Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes

Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell- and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.

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Impact of Monthly 120 Mg Denosumab on Bone Metabolism in Bone-metastatic Prostate Cancer Undergoing Androgen Deprivation Therapy

Asian Pacific Journal of Cancer Care ◽

10.31557/apjcc.2017.2.3.41-46 ◽

2017 ◽

Vol 2 (3) ◽

pp. 41-46

Author(s):

Jimpei Miyakawa ◽

Satoru Taguchi ◽

Motofumi Suzuki ◽

Kaori Endo ◽

Yorito Nose ◽

...

Keyword(s):

Prostate Cancer ◽

Lumbar Spine ◽

Femoral Neck ◽

Bone Metabolism ◽

Androgen Deprivation Therapy ◽

Metastatic Prostate Cancer ◽

Androgen Deprivation ◽

Mineral Density ◽

Bone Metabolism Markers ◽

The Impact

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear.Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly.Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both P<0.01). Bone metabolism markers were evaluable in 11 (73%) patients: uNTx decreased rapidly, while BAP declined gradually after initiating denosumab. These effects were similar to those seen by the standardized dose for osteoporosis in previous literature. There were no denosumab-related severe adverse events during the follow-up period. Conclusions: The impact of monthly 120 mg denosumab on bone metabolism was significant, but almost equivalent to that of the standard dose for osteoporosis (60mg semiannually) in bone-metastatic prostate cancer undergoing androgen deprivation therapy. Whereas the higher dose has reportedly reduced skeleton-related events, the effect on bone metabolism seemed plateaued or showed no dose-dependency.

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Rapid Screening of Glucocorticoid Receptor (GR) Effectors Using Cortisol-Detecting Sensor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22094747 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4747

Author(s):

Jeahee Ryu ◽

Euiyeon Lee ◽

Chungwon Kang ◽

Minhyeong Lee ◽

Soyoun Kim ◽

...

Keyword(s):

Adverse Effects ◽

Glucocorticoid Receptor ◽

Inflammatory Responses ◽

Rapid Screening ◽

Peppermint Oil ◽

Cellular Regulation ◽

Drug Candidates ◽

Split Intein ◽

Proinflammatory Responses ◽

Anti Inflammatory

Cortisol, a stress hormone, plays key roles in mediating stress and anti-inflammatory responses. As abnormal cortisol levels can induce various adverse effects, screening cortisol and cortisol analogues is important for monitoring stress levels and for identifying drug candidates. A novel cell-based sensing system was adopted for rapid screening of cortisol and its functional analogues under complex cellular regulation. We used glucocorticoid receptor (GR) fused to a split intein which reconstituted with the counterpart to trigger conditional protein splicing (CPS) in the presence of targets. CPS generates functional signal peptides which promptly translocate the fluorescent cargo. The sensor cells exhibited exceptional performance in discriminating between the functional and structural analogues of cortisol with improved sensitivity. Essential oil extracts with stress relief activity were screened using the sensor cells to identify GR effectors. The sensor cells responded to peppermint oil, and L-limonene and L-menthol were identified as potential GR effectors from the major components of peppermint oil. Further analysis indicated L-limonene as a selective GR agonist (SEGRA) which is a potential anti-inflammatory agent as it attenuates proinflammatory responses without causing notable adverse effects of GR agonists.

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Analysis of non-steroidal anti-inflammatory drug use in hospitalized patients and perception of their risk

Interdisciplinary Toxicology ◽

10.2478/intox-2013-0022 ◽

2013 ◽

Vol 6 (3) ◽

pp. 141-144 ◽

Cited By ~ 11

Author(s):

Zoltán Varga ◽

Milan Kriška ◽

Viera Kristová ◽

Miriam Petrová

Keyword(s):

