- Exhaled Nitric Oxide: An Update. [Review]
- IAImmunol Allergy Clin North Am 2018; 38(4):573-585
- Fractional concentration of exhaled nitric oxide (FENO) is a biomarker used to identify allergic airway inflammation. Because it is noninvasive and easy to obtain, its utility has been studied in the...
Fractional concentration of exhaled nitric oxide (FENO) is a biomarker used to identify allergic airway inflammation. Because it is noninvasive and easy to obtain, its utility has been studied in the diagnosis and management of several respiratory diseases. Much of the research has been done in asthma, and many studies support the use of FENO in aiding diagnosing asthma, predicting steroid responsiveness, and preventing exacerbations by guiding medication dosage and assessing adherence.
- The first-line antiepileptic drug carbamazepine: Reaction with biologically relevant free radicals. [Journal Article]
- FRFree Radic Biol Med 2018 Oct 17
- Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs by both adults and children. Despite its widespread use, CBZ is associated with central nervous system toxicity and severe hyper...
Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs by both adults and children. Despite its widespread use, CBZ is associated with central nervous system toxicity and severe hypersensitivity reactions, which raise concerns about its chronic use. While the precise mechanisms of CBZ-induced adverse events are still unclear, metabolic activation to the epoxide (CBZ-EP) has been thought to play a significant role. This work reports first-hand evidence that CBZ reacts readily with biologically relevant thiyl radicals with no need for bioactivation. Using liquid chromatography coupled with high resolution mass spectrometry, multiple products from direct reaction of CBZ with glutathione (GSH) and N-acetyl-L-cysteine (NAC) were unequivocally identified, including the same product obtained upon ring-opening of CBZ-EP. The product profile is complex and consistent with radical-mediated mechanisms. Importantly, side products and adducts compatible with this non-enzymatic pathway were identified in liver extracts from CBZ-treated Wistar rats. The reaction of CBZ with GSH and NAC is more extensive in the presence of oxygen. Taking into consideration that GSH conjugation is, in general, a detoxification pathway, these results suggest that under hyperoxia/oxidative stress conditions the bioavailability of the parent drug may be compromised. Additionally, this non-enzymatic process can be anticipated to play, at least in part, a role in the onset of CBZ-induced adverse effects due to the concomitant generation of reactive oxygen species. Therefore, the search for causal relationships between the formation of non-enzymatically-driven CBZ products and the occurrence of CBZ-induced adverse events in human patients merits further research, aiming the translation of basic mechanistic findings into a clinical context that may ultimately lead to a safer CBZ prescription.
- Safety of Follitropin Alfa/Lutropin Alfa for Stimulation of Follicular Development. [Journal Article]
- DSDrug Saf 2018 Oct 19
- CONCLUSIONS: Cumulative reporting rates of important identified and potential risks of r-hFSH/r-hLH during a 10-year surveillance period demonstrate the benefit-risk balance is positive. This post-marketing surveillance and continued surveillance of safety events should provide reassurance about the use of r-hFSH/r-hLH in clinical practice.
- Real World Data on the Utilization Pattern and Safety Profile of Infliximab Originator Versus Biosimilars in Italy: A Multiregional Study. [Journal Article]
- BBioDrugs 2018 Oct 20
- CONCLUSIONS: Our study demonstrates that, along with a rapid increase in the utilization of infliximab biosimilars across Italy, there was also an increase in reporting ADRs induced by infliximab biosimilars. Of the reported ADRs, 7.4% were considered preventable. In adjusted analyses, infliximab biosimilars were shown to have an increased probability of being reported as suspected drugs in infusion reactions and a decreased probability of being reported as suspected drugs in cases of lack of efficacy or infection. Considering the potential advantages offered by the utilization of biosimilars in clinical practice, we believe that the use of biosimilars, including those of infliximab, should be supported. In order to achieve this aim, increased knowledge on safety and efficacy of biosimilar drugs should be obtained from real world clinical practice.
