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Amicacina , Reacciones Cruzadas , Desensibilización Inmunológica , Neomicina , Humanos , Desensibilización Inmunológica/métodos , Amicacina/efectos adversos , Amicacina/uso terapéutico , Neomicina/efectos adversos , Antibacterianos/efectos adversos , Exantema/inducido químicamente , Hipersensibilidad a las Drogas/terapia , Hipersensibilidad a las Drogas/inmunología , Hipersensibilidad a las Drogas/diagnóstico , Femenino , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Neomycin is used in several over-the-counter pharmaceutical formulations in Brazil. In Europe and Canada, where it is not freely available, its sensitization frequency is lower than in the United States, where this does not occur. OBJECTIVE: To present the frequency of sensitization to neomycin observed in a tertiary hospital and the pharmaceutical formulations sold in Brazil containing neomycin. METHOD: Retrospective analysis of positive results to neomycin, obtained through patch tests performed in a tertiary hospital, from 2009 to 2018 and investigation of topical drugs and vaccines containing neomycin in Brazilian databases available on the internet. RESULTS: Among 1,162 patients, 71 (6%) had positive reactions to neomycin, 65% female and 35% male individuals, 46% were over 50 years old, and 24% had a personal history of atopy. The dermatitis lasted from four months to 20 years. Lesions were located in 69% of the patients on the upper limbs, in 55% they were on the lower limbs, and in 42% they were disseminated in more than 4 sites. Polysensitization was detected in 55% of cases. Of these, 28% were linked to sensitization to rubber allergens and 27% to potassium bichromate. A total of 158 topical presentations of neomycin were found: 79 ointments, 58 creams, 10 ophthalmic solutions, seven otological solutions, one oral solution, two nasal solutions, and one antiseptic powder, in addition to 11 types of vaccines. STUDY LIMITATIONS: Retrospective study. CONCLUSION: Sensitization to neomycin occurred in 6% of the studied population, affecting more females aged over 50 years, with skin lesions located mainly on the upper and lower limbs, in the context of chronic contact dermatitis. Neomycin was found in 135 formulations, most of them available over the counter, as well as in 11 miscellaneous vaccines.
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Dermatitis Alérgica por Contacto , Neomicina , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neomicina/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/epidemiología , Estudios Retrospectivos , Alérgenos/efectos adversos , Pruebas del Parche/métodos , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. METHODS: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin®) using the occlusion method to treat paronychia or PG. RESULTS: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. CONCLUSION: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.
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Hiperplasia Angiolinfoide con Eosinofilia , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paroniquia , Humanos , Femenino , Anciano , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Timolol/efectos adversos , Hiperplasia Angiolinfoide con Eosinofilia/inducido químicamente , Hiperplasia Angiolinfoide con Eosinofilia/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/efectos adversos , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Pomadas/efectos adversos , Taiwán , Inhibidores de Proteínas Quinasas/efectos adversos , Neomicina/efectos adversos , Receptores ErbB , Tirotricina/efectos adversos , Soluciones Oftálmicas/efectos adversos , MutaciónRESUMEN
Currently, adult cochlear hair cells (HCs) lack the capacity to regenerate, particularly the hearing damage caused by the HC damage are hard to recover. Remarkably, Lgr5+ inner ear progenitor cells can be activated to proliferate and regenerate hair cells (HCs) in response to injury, but the epigenetic regulatory roles in HC regeneration from Lgr5+ progenitor cells remain unresolved to date. We here investigate the possible roles of H3K4me3 modification in Lgr5+ progenitor cell proliferation and HC regeneration, and identify these differentially expressed genes associated with different binding regions between untreated Lgr5+ progenitor cells (ULPs) and neomycin-treated Lgr5+ progenitor cells (NLPs). Especially, H3K4me3 modification drives 12 genes involved in regulating proliferation and HC regeneration. Interestingly, we find that transcription factors Zeb1, Fev and Prdm5 are enriched in distinct peaks, implying their probable important roles in modulating neomycin-induced Lgr5+ progenitor cell proliferation and HC regeneration. Overall, our study demonstrates the underlying roles of H3k4me3 modification in Lgr5+ progenitor cell proliferation and HCs regeneration, and provides candidate H3K4me3 modification targets and regulators for subsequent studies.
