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1.
Protein Expr Purif ; 225: 106584, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39178976

RESUMEN

Lipases comprise the third most commercialized group of enzymes worldwide and those of microbial origin are sought for their multiple advantages. Agro-industrial waste can be an alternative culture medium for producing lipases, reducing production costs and the improper disposal of waste frying oil (WFO). This study aimed to produce yeast lipases through submerged fermentation (SF) using domestic edible oil waste as inducer and alternative culture medium. The optimal culture conditions, most effective inducer, and purification method for a new lipase from Moesziomyces aphidis BRT57 were identified. Yeast was cultured in medium containing green coconut pulp and WFO waste for 72 h. The maximum production of lipases in SF occurred in a culture medium containing WFO and yeast extract at 48 and 72 h of incubation, with enzyme activities of 8.88 and 11.39 U mL-1, respectively. The lipase was isolated through ultrafiltration followed by size exclusion chromatography, achieving a 50.46 % recovery rate. To the best of our knowledge, this is the first study to report the production and purification of lipases from M. aphidis, demonstrating the value of frying oil as inducer and alternative medium for SF, contributing to the production of fatty acids for biodiesel from food waste.


Asunto(s)
Cocos , Lipasa , Lipasa/aislamiento & purificación , Lipasa/química , Lipasa/biosíntesis , Lipasa/metabolismo , Cocos/química , Aceites de Plantas/química , Fermentación , Proteínas Fúngicas/aislamiento & purificación , Proteínas Fúngicas/química , Proteínas Fúngicas/biosíntesis , Proteínas Fúngicas/genética
2.
ACS Omega ; 9(34): 36835-36846, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220530

RESUMEN

Since 1970 acyclovir (ACV) has been the reference drug in treating herpes simplex virus (HSV) infections. However, resistant herpes simplex virus type 1 (HSV-1) strains have emerged, narrowing the treatment efficacy. The antiviral activity of classical Na+, K+ ATPase enzyme (NKA) inhibitors linked the viral replication to the NKA's activity. Herein, we evaluated the anti-HSV-1 activity of synthetic naphthoquinones, correlating their antiviral activity with NKA inhibition. We tested seven synthetic naphthoquinones initially at 50 µM on HSV-1-infected African green monkey kidney cells (VERO cells). Only one compound, 2-hydroxy-3-(2-thienyl)-1,4-naphthoquinone (AN-06), exhibited higher antiviral activity with a low cytotoxicity. AN-06 reduced the viral titer of 9 (log10) to 1.32 (log10) and decreased the steps of attachment and penetration. The addition of AN-06 up to 20 h postinfection (hpi) interfered with the viral cycle. The viral infection alone increases NKA activity 3 h postinfection (hpi), scaling up to 6 hpi. The addition of AN-06 in a culture infected with HSV-1 decreased NKA activity, suggesting that its antiviral action is linked to NKA inhibition. Also, docking results showed that this compound binds at the same site of NKA in which adenosine triphosphate (ATP) binds. AN-06 exhibited promising pharmacokinetic and toxicology properties. Thus, we postulate that AN-06 may be a good candidate for antiviral compounds with a mechanism of action targeting NKA activity.

3.
Future Microbiol ; : 1-12, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101446

RESUMEN

Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms. Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT. Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells. Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.


Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.

4.
Protein Expr Purif ; 222: 106534, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38897399

RESUMEN

Tribolium castaneum, also known as the red flour beetle, is a polyphagous pest that seriously damages agricultural products, including stored and processed grains. Researchers have aimed to discover alternative pest control mechanisms that are less harmful to the ecosystem than those currently used. We conduct the purification and characterization of a protease inhibitor from C. plumieri seeds and an in vitro evaluation of its insecticidal potential against the insect pest T. castaneum. The trypsin inhibitor was isolated from C. plumieri seeds in a single-step DEAE-Sepharose column chromatography and had a molecular mass of 50 kDA. When analyzed for interaction with different proteolytic enzymes, the inhibitor exhibited specificity against trypsin and no activity against other serine proteases such as chymotrypsin and elastase-2. The isolated inhibitor was able to inhibit digestive enzymes of T. castaneum from extracts of the intestine of this insect. Therefore, we conclude that the new protease inhibitor, specific in tryptic inhibition, of protein nature from the seeds of C. plumieri was effective in inhibiting the digestive enzymes of T. castaneum and is a promising candidate in the ecological control of pests.