Adverse Effects ◽

Questionnaire Study ◽

Pharmacological Agents ◽

Analgesic Treatment ◽

Increased Risk ◽

Chi Squared ◽

History Of ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

The Impact

ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely prescribed and used pharmacological agents worldwide. Data gathered in the last decade show increased incidence of thrombotic events during NSAID administration. Analysis of NSAID usage and assessment of risk for development of cardiovascular adverse effects is needed for improving patient safety. For limiting the impact of adverse effects on the health of patients, NSAID users should be informed about the possible adverse effects and their symptoms to ensure early detection and treatment discontinuation. In the presented study, we retrospectively analyzed the administration of NSAIDs in a group of patients (n=428) in need of analgesic treatment hospitalized at a department of internal medicine. Factors increasing the risk for cardiovascular adverse effects were also investigated. A separate questionnaire study was conducted to gather information concerning the knowledge of hospitalized NSAID users (n=251) about adverse effects of the medication used. For purpose of comparison, we conducted a similar study in a group of 234 random respondents from a shopping center. Data were evaluated using descriptive statistics, Student´s t-test and chi-squared test. Our results suggest that the majority of patients treated with NSAIDs have factors indicating increased risk of development of adverse effects, most commonly arterial hypertension (58.2% of patients). The results of our questionnaire study show limited knowledge of NSAID users about the risk of the therapy. Nearly half of the respondents were unaware of any adverse effects. We consider as alarming that only a limited number of respondents were informed by their physician or pharmacist about the possible risks of treatment. In conclusion, we found that hospitalized NSAID users often have a history of diseases predisposing to the development of cardiovascular adverse effects of NSAIDs. Despite this, their knowledge about the risk of treatment is insufficient.

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Turmeric Induced Liver Injury: A Report of Two Cases

Case Reports in Hepatology ◽

10.1155/2019/6741213 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 6

Author(s):

Raphael P. Luber ◽

Clarissa Rentsch ◽

Steve Lontos ◽

Jeffrey D. Pope ◽

Ar Kar Aung ◽

...

Keyword(s):

Liver Injury ◽

Adverse Effects ◽

Herbal Supplement ◽

Severe Hepatitis ◽

Potential Risks ◽

Anti Inflammatory

Turmeric is a commonly used oral herbal supplement with purported anti-inflammatory and antineoplastic properties. It is promoted as safe, with limited reports of severe adverse effects directly related to oral turmeric thus far in the literature. Herein we report two cases of turmeric supplement induced severe hepatitis. These cases highlight the need for physicians to be aware of patients taking this common supplement and the potential risks that exist.

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Cannabis and Inflammation in HIV: A Review of Human and Animal Studies

Viruses ◽

10.3390/v13081521 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1521

Author(s):

Ronald J. Ellis ◽

Natalie Wilson ◽

Scott Peterson

Keyword(s):

Myocardial Infarction ◽

Adverse Effects ◽

Animal Studies ◽

Endocannabinoid System ◽

Cannabis Use ◽

Review Of The Literature ◽

Barrier Integrity ◽

Persistent Inflammation ◽

Anti Inflammatory ◽

The Impact

Persistent inflammation occurs in people with HIV (PWH) and has many downstream adverse effects including myocardial infarction, neurocognitive impairment and death. Because the proportion of people with HIV who use cannabis is high and cannabis may be anti-inflammatory, it is important to characterize the impact of cannabis use on inflammation specifically in PWH. We performed a selective, non-exhaustive review of the literature on the effects of cannabis on inflammation in PWH. Research in this area suggests that cannabinoids are anti-inflammatory in the setting of HIV. Anti-inflammatory actions are mediated in many cases through effects on the endocannabinoid system (ECS) in the gut, and through stabilization of gut–blood barrier integrity. Cannabidiol may be particularly important as an anti-inflammatory cannabinoid. Cannabis may provide a beneficial intervention to reduce morbidity related to inflammation in PWH.

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Emerging Contaminants in Seafront Zones. Environmental Impact and Analytical Approaches

Separations ◽

10.3390/separations8070095 ◽

2021 ◽

Vol 8 (7) ◽

pp. 95

Author(s):

José S. Câmara ◽

Sarah Montesdeoca-Esponda ◽

Jorge Freitas ◽

Rayco Guedes-Alonso ◽

Zoraida Sosa-Ferrera ◽

...

