The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor B and proinflammatory gene expression, resu...
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PrTHYy
Πέμπτη 15 Νοεμβρίου 2018
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
A target to suppress inflammation
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PtuwEY
Differences in chronic spontaneous urticaria between Europe and Central/South America: results of the multi-center real world AWARE study
Abstract
Background
Global chronic urticaria (CU) disease experience and management is not well documented. This study descriptively compares these aspects among CU patients residing in Europe (EU) and Central and South America (C/SA).
Methods
AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global prospective, non-interventional study of CU in the real-world setting. Patients were ≥ 18 years with a diagnosis of H1-antihistamine-refractory CU for > 2 months. Differences between the EU and C/SA regions in demographic and clinical characteristics, quality of life (QoL), work and activity impairment, pharmacological treatment, and healthcare resource use were examined.
Results
In total, 4224 patients were included in the analysis (C/SA 492; EU 3732). Rates of untreated patients were greater in the C/SA region (45.1% vs. 31.9%; P < 0.005) and escalation to third-line therapy was rare in both regions. Differences in disease experience emerged, with C/SA patients more commonly experiencing angioedema (C/SA 50.8% vs. EU 46.1%; P = 0.03) or comorbid chronic inducible urticaria (C/SA 30% vs. EU 22%; P < 0.001). Correspondingly, rates of uncontrolled urticaria were higher among C/SA patients (82.8% vs. 77.5%; P = 0.017) and patients in the C/SA region showed significantly greater work and activity impairment (absenteeism: 10.4 ± 19.7 vs. 6.7 ± 19.0, P = 0.004; presenteeism: 30.3 ± 31.9 vs. 24.4 ± 25.8, P = 0.001; work productivity loss: 33.9 ± 33.9 vs. 26.5 ± 27.5, P < 0.001; activity impairment: 37.7 ± 34.7 vs. 32.7 ± 30.1, P = 0.001). However, QoL impairment was greater in the EU region (Dermatology Life Quality Index: C/SA 6.5 ± 5.9 vs. EU 8.3 ± 7.0; P < 0.001). There was a significant difference in use of healthcare resources, including emergency services (39.6% vs. 29.3%; P < 0.001), hospitalization (7.7% vs 21.9%; P < 0.001) general practitioners (31.7% vs 57.3%; P < 0.001), and additional allergists or dermatologists (50.6% vs. 47.3%, P < 0.001), among patients in the C/SA and EU region, respectively. In both regions, patients with a primary diagnosis of CU with angioedema had significantly greater impairment in work and non-work activities and healthcare resource utilization compared to those without angioedema.
Conclusions
This study revealed that CU is a heterogeneous condition with differences in healthcare utilization and outcomes between EU and C/SA. However, overall there is a high unmet need of H1-antihistamine-refractory CU patients, which is associated with high use of healthcare resources, and has a large negative effect on QoL and work productivity.
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2OLCC6I
Patients with rare, incurable digestive tract cancers respond to new drug combination
| Patients with rare, incurable digestive tract cancers respond to new drug combination EurekAlert (press release)Full coverage |
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2qLFebe
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor B and proinflammatory gene expression, resu...
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PrTHYy
DNA binding as an anti-inflammatory
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2QGGEPA
A target to suppress inflammation
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PtuwEY
Differences in chronic spontaneous urticaria between Europe and Central/South America: results of the multi-center real world AWARE study
Abstract
Background
Global chronic urticaria (CU) disease experience and management is not well documented. This study descriptively compares these aspects among CU patients residing in Europe (EU) and Central and South America (C/SA).
Methods
AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global prospective, non-interventional study of CU in the real-world setting. Patients were ≥ 18 years with a diagnosis of H1-antihistamine-refractory CU for > 2 months. Differences between the EU and C/SA regions in demographic and clinical characteristics, quality of life (QoL), work and activity impairment, pharmacological treatment, and healthcare resource use were examined.