Asunto(s)
Tribolium , Inhibidores de Tripsina , Animales , Inhibidores de Tripsina/farmacología , Inhibidores de Tripsina/química , Inhibidores de Tripsina/aislamiento & purificación , Tribolium/enzimología , Tribolium/efectos de los fármacos , Proteínas de Insectos/química , Proteínas de Insectos/aislamiento & purificación , Proteínas de Insectos/antagonistas & inhibidores , Semillas/química , Insecticidas/farmacología , Insecticidas/química , Insecticidas/aislamiento & purificación , Proteínas de Plantas/farmacología , Proteínas de Plantas/aislamiento & purificación , Proteínas de Plantas/química
5.
Curr Top Med Chem ; 24(18): 1589-1598, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38797894

RESUMEN

INTRODUCTION: Zika virus (ZIKV) is a flavivirus transmitted through the bites of infected Aedes mosquitoes. These viruses can also be transmitted through sexual contact, vertical transmission, and possibly transfusion. Most cases are asymptomatic, but symptoms can include rash, conjunctivitis, fever, and arthralgia, which are characteristic of other arboviruses. Zika infection can lead to complications such as microcephaly, miscarriage, brain abnormalities, and Guillain-Barré syndrome (GBS). OBJECTIVE: The aim is to determine the inhibitory potential of the algae Kappaphycus alvarezii (K. alvarezii) on ZIKV replication. METHODOLOGY: Cytotoxicity experiments were performed using Vero cells to determine the CC50, and ZIKV replication inhibition assays (ATCC® VR-1839™) were conducted to determine the EC50. The mechanism of action was also studied to assess any synergistic effect with Ribavirin. RESULTS: K. alvarezii demonstrated low toxicity with a CC50 of 423 µg/mL and a potent effect on ZIKV replication with an EC50 of 0.65 µg/mL and a Selectivity Index (SI) of 651, indicating the extract's safety. Virucidal effect assays were carried out to evaluate the possible mechanism of action, and the compound addition time was studied, showing the potential to delay the treatment of infected cells by up to 6 hours. A potential synergistic effect was observed when K. alvarezii extract was combined with suboptimal concentrations of Ribavirin, resulting in 99% inhibition of viral replication. CONCLUSION: Our data demonstrate the significant potential of K. alvarezii extract and highlight the need for further studies to investigate its mechanism of action. We propose this extract as a potential anti-Zika compound.


Asunto(s)
Antivirales , Algas Marinas , Replicación Viral , Virus Zika , Antivirales/farmacología , Antivirales/química , Virus Zika/efectos de los fármacos , Animales , Chlorocebus aethiops , Células Vero , Algas Marinas/química , Replicación Viral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad , Ribavirina/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Algas Comestibles , Rhodophyta
7.
J Cyst Fibros ; 23(5): 967-976, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38749891

RESUMEN

BACKGROUND: There is a paucity of knowledge on the longer-term effects of CF transmembrane conductance regulator (CFTR) modulator therapies upon the gut microbiome and associated outcomes. In a pilot study, we investigated longitudinal Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy on the gut microbiota, metabolomic functioning, and clinical outcomes in people with CF (pwCF). STUDY DESIGN: Faecal samples from 20 pwCF were acquired before and then following 3, 6, and 17+ months of ETI therapy. Samples were subjected to microbiota sequencing and targeted metabolomics to profile and quantify short-chain fatty acid composition. Ten healthy matched controls were included for comparison. Clinical data, including markers of intestinal function were integrated to investigate relationships. RESULTS: Extended ETI therapy increased core microbiota diversity and composition, which translated to gradual shifts in whole microbiota composition towards that observed in healthy controls. Despite becoming more similar over time, CF microbiota and functional metabolite compositions remained significantly different to healthy controls. Antibiotic treatment for pulmonary infection significantly explained a relatively large degree of variation within the whole microbiota and rarer satellite taxa. Clinical outcomes were not significantly different following ETI. CONCLUSIONS: Whilst differences persisted, a positive trajectory towards the microbiota observed in healthy controls was found. We posit that progression was predominately impeded by pulmonary antibiotics administration. We recommend future studies use integrated omics approaches within a combination of long-term longitudinal patient studies and model experimental systems. This will deepen our understanding of the impacts of CFTR modulator therapy and respiratory antibiotic interventions upon the gut microbiome and gastrointestinal pathophysiology in CF.


