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BACKGROUND: Peripheral venous catheters (PVCs) remain the primary mode of short-term venous access for managing intravenous fluid, obtaining blood samples, and peripheral parenteral nutrition. They may get contaminated and require regular monitoring to prevent complications. This study evaluated the occurrence of phlebitis and its associated-clinical and microbiological indicators. METHODS: The frequency of phlebitis was evaluated in hospitalized patients of both medical and surgical fields. Subsequently, the dichotomous association between the presence of phlebitis and the clinical aspects was investigated. In parallel, the bacterial contamination of PVCs was assessed through culture-based methods, microscopy observation, and 16S rRNA gene sequencing. RESULTS: Approximately one in four patients presented phlebitis (28.4%). The most frequent symptom was erythema at access site, with or without pain, corresponding to Score 1 on the phlebitis scale (17.9%). Colonization of both lumen and external surface of PVC was observed in 31.3% of the samples. Staphylococcus and Pseudomonas were the most isolated bacterial genera on the PVC surface. No significant association was observed between the presence of phlebitis and the clinical aspects, as well as the presence of microorganisms. CONCLUSION: Microorganism were present on both internal and external PVC surface, without being associated to phlebitis.
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OBJECTIVE: To verify the association between low self-reported sleep quality (LSQ) and fall in middle-aged and older adults every half-decade of life. METHOD: A cross-sectional study was conducted using data from the first wave (2015-2016) of the Brazilian Longitudinal Study of Aging (ELSI-Brazil), which is nationally representative. The sample consisted of 8,950 participants who were allocated into eight age groups: 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, and ≥ 85 years. The questionnaires used included self-reported sleep quality and the International Physical Activity Questionnaire short version. Fisher's exact test followed by binary logistic regression analysis was performed to identify the odds ratio of sleep quality for fall occurrence, controlled for confounding variables. RESULTS: Individuals aged 50-105 years (63.6 ± 10.2 years), 57.0% females and 43.0% males, participated in this study. Overall, 21.5% of participants experienced at least one fall. The relative frequency of participants classified as having high or LSQ remained constant across each half-decade of life. The LSQ exhibited a statistically significant OR (p < 0.05) for falls across age groups up to 84, even after accounting for confounding variables. CONCLUSION: LSQ is significantly associated with an increased occurrence of fall in adults aged >50 years, but not for ≥ 85 years regardless of sex and physical activity level.
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Acidentes por Quedas , Qualidade do Sono , Humanos , Feminino , Masculino , Brasil , Estudos Transversais , Idoso , Acidentes por Quedas/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Longitudinais , Autorrelato , Inquéritos e Questionários , Fatores EtáriosRESUMO
Fonsecaea pedrosoi is a melanized fungus that causes chromoblastomycosis (CBM), a tropical neglected disease responsible for chronic and disability-related subcutaneous mycosis. Given the challenging nature of CBM treatment, the study of new targets and novel bioactive drugs capable of improving patient life quality is urgent. In the present work, we detected a calcineurin activity in F. pedrosoi conidial form, employing primarily colorimetric, immunoblotting and flow cytometry assays. Our findings reveal that the calcineurin activity of F. pedrosoi was stimulated by Ca2+/calmodulin, inhibited by EGTA and specific inhibitors, such as tacrolimus (FK506) and cyclosporine A (CsA), and proved to be insensitive to okadaic acid. In addition, FK506 and CsA were able to affect the cellular viability and the fungal proliferation. This effect was corroborated by transmission electron microscopy that showed both calcineurin inhibitors promoted profound changes in the ultrastructure of conidia, causing mainly cytoplasm condensation and intense vacuolization that are clear indication of cell death. Our data indicated that FK506 exhibited the highest effectiveness, with a minimum inhibitory concentration (MIC) of 3.12 mg/L, whereas CsA required 15.6 mg/L to inhibit 100% of conidial growth. Interestingly, when both were combined with itraconazole, they demonstrated anti-F. pedrosoi activity, exhibiting a synergistic effect. Moreover, the fungal filamentation was affected after treatment with both calcineurin inhibitors. These data corroborate with other calcineurin studies in fungal cells and open up further discussions aiming to establish the role of this enzyme as a potential target for antifungal therapy against CBM infections.
