+ T cells and decreases the frequency of myeloid-derived suppressor like cells and Tregs in the tumor microenvironment of both models but with different dynamics. Our findings strongly suggest that the P. nigrum extract exerts immunomodulatory functions, slightly related to the modulation of cellular energy metabolism, which could ultimately contribute to the promising antitumor effect of P. nigrum.


Assuntos
Neoplasias da Mama , Melanoma Experimental , Piper nigrum , Camundongos , Humanos , Animais , Feminino , Neoplasias da Mama/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Modelos Animais de Doenças , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Imunidade , Microambiente Tumoral
13.
Neurosci Lett ; 810: 137357, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37355156

RESUMO

The relationship between the gut microbiota and neurocognitive outcomes is becoming increasingly recognized; however, findings in humans are inconsistent. In addition, few studies have investigated the gut microbial metabolites that may mediate this relationship. The objective of this study was to investigate associations between full-scale intelligence (FSIQ) and the composition of the gut microbiota and metabolome in preschool children. Stool samples were collected from a community sample of 245 typically developing children (3-5 years) from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. The faecal microbiome was assessed using 16S rRNA sequencing and the metabolome using LC-MS/MS. FSIQ and scores on the Verbal Comprehension, Visual Spatial, Working Memory indices of the Wechsler Preschool and Primary Scale of Intelligence-IV were used to assess neurocognition. Associations between the gut microbiota and FSIQ were determined using Pearson and Spearman correlations, which were corrected for multiple testing and relevant covariates. Verbal Comprehension correlated negatively with both Shannon alpha diversity (r = -0.14, p = 0.032) and the caffeine-derived metabolite paraxanthine (r = -0.22, p < 0.001). No other significant correlations were observed. Overall, the weak to modest correlations between Verbal Comprehension with alpha diversity and paraxanthine provide limited evidence of an association between the gut microbiota and neurocognitive outcomes in typically developing preschool children.


Assuntos
Microbioma Gastrointestinal , Humanos , Pré-Escolar , RNA Ribossômico 16S , Cromatografia Líquida , Espectrometria de Massas em Tandem , Inteligência
14.
Antimicrob Agents Chemother ; 67(7): e0027723, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37166191

RESUMO

Resistant Gram-negative bacteria are a growing concern in the United States, leading to significant morbidity and mortality. We identified a 72-year-old female patient who presented with unilateral vision loss. She was found to have a large corneal ulcer with hypopyon. Culture of corneal scrapings grew extensively drug-resistant Pseudomonas aeruginosa. Treatment involved a combination of systemic and topical antibiotics. Whole genome sequencing revealed the presence of blaVIM-80, blaGES-9, and other resistance determinants. This distinctive organism was linked to an over-the-counter artificial tears product.


Assuntos
Úlcera da Córnea , Infecções por Pseudomonas , Feminino , Humanos , Idoso , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Pseudomonas aeruginosa/genética , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas , Infecções por Pseudomonas/microbiologia , Testes de Sensibilidade Microbiana
15.
Pharmaceutics ; 15(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37111524

RESUMO

P2Et is the standardized extract of Caesalpinia spinosa (C. spinosa), which has shown the ability to reduce primary tumors and metastasis in animal models of cancer, by mechanisms involving the increase in intracellular Ca++, reticulum stress, induction of autophagy, and subsequent activation of the immune system. Although P2Et has been shown to be safe in healthy individuals, the biological activity and bioavailability can be increased by improving the dosage form. This study investigates the potential of a casein nanoparticle for oral administration of P2Et and its impact on treatment efficacy in a mouse model of breast cancer with orthotopically transplanted 4T1 cells. Animals were treated with either free or encapsulated oral P2Et orally or i.p. Tumor growth and macrometastases were evaluated. All P2Et treatments significantly delayed tumor growth. The frequency of macrometastasis was reduced by 1.1 times with P2Et i.p., while oral P2Et reduced it by 3.2 times and nanoencapsulation reduced it by 3.57 times. This suggests that nanoencapsulation led to higher doses of effective P2Et being delivered, slightly improving bioavailability and biological activity. Therefore, the results of this study provide evidence to consider P2Et as a potential adjuvant in the treatment of cancer, while the nanoencapsulation of P2Et provides a novel perspective on the delivery of these functional ingredients.