Asunto(s)
Aminofenoles , Benzodioxoles , Fibrosis Quística , Microbioma Gastrointestinal , Indoles , Quinolonas , Humanos , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Benzodioxoles/uso terapéutico , Quinolonas/uso terapéutico , Femenino , Masculino , Aminofenoles/uso terapéutico , Indoles/uso terapéutico , Proyectos Piloto , Adulto , Pirazoles/uso terapéutico , Combinación de Medicamentos , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Agonistas de los Canales de Cloruro/uso terapéutico , Heces/microbiología , Piridinas , Adolescente , Estudios Longitudinales , Adulto Joven , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Pirrolidinas
8.
J Sport Health Sci ; 13(4): 548-558, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38431193

RESUMEN

BACKGROUND: Hemodialysis (HD) per se is a risk factor for thrombosis. Considering the growing body of evidence on blood-flow restriction (BFR) exercise in HD patients, identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model. The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise (RE) with BFR on this molecule. METHODS: Two hundred and six HD patients volunteered for this study (all with a glomerular filtration rate of <15 mL/min/1.73 m2). The RE + BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD (intradialytic exercise). RE repetitions included concentric and eccentric lifting phases (each lasting 2 s) and were supervised by a strength and conditioning specialist. RESULTS: Several variables were associated with elevated levels of D-dimer, including higher blood glucose, citrate use, recent cardiovascular events, recent intercurrents, higher inflammatory status, catheter as vascular access, older patients (>70 years old), and HD vintage. Furthermore, RE + BFR significantly increases D-dimer after 4 h. Patients with borderline baseline D-dimer levels (400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range (≥500 ng/mL). CONCLUSION: These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE + BFR. D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE + BFR.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno , Diálisis Renal , Entrenamiento de Fuerza , Trombosis , Humanos , Diálisis Renal/efectos adversos , Entrenamiento de Fuerza/métodos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Masculino , Trombosis/etiología , Trombosis/sangre , Femenino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Glucemia/metabolismo , Flujo Sanguíneo Regional , Factores de Edad
9.
Rev Port Cardiol ; 43(3): 149-158, 2024 Mar.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-37716466

RESUMEN

INTRODUCTION: The limited accessibility and the lack of adherence explain, in part, the low proportion of heart failure (HF) patients undergoing exercise-based cardiac rehabilitation (CR) programs. Home-based programs showed to be as effective and less costly than centre-based ones and might address those obstacles. Whether the evidence from international studies can be applied to our population is still unclear. OBJECTIVES: To compare the clinical and economic impact of a home-based versus centre-based CR intervention in HF patients. METHODS: This is a single-center, single-blind, parallel groups, non-inferiority pragmatic randomized control trial. Adult HF patients (n=120) will be randomized to either a centre-based or home-based CR program. In both groups' patients will participate in a 12-week combined CR program with 2 sessions per week. Exercise training (ExT) protocol consists of a combination of endurance [(at 60%-80% of peak oxygen uptake (VO2peak)] and resistance training (elastic bands). Those allocated to the home-based program will start with 4-5 supervised ExT sessions to familiarize themselves with the training protocol and then will continue the remaining sessions at home. The primary endpoint is the change in VO2peak at the end of the 12-week program. Secondary outcomes include alterations in circulating biomarkers, physical fitness, physical activity, quality of life, diet, psychological wellbeing, dyspnea, and cost-effectiveness analyses. RESULTS: Patients are currently being recruited for the study. The study started in November 2019 and data collection is anticipated to be completed by December 2022. This is the first study in Portugal comparing the traditional CR program with a home-based program in HF patients. Our study results will better inform healthcare professionals who care for HF patients regarding CR.