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The use of recreational waters is a widespread activity worldwide, and one of the risks associated with this practice is the exposure of bathers to microorganisms that may arise due to pollution caused by inadequate infrastructure and sanitation. In the present work, we isolated Candida spp. (n = 24) from five recreational beaches in Rio de Janeiro, Brazil, in order to evaluate their susceptibility to antifungals, the production of virulence attributes and the in vivo virulence using Tenebrio molitor larvae as a model. The ITS1-5.8S-ITS2 gene sequencing identified thirteen isolates (54.1 %) as C. tropicalis, seven (29.1 %) as C. krusei (Pichia kudriavzevii), one (4.2 %) as C. rugosa (Diutina rugosa), one (4.2 %) as C. mesorugosa (Diutina mesorugosa), one (4.2 %) as C. utilis (Cyberlindnera jadinii) and one (4.2 %) as C. parapsilosis. C. tropicalis isolates showed resistance to azoles and susceptibility to amphotericin B, flucytosine and caspofungin. C. krusei isolates were resistant to fluconazole, caspofungin and itraconazole, with 42.8 % resistance to flucytosine, besides susceptibility to voriconazole and amphotericin B. The remaining species were susceptible to all tested antifungals. All Candida isolates adhered to abiotic surfaces and formed biofilm on polystyrene, albeit to varying degrees, and produced aspartic protease and hemolytic activity, which are considered fungal virulence attributes. C. tropicalis, C. krusei and C. utilis isolates produced phytase, while the only esterase producer was C. tropicalis. Regarding resistance to osmotic stress, all isolates of C. tropicalis, C. parapsilosis and C. mesorugosa grew up to 7.5 % NaCl; the remaining isolates grew up to 1.87-3.75 % NaCl. The mortality caused by fungal challenges in T. molitor larvae was variable, with C. tropicalis, C. utilis and C. parapsilosis being more virulent than C. krusei and C. rugosa complex. Collectively, the presence of these yeasts, particularly the virulent and resistant isolates, in recreational waters can pose a significant health risk to bathers.
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Antifúngicos , Candida , Farmacorresistência Fúngica , Brasil , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/patogenicidade , Candida/genética , Virulência , Testes de Sensibilidade Microbiana , Animais , PraiasRESUMO
3-Hydroxy-3-methylglutaric acidemia (HMGA) is a neurometabolic inherited disorder characterized by the predominant accumulation of 3-hydroxy-3-methylglutaric acid (HMG) in the brain and biological fluids of patients. Symptoms often appear in the first year of life and include mainly neurological manifestations. The neuropathophysiology is not fully elucidated, so we investigated the effects of intracerebroventricular administration of HMG on redox and bioenergetic homeostasis in the cerebral cortex and striatum of neonatal rats. Neurodevelopment parameters were also evaluated. HMG decreased the activity of glutathione reductase (GR) and increased catalase (CAT) in the cerebral cortex. In the striatum, HMG reduced the activities of superoxide dismutase, glutathione peroxidase, CAT, GR, glutathione S-transferase, and glucose-6-phosphate dehydrogenase. Regarding bioenergetics, HMG decreased the activities of succinate dehydrogenase and respiratory chain complexes II-III and IV in the cortex. HMG also decreased the activities of citrate synthase and succinate dehydrogenase, as well as complex IV in the striatum. HMG further increased DRP1 levels in the cortex, indicating mitochondrial fission. Finally, we found that the HMG-injected animals showed impaired performance in all sensorimotor tests examined. Our findings provide evidence that HMG causes oxidative stress, bioenergetic dysfunction, and neurodevelopmental changes in neonatal rats, which may explain the neuropathophysiology of HMGA.
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Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C. auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts' metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida-like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.
