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1.
Am J Case Rep ; 25: e945135, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39402814

RESUMO

BACKGROUND Managing unique anatomical structures, such as the nasopalatine canal, remains key for successful implant placement and long-term functionality. Topical oral oxygen therapy (TOOT) has gained attention for its antibacterial, regenerative properties, and ability to accelerate wound healing. This report presents a case of postoperative palatal necrosis successfully treated with TOOT oxygen-active gel (blue®m) CASE REPORT A 33-year-old male patient presented with the primary concern of needing rehabilitation of the anterior maxillary region. Clinical and imaging examinations revealed a deficient maxillary ridge and an enlarged incisive foramen. The treatment plan involved nasopalatine deflation with guided bone regeneration using particulate synthetic bone graft and a collagen membrane. Seven days after surgery, he returned with minimal pain but had necrotic tissue on the palate. The necrotic tissue and a portion of the contaminated biomaterial were removed, and the area was thoroughly cleansed with a saline solution. A thick layer of active oxygen gel (blue®m) was then applied to the palatal lesion. The patient was instructed to apply the gel 3 times daily for 30 days and attended follow-up appointments every 2 days. After 12 days, rapid healing and significant clinical improvement were observed, with the patient reporting no pain or sensitivity. By day 34, the lesion had fully closed, and re-epithelialization was achieved. CONCLUSIONS Our patient had complete resolution of palatal necrosis after nervus deflation using TOOT with active oxygen gel (blue®m), and this therapy seemed to accelerate the healing process.


Assuntos
Géis , Necrose , Humanos , Masculino , Adulto , Cicatrização , Palato , Oxigênio/uso terapêutico
2.
Acta Cir Bras ; 39: e395924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258619

RESUMO

PURPOSE: To evaluate exogenous hyaluronic acid (HA) derived from bacterial fermentation through enteral and parenteral routes in ischemic skin flaps induced in rats, using clinical and histological exams; and interleukins (IL) as tissue inflammatory biomarkers. METHODS: Sixty-four male adults Wistar rats with ischemic skin flaps on the dorsum were randomized into four groups, based on the treatment protocol: subcutaneous administration of saline solution (0.9%) (GI); oral administration of distilled water (GII); subcutaneous administration of HA (0.3%) (GIII); and oral administration of HA (1%) (GIV). Flaps of all groups were comparable regarding clinical and macroscopic evaluation, histological examination, pro-inflammatory cytokines (IL-1ß, IL-6, and tumor necrosis factor-α) and anti-inflammatory cytokine IL-10. RESULTS: A lower percentage of necrosis was identified in flaps treated with subcutaneous administration of HA (0.3%). The pro- and anti-inflammatory cytokines, epidermis thickness, blood vessels, and inflammatory cells showed statistically significant inter-group and intra-group differences (p < 0.05). CONCLUSIONS: High molecular HA (1,400 ~ 2,000 kDa) administrated by subcutaneous or oral route exhibited beneficial effects in ischemic skin flaps of rats. However, subcutaneous administration of HA (0.3%) showed better results in terms of the percentage of necrosis and epithelialization.


Assuntos
Ácido Hialurônico , Isquemia , Distribuição Aleatória , Ratos Wistar , Retalhos Cirúrgicos , Animais , Masculino , Ácido Hialurônico/administração & dosagem , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/patologia , Pele/efeitos dos fármacos , Pele/patologia , Método Duplo-Cego , Citocinas/análise , Citocinas/metabolismo , Necrose , Ratos , Administração Oral , Modelos Animais de Doenças , Reprodutibilidade dos Testes
3.
Anaerobe ; 89: 102902, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39187174