Asunto(s)
Rehabilitación Cardiaca , Insuficiencia Cardíaca , Adulto , Humanos , Calidad de Vida , Método Simple Ciego , Insuficiencia Cardíaca/terapia , Terapia por Ejercicio
10.
Prep Biochem Biotechnol ; 54(7): 910-917, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38156982

RESUMEN

Proteases are the main enzymes traded worldwide-comprising 60% of the total enzyme market-and are fundamental to the degradation and processing of proteins and peptides. Due to their high commercial demand and biological importance, there is a search for alternative sources of these enzymes. Crotalaria stipularia is highlighted for its agroecological applications, including organic fertilizers, nematode combat, and revegetation of areas contaminated with toxic substances. Considering the pronounced biotechnological functionality of the studied species and the necessity to discover alternative sources of proteases, we investigated the extraction, purification, and characterization of a protease from seeds of the C. stipularia plant. Protease isolation was achieved by three-phase partitioning and single-step molecular exclusion chromatography in Sephacryl S-100, with a final recovery of 47% of tryptic activity. The molecular mass of the isolated enzyme was 40 kDa, demonstrating optimal activities at pH 8.0 and 50 °C. Enzymatic characterization demonstrated that the protease can hydrolyze the specific trypsin substrate, BApNA. This trypsin-like protease had a Km, Vmax, Kcat, and catalytic efficiency constant of 0.01775 mg/mL, 0.1082 mM/min, 3.86 s-1, and 217.46, respectively.


Asunto(s)
Crotalaria , Semillas , Crotalaria/química , Semillas/química , Semillas/enzimología , Concentración de Iones de Hidrógeno , Tripsina/metabolismo , Tripsina/química , Cinética , Especificidad por Sustrato , Temperatura , Peso Molecular
11.
J Toxicol Environ Health A ; 87(3): 91-107, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37927232

RESUMEN

Croton heliotropiifolius Kunth, popularly known as "velame," is a shrub that resides in northeastern Brazil. The essential oil of C. heliotropiifolius contains high concentrations of volatile compounds in the leaves and is widely used in folk medicine for many purposes as an antiseptic, analgesic, sedative, and anti-inflammatory agent. Due to the apparent limited amount of information, the aim of this study was to determine the cytotoxic potential of essential oil extracted from leaves of C. heliotropiifolius, utilizing different human cancer cell lines (HL-60, leukemia; HCT-116, colon; MDA-MB435, melanoma; SF295, glioblastoma) and comparison to murine fibroblast L929 cell line. The chemical characterization of the essential oil revealed the presence of large amounts of monoterpenes and sesquiterpenes, the majority of which were aristolene (22.43%), germacrene D (11.38%), ɣ-terpinene (10.85%), and limonene (10.21%). The essential oil exerted significant cytotoxicity on all cancer cells, with low activity on murine L929 fibroblasts, independent of disruption of cell membranes evidenced by absence of hemolytic activity. The cytotoxicity identified was associated with oxidative stress, which culminated in mitochondrial respiration dysfunction and direct or indirect DNA damage (strand breaks and oxidative damage), triggering cell death via apoptosis. Our findings suggest that extracts of essential oil of C. Heliotropiifolius may be considered as agents to be used therapeutically in treatment of certain cancers.


Asunto(s)
Antineoplásicos , Croton , Aceites Volátiles , Sesquiterpenos , Humanos , Animales , Ratones , Aceites Volátiles/farmacología , Croton/química , Línea Celular Tumoral , Sesquiterpenos/análisis , Hojas de la Planta/química
12.
Nat Prod Res ; : 1-6, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38054811

RESUMEN

Herpes simplex virus type 2 (HSV-2) is the most common agent of sexually transmitted infections around the world. Currently, no vaccine is available, and acyclovir is the reference compound in treatment HSV-2 infections. However, the emergence of resistant strains has reduced the efficacy in treatment. Several studies have shown marine seaweed biological activities, but there are no studies yet about the activity anti-HSV-2 of two its secundary metabolites, atomaric acid (1) and marine dolastane (2), isolated from Stypopodium zonale and Canistrocarpus cervicornis respectively. Therefore, we evaluated the anti-HSV-2 activity of compounds 1 and 2. Both compounds showed anti-HSV-2 activity with low cytotoxicity and compound 1 inactivated 90% of the viral particles at 50 µM. Both compounds inhibited the penetration and results in silico indicated the compound 1 as possible therapy alternative anti -HSV-2.

