RESUMEN
HISTORY AND CLINICAL FINDINGS: Up to February 24th 2020 occasionally occuring SARS-CoV-2 infections in Germany without severe course. Emergency presentation of a couple in the emergency room. For seven days now, the man has fever, dry cough und physical weakness and the wife has similar symptoms of a milder form. The clinical examination shows fine crackles over both lungs and a respiratory failure of the husband. INVESTIGATIONS AND DIAGNOSIS: Laboratory increase in inflammation parameters as well as transaminases and lactate dehydrogenase. Radiologically lung infiltrates of different severity. Further on diagnosis of a SARS-CoV-2-infection of both patients with a severe course of the male. TREATMENT AND COURSE: Intubation and mechanical ventilation of the male patient with prolonged intenive care treatment. Recovery of the female patient under conventional oxygen therapy. DISCUSSION: These two cases show the starting point of an endemic spread of SARS-CoV-2 in the district of Heinsberg (North Rhine-Westphalia) and up to this point the first case of a life-threatenning course in Germany.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , COVID-19 , Tos/diagnóstico , Brotes de Enfermedades , Progresión de la Enfermedad , Femenino , Fiebre/diagnóstico , Alemania/epidemiología , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2RESUMEN
INTRODUCTION: Rheumatoid arthritis (RA) is characterized by progressive inflammation associated with rampantly proliferating synoviocytes and joint destruction due to oxidative stress. Recently, we described nuclear factor erythroid 2-related factor 2 (Nrf2) as a major requirement for limiting cartilage destruction. NF-κB and AP-1 are the main transcription factors triggering the inflammatory progression in RA. We used sulforaphane, an isothiocyanate, which is both an Nrf2 inducer and a NF-κB and AP-1 inhibitor. METHODS: Cultured synoviocytes were stimulated with sulforaphane (SFN) with or without TNF-α pre-treatment. NF-κB, AP-1, and Nrf2 activation was investigated via dual luciferase reporter gene assays. Matrix metalloproteinases (MMPs) were measured via zymography and luminex technique. Cytokine levels were detected using ELISA. Cell viability, apoptosis and caspase activity were studied. Cell proliferation was analysed by real-time cell analysis. RESULTS: SFN treatment decreased inflammation and proliferation dose-dependently in TNF-α-stimulated synoviocytes. SFN did not reduce MMP-3 and MMP-9 activity or expression significantly. Interestingly, we demonstrated that SFN has opposing effects on naïve and TNF-α-stimulated synoviocytes. In naïve cells, SFN activated the cytoprotective transcription factor Nrf2. In marked contrast to this, SFN induced apoptosis in TNF-α-pre-stimulated synoviocytes. CONCLUSIONS: We were able to show that SFN treatment acts contrary on naïve and inflammatory synoviocytes. SFN induces the cytoprotective transcription factor Nrf2 in naïve synoviocytes, whereas it induces apoptosis in inflamed synoviocytes. These findings indicate that the use of sulforaphane might be considered as an adjunctive therapeutic strategy to combat inflammation, pannus formation, and cartilage destruction in RA.