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1.
Antibiotics (Basel) ; 13(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38534683

RESUMO

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

2.
Toxins (Basel) ; 16(1)2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38251241

RESUMO

The jelleine family is a group of four peptides (jelleines I-IV) originally isolated from the royal jelly of honey bee (Apis mellifera), but later detected in some honey samples. These oligopeptides are composed of 8-9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38-50% of hydrophobic residues and a carboxamide C-terminus. Jelleines, generated by processing of the C-terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I-III have promising antimicrobial activity and low toxicity (LD50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use.


Assuntos
Mel , Peptídeos , Humanos , Abelhas , Animais , Peptídeos/farmacologia , Ácidos Graxos/farmacologia , Larva
3.
Rev. cienc. salud (Bogotá) ; 22(1): 1-9, 20240130.
Artigo em Espanhol | LILACS | ID: biblio-1554948

RESUMO

Introducción: en este artículo se aborda la nefrogeriatría como ciencia joven y el papel de la atención primaria de salud en su desarrollo, con el objetivo de abrir una reflexiónsobre los aportes teóricos y prácticos que esta rama puede ofrecer en la prevención y retardo de la progresión de la enfermedad renal crónica (erc) en adultos mayores, recalcando en la necesidad de humanizar la atención, como modo de restituir la calidad de vida y empoderar a los profesionales de la salud de un adecuado desem-peño. Desarrollo: se analiza en el artículo la situación de la erc y el envejecimiento, el desarrollo de la nefrogeriatría, la propuesta de modelación de la situación de la ciencia y la estrategia, así como los gigantes nefrogeriátricos. Se revisó la bibliografía basada fundamentalmente en las publicaciones de la biblioteca Cochrane, Dynamed, Pubmed y SciELO. Conclusión: la nefrología geriátrica (nefrogeriatría) es una disciplina médica de reciente surgimiento y que requiere la preparación integral de los profesio-nales de la salud


Introduction: This article elucidates geriatric nephrology (nephrogeriatrics) as a young science and reveals the role of primary health care in its development with the objective of highlighting the theoretical and practical contributions of this specialty in the prevention and attenuation of progression of chronic kidney disease (ckd) in older adults, emphasizing the need to humanize care, as a method of restoring the qual-ity of life and empowering health professionals. Development: A literature search was conducted in the Cochrane, Dynamed, PubMed, and SciELO databases and data were analyzed to elucidate the relationship between ckd and aging, the development of nephrogeriatrics, the proposal for modeling the situation of sci-ence and strategy as well as the nephrogeriatric giants. Conclusion: Nephrogeriatrics is a recently emerged medical discipline that warrants the integral preparation of health professionals


Introdução: este artigo aborda a nefrogeriatria como ciência jovem e o papel da Atenção Primária à Saúde em seu desenvolvimento com o objetivo de abrir uma reflexão sobre as contribuições teóricas e práticas que este ramo pode oferecer na prevenção e retardo da progressão da doença renal crônica (drc) em idosos, enfatizando a necessidade de humanizar o atendimento, como forma de restabelecer a qualidade de vida e capacitar os profissionais de saúde para uma atuação adequada. Desenvolvimento:o artigo analisa a situação da drc e do envelhecimento, o desenvolvimento da nefrogeriatria, a proposta de modelagem da situação da ciência e estratégia, bem como os gigantes da nefrogeriatria; a bibliografia revisada esteve baseada principalmente em publicações da biblioteca Cochrane, Dynamed, PubMed e SciELO. Conclusão: a nefrologia geriátrica (nefrogeriatria) é uma disciplina médica que surgiu recente-mente e que requer uma preparação integral dos profissionais de saúde


Assuntos
Humanos
4.
Environ Sci Pollut Res Int ; 30(43): 97253-97266, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37587399