13.
Injury ; 54 Suppl 6: 110777, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38143129

RESUMEN

The treatment of severe musculoskeletal injuries, such as loss of bone tissue and consolidation disorders, requires bone transplantation, and the success of this bone reconstruction depends on the grafts transplant's osteogenic, osteoconductive, and osteoinductive properties. Although the gold standard is autograft, it is limited by availability, morbidity, and infection risk. Despite their low capacity for osteoinduction and osteogenesis, decellularized bone allografts have been used in the search for alternative therapeutic strategies to improve bone regeneration. Considering that bone marrow stromal cells (BMSCs) are responsible for the maintenance of bone turnover throughout life, we believe that associating BMSCs with allograft could produce a material that is biologically similar to autologous bone graft. For this reason, this study evaluated the osteogenic potential of bone allograft cellularized with BMSCs. First, BMSC was characterized and allograft decellularization was confirmed by histology, scanning electron microscopy, and DNA quantification. Subsequently, the BMSCs and allografts were associated and evaluated for adhesion, proliferation, and in vitro and in vivo osteogenic potential. We demonstrated that, after 2 hours, BMSCs had already adhered to the surface of allografts and remained viable for 14 days. In vitro osteogenic assays indicated increased osteogenic potential of allografts compared with beta-tricalcium phosphate (ß-TCP). In vivo transplantation assays in immunodeficient mice confirmed the allograft's potential to induce bone formation, with significantly better results than ß-TCP. Finally, our results indicate that allograft can provide structural support for BMSC adhesion, offering a favorable microenvironment for cell survival and differentiation and inducing new bone formation. Taken together, our data indicate that this rapid methodology for cellularization of allograft with BMSCs might be a new therapeutic alternative in regenerative medicine and bone bioengineering.


Asunto(s)
Regeneración Ósea , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Fosfatos de Calcio/farmacología , Osteogénesis , Diferenciación Celular , Aloinjertos , Células de la Médula Ósea
14.
Pathogens ; 12(12)2023 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-38133344

RESUMEN

The CCCH-type zinc finger antiviral protein (ZAP) in humans, specifically isoforms ZAP-L and ZAP-S, is a crucial component of the cell's intrinsic immune response. ZAP acts as a post-transcriptional RNA restriction factor, exhibiting its activity during infections caused by retroviruses and alphaviruses. Its function involves binding to CpG (cytosine-phosphate-guanine) dinucleotide sequences present in viral RNA, thereby directing it towards degradation. Since vertebrate cells have a suppressed frequency of CpG dinucleotides, ZAP is capable of distinguishing foreign genetic elements. The expression of ZAP leads to the reduction of viral replication and impedes the assembly of new virus particles. However, the specific mechanisms underlying these effects have yet to be fully understood. Several questions regarding ZAP's mechanism of action remain unanswered, including the impact of CpG dinucleotide quantity on ZAP's activity, whether this sequence is solely required for the binding between ZAP and viral RNA, and whether the recruitment of cofactors is dependent on cell type, among others. This review aims to integrate the findings from studies that elucidate ZAP's antiviral role in various viral infections, discuss gaps that need to be filled through further studies, and shed light on new potential targets for therapeutic intervention.

15.
Rev. crim ; 65(3): 149-159, 20230910.
Artículo en Español | LILACS | ID: biblio-1551264

RESUMEN

La recogida de muestras indubitadas al momento de elaborar un cuerpo de escritura a una persona, es un proceso de suma importancia en la pericia caligráfica. Existen parámetros por los que se rigen los peritos calígrafos al confeccionar dicho cuerpo de escritura, que se centran de forma general en la posición del escribiente, la velocidad escritural, la espontaneidad, cantidad de muestras, entre otros. Sin embargo, el escribiente puede intentar alterarlo o manipularlo de diferentes formas, normalmente intentando dificultar la labor pericial. Así, existen diversos elementos que indican a un experto en grafística que se está intentando modificar la escritura o firma durante este proceso desde el punto de vista técnico. En este sentido, el objetivo de este estudio es resaltar la importancia de recopilar un cuerpo de escritura con todas las garantías para que pueda tratarse como un documento incuestionable, además de destacar la relevancia de que el perito tenga la capacidad de confirmar la sinceridad del escribiente, tanto mediante el análisis de su escritura (grafología) como a través del análisis de su comunicación no verbal en el momento de escribirlo. Se ha utilizado una metodología cualitativa, usando la técnica de información documental, mediante la recopilación de información para su estudio y análisis, así como de monografías, manuales de estudio y artículos científicos.