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The secreted aspartic peptidases (Saps) of Candida albicans play crucial roles in various steps of fungal-host interactions. Using a flow cytometry approach, this study investigated the expression of Saps1-3 antigens after (i) incubation with soluble proteins, (ii) interaction with mammalian cells, and (iii) infection in immunosuppressed BALB/c mice. Supplementation strategies involving increasing concentrations of bovine serum albumin (BSA) added to yeast carbon base (YCB) medium as the sole nitrogenous source revealed a positive and significant correlation between BSA concentration and both the growth rate and the percentage of fluorescent cells (%FC) labeled with anti-Saps1-3 antibodies. Supplementing the YCB medium with various soluble proteins significantly modulated the expression of Saps1-3 antigens in C. albicans. Specifically, immunoglobulin G, gelatin, and total bovine/human sera significantly reduced the %FC, while laminin, human serum albumin, fibrinogen, hemoglobin, and mucin considerably increased the %FC compared to BSA. Furthermore, co-cultivating C. albicans yeasts with either live epithelial or macrophage cells induced the expression of Saps1-3 antigens in 78% (mean fluorescence intensity [MFI] = 152.1) and 82.7% (MFI = 178.2) of the yeast cells, respectively, compared to BSA, which resulted in 29.3% fluorescent cells (MFI = 50.9). Lastly, the yeasts recovered from the kidneys of infected immunosuppressed mice demonstrated a 4.8-fold increase in the production of Saps1-3 antigens (MFI = 246.6) compared to BSA, with 95.5% of yeasts labeled with anti-Saps1-3 antibodies. Altogether, these results demonstrated the positive modulation of Saps' expression in C. albicans by various key host proteinaceous components, as well as by in vitro and in vivo host challenges.
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The increasing prevalence of Candida parapsilosis as a causative agent of fungal infections underscores the need to comprehensively understand its virulence factors. Secreted aspartic proteases (Saps) play a significant role in adhesion events, promoting biofilm formation, causing tissue damage and evading the host's immune response. In C. parapsilosis, three Saps have been identified: Sapp1, Sapp2 and Sapp3. The present study investigates the production dynamics of Sapp1 and Sapp2 across 10 clinical isolates of C. parapsilosis using various approaches. Each fungal isolate demonstrated the capability to utilize bovine serum albumin (BSA) as the sole nitrogen source, as evidenced by its degradation in a cell-free culture medium, forming low molecular mass polypeptides. Interestingly, the degradation of different proteinaceous substrates, such as BSA, human serum albumin (HSA), gelatin and hemoglobin, was typically isolate-dependent. Notably, higher proteolysis of HSA compared to BSA, gelatin and hemoglobin was observed. A quantitative assay revealed that the cleavage of a peptide fluorogenic substrate (cathepsin D) was isolate-specific, ranging from 44.15 to 270.61 fluorescence arbitrary units (FAU), with a mean proteolysis of 150.7 FAU. The presence of both Sapp1 and Sapp2 antigens on the cell surface of these fungal isolates was confirmed through immunological detection employing specific anti-Sapp1 and anti-Sapp2 antibodies. The surface levels of Sapp1 were consistently higher, up to fourfold, compared to Sapp2. Similarly, higher levels of Sapp1 than Sapp2 were detected in fungal secretions. This study provides insights into the dynamic expression and regulation of Sapps in C. parapsilosis, highlighting a known virulence factor that is considered a potential target for drug development against this increasingly prominent pathogen.
The fungal pathogen Candida parapsilosis can secrete aspartic proteases (Sapps) as part of its arsenal of virulence factors. We demonstrated that Sapps were able to cleave key host proteins, and the production of Sapp1 and Sapp2 antigens was typically dependent on the fungal isolate when grown in both planktonic- and biofilm-forming cells.
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Ácido Aspártico Proteases , Candida parapsilosis , Candida parapsilosis/enzimologia , Candida parapsilosis/genética , Humanos , Ácido Aspártico Proteases/metabolismo , Ácido Aspártico Proteases/genética , Fatores de Virulência/metabolismo , Soroalbumina Bovina , Proteólise , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Candidíase/microbiologia , Meios de Cultura/química , Catepsina D/metabolismo , Proteases Aspárticas SecretedasRESUMO
Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24 months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes.