RESUMO

Enrofloxacin (Enro) has been widely encountered in natural water sources, and that water is often used for irrigation in crop production systems. Due to its phytotoxicity and accumulation in plant tissues, the presence of Enro in water used for crop irrigation may represent economical and toxicological concerns. Here, we irrigated two ornamental plant species (Zantedeschia rehmannii Engl. and Spathiphyllum wallisii Regel.) with water artificially contaminated with the antimicrobial enrofloxacin (Enro; 0, 5, 10, 100, and 1000 µg L-1) to evaluate its effects on ornamental plant production, as well as its accumulation and distribution among different plant organs (roots, leaves, bulbs, and flower stems), and examined the economic and environmental safety of commercializing plants produced under conditions of pharmaceutical contamination. The presence of Enro in irrigation water was not found to disrupt plant growth (biomass) or flower production. Both species accumulated Enro, with its internal concentrations distributed as the following: roots > leaves > bulbs > flower stems. In addition to plant tolerance, the content of Enro in plant organs indicated that both Z. rehmannii and S. wallisii could be safety produced under Enro-contaminated conditions and would not significantly contribute to contaminant transfer. The high capacity of those plants to accumulate Enro in their tissues, associated with their tolerance to it, indicates them for use in Enro-phytoremediation programs.


Assuntos
Irrigação Agrícola , Biodegradação Ambiental , Enrofloxacina , Poluição Química da Água , Araceae/metabolismo , Enrofloxacina/metabolismo , Enrofloxacina/toxicidade
5.
Hemoglobin ; 47(2): 85-96, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37325879

RESUMO

The sickle cell disease (SCD) population has been considered particularly vulnerable to viral pandemics since the emergence of H1N1 in 2009. In this sense, the advance of the COVID-19 pandemic from 2020 has brought this group of patients to the center of concern. However, scientific knowledge about the susceptibility of patients with SCD to a severe COVID-19 pandemic is still insufficient, and efforts to establish a general profile of the disease in these patients, remain inadequate. The present study, therefore, sought to characterize the case fatality rate and severity of COVID-19 in patients with SCD throughout the world. A systematic review of Pubmed/MEDLINE, Scopus, Cochrane Library, and Virtual Health Library databases through December 2021 was then performed. Subsequently, the primary and secondary outcomes were used in the meta-analysis in RStudio® software. Seventy-two studies were included with 6,011 SCD patients confirmed to have SARS-CoV-2 infection between mid-2020 and early 2022. The mean age of patients was 27 years. During this period, 218 deaths caused by COVID-19 were reported in the studied population, corresponding to an overall case fatality rate of 3%. In addition, 10% of patients with SCD were admitted to the ICU after complications caused by COVID-19, and 4% of them required invasive ventilatory support. In conclusion, the high fatality rate, intensive care unit admission and need for mechanical ventilation due to COVID-19 in young patients with SCD indicate that this population is at high risk for severe disease progression.


Assuntos
Anemia Falciforme , COVID-19 , Vírus da Influenza A Subtipo H1N1 , Humanos , Adulto , SARS-CoV-2 , Pandemias , Anemia Falciforme/complicações
6.
Chemosphere ; 336: 139216, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37321459

RESUMO

Ciprofloxacin (CIP) is an antibiotic commonly used in human and veterinary medicine. It is present in the aquatic environment, but we still know very little about its effect on non-targeted organisms. This study aimed to evaluate the effects of long-term exposure to environmental CIP concentrations (1, 10, and 100 µg.L-1) in males and females of Rhamdia quelen. After 28 days of exposure, we collected the blood for the analysis of hematological and genotoxic biomarkers. Additionally, we measured 17 ß-estradiol and 11 keto-testosterone levels. After the euthanasia, we collected the brain and the hypothalamus to analyze acetylcholinesterase (AChE) activity and neurotransmitters, respectively. The liver and gonads were assessed for biochemical, genotoxic, and histopathological biomarkers. At 100 µg.L-1 CIP, we observed genotoxicity in the blood, nuclear morphological changes, apoptosis, leukopenia, and a reduction of AChE in the brain. In the liver was observed oxidative stress and apoptosis. At 10 µg.L-1 CIP, leukopenia, morphological changes, and apoptosis were presented in the blood and a reduction of AChE in the brain. Apoptosis, leukocyte infiltration, steatosis, and necrosis occurred in the liver. Even at the lowest concentration (1 µg.L-1), adverse effects such as erythrocyte and liver genotoxicity, hepatocyte apoptosis, oxidative stress, and a decrease in somatic indexes were observed. The results showed the importance of monitoring CIP concentrations in the aquatic environment that cause sublethal effects on fish.