RESUMO

INTRODUCTION: Chickens with Necrotic Enteritis (NE), caused by Clostridium perfringens, exhibit acute and chronic symptoms that are difficult to diagnose, leading to significant economic losses. Vaccination is the best method for controlling and preventing NE. However, only two vaccines based on the CPA and NetB toxins have been commercialized, offering partial protection, highlighting the urgent need for more effective vaccines. OBJECTIVE: This review aimed to identify promising antigens for NE vaccine formulation and discuss factors affecting their effectiveness. METHODS: A systematic review using five scientific databases identified 30 eligible studies through the Rayyan tool, which were included for quality review. RESULTS: We identified 25 promising antigens, including CPA, NetB, FBA, ZMP, CnaA, FimA, and FimB, categorized by their role in disease pathogenesis. This review discusses the biochemical, physiological, and genetic traits of recombinant antigens used in vaccine prototypes, their expression systems, and immunization potential in chickens challenged with virulent C. perfringens strains. Market supply challenges, immunogenic potential, vaccine platforms, adjuvants, and factors related to vaccination schedules-such as administration routes, dosing intervals, and age at immunization-are also addressed. Additionally, the study notes that vaccine formulations tested under mild challenges may not offer adequate field-level protection due to issues replicating aggressive conditions, strain virulence loss, and varied methodologies. CONCLUSIONS: An ideal NE vaccine should incorporate multiple antigens, molecular adjuvants, and delivery systems via in ovo and oral routes. The review underscores the challenges in developing and validating NE vaccines and the urgent need for a standardized protocol to replicate aggressive challenges accurately.


Assuntos
Vacinas Bacterianas , Galinhas , Infecções por Clostridium , Clostridium perfringens , Enterite , Doenças das Aves Domésticas , Animais , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagem , Galinhas/imunologia , Galinhas/microbiologia , Infecções por Clostridium/prevenção & controle , Infecções por Clostridium/veterinária , Infecções por Clostridium/imunologia , Clostridium perfringens/imunologia , Clostridium perfringens/genética , Enterite/prevenção & controle , Enterite/veterinária , Enterite/microbiologia , Enterite/imunologia , Necrose/veterinária , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/microbiologia , Vacinação/veterinária , Vacinação/métodos , Desenvolvimento de Vacinas/métodos
4.
Cells ; 13(16)2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39195268

RESUMO

Tracking cell death in vivo can enable a better understanding of the biological mechanisms underlying tissue homeostasis and disease. Unfortunately, existing cell death labeling methods lack compatibility with in vivo applications or suffer from low sensitivity, poor tissue penetration, and limited temporal resolution. Here, we fluorescently labeled dead cells in vivo with Trypan Blue (TBlue) to detect single scattered dead cells or to generate whole-mount three-dimensional maps of large areas of necrotic tissue during organ regeneration. TBlue effectively marked different types of cell death, including necrosis induced by CCl4 intoxication in the liver, necrosis caused by ischemia-reperfusion in the skin, and apoptosis triggered by BAX overexpression in hepatocytes. Moreover, due to its short circulating lifespan in blood, TBlue labeling allowed in vivo "pulse and chase" tracking of two temporally spaced populations of dying hepatocytes in regenerating mouse livers. Additionally, upon treatment with cisplatin, TBlue labeled dead cancer cells in livers with cholangiocarcinoma and dead thymocytes due to chemotherapy-induced toxicity, showcasing its utility in assessing anticancer therapies in preclinical models. Thus, TBlue is a sensitive and selective cell death marker for in vivo applications, facilitating the understanding of the fundamental role of cell death in normal biological processes and its implications in disease.


Assuntos
Morte Celular , Azul Tripano , Animais , Camundongos , Morte Celular/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Hepatócitos/metabolismo , Humanos , Neoplasias/patologia , Camundongos Endogâmicos C57BL , Regeneração Hepática/efeitos dos fármacos , Fígado/patologia , Fígado/efeitos dos fármacos , Rastreamento de Células/métodos , Apoptose/efeitos dos fármacos , Imageamento Tridimensional , Regeneração/efeitos dos fármacos , Necrose , Masculino
5.
Parasitol Int ; 103: 102954, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39181313

RESUMO

The present report describes a case of acanthocephaliasis associated with necrotic enteritis in quetzals (Pharomachrus mocinno). Three juvenile quetzals exhibited depression, anorexia, ruffled feathers, and sudden death. They were submitted to the laboratory for examination. The birds had hatched and lived in captivity in an aviary in Mexico. Gross lesions observed were hemorrhagic, fibrinoid necrotic enteritis, with acanthocephalans adhered to the intestinal mucosa. The specimens were identified by parasitology, electronic microscopy, and molecular biology as Plagiorhynchus (Prosthorhynchus) sp. Lesions compatible with necrotic enteritis were also confirmed by isolation and genotyping of Clostridium perfringens type E. This is the first report of Plagiorhynchus (Prosthorhynchus) sp. in quetzals in captivity in Mexico. The findings in this manuscript suggest that this parasite could be a predisposing factor for necrotic enteritis as well as a risk component in the breeding programs and survival of this avian species in captivity.