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Envelhecimento , Astrócitos , Hipotálamo , Isotiocianatos , Fármacos Neuroprotetores , Ratos Wistar , Sulfóxidos , Animais , Isotiocianatos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Fármacos Neuroprotetores/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ratos , Masculino , Células Cultivadas , Antioxidantes/farmacologiaRESUMO
Human activities have changed the natural rates at which metals are moved and accumulated in both land and water environments, resulting in negative impacts on local wildlife. In this study, concentrations of Cr, Ni, Cd, Pb, Cu, Mn, Co, and Zn were evaluated in water and riverbed sediment samples collected from the Verde River basin (VR), as well as in tissue samples from five native Loricariidae species. Sediment samples collected from the central section of the VR riverbed indicated the presence of metal concentrations, which were primarily attributed to scattered pollution sources linked to rural activities in the surrounding areas. The bioconcentration factor in the Loricariids liver presented the highest average values for Zn (1.27-58.21), Co (0.48-14.91) and Cu (1.15-11.14). The same pattern was observed in the muscle, but in a lower proportion. Regarding the bioaccumulation factor, Co (1.54-34.84), Cu (5.85-25.22) and Zn (0.64-18.08) attained the highest average values in the liver. The co-inertia analysis examined the spatial distribution of metal concentrations in riverbed sediments and in tissues of Loricariids from the upper, middle, and lower stretches of the river, including the river mouth. The analysis revealed varying patterns, with samples from some regions showing higher bioaccumulation levels. This suggests that riverbed sediments are a primary source of metal contamination in Loricariids from these areas. The pollution has had a significant impact on the bioaccumulation of metals in the VR' Loricariids, which are good indicators of sediment-associated metal bioaccumulation. The metal concentrations recorded in both the riverbed sediments and Loricariids surpassed international and Brazilian limits set for aquatic health and safe human consumption. Given the importance of the Verde River in terms of its ecological, social, cultural, and economic roles, it is essential to implement biomonitoring and control measures to safeguard both terrestrial and aquatic resources.
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Peixes-Gato , Monitoramento Ambiental , Sedimentos Geológicos , Rios , Poluentes Químicos da Água , Sedimentos Geológicos/química , Sedimentos Geológicos/análise , Animais , Poluentes Químicos da Água/análise , Rios/química , Peixes-Gato/metabolismo , Brasil , Fígado/química , Fígado/metabolismo , Metais Pesados/análise , Metais/análise , BioacumulaçãoRESUMO
Fungal diseases are often linked to poverty, which is associated with poor hygiene and sanitation conditions that have been severely worsened by the COVID-19 pandemic. Moreover, COVID-19 patients are treated with Dexamethasone, a corticosteroid that promotes an immunosuppressive profile, making patients more susceptible to opportunistic fungal infections, such as those caused by Candida species. In this study, we analyzed the prevalence of Candida yeasts in wastewater samples collected to track viral genetic material during the COVID-19 pandemic and identified the yeasts using polyphasic taxonomy. Furthermore, we investigated the production of biofilm and hydrolytic enzymes, which are known virulence factors. Our findings revealed that all Candida species could form biofilms and exhibited moderate hydrolytic enzyme activity. We also proposed a workflow for monitoring wastewater using Colony PCR instead of conventional PCR, as this technique is fast, cost-effective, and reliable. This approach enhances the accurate taxonomic identification of yeasts in environmental samples, contributing to environmental monitoring as part of the One Health approach, which preconizes the monitoring of possible emergent pathogenic microorganisms, including fungi.