Assuntos
Peixes-Gato , Leucopenia , Poluentes Químicos da Água , Animais , Masculino , Humanos , Feminino , Ciprofloxacina/farmacologia , Acetilcolinesterase , Fígado , Biomarcadores , Poluentes Químicos da Água/toxicidade
7.
Int J Mol Sci ; 24(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298516

RESUMO

Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to receive either 1% Zn sulfate solution (z) or saline (s) intraperitoneally. Body weight, hemoglobin, and RVH were measured. Zn levels were evaluated in plasma and lung tissue. Additionally, the lipid peroxidation levels, HIF2α/MTF-1/MT/ZIP12/PKCε protein expression and pulmonary artery remodeling were measured in the lung. The CIH and CH groups showed decreased plasma Zn and body weight and increased hemoglobin, RVH, and vascular remodeling; the CH group also showed increased lipid peroxidation. Zn administration under hypobaric hypoxia upregulated the HIF2α/MTF-1/MT/ZIP12/PKCε pathway and increased RVH in the intermittent zinc group. Under intermittent hypobaric hypoxia, Zn dysregulation could participate in RVH development through alterations in the pulmonary HIF2α/MTF1/MT/ZIP12/PKCε pathway.


Assuntos
Pulmão , Zinco , Ratos , Animais , Ratos Wistar , Pulmão/metabolismo , Hipóxia/metabolismo , Hipertrofia Ventricular Direita/etiologia , Peso Corporal
9.
Environ Sci Pollut Res Int ; 30(14): 41848-41863, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36639588

RESUMO

Phytoremediation has been a potential solution for the removal of pharmaceuticals from water. Here, we evaluated the toxicological safety of ciprofloxacin-contaminated water treated by 96 h with Salvinia molesta. The Neotropical catfish Rhamdia quelen was used as a model, and the potential of the phytoremediation technique for mitigating the drug accumulation in the fishes was also studied. Fish exposed to Cipro (1 and 10 µg·L-1) in untreated water showed toxic responses (alteration of hematological, genotoxicity, biochemical, and histopathological biomarkers) and accumulated Cipro in their muscles at concentrations high for human consumption (target hazardous quotient > 1). Fish exposed to water treated with S. molesta showed no toxic effect and no accumulation of Cipro in their tissues. This must be related to the fact that S. molesta removed up to 97% of Cipro from the water. The decrease in Cipro concentrations after water treatment with S. molesta not only prevented the toxic effects of Cipro on R. quelen fish but also prevented the antimicrobial accumulation in fish flesh, favouring safe consumption by humans. For the very first time, we showed the potential of phytoremediation as an efficiently nature-based solution to prevent environmental toxicological effects of antimicrobials to nontarget organisms such as fish and humans. The use of S. molesta for Cipro-removal from water is a green technology to be considered in the combat against antimicrobial resistance.


Assuntos
Peixes-Gato , Traqueófitas , Poluentes Químicos da Água , Animais , Humanos , Ciprofloxacina , Biodegradação Ambiental , Peixes-Gato/fisiologia , Poluentes Químicos da Água/análise
10.
Environ Sci Pollut Res Int ; 30(1): 622-639, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35904744

RESUMO

Ciprofloxacin (Cipro) water contamination is a global concern, having reached disturbing concentrations and threatening the aquatic ecosystems. We investigated the physiological responses and Cipro-phytoremediation capacity of one floating (Salvinia molesta D.S. Mitchell) and one submerged (Egeria densa Planch.) species of aquatic macrophytes. The plants were exposed to increased concentrations of Cipro (0, 1, 10, and 100 µg.Cipro.L-1) in artificially contaminated water for 96 and 168 h. Although the antibiotic affected the activities of mitochondrial electron transport chain enzymes, the resulting increases in H2O2 concentrations were not associated with oxidative damage or growth reductions, mainly due to the activation of antioxidant systems for both species. In addition to being tolerant to Cipro, after only 96 h, plants were able to reclaim more than 58% of that from the media. The phytoremediation capacity did not differ between the species, however, while S. molesta bioaccumulate, E. densa appears to metabolize Cipro in their tissues. Both macrophytes are indicated for Cipro-phytoremediation projects.