The collection of indubitable samples when a corpus of handwriting is taken from a person is an extremely important process in handwriting expertise. There are parameters by which handwriting experts are governed when making such a writing corpus, which generally focus on the position of the scribe, writing speed, spontaneity, number of samples, among others. However, the scribe may try to alter or manipulate it in different ways, usually in an attempt to hinder the expert's work. Thus, there are several elements that indicate to a handwriting expert that an attempt is being made to modify the handwriting or signature during this process from a technical point of view. In this sense, the aim of this study is to highlight the importance of compiling a handwriting corpus with all the guarantees that it can be treated as an unquestionable document, as well as highlighting the importance of the expert having the ability to confirm the scribe's sincerity, both through the analysis of their handwriting (graphology) and through the analysis of their non-verbal communication at the time of writing. A qualitative methodology has been used, using the documentary information technique, by means of the collection of information for study and analysis, as well as monographs, study manuals and scientific articles.


A coleta de provas indubitáveis quando um corpo de caligrafia é retirado de uma pessoa é um processo extremamente importante na perícia de caligrafia. Existem parâmetros pelos quais os peritos em caligrafia são regidos ao fazer esse corpo de escrita, que geralmente se concentram na posição do escriba, na velocidade da escrita, na espontaneidade, no número de amostras, entre outros. No entanto, o escrevente pode tentar alterá-lo ou manipulá-lo de diversas formas, geralmente na tentativa de dificultar o trabalho do perito. Assim, existem vários elementos que indicam ao perito em caligrafia que, do ponto de vista técnico, está havendo uma tentativa de modificar a caligrafia ou a assinatura durante esse processo. Nesse sentido, o objetivo deste estudo é destacar a importância de se compilar um corpo de caligrafia com todas as garantias de que possa ser tratado como um documento inquestionável, bem como destacar a importância de o perito ter a capacidade de confirmar a sinceridade do escrevente, tanto por meio da análise de sua caligrafia (grafologia) quanto por meio da análise de sua comunicação não verbal no momento da escrita. Foi utilizada uma metodologia qualitativa, com a técnica de informação documental, por meio da coleta de informações para estudo e análise, bem como de monografias, manuais de estudo e artigos científicos.


Asunto(s)
Humanos
16.
Microbiol Spectr ; : e0117523, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37607068

RESUMEN

People with cystic fibrosis (pwCF) experience a range of persistent gastrointestinal symptoms throughout life. There is evidence indicating interaction between the microbiota and gut pathophysiology in CF. However, there is a paucity of knowledge on the potential effects of CF transmembrane conductance regulator (CFTR) modulator therapies on the gut microbiome. In a pilot study, we investigated the impact of Tezacaftor/Ivacaftor dual combination CFTR modulator therapy on the gut microbiota and metabolomic functioning in pwCF. Fecal samples from 12 pwCF taken at baseline and following placebo or Tezacaftor/Ivacaftor administration were subjected to microbiota sequencing and to targeted metabolomics to assess the short-chain fatty acid (SCFA) composition. Ten healthy matched controls were included as a comparison. Inflammatory calprotectin levels and patient symptoms were also investigated. No significant differences were observed in overall gut microbiota characteristics between any of the study stages, extended also across intestinal inflammation, gut symptoms, and SCFA-targeted metabolomics. However, microbiota and SCFA metabolomic compositions, in pwCF, were significantly different from controls in all study treatment stages. CFTR modulator therapy with Tezacaftor/Ivacaftor had negligible effects on both the gut microbiota and SCFA composition across the course of the study and did not alter toward compositions observed in healthy controls. Future longitudinal CFTR modulator studies will investigate more effective CFTR modulators and should use prolonged sampling periods, to determine whether longer-term changes occur in the CF gut microbiome. IMPORTANCE People with cystic fibrosis (pwCF) experience persistent gastrointestinal (GI) symptoms throughout life. The research question "how can we relieve gastrointestinal symptoms, such as stomach pain, bloating, and nausea?" remains a top priority for clinical research in CF. While CF transmembrane conductance regulator (CFTR) modulator therapies are understood to correct underlying issues of CF disease and increasing the numbers of pwCF are now receiving some form of CFTR modulator treatment. It is not known how these therapies affect the gut microbiome or GI system. In this pilot study, we investigated, for the first time, effects of the dual combination CFTR modulator medicine, Tezacaftor/Ivacaftor. We found it had negligible effects on patient GI symptoms, intestinal inflammation, or gut microbiome composition and functioning. Our findings are important as they fill important knowledge gaps on the relative effectiveness of these widely used treatments. We are now investigating triple combination CFTR modulators with prolonged sampling periods.