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COVID-19 , Candida , Águas Residuárias , Fluxo de Trabalho , Águas Residuárias/microbiologia , Águas Residuárias/virologia , Brasil/epidemiologia , Candida/isolamento & purificação , Candida/genética , Candida/classificação , COVID-19/epidemiologia , COVID-19/virologia , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Biofilmes , Monitoramento Ambiental/métodos , PandemiasRESUMO
The chemical stability of azithromycin (AZM) may be compromised depending on the imposed thermo-oxidative conditions. This report addresses evidence of this process under varying conditions of temperature (20-80 °C), exposure time to UV radiation (1-3 h irradiation at 257 nm), and air saturation (1-3 h saturation with atmospheric air at 1.2 L min-1 and 15 kPa) through electrochemical measurements performed with a thermoactivated cerium molybdate (Ce2(MoO4)3)/multi-walled carbon nanotubes (MWCNT)-based composite electrode. Thermal treatment at 120 °C led to coordinated water elimination in Ce2(MoO4)3, improving its electrocatalytic effect on antibiotic oxidation, while MWCNT were essential to reduce the charge-transfer resistance and promote signal amplification. Theoretical-experimental data revealed remarkable reactivity for the irreversible oxidation of AZM on the working sensor using phosphate buffer (pH = 8) prepared in CH3OH/H2O (10:90%, v/v). Highly sensitive (230 nM detection limit) and precise (RSD < 4.0%) measurements were recorded under these conditions. The results also showed that AZM reduces its half-life as the temperature, exposure time to UV radiation, and air saturation increase. This fact reinforces the need for continuous quality control of AZM-based pharmaceuticals, using conditions closer to those observed during their transport and storage, reducing impacts on consumers' health.
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Species of Haemogregarina are blood parasites known to parasitise vertebrate hosts, including fishes (Haemogregarina sensu lato) and freshwater turtles (Haemogregarina sensu stricto). Their vectors, include gnathiid isopods and leeches, respectively. In turtles, Haemogregarina balli has the best-characterized life cycle in the genus. However, no studies in Brazil have suggested a possible vector for any species of Haemogregarina from freshwater turtles. Therefore, in the present study, we provide insights into a leech vector based on specimens found feeding on two species of freshwater turtles, Podocnemis unifilis and Podocnemis expansa, using morphological and molecular data. In 2017 and 2019, freshwater turtles were collected in Goiás State, Brazil. Hosts were inspected for ectoparasites and leeches were collected from two specimens of P. expansa and nine specimens of P. unifilis. Leeches were subsequently identified as members of the genus Unoculubranchiobdella. Leech histological slides revealed haemogregarine-like structures, similar to post-sporogonic merogony, found near the gills and within the posterior sucker. Molecular analysis of the haemeogregarines resulted in the identification of three species of Haemogregarina: Haemogregarina embaubali, Haemogregarina goianensis, and Haemogregarina brasiliana. Therefore, our findings, based on morphology and DNA data suggest leeches of the genus Unoculubranchiondella as vectors for at least three species of Haemogregarina from Brazilian turtles.
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Água Doce , Sanguessugas , Tartarugas , Animais , Tartarugas/parasitologia , Brasil , Água Doce/parasitologia , Sanguessugas/classificação , Sanguessugas/anatomia & histologia , Sanguessugas/parasitologia , Filogenia , Vetores de Doenças , Eucoccidiida/isolamento & purificação , Eucoccidiida/genética , Eucoccidiida/classificaçãoRESUMO
Candida species undeniably rank as the most prevalent opportunistic human fungal pathogens worldwide, with Candida albicans as the predominant representative. However, the emergence of non-albicans Candida species (NACs) has marked a significant shift, accompanied by rising incidence rates and concerning trends of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our research group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as "CTP" - Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP demonstrated significant efficacy in inhibiting mitochondrial dehydrogenases, leading to heightened intracellular reactive oxygen species production. CTP treatment resulted in substantial damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and induced DNA fragmentation as revealed by the TUNEL assay. Scanning electron microscopy images of post-CTP treatment NACs further illustrated profound alterations in the fungal surface morphology, including invaginations, cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to a polystyrene surface and to form robust biofilm structures. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. In conclusion, CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.
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Antifúngicos , Candida , Complexos de Coordenação , Cobre , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Fenantrolinas , Teofilina , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Fenantrolinas/farmacologia , Fenantrolinas/química , Candida/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Teofilina/farmacologia , Teofilina/química , Espécies Reativas de Oxigênio/metabolismo , HumanosRESUMO
The present study aimed to evaluate the antimicrobial and modulating activity of the ethanol extract obtained from the leaves, stems, and roots of Cnidoscolus urens in multiresistant bacteria. The Minimum Inhibitory Concentration (MIC) values obtained for the extracts of leaves, stems, and roots were greater than 1024 µg/mL for all isolates. In the antimicrobial resistance modulation test, the extract of the leaves of C. urens showed a better modulating effect than that of the stems and roots for gentamicin, highlighting the reduction of MIC for Escherichia coli, Lactococcus garvieae and Staphylococcus sciuri. For erythromycin, a reduction of MIC was observed in L. garvieae, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae. The extract from the leaves of C. urens has an important modulating effect on resistance in multiresistant bacteria, especially with gentamicin and erythromycin.