Assuntos
Ciprofloxacina , Ecossistema , Ciprofloxacina/metabolismo , Biodegradação Ambiental , Peróxido de Hidrogênio/metabolismo , Plantas/metabolismo , Água/metabolismo
11.
Front Mol Biosci ; 9: 1001508, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36310605

RESUMO

The biological activity of antimicrobial peptides and proteins is closely related to their structural aspects and is sensitive to certain post-translational modifications such as glycosylation, lipidation and PEGylation. However, PEGylation of protein and peptide drugs has expanded in recent years due to the reduction of their toxicity. Due to their size, the PEGylation process can either preserve or compromise the overall structure of these biopolymers and their biological properties. The antimicrobial peptide LyeTx I-bcys was synthesized by Fmoc strategy and coupled to polyethylene glycol 2.0 kDa. The conjugates were purified by HPLC and characterized by MALDI-ToF-MS analysis. Microbiological assays with LyeTx I-bcys and LyeTx I-bPEG were performed against Staphylococcus aureus (ATCC 33591) and Escherichia coli (ATCC 25922) in liquid medium. MIC values of 2.0 and 1.0 µM for LyeTx I-bcys and 8.0 and 4.0 µM for LyeTx I-bPEG were observed against S. aureus and E. coli, respectively. PEGylation of LyeTx I-bcys (LyeTx I-bPEG) decreased the cytotoxicity determined by MTT method for VERO cells compared to the non-PEGylated peptide. In addition, structural and biophysical studies were performed to evaluate the effects of PEGylation on the nature of peptide-membrane interactions. Surface Plasmon Resonance experiments showed that LyeTx I-b binds to anionic membranes with an association constant twice higher than the PEGylated form. The three-dimensional NMR structures of LyeTx I-bcys and LyeTx I-bPEG were determined and compared with the LyeTx I-b structure, and the hydrodynamic diameter and zeta potential of POPC:POPG vesicles were similar upon the addition of both peptides. The mPEG-MAL conjugation of LyeTx I-bcys gave epimers, and it, together with LyeTx I-bPEG, showed clear α-helical profiles. While LyeTx I-bcys showed no significant change in amphipathicity compared to LyeTx I-b, LyeTx I-bPEG was found to have a slightly less clear separation between hydrophilic and hydrophobic faces. However, the similar conformational freedom of LyeTx I-b and LyeTx I-bPEG suggests that PEGylation does not cause significant structural changes. Overall, our structural and biophysical studies indicate that the PEGylation does not alter the mode of peptide interaction and maintains antimicrobial activity while minimizing tissue toxicity, which confirmed previous results obtained in vivo. Interestingly, significantly improved proteolytic resistance to trypsin and proteinase K was observed after PEGylation.

12.
Int J Mol Sci ; 23(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36293512

RESUMO

Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic alterations in an organism. In the lung, one of the principal responses to hypoxia is the development of hypoxic pulmonary vasoconstriction (HPV), which improves gas exchange. However, when HPV is exacerbated, it induces high-altitude pulmonary hypertension (HAPH). Another important illness in hypobaric hypoxia is high-altitude pulmonary edema (HAPE), which occurs under acute exposure. Several studies have shown that inflammatory processes are activated in high-altitude illnesses, highlighting the importance of the crosstalk between hypoxia and inflammation. The aim of this review is to determine the inflammatory pathways involved in hypobaric hypoxia, to investigate the key role of inflammation in lung pathologies, such as HAPH and HAPE, and to summarize different anti-inflammatory treatment approaches for these high-altitude illnesses. In conclusion, both HAPE and HAPH show an increase in inflammatory cell infiltration (macrophages and neutrophils), cytokine levels (IL-6, TNF-α and IL-1ß), chemokine levels (MCP-1), and cell adhesion molecule levels (ICAM-1 and VCAM-1), and anti-inflammatory treatments (decreasing all inflammatory components mentioned above) seem to be promising mitigation strategies for treating lung pathologies associated with high-altitude exposure.