17.
Acta Biomed ; 94(2): e2023012, 2023 04 24.
Artículo en Inglés | MEDLINE | ID: mdl-37092639

RESUMEN

BACKGROUND AND AIM: Cardiovascular diseases are characterized by problems affecting the circulatory system, specifically the heart and blood vessels. This study evaluates the relationship between cardiovascular events and pharmacological treatment for Type II Diabetes Mellitus (T2DM). METHODS: We recruited 227 individuals, 191 with T2DM (EG) and 36 pre-diabetics (CG), with a mean age of 70.3 years (SD=8.3), and 62 years (SD=10.3) respectively. The individuals were distributed into five groups concerning the following variables: body mass index (BMI), age, diagnosis age of T2DM, glycated hemoglobin value (HbA1c), Homeostatic model that estimates the function of ß cells value (HOMA2-B), and Homeostatic model that estimates insulin resistance (HOMA-IR) value. At the time of data collection, there were no individuals with T1DM, so it was decided to use prediabetic individuals (with a high risk of developing T2DM). RESULTS: Group 1 had the pre-diabetic patients (15.9%), while diabetic individuals were divided into groups 2 (1.8%), 3 (17.6%), 4 (21.1%) and 5 (43.6%). It was possible to conclude that most of the patients in the different groups had a history of acute myocardial infarction (AMI). Regarding the prevalence of pharmacological treatment, it was possible to conclude that metformin was the most used drug in most of the groups. CONCLUSIONS: It was possible to create different groups and to observe the existence of dependency relationships between different cardiovascular events and pharmacological treatment.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Metformina , Humanos , Anciano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Glucemia , Metformina/uso terapéutico , Hemoglobina Glucada , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/tratamiento farmacológico
18.
DST j. bras. doenças sex. transm ; 35jan. 31, 2023. ilus
Artículo en Inglés | LILACS | ID: biblio-1451615

RESUMEN

Introduction: In 2022, many countries, such as Brazil, experienced outbreaks of mpox (formerly called monkeypox) in sexually active people with multiple sexual partners. Objective: Report cases of patients diagnosed with Mpox. Methods: Report three cases of patients diagnosed with Mpox treated at the STD Sector at Universidade Federal Fluminense. Results: We report three cases of young adult patients who spontaneously sought our STD service with wounds in the anogenital area, mouth and other parts of the body. These cases include a 28-year-old man (HIV positive) who had lesions on his penis and body, a 34-year-old man with perianal ulcers and adenopathy, and a 40-year-old man with painful ulcers on his penis. Conclusion: The article provides information on the symptoms, transmission, and prevention of mpox, highlighting the need for early detection, diagnosis, and prompt treatment to contain and prevent the spread of the disease. The cases presented in this study show all the characteristics of a sexually transmitted disease


Introdução: Em 2022, muitos países, como o Brasil, experimentaram surtos de mpox (anteriormente chamada de monkeypox) em pessoas sexualmente ativas com múltiplos parceiros sexuais. Objetivo: Relatar casos de pacientes diagnosticados com mpox. Métodos: Relatar três casos de pacientes com diagnóstico de mpox atendidos no Setor de Doenças Sexualmente Transmissíveis (DST) da Universidade Federal Fluminense (UFF). Resultados: Relatam-se três casos de pacientes adultos jovens que procuraram espontaneamente o Setor de DST da UFF com feridas na região anogenital, boca e outras partes do corpo. Esses casos incluem um homem de 28 anos (HIV positivo) que apresentava lesões no pênis e no corpo, um homem de 34 anos com úlceras perianais e adenopatia e um homem de 40 anos com úlceras dolorosas no pênis. Conclusão: O artigo fornece informações sobre os sintomas, transmissão e prevenção da mpox, destacando a necessidade de detecção precoce, diagnóstico e tratamento imediato para conter e prevenir a propagação da doença. Os casos apresentados apresentam todas as características de uma doença sexualmente transmissível.