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Neomicina , Transcriptoma , Proliferación Celular/genética , Epigenómica , Células Ciliadas Auditivas/metabolismo , Histonas , Neomicina/efectos adversos , Neomicina/metabolismo , Células Madre/metabolismo , Transcriptoma/genéticaRESUMEN
BACKGROUND: Neratinib is a pan-ErbB tyrosine kinase inhibitor used for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the main adverse event associated with neratinib treatment. We aimed here to determine whether antibiotic-induced gut microbial shifts altered development of neratinib-induced diarrhea. METHODS: Female Albino Wistar rats (total n = 44) were given antibiotics (vancomycin, neomycin, or a cocktail of vancomycin, neomycin and ampicillin) in drinking water for four weeks, and then treated daily with neratinib (50 mg/kg) for 28 days. Diarrhea, along with markers of gastrointestinal damage and microbial alterations were measured by histopathology and 16S sequencing, respectively. RESULTS: Rats treated with vancomycin or neomycin had significantly lower levels of diarrhea than rats treated with neratinib alone. In the distal ileum, neratinib was associated with a statistically significant increase in histological damage in all treatment groups expect the antibiotic cocktail. Key features included villous blunting and fusion and some inflammatory infiltrate. Differences in microbial composition at necropsy in vehicle control, neratinib and neratinib + neomycin groups, were characterized by a neratinib-induced increase in gram-negative bacteria that was reversed by neomycin. Neomycin shifted bacterial composition so that Blautia become the dominant genus. CONCLUSIONS: Narrow spectrum antibiotics reduced neratinib-induced diarrhea. This suggests that the microbiome may play a key role in the development and prolongation of diarrhea following neratinib treatment, although further research is required to understand the key bacteria and mechanisms by which they reduce diarrhea, as well as how this may impact presentation of diarrhea in clinical cohorts.
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Neoplasias de la Mama , Quinolinas , Animales , Antibacterianos/efectos adversos , Neoplasias de la Mama/patología , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Femenino , Bacterias Gramnegativas , Humanos , Neomicina/efectos adversos , Quinolinas/farmacología , Ratas , Receptor ErbB-2 , Vancomicina/efectos adversosRESUMEN
Aminoglycoside antibiotics are lifesaving medicines, crucial for the treatment of chronic or drug resistant infections. However, aminoglycosides are toxic to the sensory hair cells in the inner ear. As a result, aminoglycoside-treated individuals can develop permanent hearing loss and vestibular impairment. There is considerable evidence that reactive oxygen species (ROS) production and the subsequent phosphorylation of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38) drives apoptosis in aminoglycoside-treated hair cells. However, treatment strategies that directly inhibit ROS, JNK, or P38 are limited by the importance of these molecules for normal cellular function. Alternatively, the upstream regulator apoptosis signal-regulating kinase 1 (ASK1/MAP3K5) is a key mediator of ROS-induced JNK and P38 activation under pathologic but not homeostatic conditions. We investigated ASK1 as a mediator of drug-induced hair cell death using cochlear explants from Ask1 knockout mice, demonstrating that Ask1 deficiency attenuates neomycin-induced hair cell death. We then evaluated pharmacological inhibition of ASK1 with GS-444217 as a potential otoprotective therapy. GS-444217 significantly attenuated hair cell death in neomycin-treated explants but did not impact aminoglycoside efficacy against P. aeruginosa in the broth dilution test. Overall, we provide significant pre-clinical evidence that ASK1 inhibition represents a novel strategy for preventing aminoglycoside ototoxicity. KEY MESSAGES: ASK1 is an upstream, redox-sensitive regulator of P38 and JNK, which are known mediators of hair cell death. Ask1 knockout does not affect hair cell development in vivo, but significantly reduces aminoglycoside-induced hair cell death in vitro. A small-molecule inhibitor of ASK1 attenuates neomycin-induced hair cell death, and does not impact antibiotic efficacy in vitro. ASK1 may be a novel molecular target for preventing aminoglycoside-induced hearing loss.