Assuntos
Doença da Altitude , Hipertensão Pulmonar , Infecções por Papillomavirus , Edema Pulmonar , Humanos , Hipertensão Pulmonar/metabolismo , Molécula 1 de Adesão Intercelular , Altitude , Edema Pulmonar/patologia , Molécula 1 de Adesão de Célula Vascular , Fator de Necrose Tumoral alfa , Interleucina-6 , Infecções por Papillomavirus/complicações , Doença da Altitude/metabolismo , Hipóxia/metabolismo , Edema/complicações , Citocinas , Inflamação/complicações , Oxigênio
13.
Rev. cienc. med. Pinar Rio ; 26(4): e5517, jul.-ago. 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1407899

RESUMO

RESUMEN Introducción: el estudio de la historia local de la medicina aporta relevantes saberes sobre la actividad del hombre en la sociedad. Objetivo: validar un material de apoyo a la docencia sobre historia de la medicina local pinareña. Métodos: investigación de desarrollo en la Facultad de Ciencias Médicas de Pinar del Río, durante el período de septiembre 2018 a diciembre de 2020. La muestra estuvo conformada por 69 estudiantes de segundo año de la carrera de Medicina y 26 profesores licenciados en Historia y Ciencias Sociales. Para el montaje digital y procesamiento se utilizó Adobe Master Colection CS6. Resultados: se configuró para hojas de papel formato A4, 21 cm x 29,7 cm, formado por seis capítulos y 280 páginas. El 96,15 de los profesores calificaron todos los indicadores como adecuados, el 100 % se evaluó como adecuado el valor como medio de enseñanza. Según criterio de los estudiantes, todos los indicadores recibieron calificaciones de adecuadas o superior por parte del 97,10 % de los estudiantes, donde la categoría 4 (valor como medio de enseñanza), fue evaluada como muy adecuada por el 50,73 %. Conclusiones: se confeccionó un medio de enseñanza sobre la historia de la medicina local, el cual fue evaluado como adecuado para integrar los contenidos de historia de la medicina local pinareña, con una adecuada estructura pedagógica para el logro de un aprendizaje significativo y contextualización de los contenidos y de gran valor como medio de enseñanza.


ABSTRACT Introduction: The study of the local history of medicine provides relevant knowledge about man's activity in society. Objective: to validate a teaching support material on the history of local medicine in Pinar del Rio. Methods: development research in the Faculty of Medical Sciences of Pinar del Río, during the period from September 2018 to December 2020. The sample consisted of 69 second year students of the Medicine career and 26 teachers with a degree in History and Social Sciences. Adobe Master Collection CS6 was used for digital assembly and processing. Results: It was configured for A4 format paper sheets, 21 cm x 29,7 cm, consisting of 6 chapters and 280 pages. 96,15 % of the teachers rated all the indicators as adequate, 100 % of them evaluated as adequate the value as a teaching medium. According to students' criteria, all indicators received ratings of adequate or higher by 97,10 % of the students, where category 4 (value as a teaching medium), was evaluated as very adequate by 50,73 %. Conclusions: A teaching medium on the history of local medicine was made, which was evaluated as adequate to integrate the contents of the history of local medicine in Pinar del Río, with an adequate pedagogical structure for the achievement of significant learning and contextualization of the contents and of great value as a teaching medium.

14.
Int J Mol Sci ; 23(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35805984

RESUMO

Hypobaric hypoxia is a condition that occurs at high altitudes (>2500 m) where the partial pressure of gases, particularly oxygen (PO2), decreases. This condition triggers several physiological and molecular responses. One of the principal responses is pulmonary vascular contraction, which seeks to optimize gas exchange under this condition, known as hypoxic pulmonary vasoconstriction (HPV); however, when this physiological response is exacerbated, it contributes to the development of high-altitude pulmonary hypertension (HAPH). Increased levels of zinc (Zn2+) and oxidative stress (known as the "ROS hypothesis") have been demonstrated in the vasoconstriction process. Therefore, the aim of this review is to determine the relationship between molecular pathways associated with altered Zn2+ levels and oxidative stress in HPV in hypobaric hypoxic conditions. The results indicate an increased level of Zn2+, which is related to increasing mitochondrial ROS (mtROS), alterations in nitric oxide (NO), metallothionein (MT), zinc-regulated, iron-regulated transporter-like protein (ZIP), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced protein kinase C epsilon (PKCε) activation in the development of HPV. In conclusion, there is an association between elevated Zn2+ levels and oxidative stress in HPV under different models of hypoxia, which contribute to understanding the molecular mechanism involved in HPV to prevent the development of HAPH.