- Modulatory potential on immune system of a new alkaloid isolated from Coccinea cordifolia root. [Journal Article]
- IJInt J Biol Macromol 2018 Oct 16; 121:643-649
- In this study, a new alkaloid was isolated from methanolic extract of Coccinea cordifolia root using flash chromatography and was subjected to spectral analysis like 1H NMR, 13C NMR, FTIR analysis an...
In this study, a new alkaloid was isolated from methanolic extract of Coccinea cordifolia root using flash chromatography and was subjected to spectral analysis like 1H NMR, 13C NMR, FTIR analysis and GCMS for confirming the structure of the isolated alkaloid. The isolated alkaloid was also subjected to immunomodulatory assays to verify its role in the claims against the plant. It was found that the isolated compound at a dose of 2.5 mg/kg has shown competitive immunomodulatory potential when evaluated by carbon clearance, delayed type hypersensitivity and haemagglutination titer models and using Levamisole at a dose of 50 mg/kg as the standard drug.
- Stimulating muscarinic M1 receptors in the anterior cingulate cortex reduces mechanical hypersensitivity via GABAergic transmission in nerve injury rats. [Journal Article]
- BRBrain Res 2018 Oct 16
- Cholinergic systems modulate synaptic transmission across the neuraxis and play an important role in higher brain function including cognition, arousal and nociception. The anterior cingulate cortex ...
Cholinergic systems modulate synaptic transmission across the neuraxis and play an important role in higher brain function including cognition, arousal and nociception. The anterior cingulate cortex (ACC) is a fundamental brain region for nociception and chronic pain, and receives cholinergic projections mainly from basal forebrain. Recently, we found that the activation of muscarinic M1 receptors in the ACC produced antinociceptive behavior in response to mechanical stimulation. However, it has not been tested whether stimulating muscarinic receptors in the ACC can reduce mechanical hypersensitivity in animal models of chronic pain. Here, we tested whether the activation of muscarinic M1 receptors in the ACC can alleviate mechanical hypersensitivity in a nerve injury model. The activation of muscarinic M1/M4 receptors by McN-A-343 injected into the contralateral side of the ACC, but not into the ventral posterolateral nucleus, was found to dose-dependently reduce mechanical hypersensitivity 7 days following partial sciatic nerve ligation in rats. The reduction of mechanical hypersensitivity by McN-A-343, was blocked by a selective muscarinic M1 antagonist, but not a M4 receptor antagonist. Importantly, the nerve injury model did not change the protein expression of muscarinic M1 receptors in the ACC. Additionally, a type Aγ-aminobutyric acid (GABAA) receptor agonist injected into the ACC reduced the mechanical hypersensitivity in this injury model. Finally, a GABAA receptor antagonist blocked the reduction of mechanical hypersensitivity by McN-A-343 in the injury model. Collectively, these results suggest that activations of muscarinic M1 receptors in the ACC reduce nerve injury-induced mechanical hypersensitivity through GABAergic transmission via GABAA receptors.
- Impact of patient satisfaction with his or her inhaler on adherence and asthma control. [Journal Article]
- AAAllergy Asthma Proc 2018 Oct 18
- CONCLUSIONS: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.
- Asthma medication usage is significantly reduced following bariatric surgery. [Journal Article]
- SESurg Endosc 2018 Oct 17
- CONCLUSIONS: BS significantly decreases asthma medication use starting 30 days post-operation with a sustained reduction for up to 3 years.
- The Superior Antitumor Effect of Self-Assembled Paclitaxel Nano-filaments for Lung Cancer Cells. [Journal Article]
- CDCurr Drug Deliv 2018 Oct 16
- CONCLUSIONS: The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.
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- An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells. [Journal Article]
- BTBiomol Ther (Seoul) 2018 Oct 11
- Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under de...
Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation (IC50, ~1.42 μM). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-α (IC50, ~1.10 μM), and IL-6 (IC50, ~1.24 μM). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, PLCγ, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.