16.
Antibiotics (Basel) ; 12(3)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36978355

RESUMO

We report the presence of the mcr-1 gene among 880 Escherichia coli clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL). These colistin-resistant isolates were screened for the presence of the mcr-1 gene; five carried the gene. These five isolates were subjected to whole genome sequencing (WGS) to identify additional resistomes and their ST. In addition, antimicrobial susceptibility testing revealed that all E. coli isolates carrying mcr-1 were susceptible to third generation-cephalosporin and carbapenems, except one, which carried an extended-spectrum ß-lactamase (CTX-M-55), along with the fosfomycin resistance encoding gene, fosA. WGS indicated that these isolates belonged to four distinct sequence types (ST58, ST46, ST393, and a newly described ST14315) and to phylogroups B1, A, and D. In this geographic region, the spread of mcr-1 in E. coli is low and has not been inserted into high-risk clones such as ST131, which has been present in the country longer.

17.
Open Forum Infect Dis ; 10(2): ofad014, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36820316

RESUMO

Background: Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen. Methods: Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of ß-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-ß-lactamase (MBL) encoding genes to the resistance profile, bla BlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B. Results: WGS identified the organism as E. anophelis. MBL genes bla BlaB-1 and bla GOB-26 were identified, in addition to bla CME-2, which encodes for an extended-spectrum ß-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available ß-lactams, carbapenems, newer ß-lactam ß-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM. Conclusions: Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.

18.
Antimicrob Agents Chemother ; 67(1): e0093022, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36602311

RESUMO

Design of novel ß-lactamase inhibitors (BLIs) is one of the currently accepted strategies to combat the threat of cephalosporin and carbapenem resistance in Gram-negative bacteria. Boronic acid transition state inhibitors (BATSIs) are competitive, reversible BLIs that offer promise as novel therapeutic agents. In this study, the activities of two α-amido-ß-triazolylethaneboronic acid transition state inhibitors (S02030 and MB_076) targeting representative KPC (KPC-2) and CTX-M (CTX-M-96, a CTX-M-15-type extended-spectrum ß-lactamase [ESBL]) ß-lactamases were evaluated. The 50% inhibitory concentrations (IC50s) for both inhibitors were measured in the nanomolar range (2 to 135 nM). For S02030, the k2/K for CTX-M-96 (24,000 M-1 s-1) was twice the reported value for KPC-2 (12,000 M-1 s-1); for MB_076, the k2/K values ranged from 1,200 M-1 s-1 (KPC-2) to 3,900 M-1 s-1 (CTX-M-96). Crystal structures of KPC-2 with MB_076 (1.38-Å resolution) and S02030 and the in silico models of CTX-M-96 with these two BATSIs show that interaction in the CTX-M-96-S02030 and CTX-M-96-MB_076 complexes were overall equivalent to that observed for the crystallographic structure of KPC-2-S02030 and KPC-2-MB_076. The tetrahedral interaction surrounding the boron atom from S02030 and MB_076 creates a favorable hydrogen bonding network with S70, S130, N132, N170, and S237. However, the changes from W105 in KPC-2 to Y105 in CTX-M-96 and the missing residue R220 in CTX-M-96 alter the arrangement of the inhibitors in the active site of CTX-M-96, partially explaining the difference in kinetic parameters. The novel BATSI scaffolds studied here advance our understanding of structure-activity relationships (SARs) and illustrate the importance of new approaches to ß-lactamase inhibitor design.


Assuntos
Triazóis , beta-Lactamases , beta-Lactamases/genética , beta-Lactamases/química , Inibidores de beta-Lactamases/farmacologia , Ácidos Borônicos/farmacologia , Ácidos Borônicos/química , Penicilinas , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
19.
Rev. cienc. cuidad ; 20(2): 51-65, 2023.
Artigo em Espanhol | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-1518303

RESUMO

Objetivo: Determinar los conocimientos, las actitudes y las prácticas en el uso de méto-dos anticonceptivos en mujeres en edad reproductiva del barrio las Delicias de la ciudad de Duitama ­ Boyacá en el año 2021. Materiales y métodos: Estudio cuantitativo descriptivo ­ transversal, contando con una muestra calculada de 88 mujeres con muestreo a conveni-encia, incluyendo a mujeres entre los 18 y 54 años, aplicando la encuesta validada "Conoci-mientos, actitudes y prácticas sobre los métodos anticonceptivos" y el análisis estadístico fue de tipo univariado por medio del Software SPPS versión 23. Resultados: Las participantes tenían una edad promedio de 30.67 años (DE: 9,5), la mayoría tenía como estado civil ser soltera (48%; n: 43) y acudían a los programas de planificación familiar (71,6%; n: 63). To-das manifestaron conocer los métodos anticonceptivos (100%; n:88), sin embargo, el 40% (n:36) no tiene claridad sobre las reacciones adversas de la píldora; además el 43,1% (n:38) consideran que al usar el preservativo se disfruta menos de la relación sexual. En mujeres jóvenes predomina la preferencia de métodos de corta duración y hormonales, a diferencia de mujeres con mayor edad en donde predominaron los métodos larga duración o definitivos.Conclusiones: Los profesionales de la salud juegan un papel importante en la asesoría en planificación familiar al detectar las necesidades de la mujer, fortaleciendo la educación en derechos sexuales y reproductivos, para que esta población logre el disfrute de su vida sexual al adquirir una educación integral y con acceso a los métodos anticonceptivos.