Assuntos
Infecções por Papillomavirus , Vasoconstrição , Doença da Altitude , Humanos , Hipertensão Pulmonar , Hipóxia/metabolismo , NADPH Oxidases/metabolismo , Estresse Oxidativo , Infecções por Papillomavirus/metabolismo , Proteína Quinase C-épsilon/metabolismo , Artéria Pulmonar/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Vasoconstrição/fisiologia , Zinco/metabolismo
15.
Int J Mol Sci ; 23(11)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35682884

RESUMO

Hypoxic pulmonary hypertension (HPH) is characterized by sustained elevation of pulmonary artery pressure produced by vasoconstriction and hyperproliferative remodeling of the pulmonary artery and subsequent right ventricular hypertrophy (RVH). The search for therapeutic targets for cardiovascular pathophysiology has extended in many directions. However, studies focused on mitigating high-altitude pulmonary hypertension (HAPH) have been rare. Because AMP-activated protein kinase (AMPK) is involved in cardiovascular and metabolic pathology, AMPK is often studied as a potential therapeutic target. AMPK is best characterized as a sensor of cellular energy that can also restore cellular metabolic homeostasis. However, AMPK has been implicated in other pathways with vasculoprotective effects. Notably, cellular metabolic stress increases the intracellular ADP/ATP or AMP/ATP ratio, and AMPK activation restores ATP levels by activating energy-producing catabolic pathways and inhibiting energy-consuming anabolic pathways, such as cell growth and proliferation pathways, promoting cardiovascular protection. Thus, AMPK activation plays an important role in antiproliferative, antihypertrophic and antioxidant pathways in the pulmonary artery in HPH. However, AMPK plays contradictory roles in promoting HPH development. This review describes the main findings related to AMPK participation in HPH and its potential as a therapeutic target. It also extrapolates known AMPK functions to discuss the less-studied HAPH context.


Assuntos
Proteínas Quinases Ativadas por AMP , Hipertensão Pulmonar , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina , Doença da Altitude , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia , Artéria Pulmonar/patologia
16.
Arch Virol ; 167(9): 1763-1772, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35723756

RESUMO

Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses.


Assuntos
Arbovírus , Febre de Chikungunya , Vírus Chikungunya , Dengue , Vírus do Nilo Ocidental , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Dengue/tratamento farmacológico , Peptídeos/farmacologia , Peçonhas/farmacologia , Peçonhas/uso terapêutico , Vírus da Febre Amarela
17.
Rev. cuba. med. gen. integr ; 38(2): e1762, abr.-jun. 2022.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1408701

RESUMO

Introducción: La atención a pacientes nefrogeriátricos requiere de nuevas acciones que propicien mejores resultados de forma armónica e integrada. Objetivo: Caracterizar el estado actual del desempeño profesional del médico de familia en nefrogeriatría en la Atención Primaria de Salud. Métodos: Estudio observacional, descriptivo y transversal, desde mayo de 2014 a mayo de 2015, dirigido a 39 médicos de familia del área 5 de septiembre. Se emplearon métodos teóricos, empíricos y estadísticos para evaluar el desempeño profesional del médico de familia en nefrogeriatría. Se tuvo en cuenta el consentimiento informado. Resultados: Se identificó el estado actual de la variable estudiada, con la identificación de problemas relacionados con la dimensión cognitiva, asistencial, educativa e investigativa en la atención al paciente nefrogeriátrico en la Atención Primaria de Salud. Conclusiones: El desempeño profesional del médico de familia en nefrogeriatría carece de integración en la atención integral a los pacientes, la familia y la comunidad(AU)


Introduction: The care for nephrogeriatric patients requires new actions with better outcomes in a harmonic and integrated way. Objective: To characterize the current state of professional performance of family physicians in nephrogeriatrics in primary healthcare. Methods: Observational, descriptive and cross-sectional study carried out from May 2014 to May 2015, targeted at 39 family physicians belonging to 5 de Septiembre health area. Theoretical, empirical and statistical methods were used to evaluate the professional performance of the family physician in nephrogeriatrics. Informed consent was taken into account. Results: The current state of the studied variable was identified, with the identification of problems related to the cognitive, assistance, educational and investigative dimensions in the care of nephrogeriatric patients in primary healthcare. Conclusions: The professional performance of the family physician in nephrogeriatrics lacks integration regarding the comprehensive care of patients, family and the community(AU)