Asunto(s)
Humanos , Masculino , Adulto , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/transmisión , Mpox/diagnóstico , Mpox/transmisión
19.
Exp Gerontol ; 171: 112030, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36423855

RESUMEN

INTRODUCTION: Faced with lockdowns, it was mandatory the development of supervised home-based RT protocols to keep patients with chronic kidney disease engaged in programs. Nonetheless, there is a lack of scientific literature regarding its effects on patients. PURPOSE: To investigate the effects of a supervised home-based progressive resistance training program on functional performance, bone mineral density, renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, redox balance, and the modulation of exerkines in patients with CKD in stage 2. METHODS: Patients (n = 31) were randomized and allocated into the control group (CTL; n = 15; 58.07 ± 5.22 yrs) or resistance training group (RT; n = 16; 57.94 ± 2.74 yrs). RT group performed 22 weeks of supervised progressive home-based resistance exercises. Bone mineral density, anthropometric measurements, and functional performance were assessed. Venous blood samples were collected at baseline and after the intervention for the analysis of markers of renal function, endothelial health, inflammation, glycemic homeostasis, metabolism, and redox balance. RESULTS: Twenty-two weeks of home-based RT were effective in improving (P < 0.05) functional performance, bone mineral density, uremic profile, ADMA, inflammatory markers, the Klotho-FGF23 axis, glycemic homeostasis markers, and exerkines. These improvements were accompanied by higher concentrations of exerkines and anti-inflammatory cytokines. RT group displayed a decrease in cases of osteopenia after the intervention (RT: 50 % vs. CTL: 86.7 %; X2 = 4.763; P = 0.029). CONCLUSION: Results provide new evidence that supervised home-based progressive RT may be a relevant intervention to attenuate the progression of CKD and improve functional capacity, bone mineral density, and the immunometabolic profile. These improvements are associated with positive modulation of several exerkines.


Asunto(s)
Insuficiencia Renal Crónica , Entrenamiento de Fuerza , Humanos , Entrenamiento de Fuerza/métodos , Insuficiencia Renal Crónica/terapia , Ejercicio Físico , Terapia por Ejercicio , Densidad Ósea , Inflamación
20.
Curr Top Med Chem ; 23(4): 257-264, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36545716

RESUMEN

BACKGROUND: Since the emergence of HSV resistant strains, new antiviral agents have emerged and still are urgently needed, especially those with alternative targets. OBJECTIVE: In this work, we evaluated new quinolone derivatives as anti-HSV. METHODS: For this study, cells were infected and treated with different components to evaluate the profile of HSV replication in vitro. In addition, studies were performed to determine the pharmacokinetic toxicity and profile of the compound. RESULTS: Indeed the EC50 values of these promising molecules ranged between 8 µM and 32 µM. We have also showed that all compounds inhibited the expression of ICP27 viral proteins, which gives new insights in the search for new target for antiherpetic therapy. Chlorine in positions C6 and phosphonate in position C1 have shown to be important for viral inhibition. The chloroquinolone carboxamide derivatives fulfilled "Lipinsky Rule of Five" for good oral bioavailability and showed higher intestinal absorption and blood brain barrier penetration, as well as lower toxicity profile. CONCLUSION: Although the inhibition activities of chloroquinolone carboxamide derivatives were lower than acyclovir, they showed different modes of action in comparison to the drugs currently available. These findings encourage us to continue pre-clinical studies for the development of new anti-HSV-1 agents.


Asunto(s)
Herpesvirus Humano 1 , Replicación Viral , Herpesvirus Humano 2/fisiología , Aciclovir/farmacología , Aciclovir/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Herpesvirus Humano 1/fisiología
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