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1.
PLoS Negl Trop Dis ; 18(6): e0012247, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38885283

RESUMO

BACKGROUND: Fusarium and allied genera (fusarioid) species are common colonizers of roots and aerial plant parts, or act as phytopathogens in forestry and horticultural or grain crops. However, they can also cause a wide range of infections in humans, including onychomycosis, cutaneous and invasive infections. Fusarioid keratitis is characterized by an infection of the cornea with a suppurative and ulcerative appearance, which may cause damage to vision and permanent blindness. The aim of the present study was to investigate the prevalence of fusarioid species, biofilm formation and antifungal susceptibility profiling of clinical isolates recovered from patients with keratitis and dermatomycoses. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed between March, 2012-December, 2022. Demographic, clinical and epidemiological data of patients were also collected. In the present study, most of the patients with keratitis were male (74%), had a median age of 42 years old, worked with plant material or debris and 26% of them reported eye trauma. Regarding dermatomycosis, most of patients were female and exhibited toenail lesions. Forty-seven isolates belonged to the genus Neocosmospora (78.33%), nine to the Fusarium fujikuroi (15%) and four to the Fusarium oxysporum (6.66%) species complexes. Several strains were moderate biofilm producers, specifically among Fusarium annulatum. Most strains showed increased MICs to amphotericin B and ketoconazole and low MICs to itraconazole. MICs ranged from 0.25 to 16 µg/mL for amphotericin B, 0.0625 to >16 µg/mL for ketoconazole and 0.125 to 8 for itraconazole. CONCLUSIONS/SIGNIFICANCE: It is possible to conclude that fusarioid keratitis in Northeastern Brazil is an important and neglected disease, given the high number of cases, increased need for keratoplasty and poor outcome of the disease.


Assuntos
Antifúngicos , Fusarium , Ceratite , Testes de Sensibilidade Microbiana , Humanos , Feminino , Masculino , Adulto , Brasil/epidemiologia , Ceratite/microbiologia , Ceratite/epidemiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Antifúngicos/farmacologia , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Fusarium/classificação , Fusariose/microbiologia , Fusariose/epidemiologia , Fusariose/tratamento farmacológico , Adulto Jovem , Dermatomicoses/epidemiologia , Dermatomicoses/microbiologia , Dermatomicoses/tratamento farmacológico , Idoso , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Prevalência , Adolescente , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/tratamento farmacológico
3.
Bioconjug Chem ; 35(6): 758-765, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38857526

RESUMO

Bacterial keratitis, an ocular emergency, is the predominant cause of infectious keratitis. However, diagnostic procedures for it are invasive, time-consuming, and expeditious, thereby limiting effective treatment for the disease in the clinic. It is imperative to develop a timely and convenient method for the noninvasive diagnosis of bacterial keratitis. Fluorescence imaging is a convenient and noninvasive diagnostic method with high sensitivity. In this study, a type of nitroreductase-responsive probe (NTRP), which responds to nitroreductase to generate fluorescence signals, was developed as an activatable fluorescent probe for the imaging diagnosis of bacterial keratitis. Imaging experiments both in vitro and in vivo demonstrated that the probe exhibited "turn-on" fluorescence signals in response to nitroreductase-secreting bacteria within 10 min. Furthermore, the fluorescence intensity reached its highest at 4 or 6 h in vitro and at 30 min in vivo when the excitation wavelength was set at 520 nm. Therefore, the NTRP has the potential to serve as a feasible agent for the rapid and noninvasive in situ fluorescence diagnosis of bacterial keratitis.


Assuntos
Corantes Fluorescentes , Ceratite , Nitrorredutases , Corantes Fluorescentes/química , Nitrorredutases/metabolismo , Nitrorredutases/análise , Ceratite/diagnóstico , Ceratite/microbiologia , Animais , Humanos , Imagem Óptica/métodos , Camundongos
4.
Int Ophthalmol ; 44(1): 238, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904686