Assuntos
Humanos , Masculino , Feminino , Médicos de Família , Prática Profissional , Desempenho Profissional , Epidemiologia Descritiva , Estudos Transversais , Estudo Observacional
18.
FEMS Microbiol Ecol ; 98(4)2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35348680

RESUMO

Cryptococcus gattii, an environmental yeast isolated from plants, is one of the agents of cryptococcosis. Here, we aimed to develop a plant model to study C. gattii-plant interaction, since it is unclear how it affects the plant and the yeast. We tested three inoculation methods (scarification, infiltration, and abrasion) in three plant species: Arabidopsis thaliana, Nicotiana tabacum, and N. benthamiana. Cryptococcus gattii was able to grow in all three models, with a peak of yeast cell burden after 7 days, without any pathological effects. Furthermore, the fungal burden was reduced later, confirming that C. gattii is not a phytopathogen. Cryptococcus gattii proliferation was higher in N. benthamiana, which presented an increase in the hydrogen peroxide content, antioxidant system activity, and indoleacetic acid (IAA) production. Cryptococcus gattii colonies recovered from N. benthamiana presented lower ergosterol content, reduced capsule, and increased growth rate in vitro and inside macrophages. In vitro, IAA altered C. gattii morphology and susceptibility to antifungal drugs. We hypothesize that C. gattii can temporarily colonize plant living tissues, which can be a potential reservoir of yeast virulence, with further dissemination to the environment, birds, and mammals. In conclusion, N. benthamiana is suitable for studying C. gattii-plant interaction.


Assuntos
Arabidopsis , Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Arabidopsis/microbiologia , Criptococose/microbiologia , Mamíferos , Saccharomyces cerevisiae , Nicotiana
19.
Nat Prod Res ; 36(24): 6381-6388, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35073796

RESUMO

Here, we demonstrated the in vitro and in vivo antibacterial and anti-biofilm activities of melittin, a peptide derived from honeybee venom, against uropathogenic Escherichia coli (UPEC) resistant to quinolones. The minimum inhibitory concentration (MIC) of melittin varied from 0.5 to 8 µM. The bactericidal effect was considered rapid and potent (ranging from 3.0 to 6.0 h after incubation) against a quinolone-resistant and Extended Spectrum Beta-lactamase (ESBL)-producing UPEC strain. Prior exposure to melittin did not reduce the MIC of the quinolones tested, but it decreased the MIC of ceftizoxime by 8-fold due to its ability to form pores in the membrane. Furthermore, melittin disrupted mature biofilms (39.58% at 32 µM) and inhibited the adhesion of this uropathogen to the surfaces of urethral catheter. These results show that melittin is a promising molecule that can be incorporated into invasive urethral medical devices to prevent urinary infections caused by multidrug-resistant UPECs.


Assuntos
Venenos de Abelha , Quinolonas , Infecções Urinárias , Escherichia coli Uropatogênica , Humanos , Meliteno/farmacologia , Quinolonas/farmacologia , Venenos de Abelha/farmacologia , Adesivos , Biofilmes , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
20.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1408621

RESUMO

Estimado director: A nivel mundial se observan varias realidades que desde el campo de las Ciencias Médicas debemos valorar: una población envejecida que se incrementa considerablemente, un aumento de estos pacientes con enfermedades crónicas no trasmisibles a expensas de diabetes mellitus e hipertensión arterial, presencia de más de una enfermedad en un mismo paciente, principalmente enfermedad cardiovascular, incremento sostenido de los pacientes con enfermedad renal crónica (ERC), muchos de los cuales requieren tratamientos renales de reemplazo (TRR) o trasplante renal y, a pesar de ello, subregistro de la enfermedad, situación de la que no escapa Cuba. La Nefrogeriatría se ha comenzado a estudiar recientemente, por lo que existen...(AU)


Assuntos
Humanos , Masculino , Feminino , Geriatria , Nefrologia
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