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Mastite Bovina , Testes de Sensibilidade Microbiana , Extratos Vegetais , Animais , Antibacterianos/farmacologia , Mastite Bovina/microbiologia , Bovinos , Extratos Vegetais/farmacologia , Feminino , Alismatales/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Eritromicina/farmacologia , Folhas de Planta/microbiologia , Folhas de Planta/químicaRESUMO
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
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Three sequential batch reactors (SBR) were operated to evaluate salt addition's impact on granulation, performance, and biopolymer production in aerobic granular sludge (AGS) systems. System R1 was fed without adding salt (control); system R2 operated with saline pulses, i.e., one cycle with salt (2.5 g NaCl/L) addition followed by another without salt; and R3 received continuous supplementation of 2.5 g NaCl/L. The results indicated that the reactors supplemented with salt presented higher concentrations of mixed liquor volatile suspended solids (MLVSS) and better settleability than R1, showing that osmotic pressure contributed to biomass growth, accelerated granulation, and improved physical characteristics. The faster granulation occurred in R2, thus proving the beneficial effects of intermittent salt addition through alternating pulses. Salt addition did not impair the simultaneous removal of carbon, nitrogen, and phosphorus. In fact, R2 showed better carbon removals. In conclusion, continuous or intermittent (pulsed) supplementation of 2.5 g NaCl/L did not lead to increased production of extracellular polymeric substances (EPS) and alginate-like exopolymers (ALE). This outcome could be attributed to the low saline concentration employed, a higher food-to-microorganism (F/M) ratio observed in R1, and possibly greater endogenous consumption of biopolymers in the famine period in R2 and R3 due to the greater solids retention time (SRT). Therefore, this study brings important results that contribute to a better understanding of the effect of salt in continuous dosing or in pulses as a selection pressure strategy to accelerate granulation, as well as the behavior of the AGS systems for saline effluents.
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Reatores Biológicos , Esgotos , Eliminação de Resíduos Líquidos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Fósforo , Aerobiose , Biomassa , Nitrogênio , Biopolímeros , Carbono/metabolismo , Estresse Salino , Cloreto de SódioRESUMO
Leishmaniasis is a neglected tropical disease caused by protozoa parasites from the Leishmania genus. Vertebrate hosts acquire the infection through the bite of a female sandfly, initiating a complex parasite development cycle. Contrary to previous beliefs regarding cats' resistance, these animals have recently been identified as potential reservoirs for leishmaniasis. Clinical symptoms in cats can manifest in diverse forms, including cutaneous, mucocutaneous, and visceral manifestations. The diagnosis of feline leishmaniasis is complicated by nonspecific symptoms and the relatively lower specificity of serological tests. The recommended treatment for feline leishmaniasis involves the administration of medications; however, success varies in each cat. This review aims to present cases of feline leishmaniasis, highlighting clinical symptoms, diagnostic methods, therapy schedules, and outcomes. Among the 24 cases documented in the available literature, 12 achieved successful treatment without relapses, resulting in a reduced parasite load and improved symptoms. Three cases responded well but presented persistent sequelae. Two feline leishmaniasis cases initially had treatment success but later experienced recurrences. Finally, no response was observed in seven cases, leading to the euthanasia of cats due to ineffectiveness or irregularities along the therapy. Conventional treatments, despite potential hepatotoxicity and nephrotoxicity, exhibit a high efficacy in reducing parasitic load, thereby improving clinical symptoms and increasing the life expectancy of affected cats. Nevertheless, consistent adherence is crucial, as interruptions may render the therapy ineffective and contribute to parasite resistance. Therefore, addressing the challenges associated with feline leishmaniasis treatment necessitates the development of new strategies to ensure a more effective and sustained approach.
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Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.