RESUMO

PURPOSE: This study aimed to evaluate how the SARS-CoV-2 pandemic and associated lockdown measures influenced microbial keratitis in Taiwan by comparing demographic data, predisposing factors, pathogen profiles, and treatment outcomes in 2019 and 2020. METHODS: Data from patients diagnosed with microbial keratitis at National Chung Kung University Hospital between January 2019 and December 2020 were examined, focusing on patient demographics, predisposing factors, isolated pathogens, antibiotic usage, and clinical progress. RESULTS: No significant differences were found in patient sex, laterality, or average age between the two years. Predisposing factors, such as contact lens use and chronic ocular/systemic disorders, remained unchanged. While fungal isolates slightly increased during the lockdown, bacterial isolates remained consistent. Medical treatment effectiveness, treatment strategies, and antibiotic susceptibility for common bacteria showed no significant alterations. CONCLUSION: Despite the challenges posed by the SARS-CoV-2 pandemic and lockdown measures, this study revealed minimal changes in microbial keratitis trends in Taiwan. This highlights the importance of maintaining access to medical care during crises and offers insights into potential treatment strategies for patients facing difficulties in receiving timely care. Further research should investigate the pandemic's impact on healthcare access and patient outcomes in various populations and regions.


Assuntos
COVID-19 , Infecções Oculares Bacterianas , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Taiwan/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Idoso , Ceratite/epidemiologia , Ceratite/microbiologia , Estudos Retrospectivos , Pandemias , Quarentena , Antibacterianos/uso terapêutico , Adulto Jovem , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia
5.
Int Ophthalmol ; 44(1): 246, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907102

RESUMO

PURPOSE: The objective of this study was to assess the clinical diagnostic value of metagenomic next-generation sequencing (mNGS) in cases of challenging corneal infections using corneal tissue samples. METHODS: This retrospective study involved 42 patients with corneal infections, where conventional diagnostic techniques failed to identify the causative pathogen. Corneal tissue specimens underwent mNGS, followed by microbial culture for validation. Sensitivity-guided antimicrobial therapy was administered upon identification of the pathogen. The diagnostic and therapeutic efficacy of mNGS was analyzed to evaluate its clinical utility. RESULTS: A total of 42 patients were included in this study, with mNGS detection results obtained for 38 cases (90.48%). Among them, 30 cases (71.43%) were clinically significant, eight cases (19.05%) had low clinical relevance, and four cases (9.52%) showed no detection. Following corresponding antimicrobial treatment, 30 patients exhibited significant improvement, resulting in a treatment effectiveness of 71.43%. The prognosis of mNGS-positive patients was superior to that of mNGS-negative patients, with statistically significant differences observed (P < 0.001). CONCLUSIONS: Corneal tissue mNGS facilitated the rapid identification of causative agents in challenging corneal infections with unclear clinical diagnoses. It could be seamlessly integrated with traditional diagnostic methods to guide the diagnosis and treatment of corneal diseases.


Assuntos
Córnea , Infecções Oculares Bacterianas , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Masculino , Estudos Retrospectivos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pessoa de Meia-Idade , Adulto , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Córnea/microbiologia , Metagenômica/métodos , Idoso , Bactérias/isolamento & purificação , Bactérias/genética , Adulto Jovem , Adolescente , Criança , Ceratite/diagnóstico , Ceratite/microbiologia , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico
6.
Emerg Infect Dis ; 30(7): 1406-1409, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916573

RESUMO

We describe a case of a 46-year-old man in Missouri, USA, with newly diagnosed advanced HIV and PCR-confirmed mpox keratitis. The keratitis initially resolved after intravenous tecovirimat and penicillin for suspected ocular syphilis coinfection. Despite a confirmatory negative PCR, he developed relapsed, ipsilateral PCR-positive keratitis and severe ocular mpox requiring corneal transplant.


Assuntos
Ceratite , Recidiva , Humanos , Pessoa de Meia-Idade , Masculino , Ceratite/diagnóstico , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Missouri , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Sífilis/diagnóstico , Sífilis/tratamento farmacológico
7.
Invest Ophthalmol Vis Sci ; 65(6): 13, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38848078