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Aminoglicósidos , Células Ciliadas Auditivas , Pérdida Auditiva , MAP Quinasa Quinasa Quinasa 5 , Aminoglicósidos/efectos adversos , Animales , Antibacterianos/efectos adversos , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/metabolismo , Pérdida Auditiva/patología , Pérdida Auditiva/prevención & control , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Ratones , Neomicina/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The Hippo/Yes-associated protein (YAP) signaling pathway has been shown to be able to maintain organ size and homeostasis by regulating cell proliferation, differentiation, and apoptosis. The abuse of aminoglycosides is one of the main causes of sensorineural hearing loss (SSNHL). However, the role of the Hippo/YAP signaling pathway in cochlear hair cell (HC) damage protection in the auditory field is still unclear. In this study, we used the YAP agonist XMU-MP-1 (XMU) and the inhibitor Verteporfin (VP) to regulate the Hippo/YAP signaling pathway in vitro. We showed that YAP overexpression reduced neomycin-induced HC loss, while downregulated YAP expression increased HC vulnerability after neomycin exposure in vitro. We next found that activation of YAP expression inhibited C-Abl-mediated cell apoptosis, which led to reduced HC loss. Many previous studies have reported that the level of reactive oxygen species (ROS) is significantly increased in cochlear HCs after neomycin exposure. In our study, we also found that YAP overexpression significantly decreased ROS accumulation, while downregulation of YAP expression increased ROS accumulation. In summary, our results demonstrate that the Hippo/YAP signaling pathway plays an important role in reducing HC injury and maintaining auditory function after aminoglycoside exposure. YAP overexpression could protect against neomycin-induced HC loss by inhibiting C-Abl-mediated cell apoptosis and decreasing ROS accumulation, suggesting that YAP could be a novel therapeutic target for aminoglycosides-induced sensorineural hearing loss in the clinic.
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Antibacterianos/efectos adversos , Células Ciliadas Auditivas/efectos de los fármacos , Vía de Señalización Hippo/efectos de los fármacos , Neomicina/efectos adversos , Proteínas Señalizadoras YAP/metabolismo , Animales , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Ratones , Factores Protectores , Inhibidores de la Síntesis de la Proteína/efectos adversos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10-/-] mouse model. METHODS: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. RESULTS: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. CONCLUSIONS: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.
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Ampicilina/efectos adversos , Antibacterianos/efectos adversos , Colitis/inducido químicamente , Interleucina-10/genética , Neomicina/efectos adversos , Animales , Colitis/metabolismo , Colitis/microbiología , Colitis/patología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Femenino , Hipersensibilidad a los Alimentos , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Masculino , Ratones Noqueados , Mucina 2/metabolismo , PermeabilidadRESUMEN
BACKGROUND: A patient received enoxaparin sodium subcutaneous injections for prophylaxis after surgery and developed inflammatory skin reactions on injection sites on Day 5 after the first administration. Patch test was performed with baseline series and low-molecular-weight heparins (LMWHs) at different concentrations and showed positive reactions to neomycin and LMWHs. Cross-reactivity between neomycin and LMWHs was suspected due to similar structure. OBJECTIVES: To establish the evidence of possible cross reaction between neomycin and LMWHs by patch testing. MATERIALS & METHODS: Patch testing of 12 individual controls with a history of neomycin contact allergy was performed. RESULTS: Positive patch test reactions to enoxaparin sodium, tinzaparin sodium, and neomycin sulphate were reported in the patients. None of the controls reacted to LMWHs. CONCLUSION: There was no proof of cross reaction between neomycin and LMWHs in this study, suggesting that the simultaneous reaction may be a coincidence. Since the number of individuals studied was low, allergy to LMWHs following injection in individuals with a history of neomycin allergy should be further investigated.
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Antibacterianos/efectos adversos , Anticoagulantes/efectos adversos , Reacciones Cruzadas , Erupciones por Medicamentos/etiología , Enoxaparina/análogos & derivados , Neomicina/efectos adversos , Anciano , Antibacterianos/administración & dosificación , Anticoagulantes/administración & dosificación , Enoxaparina/administración & dosificación , Enoxaparina/efectos adversos , Humanos , Inyecciones Subcutáneas , Masculino , Neomicina/administración & dosificación , Pruebas del ParcheRESUMEN
To identify small molecules that shield mammalian sensory hair cells from the ototoxic side effects of aminoglycoside antibiotics, 10,240 compounds were initially screened in zebrafish larvae, selecting for those that protected lateral-line hair cells against neomycin and gentamicin. When the 64 hits from this screen were retested in mouse cochlear cultures, 8 protected outer hair cells (OHCs) from gentamicin in vitro without causing hair-bundle damage. These 8 hits shared structural features and blocked, to varying degrees, the OHC's mechano-electrical transducer (MET) channel, a route of aminoglycoside entry into hair cells. Further characterization of one of the strongest MET channel blockers, UoS-7692, revealed it additionally protected against kanamycin and tobramycin and did not abrogate the bactericidal activity of gentamicin. UoS-7692 behaved, like the aminoglycosides, as a permeant blocker of the MET channel; significantly reduced gentamicin-Texas red loading into OHCs; and preserved lateral-line function in neomycin-treated zebrafish. Transtympanic injection of UoS-7692 protected mouse OHCs from furosemide/kanamycin exposure in vivo and partially preserved hearing. The results confirmed the hair-cell MET channel as a viable target for the identification of compounds that protect the cochlea from aminoglycosides and provide a series of hit compounds that will inform the design of future otoprotectants.