Keyword(s):

High Resolution ◽

Adverse Effects ◽

Emerging Contaminants ◽

Coastal Zones ◽

Chemical Substances ◽

Microextraction Techniques ◽

Potential Risks ◽

The Impact ◽

Analytical Approaches ◽

Analytical Platforms

Some chemical substances have the potential to enter the coastal and marine environment and cause adverse effects on ecosystems, biodiversity and human health. For a large majority of them, their fate and effects are poorly understood as well as their use still unregulated. Finding effective and sustainable strategies for the identification of these emerging and/or anthropogenic contaminants that might cause polluting effects in marine environments to mitigate their adverse effects, is of utmost importance and a great challenge for managers, regulators and researchers. In this review we will evaluate the impact of emerging contaminants (ECs) on marine coastal zones namely in their ecosystems and biodiversity, highlighting the potential risks of organic pollutants, pharmaceuticals and personal care products. Emerging microextraction techniques and high-resolution analytical platforms used in isolation, identification and quantification of ECs will be also reviewed.

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Cross Talk of Signaling Pathways in the Regulation of the Glucocorticoid Receptor Function

Molecular Endocrinology ◽

10.1210/me.2007-0360 ◽

2008 ◽

Vol 22 (6) ◽

pp. 1331-1344 ◽

Cited By ~ 69

Author(s):

Laura Davies ◽

Nirupama Karthikeyan ◽

James T. Lynch ◽

Elin-Alia Sial ◽

Areti Gkourtsa ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Cross Talk ◽

Posttranslational Modifications ◽

Transcriptional Activity ◽

Leucine Zipper ◽

Target Genes ◽

Combinatorial Regulation ◽

Apoptosis Gene ◽

The Impact ◽

In Cells

Abstract Several posttranslational modifications including phosphorylation have been detected on the glucocorticoid receptor (GR). However, the interdependence and combinatorial regulation of these modifications and their role in GR functions are poorly understood. We studied the effects of c-Jun N-terminal kinase (JNK)-dependent phosphorylation of GR on its sumoylation status and the impact that these modifications have on GR transcriptional activity. GR is targeted for phosphorylation at serine 246 (S246) by the JNK protein family in a rapid and transient manner. The levels of S246 phosphorylation of endogenous GR increased significantly in cells treated with UV radiation that activates JNK. S246 GR phosphorylation by JNK facilitated subsequent GR sumoylation at lysines 297 and 313. GR sumoylation increased with JNK activation and was inhibited in cells treated with JNK inhibitor. GR sumoylation in cells with activated JNK was mediated preferentially by small ubiquitin-like modifier (SUMO)2 rather than SUMO1. An increase in GR transcriptional activity was observed after inhibition of JNK or SUMO pathways and suppression of GR transcriptional activity after activation of both pathways in cells transfected with GR-responsive reporter genes. Endogenous GR transcriptional activity was inhibited on endogenous target genes IGF binding protein (IGFBP) and glucocorticoid-induced leucine zipper (GILZ) when JNK and SUMO pathways were induced individually or simultaneously. Activation of both of these signals inhibited GR-mediated regulation of human inhibitor of apoptosis gene (hIAP), whereas simultaneous activation had no effect. We conclude that phosphorylation aids GR sumoylation and that cross talk of JNK and SUMO pathways fine tune GR transcriptional activity in a target gene-specific manner, thereby modulating the hormonal response of cells exposed to stress.

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Cooked navy and black bean diets improve biomarkers of colon health and reduce inflammation during colitis

British Journal Of Nutrition ◽

10.1017/s0007114513004352 ◽

2014 ◽

Vol 111 (9) ◽

pp. 1549-1563 ◽

Cited By ~ 49

Author(s):

Claire Zhang ◽

Jennifer M. Monk ◽

Jenifer T. Lu ◽

Leila Zarepoor ◽

Wendy Wu ◽

...