RESUMO

Purpose: Fungal keratitis (FK) is an invasive corneal infection associated with significant risk to vision. Although the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has been recognized for its role in defending against viral infections, its involvement in FK still remains largely unclear. This study sought to elucidate the contribution of the cGAS/STING signaling pathway to the pathogenesis of FK. Methods: The expression of cGAS/STING signaling components was assessed in a murine model of Candida albicans keratitis through RNA sequencing, western blot analysis, immunofluorescence staining, and real-time PCR. Both genetic (utilizing Sting1gt/gt mice) and pharmacological (using C176) interventions were employed to inhibit STING activity, allowing for the evaluation of resultant pathogenic alterations in FK using slit-lamp examination, clinical scoring, hematoxylin and eosin (H&E) staining, fungal culture, and RNA sequencing. Subconjunctival administration of the NOD-like receptor protein 3 (NLRP3) inflammasome inhibitor MCC950 was performed to evaluate FK manifestations following STING activity blockade. Furthermore, the impact of the STING agonist diABZI on FK progression was investigated. Results: Compared to uninfected corneas, those infected with C. albicans exhibited increased expression of cGAS/STING signaling components, as well as its elevated activity. Inhibiting cGAS/STING signaling exacerbated the advancement of FK, as evidenced by elevated clinical scores, augmented fungal load, and heightened inflammatory response, including NLRP3 inflammasome activation and pyroptosis. Pharmacological inhibition of the NLRP3 inflammasome effectively mitigated the exacerbated FK by suppressing STING activity. Conversely, pre-activation of STING exacerbated FK progression compared to the PBS control, characterized by increased fungal burden and reinforced inflammatory infiltration. Conclusions: This study demonstrates the essential role of the cGAS/STING signaling pathway in FK pathogenesis and highlights the necessity of its proper activation for the host against FK.


Assuntos
Candida albicans , Candidíase , Modelos Animais de Doenças , Infecções Oculares Fúngicas , Proteínas de Membrana , Nucleotidiltransferases , Transdução de Sinais , Animais , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/metabolismo , Camundongos , Candida albicans/fisiologia , Candidíase/microbiologia , Candidíase/metabolismo , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Ceratite/microbiologia , Ceratite/metabolismo , Western Blotting , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Feminino , Úlcera da Córnea/microbiologia , Úlcera da Córnea/metabolismo , Inflamassomos/metabolismo
8.
BMC Ophthalmol ; 24(1): 244, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858630

RESUMO

BACKGROUND: This study aimed to report a case of neurotrophic keratitis caused by lightning. CASE PRESENTATION: A 38-year-old man was hit by lightning and suffered eye injury. He eventually developed neurotrophic keratitis. RESULTS: The patient's injury history and burn site were analyzed, and it was judged that lightning directly damaged his cornea, eventually resulting in neurotrophic keratitis. Fortunately, the patient's vision improved after treatment. CONCLUSION: Lightning can cause eye damage, and the clinical manifestations are diverse. Lightning currents cause corneal nerve loss, resulting in neurotrophic keratitis. To maintain corneal integrity and prevent disease progression, early assessment and appropriate treatment are necessary.


Assuntos
Ceratite , Lesões Provocadas por Raio , Humanos , Masculino , Adulto , Lesões Provocadas por Raio/complicações , Ceratite/etiologia , Ceratite/diagnóstico , Acuidade Visual , Córnea/patologia
9.
Sci Data ; 11(1): 627, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871784

RESUMO

Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.


Assuntos
Aprendizado Profundo , Ceratite , Tomografia de Coerência Óptica , Humanos , Ceratite/diagnóstico por imagem , Imageamento Tridimensional , Córnea/diagnóstico por imagem , Processamento de Imagem Assistida por Computador
11.
J Virol ; 98(6): e0010824, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38742874

RESUMO

Numerous studies have demonstrated the presence of covert viral infections in insects. These infections can be transmitted in insect populations via two main routes: vertical from parents to offspring, or horizontal between nonrelated individuals. Thirteen covert RNA viruses have been described in the Mediterranean fruit fly (medfly). Some of these viruses are established in different laboratory-reared and wild medfly populations, although variations in the viral repertoire and viral levels have been observed at different time points. To better understand these viral dynamics, we characterized the prevalence and levels of covert RNA viruses in two medfly strains, assessed the route of transmission of these viruses, and explored their distribution in medfly adult tissues. Altogether, our results indicated that the different RNA viruses found in medflies vary in their preferred route of transmission. Two iflaviruses and a narnavirus are predominantly transmitted through vertical transmission via the female, while a nodavirus and a nora virus exhibited a preference for horizontal transmission. Overall, our results give valuable insights into the viral tropism and transmission of RNA viruses in the medfly, contributing to the understanding of viral dynamics in insect populations. IMPORTANCE: The presence of RNA viruses in insects has been extensively covered. However, the study of host-virus interaction has focused on viruses that cause detrimental effects to the host. In this manuscript, we uncovered which tissues are infected with covert RNA viruses in the agricultural pest Ceratitis capitata, and which is the preferred transmission route of these viruses. Our results showed that vertical and horizontal transmission can occur simultaneously, although each virus is transmitted more efficiently following one of these routes. Additionally, our results indicated an association between the tropism of the RNA virus and the preferred route of transmission. Overall, these results set the basis for understanding how viruses are established and maintained in medfly populations.