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Aminoglicósidos/efectos adversos , Cóclea/efectos de los fármacos , Ototoxicidad/prevención & control , Animales , Cóclea/citología , Evaluación Preclínica de Medicamentos/métodos , Embrión no Mamífero/efectos de los fármacos , Femenino , Gentamicinas/efectos adversos , Gentamicinas/farmacología , Células Ciliadas Auditivas/efectos de los fármacos , Masculino , Mecanotransducción Celular/efectos de los fármacos , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Factor de Transcripción Asociado a Microftalmía/genética , Neomicina/efectos adversos , Técnicas de Cultivo de Órganos , Ototoxicidad/etiología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
Ferroptosis is a recently discovered iron-dependent form of oxidative programmed cell death distinct from caspase-dependent apoptosis. In this study, we investigated the effect of ferroptosis in neomycin-induced hair cell loss by using selective ferroptosis inhibitor liproxstatin-1 (Lip-1). Cell viability was identified by CCK8 assay. The levels of reactive oxygen species (ROS) were determined by DCFH-DA and cellROX green staining. The mitochondrial membrane potential (ΔΨm) was evaluated by TMRM staining. Intracellular iron and lipid peroxides were detected with Mito-FerroGreen and Liperfluo probes. We found that ferroptosis can be induced in both HEI-OC1 cells and neonatal mouse cochlear explants, as evidenced by Mito-FerroGreen and Liperfluo staining. Further experiments showed that pretreatment with Lip-1 significantly alleviated neomycin-induced increased ROS generation and disruption in ΔΨm in the HEI-OC1 cells. In parallel, Lip-1 significantly attenuated neomycin-induced hair cell damage in neonatal mouse cochlear explants. Collectively, these results suggest a novel mechanism for neomycin-induced ototoxicity and suggest that ferroptosis inhibition may be a new clinical intervention to prevent hearing loss.
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Células Ciliadas Auditivas/metabolismo , Neomicina/efectos adversos , Ototoxicidad/prevención & control , Quinoxalinas/farmacología , Compuestos de Espiro/farmacología , Animales , Línea Celular , Células Ciliadas Auditivas/patología , Ratones , Neomicina/farmacología , Ototoxicidad/metabolismo , Ototoxicidad/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To compare the outcomes of the addition of silver nitrate cautery versus antiseptic cream alone in paediatric patients with recurrent epistaxis. METHODS: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and a search of electronic information was conducted to identify all Randomised Controlled Trials (RCTs) and non-randomised studies comparing the outcomes of the addition of silver nitrate cautery versus antiseptic cream alone in paediatric patients with recurrent epistaxis. Treatment success and persistence of bleeding were primary outcome measures. Secondary outcome measures included treatment side effects. Fixed effects modelling was used for the analysis. RESULTS: Four studies enrolling 240 patients were identified. There was no significant difference between silver nitrate cautery group and antiseptic cream alone group in terms of complete resolution (Odds Ratio [OR] = 1.07, P = 0.81), the partial resolution (OR = 1.02, P = 0.96) and persistence of bleeding (OR = 0.91, P = 0.71). For secondary outcomes, antiseptic nasal cream was associated with few side effects such as rash in one case and several complaints of bad smell or taste. CONCLUSIONS: The addition of silver nitrate cautery is not superior to the use of antiseptic cream alone in paediatric patients with recurrent epistaxis as it does not improve treatment success or persistence of bleeding.