Assuntos
Acantocéfalos , Doenças das Aves , Enterite , Helmintíase Animal , Necrose , Animais , Doenças das Aves/parasitologia , Enterite/veterinária , Enterite/parasitologia , Necrose/veterinária , Helmintíase Animal/parasitologia , México , Clostridium perfringens/isolamento & purificação , Masculino
7.
Poult Sci ; 103(9): 103986, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39003795

RESUMO

Necrotic enteritis (NE) is a disease of worldwide distribution, which affects young broilers and causes economic losses on a scale of 6 billion dollars per year. For decades, NE was controlled in poultry flocks by dietary administration of low doses of antimicrobial growth promoters (AGPs). However, an increase in NE incidence was noted after the AGP ban. This study aimed to compare the effect of an antibiotic (Enramycin) diet to a combination of sodium butyrate, hydrolyzed yeast, and zinc proteinate (ViligenTM) on broiler diets regarding performance, blood parameters, intestinal permeability, morphology and lesions, and carcass yield of broilers challenged with Eimeria spp. and Clostridium perfringens to simulate subclinical necrotic enteritis. A total of 1,150 one-day-old male broiler chickens with an initial average weight of 43.9 ± 0.65 g were allocated to 50 experimental pens. Animals were divided into 5 groups: Negative control (NC) without additives; Positive control (PC) with 0.12 g/ton of Enramycin (8%); V500, V1000, and V1500 with the addition of 500, 1.000, and 1.500 g/ton of Viligen, respectively. All animals were challenged by Eimeria spp. at 7 d of age and by C. perfringens at 17, 18, and 19 d for induction of subclinical NE. The broilers fed with all concentrations of Viligen showed similar performance, blood parameters, intestinal permeability, and carcass yield compared to PC broilers. However, NC broilers showed higher FCR compared to PC broilers from 1 to 33 d (1.42 vs. 1.39) (P = 0.048) and from 1 to 42 d (1.51 vs. 1.49) (P < 0.001). V1500 broilers had fewer intestinal lesions at 28 d when compared to the PC treatment (P < 0.05) and showed that higher Viligen inclusion resulted in lower intestinal damage. At 21 d, the V500 group showed higher intestinal morphology characteristics (VH:VD 4.9 vs. 3.5) compared to the PC treatment (P < 0.001). Thus, in this study, the dietary addition of Viligen to broilers challenged by an experimental model of subclinical NE resulted in lower intestinal damage and similar performance to that obtained by the addition of Enramycin.


Assuntos
Ração Animal , Galinhas , Infecções por Clostridium , Clostridium perfringens , Coccidiose , Dieta , Eimeria , Enterite , Doenças das Aves Domésticas , Animais , Galinhas/crescimento & desenvolvimento , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/microbiologia , Ração Animal/análise , Masculino , Dieta/veterinária , Enterite/veterinária , Enterite/parasitologia , Coccidiose/veterinária , Coccidiose/parasitologia , Infecções por Clostridium/veterinária , Eimeria/fisiologia , Clostridium perfringens/fisiologia , Suplementos Nutricionais/análise , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Ácido Butírico/administração & dosagem , Distribuição Aleatória , Necrose/veterinária , Peptídeos Cíclicos
8.
Biochimie ; 227(Pt A): 1-14, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38857695

RESUMO

Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with bacteremia, correlating with thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis. This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating calpain and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. Electron microscopy reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets. The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.