Assuntos
Ceratitis capitata , Vírus de RNA , Tropismo Viral , Animais , Vírus de RNA/genética , Vírus de RNA/fisiologia , Feminino , Ceratitis capitata/virologia , Masculino , Infecções por Vírus de RNA/transmissão , Infecções por Vírus de RNA/virologia
12.
Exp Eye Res ; 244: 109944, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797260

RESUMO

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.


Assuntos
Aspergilose , Aspergillus fumigatus , Autofagia , Cinamatos , Depsídeos , Infecções Oculares Fúngicas , Macrófagos , Espécies Reativas de Oxigênio , Ácido Rosmarínico , Depsídeos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Camundongos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/metabolismo , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Cinamatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Modelos Animais de Doenças , Células RAW 264.7 , Citocinas/metabolismo , Fagocitose/efeitos dos fármacos
13.
Exp Eye Res ; 244: 109950, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38815789

RESUMO

Loss of tear homeostasis, characterized by hyperosmolarity of the ocular surface, induces cell damage through inflammation and oxidation. Transient receptor potential vanilloid 1 (TRPV1), a sensor for osmotic changes, plays a crucial role as a calcium ion channel in the pathogenesis of hypertonic-related eye diseases. Capsaicin (CAP), a potent phytochemical, alleviates inflammation during oxidative stress events by activating TRPV1. However, the pharmacological use of CAP for eye treatment is limited by its pungency. Nitro dihydrocapsaicin (NDHC) was synthesized with aromatic ring modification of CAP structure to overcome the pungent effect. We compared the molecular features of NDHC and CAP, along with their biological activities in human corneal epithelial (HCE) cells, focusing on antioxidant and anti-inflammatory activities. The results demonstrated that NDHC maintained cell viability, cell shape, and exhibited lower cytotoxicity compared to CAP-treated cells. Moreover, NDHC prevented oxidative stress and inflammation in HCE cells following lipopolysaccharide (LPS) administration. These findings underscore the beneficial effect of NDHC in alleviating ocular surface inflammation, suggesting that NDHC may serve as an alternative anti-inflammatory agent targeting TRPV1 for improving hyperosmotic stress-induced ocular surface damage.


Assuntos
Capsaicina , Sobrevivência Celular , Epitélio Corneano , Lipopolissacarídeos , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/metabolismo , Epitélio Corneano/patologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Antioxidantes/farmacologia , Células Cultivadas , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Ceratite/patologia , Espécies Reativas de Oxigênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo
14.
JAMA Ophthalmol ; 142(6): 568-571, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696206

RESUMO

Importance: While UV radiation displays may be used for recreational purposes at outdoor events, unprotected eyes have been reported to have symptoms consistent with photokeratitis. Such symptoms warrant documentation and evaluation in ophthalmic peer reviewed literature. Objective: To describe a case series of photokeratitis associated with a single ultraviolet radiation display at an outdoor event. Design, Setting, and Participants: This case series involved a retrospective record review of 8 patients who presented in public and private health sectors in November 2023 after developing photokeratitis following UV radiation exposure at an outdoor event in Hong Kong on the night of November 4, 2023. Main Outcomes and Measures: Clinical symptoms, signs, and clinical course of patients who were diagnosed acute photokeratitis following exposure to UV radiation. Results: The mean time of UV display exposure for the 8 patients (mean [SD] age, 33.12 [5.19] years; 4 [50%] female) was 3.00 (1.41) hours, and symptoms presented at a mean (SD) 8.88 (8.24) hours after the exposure. None of the patients were wearing spectacles during the exposed period. All patients were affected bilaterally. All patients experienced eye pain, 6 experienced red eye, and 5 experienced tearing and photophobia. Mean (SD) presenting visual acuity was logMAR 0.10 (0.14) (approximate Snellen equivalent, 20/25) for right eyes and 0.06 (0.89) (approximate Snellen equivalent, 20/25) for left eyes. On examination, there were findings of cornea and conjunctival involvement with punctate epithelial erosions and ciliary vasodilation, but none of the patients presented with anterior chamber reaction. Corticosteroids, lubricants, and antibiotics, all provided topically, were prescribed. Five patients were not scheduled for a review, and 3 had follow-up visits, with the length of follow-up ranging from 7 to 10 days. All patients had undergone a complete recovery. Conclusions and Relevance: These findings provide evidence of an association between UV radiation used for recreational purposes and photokeratitis, which may help guide evaluation and management of future cases.


