- Blocking TRPA1 and TNF-α Signal Improves Bortezomib-Induced Neuropathic Pain. [Journal Article]
- CPCell Physiol Biochem 2018 Dec 06; 51(5):2098-2110
- CONCLUSIONS: We revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ. The data also suggest that blocking TRPA1 and tumor necrosis factor alpha is beneficial to alleviate neuropathic pain during BTZ intervention.
- Cigarette Smoke Extract Promotes TIM4 Expression in Murine Dendritic Cells Leading to Th2 Polarization through ERK-Dependent Pathways. [Journal Article]
- IAInt Arch Allergy Immunol 2018 Dec 06; :1-10
- Smoking is considered to be the main source of indoor pollution, and it has been identified as an important environmental factor contributing to asthma onset. We know that T helper 2 (Th2) response p...
Smoking is considered to be the main source of indoor pollution, and it has been identified as an important environmental factor contributing to asthma onset. We know that T helper 2 (Th2) response plays a crucial role in the process of asthma disease. We have investigated the reaction of cigarette smoke extract (CSE) on Th polarization which is controlled by dendritic cells (DCs). Stimulated by CSE, immature DCs from murine bone marrow showed upregulated levels of TIM4. Cocultured with CD4+ T cells, stimulated DCs increased the ratio of IL-4+ versus IFN-γ+ of CD4+ T cells. This suggests a differentiation towards Th2 response. Moreover, antibodies against TIM4 reversed the upexpression of the IL-4+/IFN-γ+ ratio provoked by CSE, indicating that the Th2 polarization which was induced by CSE is via TIM4 mechanisms. CSE could activate mitogen-activated protein kinase pathways like ERK and p38. Upregulation of TIM4 expression by CSE stimulation was found to be inhibited by an ERK inhibitor but not p38 and JNK. In conclusion, DC-induced Th2 polarization is a hallmark of CSE allergy, and this aspect can be explained by CSE-induced TIM4 expression.
- Are environmental factors for atopic eczema in ISAAC Phase Three due to reverse causation? [Journal Article]
- JIJ Invest Dermatol 2018 Dec 03
- Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level result...
Some previously described environmental associations for atopic eczema (AE) may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple AE risk factors. ISAAC Phase Three surveyed children within schools (the sampling unit) on AE symptoms and potential risk factors. We assessed the effect of these risk factors on AE symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. 546,348 children from 53 countries were included. At age 6-7 the strongest individual-level associations were with current paracetamol use (odds ratio=1.45, 95% confidence interval 1.37-1.54), which persisted at school-level (1.55, 1.10-2.21), antibiotics (1.41, 1.34-1.48) and early life paracetamol use (1.28, 1.21-1.36) with the former persisting at school-level while the latter was no longer observed (1.35, 1.00-1.82 and 0.94, 0.69-1.28 respectively). At age 13-14 the strongest associations at individual-level were with current paracetamol use (1.57, 1.51-1.63) and open-fire cooking (1.46, 1.33-1.62); both were stronger at school-level (2.57, 1.84-3.59 and 2.38, 1.52-3.73 respectively). Association with exposure to heavy traffic (1.31, 1.27-1.36) also persisted at school-level (1.40, 1.07-1.82). Most individual- and school level effects were consistent tending to exclude reverse causation.
- Metabolome-wide association study of anti-epileptic drug treatment during pregnancy. [Journal Article]
- TAToxicol Appl Pharmacol 2018 Dec 03
- Pregnant women with epilepsy (PWWE) require continuous anti-epileptic drug (AED) treatment to avoid risk to themselves and fetal risks secondary to maternal seizures, resulting in prolonged AED expos...
Pregnant women with epilepsy (PWWE) require continuous anti-epileptic drug (AED) treatment to avoid risk to themselves and fetal risks secondary to maternal seizures, resulting in prolonged AED exposure to the developing embryo and fetus. The objectives of this study were to determine whether high-resolution metabolomics is able to link the metabolite profile of PWWE receiving lamotrigine or levetiracetam for seizure control to associated pharmacodynamic (PD) biological responses. Untargeted metabolomic analysis of plasma obtained from 82 PWWE was completed using high-resolution mass spectrometry. Biological alterations due to lamotrigine or levetiracetam monotherapy were determined by a metabolome-wide association study that compared patients taking either drug to those who did not require AED treatment. Metabolic changes associated with AED use were then evaluated by testing for drug-dose associated metabolic variations and pathway enrichment. AED therapy resulted in drug-associated metabolic profiles recognizable within maternal plasma. Both the parent compounds and major metabolites were detected, and each AED was correlated with other metabolic features and pathways. Changes in metabolites and metabolic pathways important to maternal health and linked to fetal neurodevelopment were detected for both drugs, including changes in one‑carbon metabolism, neurotransmitter biosynthesis and steroid metabolism. In addition, decreased levels of 5-methyltetrahydrofolate and tetrahydrofolate were detected in women taking lamotrigine, which is consistent with recent findings showing increased risk of autism spectrum disorder traits in PWWE using AED. These results represent a first step in development of pharmacometabolomic framework with potential to detect adverse AED-related metabolic changes during pregnancy.