Assuntos
Plaquetas , Proteínas de Escherichia coli , Proteínas Hemolisinas , Proteínas Hemolisinas/metabolismo , Humanos , Plaquetas/metabolismo , Proteínas de Escherichia coli/metabolismo , Necrose , Coagulação Sanguínea/efeitos dos fármacos , Escherichia coli , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/patogenicidade , Cálcio/metabolismo
9.
Parasitol Res ; 123(5): 217, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772951

RESUMO

Toxoplasmosis poses a global health threat, ranging from asymptomatic cases to severe, potentially fatal manifestations, especially in immunocompromised individuals and congenital transmission. Prior research suggests that oregano essential oil (OEO) exhibits diverse biological effects, including antiparasitic activity against Toxoplasma gondii. Given concerns about current treatments, exploring new compounds is important. This study was to assess the toxicity of OEO on BeWo cells and T. gondii tachyzoites, as well as to evaluate its effectiveness in in vitro infection models and determine its direct action on free tachyzoites. OEO toxicity on BeWo cells and T. gondii tachyzoites was assessed by MTT and trypan blue methods, determining cytotoxic concentration (CC50), inhibitory concentration (IC50), and selectivity index (SI). Infection and proliferation indices were analyzed. Direct assessments of the parasite included reactive oxygen species (ROS) levels, mitochondrial membrane potential, necrosis, and apoptosis, as well as electron microscopy. Oregano oil exhibited low cytotoxicity on BeWo cells (CC50: 114.8 µg/mL ± 0.01) and reduced parasite viability (IC50 12.5 ± 0.06 µg/mL), demonstrating 9.18 times greater selectivity for parasites than BeWo cells. OEO treatment significantly decreased intracellular proliferation in infected cells by 84% after 24 h with 50 µg/mL. Mechanistic investigations revealed increased ROS levels, mitochondrial depolarization, and lipid droplet formation, linked to autophagy induction and plasma membrane permeabilization. These alterations, observed through electron microscopy, suggested a necrotic process confirmed by propidium iodide labeling. OEO treatment demonstrated anti-T. gondii action through cellular and metabolic change while maintaining low toxicity to trophoblastic cells.


Assuntos
Autofagia , Óleos Voláteis , Origanum , Espécies Reativas de Oxigênio , Toxoplasma , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Origanum/química , Humanos , Autofagia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Antiprotozoários/farmacologia , Concentração Inibidora 50 , Necrose/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
10.
Lasers Med Sci ; 39(1): 109, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649643

RESUMO

Necrosis is common in skin flap surgeries. Photobiomodulation, a noninvasive and effective technique, holds the potential to enhance microcirculation and neovascularization. As such, it has emerged as a viable approach for mitigating the occurrence of skin flap necrosis. The aim of this systematic review was to examine the scientific literature considering the use of photobiomodulation to increase skin-flap viability. The preferred reporting items for systematic reviews and meta-analyses (PRISMA), was used to conducted systematic literature search in the databases PubMed, SCOPUS, Elsevier and, Scielo on June 2023. Included studies investigated skin-flap necrosis employing PBMT irradiation as a treatment and, at least one quantitative measure of skin-flap necrosis in any animal model. Twenty-five studies were selected from 54 original articles that addressed PBMT with low-level laser (LLL) or light-emitting diode (LED) in agreement with the qualifying requirements. Laser parameters varied markedly across studies. In the selected studies, the low-level laser in the visible red spectrum was the most frequently utilized PBMT, although the LED PBMT showed a similar improvement in skin-flap necrosis. Ninety percent of the studies assessing the outcomes of the effects of PBMT reported smaller areas of necrosis in skin flap. Studies have consistently demonstrated the ability of PBMT to improve skin flap viability in animal models. Evidence suggests that PBMT, through enhancing angiogenesis, vascular density, mast cells, and VEGF, is an effective therapy for decrease necrotic tissue in skin flap surgery.


Assuntos
Terapia com Luz de Baixa Intensidade , Necrose , Retalhos Cirúrgicos , Animais , Terapia com Luz de Baixa Intensidade/métodos , Pele/efeitos da radiação , Pele/irrigação sanguínea , Retalhos Cirúrgicos/irrigação sanguínea
11.
Medicina (B Aires) ; 84(2): 333-336, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38683519

RESUMO

Enteral nutrition through jejunostomy is a common practice in any general surgery service; it carries a low risk of complications and morbidity and mortality. We present the case of a patient with an immediate history of subtotal gastrectomy that began nutrition through jejunostomy and complicated with intestinal necrosis due to non-occlusive ischemia in the short period. The purpose of this work is to report on this complication, its pathophysiology and risk factors to take it into account and be able to take appropriate therapeutic action early.


