Anti-inflammatory effects of α-humulene on the release of pro-inflammatory cytokines in lipopolysaccharide-induced THP-1 cells.

While acute inflammation is an essential physical response to harmful external influences, the transition to chronic inflammation is problematic and associated with the development and worsening of many deadly diseases. Until now, established pharmaceutical agents have had many side effects when used for long periods. In this study, a possible anti-inflammatory effect of the sesquiterpene α-humulene on lipopolysaccharide (LPS) induction was tested. Herein, human THP-1-derived macrophages were used and their pro-inflammatory interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1ß (IL-1ß) cytokine release was measured by means of enzyme-linked immunosorbent assay. A dose-dependent effect of α-humulene on IL-6 release was observed at 0.5 and 100 µM α-humulene, with a maximum IL-6 inhibition of 60% compared to the LPS reference value after the addition of 100 µM α-humulene. TNF-α as well as IL-1ß cytokine concentrations were not reduced by the addition of 0.5 and 100 µM α-humulene. This study suggests that α-humulene has potential as a promising natural alternative to established pharmaceuticals for the treatment of elevated IL-6 levels and chronic inflammation in humans.

Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma.

Background: Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy. Methods: Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology. Results: We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all P < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all P < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all P < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples. Conclusions: Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.

Varfarina e femprocumona: experiência de um ambulatório de anticoagulação / Warfarin and phenprocoumon: experience of an outpatient anticoagulation clinic / Warfarina y femprocumona: experiencia de una unidad de anticoagulación

Fundamento: Os anticoagulantes orais são amplamente utilizados na cardiologia. Contudo, uma avaliação sobre o seu uso na prática clínica ainda é necessária. Objetivos: Descrever as diferenças na manutenção do controle da anticoagulação, bem como a incidência de eventos hemorrágicos e tromboembólicos entre os usuários de varfarina e femprocumona. Métodos: Estudo de coorte não concorrente de 127 pacientes em uso de anticoagulação oral. Resultados: A femprocumona foi o anticoagulante mais utilizado em 60 por cento dos pacientes. A prevalência de INR<2 na última consulta era maior entre os usuários de varfarina (46 por cento vs. 19,5 por cento; p<0,001). Durante o seguimento, os usuários da femprocumona estiveram dentro dos níveis terapêuticos em 60,7 por cento do período em comparação com 45,6 por cento dos usuários da Varfarina (OR:1,84;CI95 por cento:1,59-2,13;p<0,001). A incidência de sangramentos foi de 5,3/100 pacientes/ano no grupo da femprocumona contra 18,8/100 pacientes/anos no grupo varfarina (RR:3,5;CI95 por cento:1,87-6,48;p<0,001). Conclusão: Pacientes que faziam uso da varfarina permaneceram em níveis subterapêuticos por um maior período, contudo também apresentaram mais eventos hemorrágicos. Usuários da femprocumona eram mais jovens e estavam utilizando a anticoagulação oral por um período maior, tendo apresentado menos efeitos adversos dessas medicações.

Background: Oral anticoagulants are broadly used in cardiology. However, it is still necessary to evaluate their use in clinical practice. Objectives: To describe the differences in the maintenance of anticoagulation control, as well as the incidence of hemorrhagic and thromboembolic events among users of warfarin and phenprocoumon. Methods: Non-concurrent cohort study of 127 patients using oral anticoagulation. Results: Phenprocoumon was the most frequently used anticoagulant in 60 percent of the patients. The prevalence of RNI<2 at the last medical appointment was higher among warfarin users (46 percent vs. 19.5 percent; p<0.001). During the follow-up, Phenprocoumon users were within the therapeutic range during 60.7 percent of the period, in comparison with 45.6 percent of warfarin users (OR:1.84; 95 percentCI:1.59-2.13; P<0.001). The incidence of bleeding was 5.3/100 patients/year in the phenprocoumon group versus 18.8/100 patients/year in the warfarin group (RR: 3.5; 95 percentCI: 1.87-6.48; P<0.001). Conclusion: Patients that used Warfarin remained at subtherapeutic levels for a longer period; however, they also presented more hemorrhagic events. Phenprocoumon users were younger and had been using oral anticoagulation for longer periods, presenting fewer drug-related adverse events.

Fundamento: Los anticoagulantes orales son ampliamente utilizados en la cardiología. Con todo, una evaluación acerca de su utilización en la práctica clínica es necesaria todavía. Objetivo: Describir las diferencias en el mantenimiento del control de la anticoagulación, así como la incidencia de eventos hemorrágicos y tromboembólicos entre sus usuarios de warfarina y femprocumona. Métodos: Estudio de cohorte no concurrente de 127 pacientes en tratamiento con anticoagulación oral. Resultados: La femprocumona fue el anticoagulante más utilizado en el 60 por ciento de los pacientes. La prevalencia de INR<2 en la última consulta era mayor entre los usuarios de warfarina (46 por ciento vs 19,5 por ciento; P<0,001). Durante el seguimiento, los usuarios de la femprocumona estuvieron dentro de los niveles terapéuticos en el 60,7 por ciento del período en comparación con el 45,6 por ciento de los usuarios de la warfarina (OR:1,84;CI95 por ciento:1,59-2,13;P<0,001). La incidencia de sangrados fue de 5,3/100 pacientes/año en el grupo de la femprocumona contra 18,8/100 pacientes/años en el grupo warfarina (RR:3,5;CI95 por ciento:1,87-6,48;P<0,001). Conclusión: Pacientes que hacían uso de la warfarina permanecieron en niveles subterapéuticos por un mayor período, sin embargo presentaron también más eventos hemorrágicos. Los usuarios de la femprocumona eran más jóvenes y estaban utilizando la anticoagulación oral por un período mayor, habiendo presentado menos efectos adversos de estas medicaciones.