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Antibacterianos/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Clorhexidina/uso terapéutico , Epistaxis/tratamiento farmacológico , Neomicina/uso terapéutico , Nitrato de Plata/uso terapéutico , Adolescente , Antibacterianos/efectos adversos , Antiinfecciosos Locales/efectos adversos , Cauterización , Niño , Preescolar , Clorhexidina/efectos adversos , Combinación de Medicamentos , Quimioterapia Combinada , Humanos , Lactante , Recién Nacido , Neomicina/efectos adversos , Pomadas , Recurrencia , Nitrato de Plata/efectos adversos , Resultado del TratamientoAsunto(s)
Dermatitis Alérgica por Contacto/complicaciones , Erupciones por Medicamentos/diagnóstico , Otitis Externa/etiología , Ácido Acético/efectos adversos , Administración Tópica , Dermatitis Alérgica por Contacto/diagnóstico , Femenino , Humanos , Hidrocortisona/efectos adversos , Persona de Mediana Edad , Neomicina/efectos adversos , Otitis Externa/tratamiento farmacológico , Pruebas del Parche , RecurrenciaRESUMEN
SCOPE: Soy protein is a high-quality protein and its consumption has been associated with a reduction of serum cholesterol and triglycerides and an improvement in insulin resistance. However, it is not known whether the effects of soy protein are mediated by the gut microbiota. Thus, the aim of this study is to assess whether using antibiotics to partially eradicate the gut microbiota can prevent the beneficial effects of soy protein in rats. METHODS AND RESULTS: Thus, rats are fed one of the following diets for 16 weeks: casein control, soy protein control, high-fat casein, and high-fat soy protein. The rats are then treated for 4 weeks with antibiotics. Body weight and composition, energy expenditure, glucose tolerance test, metabolic endotoxemia, and gut microbiota are measured before and after treatment with antibiotic. The results show that soy protein consumption decreases weight gain, body fat, metabolic endotoxemia, and increases energy expenditure and glucose tolerance. Antibiotic treatment suppresses all these metabolic effects. These changes are accompanied by modifying the diversity and taxonomy of the gut microbiota. CONCLUSION: In conclusion, the evidence suggests that the health benefits of soy protein are partly dependent of the gut microbiota.
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Antibacterianos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Proteínas de Soja/farmacología , Tejido Adiposo/efectos de los fármacos , Ampicilina/efectos adversos , Ampicilina/farmacología , Animales , Antibacterianos/efectos adversos , Biomarcadores/metabolismo , Composición Corporal/efectos de los fármacos , Caseínas/farmacología , Dieta Alta en Grasa/efectos adversos , Endotoxemia/inducido químicamente , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal/fisiología , Inflamación/genética , Inflamación/metabolismo , Masculino , Neomicina/efectos adversos , Neomicina/farmacología , Ratas Wistar , Aumento de Peso/efectos de los fármacosRESUMEN
It has been claimed that salvianolic acid B (Sal B), a natural bioactive antioxidant, exerts protective effects in various types of cells. This study aims to evaluate the antioxidant and anti-apoptosis effects of Sal B in a cultured HEI-OC1 cell line and in transgenic zebrafish (Brn3C: EGFP). A CCK-8 assay, Annexin V Apoptosis Detection Kit, TUNEL and caspase-3/7 staining, respectively, examined apoptosis and cell viability. The levels of reactive oxygen species (ROS) were evaluated by CellROX and MitoSOX Red staining. JC-1 staining was employed to detect the mitochondrial membrane potential (ΔΨm). Western blotting was used to assess expressions of Bax and Bcl-2. The expression pattern of p-PI3K and p-Akt was determined by immunofluorescent staining. We found that Sal B protected against neomycin- and cisplatin-induced apoptotic features, enhanced cell viability and accompanied with decreased caspase-3 activity in the HEI-OC1 cells. Supplementary experiments determined that Sal B reduced ROS production (increased ΔΨm), promoted Bcl-2 expression and down-regulated the expression of Bax, as well as activated PI3K/AKT signalling pathways in neomycin- and cisplatin-injured HEI-OC1 cells. Moreover, Sal B markedly decreased the TUNEL signal and protected against neomycin- and cisplatin-induced neuromast HC loss in the transgenic zebrafish. These results unravel a novel role for Sal B as an otoprotective agent against ototoxic drug-induced HC apoptosis, offering a potential use in the treatment of hearing loss.