La nutrición enteral por yeyunostomía es una práctica frecuente en cualquier servicio de cirugía general, esta conlleva bajo riesgo de complicaciones y morbimortalidad. Presentamos el caso de una paciente con antecedente inmediato de gastrectomía subtotal que inició nutrición por yeyunostomía y complicó con necrosis intestinal por isquemia no oclusiva en el corto lapso. La finalidad de este trabajo es informar sobre esta complicación, su fisiopatología y factores de riesgo para tenerla en cuenta y poder tomar precozmente una conducta terapéutica adecuada.


Assuntos
Nutrição Enteral , Perfuração Intestinal , Jejunostomia , Necrose , Feminino , Humanos , Pessoa de Meia-Idade , Nutrição Enteral/efeitos adversos , Gastrectomia/efeitos adversos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Jejunostomia/efeitos adversos , Necrose/etiologia
12.
Rev. cuba. med. mil ; 53(1)mar. 2024. ilus, tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1569885

RESUMO

Introducción: Dentro de las causas poco frecuentes de oclusión intestinal se encuentra el vólvulo de intestino delgado, el cual consiste en una torsión anormal del intestino alrededor del su propio eje de mesenterio, que provoca una obstrucción mecánica del intestino. Objetivo: Describir la semiografía del vólvulo de intestino delgado en un paciente de edad avanzada. Caso clínico: Paciente masculino de 62 años de edad, que ingresa en el cuerpo de guardia de cirugía, por dolor abdominal, tipo cólico intermitente, con una evolución de 72 horas; además, presenta distensión abdominal, náuseas y vómitos. Con el cuadro clínico, más los exámenes complementarios, se constata oclusión intestinal mecánica, causada por un vólvulo del intestino delgado. A los 5 días de ser intervenido quirúrgicamente se complicó por una perforación intestinal debido a necrosis del asa. Conclusiones: Debido a su presentación atípica y sus graves complicaciones, se precisa un diagnóstico certero y tratamiento urgente al paciente con vólvulo del intestino delgado, ya que pone en riesgo la vida(AU)


Introduction: Among the rare causes of intestinal obstruction is small intestine volvulus, which consists of an abnormal twisting of the intestine around its own mesentery axis, which causes a mechanical obstruction of the intestine. Objective: To describe the semiography of small intestine volvulus in an elderly patient. Clinical case: 62-year-old male patient, admitted to the surgery ward, due to abdominal pain, intermittent colic type, with an evolution of 72 hours; In addition, he presents abdominal distention, nausea and vomiting. With the clinical picture, plus complementary examinations, mechanical intestinal occlusion is confirmed, caused by a volvulus of the small intestine. Five days after undergoing surgery, it was complicated by intestinal perforation due to necrosis of the loop. Conclusions: Due to its atypical presentation and serious complications, an accurate diagnosis and urgent treatment are required for patients with small intestine volvulus, since it puts life at risk(AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Volvo Intestinal/cirurgia , Obstrução Intestinal/cirurgia , Perfuração Intestinal/complicações , Intestino Delgado/cirurgia , Necrose/etiologia , Vômito , Dor Abdominal/complicações , Cólica/diagnóstico , Náusea
13.
Food Chem Toxicol ; 186: 114521, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38369054

RESUMO

Phthalates are synthetic plasticizers present in the daily lives of humans, as part of the composition of different products, such as food packaging, water bottles, and toys. These compounds can migrate from plastic materials to the environment changing biological systems. Although diisopentyl phthalate (DiPeP) is largely used in Brazil, there is a lack of information on the possible toxic effects of this compound. This research aims to evaluate the toxicity of DiPeP in the Vero renal cells. These cells were exposed to the 1-1000 µM of DiPeP for 24 and 72 h and subsequently, the cytotoxicity, apoptosis and necrosis-inducing potential, and antioxidant system (SOD, GPx, and GST) were investigated. DiPeP neither caused cytotoxicity nor altered SOD and GPx activity, although GST has been increased at 100 or 1 µM (24 and 72 h, respectively). However, cell death by apoptosis and necrosis was observed. These results indicate that DiPeP caused cell death by a non-oxidative stress-mediated mechanism, which shows the relevance of investigate other process in further researches.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Plastificantes/toxicidade , Ácidos Ftálicos/toxicidade , Necrose/induzido quimicamente , Superóxido Dismutase , Linhagem Celular
14.
Semin Liver Dis ; 44(1): 1-22, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38378025