Objective: To determine the knowledge, attitudes and practices in the use of contraceptive methods in women of reproductive age in the Las Delicias neighborhood of the city of Duita-ma - Boyacá in the year 2021. Materials and methods: Quantitative descriptive - cross-sec-tional study, with a calculated sample of 88 women with convenience sampling, including women between 18 and 54 years old, applying the validated survey "Knowledge, attitudes and practices about contraceptive methods" and the statistical analysis was of univariate type using SPPS Software version 23. Results: The participants had an average age of 30.67 years (SD: 9.5), most of them had single marital status (48%; n: 43) and attended family planning programs (71.6%; n: 63). All stated that they knew the contraceptive methods (100%; n:88) however, 40% (n:36) were not clear about the adverse reactions of the pill; In addition, 43.1% (n:38) consider that when using the preservative they enjoy sexual intercourse less. In young women, the preference for short-term and hormonal methods predominates, unlike older wom-en, where long-term or definitive methods predominated. Conclusions: Health profession-als play an important role in family planning counseling by detecting the needs of women, strengthening education in sexual and reproductive rights, so that this population achieves the enjoyment of their sexual life by acquiring a comprehensive education. and with access to contraceptive methods.


Objetivo: Determinar os conhecimentos, atitudes e práticas de mulheres na comunidade re-produtiva no bairro Las Delicias da cidade de Duitama - Boyacá no ano de 2021. Materiais e métodos: Quantitativo descritivo - estudo transversal, com amostra calculada de 88 mul-heres com amostragem de conveniência, incluindo mulheres entre 18 e 54 anos, aplicando o questionário validado "Conhecimentos, atitudes e práticas sobre métodos contraceptivos" e a análise estatística foi do tipo univariada usando o software SPPS versão 23. Resultados: Os participantes tinham idade média de 30,67 anos (DP: 9,5), a maioria era solteira (48%; n: 43) e frequentava programas de planejamento familiar (71,6%; n: 63). Todas afirmaram conhecer os métodos contraceptivos (100%; n:88), porém, 40% (n:36) não tinham clareza sobre as reações adversas da pílula; Além disso, 43,1% (n:38) consideram que ao usar o preservativo desfrutam menos das relações sexuais. Em mulheres jovens predomina a preferência por métodos de curta duração e hormonais, ao contrário das mulheres mais velhas, onde predom-inaram métodos de longa duração ou definitivos. Conclusões: Os profissionais de saúde de-sempenham um papel importante no aconselhamento em planejamento familiar, detectando as necessidades das mulheres, fortalecendo a educação em direitos sexuais e reprodutivos, para que essa população alcance o gozo de sua vida sexual adquirindo uma educação integral e com acesso a métodos contraceptivos.


Assuntos
Anticoncepcionais , Comportamento Sexual , Mulheres , Conhecimentos, Atitudes e Prática em Saúde
20.
Microorganisms ; 12(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38257865

RESUMO

Many bacteria have the ability to survive in challenging environments; however, they cannot all grow on standard culture media, a phenomenon known as the viable but non-culturable (VBNC) state. Bacteria commonly enter the VBNC state under nutrient-poor environments or under stressful conditions. This review explores the concept of the VBNC state, providing insights into the beneficial bacteria known to employ this strategy. The investigation covers different chemical and physical factors that can induce the latency state, cell features, and gene expression observed in cells in the VBNC state. The review also covers the significance and applications of beneficial bacteria, methods of evaluating bacterial viability, the ability of bacteria to persist in environments associated with higher organisms, and the factors that facilitate the return to the culturable state. Knowledge about beneficial bacteria capable of entering the VBNC state remains limited; however, beneficial bacteria in this state could face adverse environmental conditions and return to a culturable state when the conditions become suitable and continue to exert their beneficial effects. Likewise, this unique feature positions them as potential candidates for healthcare applications, such as the use of probiotic bacteria to enhance human health, applications in industrial microbiology for the production of prebiotics and functional foods, and in the beer and wine industry. Moreover, their use in formulations to increase crop yields and for bacterial bioremediation offers an alternative pathway to harness their beneficial attributes.

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