Results
In total, 4224 patients were included in the analysis (C/SA 492; EU 3732). Rates of untreated patients were greater in the C/SA region (45.1% vs. 31.9%; P < 0.005) and escalation to third-line therapy was rare in both regions. Differences in disease experience emerged, with C/SA patients more commonly experiencing angioedema (C/SA 50.8% vs. EU 46.1%; P = 0.03) or comorbid chronic inducible urticaria (C/SA 30% vs. EU 22%; P < 0.001). Correspondingly, rates of uncontrolled urticaria were higher among C/SA patients (82.8% vs. 77.5%; P = 0.017) and patients in the C/SA region showed significantly greater work and activity impairment (absenteeism: 10.4 ± 19.7 vs. 6.7 ± 19.0, P = 0.004; presenteeism: 30.3 ± 31.9 vs. 24.4 ± 25.8, P = 0.001; work productivity loss: 33.9 ± 33.9 vs. 26.5 ± 27.5, P < 0.001; activity impairment: 37.7 ± 34.7 vs. 32.7 ± 30.1, P = 0.001). However, QoL impairment was greater in the EU region (Dermatology Life Quality Index: C/SA 6.5 ± 5.9 vs. EU 8.3 ± 7.0; P < 0.001). There was a significant difference in use of healthcare resources, including emergency services (39.6% vs. 29.3%; P < 0.001), hospitalization (7.7% vs 21.9%; P < 0.001) general practitioners (31.7% vs 57.3%; P < 0.001), and additional allergists or dermatologists (50.6% vs. 47.3%, P < 0.001), among patients in the C/SA and EU region, respectively. In both regions, patients with a primary diagnosis of CU with angioedema had significantly greater impairment in work and non-work activities and healthcare resource utilization compared to those without angioedema.
Conclusions
This study revealed that CU is a heterogeneous condition with differences in healthcare utilization and outcomes between EU and C/SA. However, overall there is a high unmet need of H1-antihistamine-refractory CU patients, which is associated with high use of healthcare resources, and has a large negative effect on QoL and work productivity.
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2OLCC6I
Patients with rare, incurable digestive tract cancers respond to new drug combination
| Patients with rare, incurable digestive tract cancers respond to new drug combination EurekAlert (press release)Full coverage |
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2qLFebe
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor B and proinflammatory gene expression, resu...
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PrTHYy
DNA binding as an anti-inflammatory
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2QGGEPA
A target to suppress inflammation
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PtuwEY
Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor–α–induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor B and proinflammatory gene expression, resu...
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PrTHYy
DNA binding as an anti-inflammatory
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2QGGEPA
A target to suppress inflammation
(Source: ScienceNOW)
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PtuwEY
Reply: [LETTERS]
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2RYuNNd
Reply: [LETTERS]
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2RWsES2
Methodologic Issues on Interrater Reliability Regarding Structural and DTI-Based Corticospinal Tract Asymmetry [LETTERS]
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PYl9fT
MR Neurography of the Lumbosacral Plexus for Lower Extremity Radiculopathy: Frequency of Findings, Characteristics of Abnormal Intraneural Signal, and Correlation with Electromyography [SPINE]
BACKGROUND AND PURPOSE:
MR neurography enables high resolution imaging of peripheral nerves. Our aim was to evaluate the utility of MR neurography in lumbosacral radiculopathy and correlate abnormal intraneural signal with history, physical examination, and abnormal electrodiagnostic study findings.
MATERIALS AND METHODS:Retrospective review of lumbosacral MR neurography examinations performed from December 2014 through January 2017 on a 3T scanner was undertaken. MR neurography examinations were independently reviewed in a blinded fashion by 2 radiologists, and the intraneural signal was graded on a 0–2 scale relative to adjacent vasculature. Abnormal nerve signal was correlated with subjective and objective findings from clinical notes in the electronic medical record and compared with results of electrodiagnostic studies (nerve conduction study/electromyography).
RESULTS:Three hundred three lumbosacral MR neurography examinations were performed during the study period, 64 of which met the inclusion criteria, including symptoms of radiculopathy on electromyography performed within 3 months of MR neurography. Twenty-nine (45%) MR neurography examinations had abnormal intraneural signal. There was no statistically significant correlation between subjective clinical findings and intraneural signal abnormality on MR neurography. There was a statistically significant correlation between abnormal intraneural T2 signal and findings of active radiculopathy on electromyography (P < .001).
CONCLUSIONS:Lumbosacral MR neurography appears to demonstrate abnormal intraneural signal in a substantial portion of patients with clinical symptoms of lower extremity radiculopathy and correlates with findings of active radiculopathy on electromyography. This finding further bolsters the growing body of evidence on the utility of MR neurography and suggests that abnormal intraneural signal may provide a useful adjunct to electrodiagnostic testing. Further research is required to evaluate the prognostic value of MR neurography, which may help guide therapeutic decision-making.
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2PXSk3u
Celebrating 35 Years of the AJNR: November 1983 edition [other]
from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader https://ift.tt/2RW2v5H