RESUMO

Drug-induced liver injury (DILI) is an adverse reaction to medications and other xenobiotics that leads to liver dysfunction. Based on differential clinical patterns of injury, DILI is classified into hepatocellular, cholestatic, and mixed types; although hepatocellular DILI is associated with inflammation, necrosis, and apoptosis, cholestatic DILI is associated with bile plugs and bile duct paucity. Ursodeoxycholic acid (UDCA) has been empirically used as a supportive drug mainly in cholestatic DILI, but both curative and prophylactic beneficial effects have been observed for hepatocellular DILI as well, according to preliminary clinical studies. This could reflect the fact that UDCA has a plethora of beneficial effects potentially useful to treat the wide range of injuries with different etiologies and pathomechanisms occurring in both types of DILI, including anticholestatic, antioxidant, anti-inflammatory, antiapoptotic, antinecrotic, mitoprotective, endoplasmic reticulum stress alleviating, and immunomodulatory properties. In this review, a revision of the literature has been performed to evaluate the efficacy of UDCA across the whole DILI spectrum, and these findings were associated with the multiple mechanisms of UDCA hepatoprotection. This should help better rationalize and systematize the use of this versatile and safe hepatoprotector in each type of DILI scenarios.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Colestase , Hepatopatias , Humanos , Ácido Ursodesoxicólico/uso terapêutico , Ácido Ursodesoxicólico/farmacologia , Colestase/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Necrose/tratamento farmacológico , Fígado
15.
Photochem Photobiol Sci ; 23(2): 271-284, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305951

RESUMO

Ultraviolet A (UVA) radiation, present in sunlight, can induce cell redox imbalance leading to cellular damage and even cell death, compromising skin health. Here, we evaluated the in vitro antioxidant and photochemoprotective effect of dithiothreitol (DTT). DTT neutralized the free radicals 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+), 2,2-diphenyl-1-picrylhydrazyl (DPPH·), and superoxide anion (O2·-) in in vitro assays, as well as the ferric ion (Fe3+) in the ferric reducing antioxidant power (FRAP) assay. We also evaluated the effect of DTT pre-treatment in L929 dermal fibroblasts and DTT (50 and 100 µM) led to greater cell viability following UVA-irradiation compared to cells that were untreated. Furthermore, the pre-treatment of cells with DTT prevented the increase of intracellular reactive oxygen species (ROS) production, including hydrogen peroxide (H2O2), lipid peroxidation, and DNA condensation, as well as the decrease in mitochondrial membrane potential (Δψm), that occurred following irradiation in untreated cells. The endogenous antioxidant system of cells was also improved in irradiated cells that were DTT pre-treated compared to the untreated cells, as the activity of the superoxide dismutase (SOD) and catalase (CAT) enzymes remained as high as non-irradiated cells, while the activity levels were depleted in the untreated irradiated cells. Furthermore, DTT reduced necrosis in UVA-irradiated fibroblasts. Together, these results showed that DTT may have promising use in the prevention of skin photoaging and photodamage induced by UVA, as it provided photochemoprotection against the harmful effects of this radiation, reducing oxidative stress and cell death, due mainly to its antioxidant capacity.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Ditiotreitol/farmacologia , Ditiotreitol/metabolismo , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Necrose , Fibroblastos
16.
Microb Cell Fact ; 23(1): 51, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355518

RESUMO

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.


Assuntos
Hypocreales , Leucemia , Neoplasias , Trichoderma , Humanos , Lisina , Apoptose , Leucemia/tratamento farmacológico , Necrose
17.
Eur J Pharmacol ; 966: 176328, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38237714