Assuntos
Ceratite , Raios Ultravioleta , Acuidade Visual , Humanos , Feminino , Raios Ultravioleta/efeitos adversos , Masculino , Estudos Retrospectivos , Adulto , Ceratite/etiologia , Ceratite/diagnóstico , Hong Kong , Adulto Jovem , Recreação
15.
Redox Biol ; 73: 103206, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796864

RESUMO

Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1ß, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.


Assuntos
Anti-Inflamatórios , Antifúngicos , Azóis , Isoindóis , Ceratite , Compostos Organosselênicos , Estresse Oxidativo , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/uso terapêutico , Animais , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Azóis/farmacologia , Azóis/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células RAW 264.7 , Antioxidantes/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/metabolismo , Modelos Animais de Doenças
16.
Front Cell Infect Microbiol ; 14: 1346821, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694515

RESUMO

Background: Microbial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions' pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears. Methods: Corneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1ß, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay. Results: A total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) <-2 or > 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <-3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance. Conclusions: During corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight.


Assuntos
Túnica Conjuntiva , Córnea , Citocinas , Ceratite , Lágrimas , Transcriptoma , Humanos , Lágrimas/metabolismo , Citocinas/metabolismo , Citocinas/genética , Córnea/metabolismo , Córnea/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/imunologia , Ceratite/genética , Ceratite/imunologia , Ceratite/metabolismo , Idoso , Perfilação da Expressão Gênica
17.
BMJ Case Rep ; 17(5)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719269

RESUMO

A middle-aged male patient presented with a central corneal perforation in a deep stromal infiltrate in his left eye. An emergency therapeutic penetrating keratoplasty was performed. Microbiological evaluation of the corneal scraping specimen revealed septate fungal filaments on stains. However, culture reports after 24 hours from the scraping sample and the excised half corneal button showed growth of gram-negative bacilli. This pathogen was identified as an aerobic, non-fermentative, gram-negative, bacillus by conventional microbiology and confirmed as Myroides species by the VITEK 2 Compact system (bioMérieux, Marcy l'Etoile, France). Susceptibility to chloramphenicol was noted based on which the patient was treated with topical chloramphenicol 0.5%. No recurrence of the infection was noted. This is the first reported case of corneal infection with the Myroides species of bacteria which, heretofore, have been known to cause endocarditis and urinary tract infections.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Humanos , Masculino , Pessoa de Meia-Idade , Ceratite/microbiologia , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Antibacterianos/uso terapêutico , Ceratoplastia Penetrante , Cloranfenicol/uso terapêutico , Cloranfenicol/administração & dosagem , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Perfuração da Córnea/microbiologia , Perfuração da Córnea/diagnóstico
18.
Int Immunopharmacol ; 136: 112195, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38820965

RESUMO

Proper hydration and the clarity of the cornea are maintained through the crucial function of the corneal endothelium. Inflammation of the corneal endothelium, known as endotheliitis, can disrupt endothelial function, resulting in alterations to vision. Corneal endotheliitis is characterised by corneal oedema, the presence of keratic precipitates, inflammation within the anterior chamber, and occasionally, limbal injection, neovascularisation, and the concurrent or overlapping presence of uveitis. The aetiology of this condition is diverse, predominantly viral, but it may also be drug-induced, result from bacterial or fungal infections, be associated with systemic diseases and procedures, or remain idiopathic with no identifiable cause. To date, no standardised protocol for the treatment of this ocular disease exists, and in severe cases, corneal transplantation may be required. A 31-year-old male was transferred to our hospital for the management of corneal endothelial decompensation resulting from corneal endotheliitis. Hormonal therapy and antiviral medications proved ineffective, rendering the patient a candidate for corneal transplantation. As a final measure, treatment with the ROCK inhibitor netarsudil was initiated. The patient demonstrated significant improvement in symptoms, and the inflammation was successfully managed after nine months. In this study, a novel approach employing ROCK inhibitor therapy was utilised for the treatment of corneal endotheliitis, leading to marked recovery during patient follow-up. This case report represents the inaugural application of the ROCK inhibitor netarsudil in managing corneal endothelial decompensation attributed to corneal endotheliitis. These findings suggest that this method warrants consideration as a potential novel treatment option for similar conditions.