- Reasons for Declining Venom Immunotherapy. [Journal Article]
- AMActa Med Port 2018 Nov 30; 31(11):618-623
- CONCLUSIONS: The number of patients refusing venom immunotherapy doubled since reimbursement was withdrawn. Price was identified as the major obstacle to treatment completion. Immunotherapy proposal after reimbursement was stopped was associated with a 3-fold increase in the risk of refusing treatment.These findings show how economic decisions may have a detrimental effect on patient care, as immunotherapy refusal left them exposed to an avoidable life-threatening risk.
- Antibiotic allergy labels in hospitalised and critically ill adults: a review of current impacts of inaccurate labelling. [Review]
- BJBr J Clin Pharmacol 2018 Dec 06
- Antibiotic Allergy Labels (AAL) are reported by approximately 20% of hospitalised patients, yet over 85% will be negative on formal allergy testing. Hospitalised patients with an AAL have inferior pa...
Antibiotic Allergy Labels (AAL) are reported by approximately 20% of hospitalised patients, yet over 85% will be negative on formal allergy testing. Hospitalised patients with an AAL have inferior patient outcomes, increased colonization with multidrug resistant organisms and frequently receive inappropriate antimicrobials. Hospitalised populations have been well studied, yet to date the impact of AALs on patients with critical illness remain less well defined. We review the prevalence and impact of AALs on hospitalised patients, including those in in critical care.
- Diffuse Tibiofemoral Cartilage Change Prior to the Development of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis Initiative. [Journal Article]
- CAClin Anat 2018 Dec 06
- CONCLUSIONS: These results provide preliminary evidence of a different spatial pattern of cartilage change between individuals that will develop accelerated versus typical KOA. These data suggest there may be different mechanisms driving the early structural disease progression between accelerated versus typical KOA. This article is protected by copyright. All rights reserved.
- Out-of-pocket Costs for Individuals with Atopic Eczema: A Cross-sectional Study in Nine European Countries. [Journal Article]
- ADActa Derm Venereol 2018 Dec 06
- Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are ...
Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are limited. To estimate the annual extra out-of-pocket spending due to AE among patients in Europe, a cross-sectional study using computer-assisted phone interviewing of patients with AE was performed in 9 European countries. A total of 1,189 patients (56% women) with AE, who were either eligible for, or on, systemic treatment, participated in the study between October 2017 and March 2018. Mean extra spending on everyday necessities was €927 per patient per year for healthcare expenses, and this figure was slightly, but not statistically significantly, influenced by the severity of AE. Emollients and moisturizers accounted for the highest monthly costs, followed by medication that was not reimbursed, doctors' and hospital costs. AE-related out-of-pocket costs pose a substantial burden for affected individuals, are higher than in other chronic diseases, and should always be included in economic assessments of the impact of this disease.
- Rheumatoid Arthritis and Mortality in End Stage Renal Disease. [Journal Article]
- JCJ Clin Rheumatol 2018 Dec 05
- CONCLUSIONS: Clinicians should be aware that persons with RA who develop ESRD incur cardiac events sooner ESRD than the general population. However, RA is not an independent risk factor for all-cause or cardiovascular mortality in ESRD.
New Search Next
- A secretory pathway kinase regulates sarcoplasmic reticulum Ca2+ homeostasis and protects against heart failure. [Journal Article]
- EElife 2018 Dec 06; 7
- Ca2+ signaling is important for many cellular and physiological processes, including cardiac function. Although sarcoplasmic reticulum (SR) proteins involved in Ca2+ signaling have been shown to be p...
Ca2+ signaling is important for many cellular and physiological processes, including cardiac function. Although sarcoplasmic reticulum (SR) proteins involved in Ca2+ signaling have been shown to be phosphorylated, the biochemical and physiological roles of protein phosphorylation within the lumen of the SR remain essentially uncharacterized. Our laboratory recently identified an atypical protein kinase, Fam20C, which is uniquely localized to the secretory pathway lumen. Here we show that Fam20C phosphorylates several SR proteins involved in Ca2+ signaling, including calsequestrin2 and Stim1, whose biochemical activities are dramatically regulated by Fam20C mediated phosphorylation. Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca2+ entry. Physiologically, mice with Fam20c ablated in cardiomyocytes develop heart failure following either aging or induced pressure overload. We extended these observations to show that non-muscle cells lacking Fam20C display altered ER Ca2+ signaling. Overall, we show that Fam20C plays an overarching role in ER/SR Ca2+ homeostasis and cardiac pathophysiology.