RESUMO

In 2020, breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer in the world. Tumor microenvironment (TME) plays a critical role in resistance to standard therapies and tumor progression. Two key factors within the TME include adenosine, an immunosuppressive molecule, and glucose, which serves as the primary energy source for tumor cells. In this scenario, inhibiting the purinergic pathway and glucose uptake might be a promising strategy. Therefore, we sought to evaluated different treatment approaches in BC cells (Dapagliflozin, a SGLT2 inhibitor; Paclitaxel, the standard chemotherapy for BC; and ARL67156/APCP, inhibitors of CD39 and CD73, respectively). The expression of some membrane markers relevant to resistance was assessed. BC cell-lines (MCF-7 and MDA-MB-231) were co-treated and cell viability, cell cycle, and annexin/PI assays were performed. Our analysis showed promising results, where the combination of these compounds led to cell death by apoptosis/necrosis and cell cycle arrest. Dapagliflozin showed more impact on early apoptosis, whereas Paclitaxel led to late apoptosis/necrosis as the main mechanism of cell death. Inhibiting purinergic signaling also contributed to reducing cell viability together with the other drugs, suggesting it could have an influence on breast cancer survival mechanisms. Indeed, the overexpression of the NT5E gene in patients with ER+ tumors is strongly associated with reduced overall survival and progression-free interval. However, more studies are needed to fully understand the interactions and mechanism underlying these co-treatment multi-targeting approaches.


Assuntos
Compostos Benzidrílicos , Neoplasias da Mama , Glucosídeos , Humanos , Feminino , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Paclitaxel/farmacologia , Apoptose , Necrose , Proliferação de Células , Microambiente Tumoral
18.
Int J Biol Macromol ; 254(Pt 1): 127741, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38287568

RESUMO

Mammaliicoccus sciuri, a commensal and pathogenic bacterium of significant clinical and veterinary relevance, expresses exfoliative toxin C (ExhC), a specific glutamyl endopeptidase belonging to the chymotrypsin family as the principal virulence factor. However, unlike most members of this family, ETs are inactive against a wide range of substrates and possess exquisite specificity for desmoglein-1 (Dsg1), a cadherin-like adhesion molecule that is crucial to maintain tissue integrity, thereby preventing the separation of skin cells and the entry of pathogens. ExhC is of clinical importance since in addition to causing exfoliation in pigs and mice, it induces necrosis in multiple mammalian cell lines, a property not observed for other ETs. Previous experiments have implicated the ExhC79-128 fragment in causing necrosis. Site-directed mutagenesis of specific residues within this fragment were studied and led to the design of an ExhC variant containing four-point mutations (ExhCmut4) lacking necrotic potential but retaining nearly wild-type (wt) levels of enzymatic activity. Moreover, the determination of the ExhCwt and ExhCmut4 crystal structures identified the conformation in the necrosis-linked region. These results constitute an important step toward the understanding of the mechanisms underlying the necrotic and epidermolytic activity of ExhC.


Assuntos
Aminoácidos , Exfoliatinas , Animais , Suínos , Camundongos , Aminoácidos/metabolismo , Exfoliatinas/genética , Exfoliatinas/metabolismo , Exfoliatinas/farmacologia , Staphylococcus , Necrose , Mamíferos/metabolismo
19.
Artigo em Português | LILACS | ID: biblio-1572927

RESUMO

Objetivo: Revisar a literatura a respeito da ocorrência de possíveis reações adversas e complicações decorrentes da utilização do ácido hialurônico para preenchimento labial. Revisão de literatura: As reações foram classificadas em imediatas ou precoces e tardias. Dentre as reações imediatas e precoces, foram encontrados eritema, dor, edema, hematoma, necrose, reações de hipersensibilidade, coloração azulada, processos infecciosos e presença de nódulos. As reações tardias foram descritas como granulomas e reações de corpo estranho, migração do material de preenchimento e cicatriz hipertrófica. Discussão: As reações adversas ao preenchimento labial acontecem devido às propriedades físico-químicas do material, falta de conhecimento anatômico e técnica inadequada. A maior parte das reações adversas podem ser diagnosticadas por meio de seus aspectos clínicos. No entanto, outros exames podem ser empregados, sendo a ultrassonografia é o método mais confiável para a investigação e identificação do agente de preenchimento. O tratamento, quando necessário, se baseia principalmente na injeção intralesional de corticoide ou hialuronidase. Conclusão: A identificação, formas de prevenção e intervenção precoce nas possíveis reações adversas são fundamentais para evitar o agravamento da complicação a longo prazo, além de aumentar a segurança na realização do preenchimento labial.