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Apoptosis , Benzofuranos/uso terapéutico , Mitocondrias/metabolismo , Ototoxicidad/tratamiento farmacológico , Ototoxicidad/patología , Transducción de Señal , Animales , Apoptosis/efectos de los fármacos , Benzofuranos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cisplatino/efectos adversos , Citoprotección/efectos de los fármacos , Sistema de la Línea Lateral/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Neomicina/efectos adversos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Pez CebraRESUMEN
BACKGROUND: Patch testing is the criterion standard for diagnosis of allergic contact dermatitis (ACD). OBJECTIVE: The aim of the study was to report the trends of patch testing results with the standard series at Massachusetts General Hospital from January 1, 2007, to December 31, 2016, compared with previous data from 1998 to 2006 and from 1990 to 2006 and those reported by the North American Contact Dermatitis Group. METHODS: Data were collected and analyzed from retrospective chart reviews, focusing on 50 allergens in our standard series. RESULTS: A total of 2373 patients were patch tested. One or more positive reactions were observed in 1428 patients (60.2%), and 1153 patients (48.6%) had a final primary diagnosis of ACD. Top 5 allergens were nickel (19.8%), fragrance mix I (14.6%), Myroxylon pereirae (balsam of Peru) (13.5%), neomycin (9.4%), and bacitracin (7.7%). Sensitization frequencies statistically increased over time for 3 allergens: nickel, neomycin, and propylene glycol, and decreased for 5 allergens: formaldehyde, paraben mix, thiuram mix, n-isopropyl-N-phenyl-4-phenylenediamine, and epoxy resin (P ≤ 0.001). CONCLUSIONS: Surveillance of ACD trends is essential to detect emerging sensitizers. Patch testing is an important diagnostic tool for detection of ACD to commonly encountered and potential allergens.
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Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Atópica/diagnóstico , Dermatitis Profesional/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacitracina/efectos adversos , Bálsamos/efectos adversos , Niño , Preescolar , Dermatitis Alérgica por Contacto/etiología , Dermatitis Profesional/etiología , Resinas Epoxi/efectos adversos , Femenino , Formaldehído/efectos adversos , Humanos , Lactante , Masculino , Massachusetts , Persona de Mediana Edad , Neomicina/efectos adversos , Níquel/efectos adversos , Odorantes , Parabenos/efectos adversos , Pruebas del Parche , Fenilendiaminas/efectos adversos , Propilenglicol/efectos adversos , Estudios Retrospectivos , Tiram/efectos adversos , Adulto JovenRESUMEN
Three patients using a postoperative combination of topical ketorolac (Acular) and neomycin/polymyxin B sulfate/dexamethasone (Maxitrol) were diagnosed with atypical keratopathy soon after routine cataract surgery. An immediate retrospective analysis of hospital patients who had used this topical drug combination in the previous year identified 10 other patients who also had significant corneal pathology after uneventful cataract surgery. Five of the 13 affected patients had corneal melting and 1 patient had corneal perforation and endophthalmitis. At the last recorded follow-up appointment, 8 of the 13 patients had a visual acuity of 6/36 or worse. Corneal melting is a rare complication of topical nonsteroidal anti-inflammatory drugs (NSAIDs). We propose that the combined use of topical NSAIDs and other agents, such as neomycin and benzalkonium, that further compromise the corneal epithelium, should be used with vigilance and increased awareness of potential keratopathy and permanent visual morbidity.
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Antiinflamatorios no Esteroideos/efectos adversos , Extracción de Catarata/efectos adversos , Enfermedades de la Córnea/inducido químicamente , Fluprednisolona/efectos adversos , Ketorolaco/efectos adversos , Neomicina/efectos adversos , Polimixina B/efectos adversos , Administración Oftálmica , Anciano , Anciano de 80 o más Años , Enfermedades de la Córnea/diagnóstico , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/fisiopatología , Combinación de Medicamentos , Femenino , Humanos , Masculino , Soluciones Oftálmicas , Medicamentos bajo Prescripción , Estudios Retrospectivos , Agudeza Visual/fisiologíaRESUMEN
Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.