Keyword(s):

Adverse Effects ◽

Mrna Expression ◽

Phenolic Compound ◽

Experimental Colitis ◽

Sodium Sulphate ◽

Navy Bean ◽

Black Bean ◽

Anti Inflammatory ◽

The Impact

Common beans contain non-digestible fermentable components (SCFA precursors) and phenolic compounds (phenolic acids, flavonoids and anthocyanins) with demonstrated antioxidant and anti-inflammatory potential. The objective of the present study was to assess the in vivo effect of cooked whole-bean flours, with differing phenolic compound levels and profiles, in a mouse model of acute colitis. C57BL/6 mice were fed a 20 % navy bean or black bean flour-containing diet or an isoenergetic basal diet (BD) for 2 weeks before the induction of experimental colitis via 7 d dextran sodium sulphate (DSS, 2 % (w/v) in the drinking-water) exposure. Compared with the BD, both bean diets increased caecal SCFA and faecal phenolic compound concentrations (P< 0·05), which coincided with both beneficial and adverse effects on colonic and systemic inflammation. On the one hand, bean diets reduced mRNA expression of colonic inflammatory cytokines (IL-6, IL-9, IFN-γ and IL-17A) and increased anti-inflammatory IL-10 (P< 0·05), while systemically reduced circulating cytokines (IL-1β, TNFα, IFNγ, and IL-17A, P< 0·05) and DSS-induced oxidative stress. On the other hand, bean diets enhanced DSS-induced colonic damage as indicated by an increased histological injury score and apoptosis (cleaved caspase-3 and FasL mRNA expression) (P< 0·05). In conclusion, bean-containing diets exerted both beneficial and adverse effects during experimental colitis by reducing inflammatory biomarkers both locally and systemically while aggravating colonic mucosal damage. Further research is required to understand the mechanisms through which beans exert their effects on colonic inflammation and the impact on colitis severity in human subjects.

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Impact of Non-steroidal Anti-inflammatory Drug Administration for 12 Months on Renal Function

Frontiers in Pain Research ◽

10.3389/fpain.2021.644391 ◽

2021 ◽

Vol 2 ◽

Author(s):

Kazuhiro Hayashi ◽

Kenji Miki ◽

Hiroshi Kajiyama ◽

Tatsunori Ikemoto ◽

Masao Yukioka

Keyword(s):

Adverse Effects ◽

Musculoskeletal Pain ◽

Aspartate Aminotransferase ◽

Alanine Transaminase ◽

Chronic Musculoskeletal Pain ◽

Tramadol Hydrochloride ◽

Increased Risk ◽

Significant Difference ◽

Anti Inflammatory ◽

The Impact

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of renal complications. Resolution of renal adverse effects after NSAID administration has been observed after short-term use. Thus, the present study aimed to investigate a series of patients with chronic musculoskeletal pain who underwent long-term NSAID administration followed by switching to tramadol hydrochloride/acetaminophen (TA) combination tablets to study the impact of NSAID-induced renal adverse effects.Methods: This was a longitudinal retrospective study of 99 patients with chronic musculoskeletal pain. The patients were administrated with NSAIDs daily during the first 12 months, followed by daily TA combination tablets for 12 months. Estimated glomerular filtration rate (eGFR) and serum levels of aspartate aminotransferase and alanine transaminase were measured at baseline, after NSAID administration and after TA administration.Results: eGFR was significantly reduced after 12-month NSAID administration (median, from 84.0 to 72.8 ml/min/1.73 m2), and the reduction was not shown after the subsequent 12-month TA administration (median, 71.5 ml/min/1.73 m2). Reduction in eGFR was less in patients who received celecoxib (median, −1.8 ml/min/1.73 m2) during the first 12 months. There was no significant difference in aspartate aminotransferase and alanine transaminase in each period.Conclusions: Thus, patients receiving NSAIDs for 12 months displayed both reversible and irreversible reduction of eGFR upon cessation of NSAIDs and switching to TA. Our data highlight the potential safety benefit of utilizing multimodal analgesic therapies to minimize the chronic administration of NSAIDs.

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The anti-inflammatory effect of external use and the impact on scalded mice model of Arisaema

Human Health and Medical Engineering ◽

10.2495/hhme130241 ◽

2014 ◽

Author(s):

Mingsan Miao ◽

Dandan Liu ◽

Jiaojiao Jia ◽

Xiaofang Guo ◽

Kai Xiao

Keyword(s):

Mice Model ◽

Anti Inflammatory ◽

The Impact ◽

Inflammatory Effect

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