Aim: The aim of this study was to review the literature regarding the occurrence of possible adverse reactions and complications resulting from the use of hyaluronic acid for lip filling. Literature review: The reactions were classifiedas immediate or early and late. Among the immediate and early reactions, erythema, pain, edema, hematoma, necrosis, hypersensitivity reactions, bluish color, infectious processes and the presence of nodules were found. Late reactions have been described as granulomas and foreign body reactions, migration of filling material and hypertrophic scarring.Discussion: Adverse reactions to lip fillers occur due to the physical-chemical properties of the material, lack of anatomical knowledge and inadequate technique. Most adverse reactions can be diagnosed through their clinical aspects. However, other tests can be used, with ultrasound being the most reliable method for investigating and identifying the filling agent. Treatment, when necessary, is mainly based onintralesional injection of corticosteroids or hyaluronidase. Conclusion: The identification, forms of prevention and early intervention in possible adverse reactions are essential to avoid worsening the complication in the long term, in addition to increasing safety in the performance of lip filling.


Assuntos
Hialuronoglucosaminidase , Odontólogos , Edema , Eritema , Necrose
20.
J Pediatr Orthop ; 44(2): 82-88, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37982458

RESUMO

OBJECTIVES: Lateral humeral condyle fractures account for 12% to 17% of all distal humerus fractures in children, and usually occur as an isolated injury or are associated with radial neck and/or proximal ulna fractures. The presentation with a concomitant dislocation of the elbow is rare. Therefore, literature on young patients with this uncommon combination is sparse and mostly limited to case reports and small case series. The aim of the present study is to identify the best treatment strategy for this injury, recognize potential risk factors for the development of complications, and identify predictors of outcome. METHODS: This is a multicenter retrospective review of electronic and written medical records for skeletally immature patients who were diagnosed with a lateral condyle fracture of the humerus associated with elbow dislocation (ED). Data recorded included patient demographics, fracture classification, direction of the dislocation, treatment strategy, time to union, elbow range of motion, complications, and additional procedures. The modified Flynn criteria were used to determine the outcomes. RESULTS: We identified 23 patients who presented to 3 institutions with a concomitant lateral humeral condyle fractures and an ED. The mean age at the time of injury was 8.7 years (range: 6 to 13 y). The median time from injury to surgery was 1 day (interquartile range: 0.5, minimum to maximum: 0 to 29 d). The median follow-up was 24 weeks (interquartile range: 16, minimum to maximum: 4 to 120 wk). The injury occurred more commonly in males (79%) with Weiss type 3 fractures. The direction of the dislocation was posterior or posteromedial in most cases. Open reduction through a modified Kocher lateral approach and fixation with either Kirschner wires (N = 12) or cannulated screws (N = 9) was the preferred method of treatment. Eight patients (34.8%) developed complications, including persistent elbow stiffness (N = 5), elbow instability (N = 1), and avascular necrosis (N = 2). There were no cases of delayed union, nonunion, malunion, heterotopic ossification, neurological injury, or hardware failure. Patients treated with casting or Kirschner wire fixation had a significantly increased rate of elbow stiffness compared with screw fixation (50%, 25%, and 11%, respectively, P = 0.015). According to Flynn's criteria, 65% of the patients had good or excellent outcomes, and 35% had poor. CONCLUSION: The findings of this study demonstrate a higher than previously described rate of complications in children with lateral condyle humerus fracture associated with ED, including persistent elbow stiffness, avascular necrosis, and chronic elbow instability, leading to unsatisfactory clinical outcomes in over one-third of the cases. Our findings suggest that the internal fixation with screws, combined with a shorter postoperative immobilization period (2 wk) may lead to improved clinical outcomes. LEVEL OF EVIDENCE: Level III-therapeutic, case series.


Assuntos
Articulação do Cotovelo , Fraturas Distais do Úmero , Fraturas do Úmero , Luxações Articulares , Instabilidade Articular , Masculino , Criança , Humanos , Adolescente , Cotovelo , Estudos Retrospectivos , Articulação do Cotovelo/cirurgia , Instabilidade Articular/etiologia , Fraturas do Úmero/complicações , Fraturas do Úmero/cirurgia , Úmero/cirurgia , Fixação Interna de Fraturas/métodos , Luxações Articulares/complicações , Amplitude de Movimento Articular , Necrose/complicações , Resultado do Tratamento
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