Assuntos
Benzoatos , Endotélio Corneano , Ceratite , beta-Alanina , Quinases Associadas a rho , Humanos , Adulto , Masculino , Ceratite/tratamento farmacológico , Ceratite/diagnóstico , Quinases Associadas a rho/antagonistas & inibidores , Endotélio Corneano/patologia , Benzoatos/uso terapêutico , beta-Alanina/análogos & derivados , beta-Alanina/uso terapêutico , Nitrilas/uso terapêutico , Edema da Córnea/tratamento farmacológico , Edema da Córnea/etiologia , Edema da Córnea/diagnóstico , Resultado do Tratamento
19.
Microbiology (Reading) ; 170(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38739119

RESUMO

Introduction. Bacterial keratitis, particularly caused by Pseudomonas aeruginosa, is challenging to treat because of multi-drug tolerance, often associated with the formation of biofilms. Antibiotics in development are typically evaluated against planktonic bacteria in a culture medium, which may not accurately represent the complexity of infections in vivo.Hypothesis/Gap Statement. Developing a reliable, economic ex vivo keratitis model that replicates some complexity of tissue infections could facilitate a deeper understanding of antibiotic efficacy, thus aiding in the optimization of treatment strategies for bacterial keratitis.Methodology. Here we investigated the efficacy of three commonly used antibiotics (gentamicin, ciprofloxacin and meropenem) against Pseudomonas aeruginosa cytotoxic strain PA14 and invasive strain PA01 using an ex vivo porcine keratitis model.Results. Both strains of P. aeruginosa were susceptible to the MIC of the three tested antibiotics. However, significantly higher concentrations were necessary to inhibit bacterial growth in the minimum biofilm eradication concentration (MBEC) assay, with both strains tolerating concentrations greater than 512 mg l-1 of meropenem. When MIC and higher concentrations than MBEC (1024 mg l-1) of antibiotics were applied, ciprofloxacin exhibited the highest potency against both P. aeruginosa strains, followed by meropenem, while gentamicin showed the least potency. Despite this, none of the antibiotic concentrations used effectively cleared the infection, even after 18 h of continuous exposure.Conclusions. Further exploration of antibiotic concentrations and aligning dosing with clinical studies to validate the model is needed. Nonetheless, our ex vivo porcine keratitis model could be a valuable tool for assessing antibiotic efficacy.


Assuntos
Antibacterianos , Biofilmes , Ciprofloxacina , Modelos Animais de Doenças , Ceratite , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Antibacterianos/farmacologia , Suínos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Biofilmes/efeitos dos fármacos , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ciprofloxacina/farmacologia , Gentamicinas/farmacologia , Meropeném/farmacologia
20.
Harefuah ; 163(5): 295-297, 2024 May.
Artigo em Hebraico | MEDLINE | ID: mdl-38734942

RESUMO

INTRODUCTION: During the global outbreak of coronavirus disease 2019 pandemic, people sought ways to disinfect their domestic and public surroundings. One of the sanitation options included the usage of ultraviolet-C (UVC) lamps since UVC radiation has been shown to effectively inactivate the SARS-Coronavirus. UVC radiation may also be effective against the SARS-CoV-2 virus. Here we report four cases of bilateral photokeratitis due to the improper usage of UV lamps during the first outbreak of COVID-19 in Israel. METHODS: We collected 4 case reports from patients who were diagnosed with bilateral photokeratitis due to improper usage of UV lamps in their domestic environment from May to December 2020 during the first outbreak of COVID-19 in Israel. RESULTS: A total of four patients presented with signs and symptoms of bilateral photokeratitis after exposure to UV lamps. DISCUSSION: Acute exposure of UVC to the cornea may cause "burns", known as photokeratitis. The signs of photokeratitis usually appear a few hours after the exposure. Precautious steps to educate the population must include using protective eyewear in any exposure to UV light and avoiding the use of germicidal lamps in public locations with exposure to the population.


Assuntos
COVID-19 , Ceratite , Raios Ultravioleta , Humanos , Raios Ultravioleta/efeitos adversos , COVID-19/prevenção & controle , Masculino , Israel/epidemiologia , Feminino , Ceratite/etiologia , Pessoa de Meia-Idade , Adulto
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