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Antibacterianos/efectos adversos , Disbiosis/inducido químicamente , Microbiota/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Vitíligo/inmunología , Administración Oral , Ampicilina/administración & dosificación , Ampicilina/efectos adversos , Animales , Antibacterianos/administración & dosificación , Bacteroides/genética , Bacteroides/aislamiento & purificación , Citocinas/análisis , Citocinas/inmunología , Citocinas/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Modelos Animales de Enfermedad , Disbiosis/inmunología , Disbiosis/microbiología , Heces/microbiología , Femenino , Humanos , Mucosa Intestinal/citología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Masculino , Ratones , Microbiota/inmunología , Neomicina/administración & dosificación , Neomicina/efectos adversos , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , ARN Ribosómico 16S/genética , Piel/citología , Piel/inmunología , Piel/microbiología , Piel/patología , Vitíligo/sangre , Vitíligo/microbiología , Vitíligo/patologíaRESUMEN
HYPOTHESIS: Commercial quinolone ear drops may promote the development of perforations (TMPs) in intact tympanic membrane (TMs). BACKGROUND: Quinolone ear drops have been associated with TMPs after myringotomy +/- tube placement in a drug-specific manner and potentiation by steroids. METHODS: Rats were randomized to six groups (10/group), with one ear receiving otic instillation of dexamethasone, ofloxacin, ciprofloxacin, ofloxacin + dexamethasone, ciprofloxacin + dexamethasone, or neomycin + polymyxin + hydrocortisone-all commercial formulations and at standard clinical concentrations-and the contralateral ear receiving saline, twice daily for 10 days. TMs were assessed over 42 days. RESULTS: No TMPs were seen in ears treated with saline, dexamethasone, or neomycin. At day 10, TMPs were seen in one of 10 ofloxacin- and three of 10 ciprofloxacin + dexamethasone-treated ears (pâ=â0.038). At day 14, the ofloxacin TMP healed. In contrast, the three ciprofloxacin + dexamethasone TMPs remained and one new TMP developed in this group. A ciprofloxacin and an ofloxacin + dexamethasone-treated ears also had TMPs (pâ=â0.023). By day 21, the ofloxacin + dexamethasone TMP and two of four of the ciprofloxacin + dexamethasone TMPs healed but two new TMPs were seen in ciprofloxacin + dexamethasone ears (pâ=â0.0006). At day 28, 1 of 10 ciprofloxacin and 4 of 10 ciprofloxacin + dexamethasone-treated ears had TMPs (pâ=â0.0006). By day 35, only one ciprofloxacin + dexamethasone had TMP (pâ=â0.42). All TMPS were healed at day 42. CONCLUSIONS: Application of commercial quinolone ear drops can cause TMPs in intact TMs. This effect appears to be drug-specific and potentiated by steroids.
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Ciprofloxacina/efectos adversos , Dexametasona/efectos adversos , Neomicina/efectos adversos , Ofloxacino/efectos adversos , Quinolonas/efectos adversos , Perforación de la Membrana Timpánica/inducido químicamente , Membrana Timpánica/efectos de los fármacos , Animales , Ciprofloxacina/administración & dosificación , Dexametasona/administración & dosificación , Femenino , Hidrocortisona/administración & dosificación , Masculino , Hemisuccinato de Metilprednisolona/análogos & derivados , Ventilación del Oído Medio , Neomicina/administración & dosificación , Ofloxacino/administración & dosificación , Prótesis e Implantes , Quinolonas/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: An empirical treatment of infectious vaginitis is justified because of its multiple etiologies, the frequent uncertainty of clinical diagnosis and limits of microbiological analysis. Our aim was to comparatively investigate nystatin-neomycin-polymyxin B combination (NNP, Polygynax®) and miconazole. PATIENTS AND METHODS: In this European multicenter, double-blind PRISM trial, participating women presenting with infectious vaginitis were randomized to receive one vaginal capsule containing either NNP for 12 days or miconazole for 3 days followed by 9 days of placebo. RESULTS: The clinical success rate was higher in the NNP group (n=302) than the miconazole group (n=309), with a difference between groups close to statistical significance (91.1% vs. 86.7%, P=0.0906). The risk of treatment failure was 36% lower in the NNP group (odds ratio, 0.64; 95% confidence interval, 0.38-1.07). Vaginal burning on Day 2 and vaginal discharge on Day 4 were significantly less intense in the NNP group than in the miconazole group (39.1 vs. 42.3, P=0.031 and 34.6 vs. 37.6, P=0.031, respectively). Adverse drug reactions were reported by 1.2% and 2.1% of patients in the NNP and miconazole group respectively, with the ratio of adverse drug reactions relative to total adverse events significantly higher in the miconazole group (20.3% vs. 6.9%, P=0.022). CONCLUSION: The widespread use of NNP for several decades and its good efficacy and safety profile, as well as the frequent diagnostic uncertainties due to the various pathogens sustain the initiation of this broad-spectrum empirical treatment in infectious vaginitis.