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CNS & Neurological Disorders Drug... Sep 2023Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly...
Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF.
BACKGROUND
Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders.
OBJECTIVE
This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation.
METHODS
Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect.
RESULTS
Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05) Conclusion: Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.
PubMed: 37779395
DOI: 10.2174/0118715273258337230925040049 -
Alcohol (Fayetteville, N.Y.) Dec 2023The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene...
The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene receptor, and the involvement of the NO-cGMP-K channel pathway, were evaluated in gastric damage induced by ethanol in rats. For this, l-arginine, l-NAME, methylene blue (guanylate cyclase inhibitor), sildenafil, diazoxide, or glibenclamide (ATP-sensitive potassium channel blocker) were administered 30 min before montelukast (0.1, 1, 10, and 20 mg/kg, by mouth [p.o.]). After 1 h, to induce gastric damage, the rats received absolute ethanol (4 mL/kg, p.o.), and then microscopic, macroscopic, and pro-inflammatory parameters (TNF-α and IL-1β) were assessed. Results obtained here revealed that montelukast significantly attenuated the macroscopic and microscopic lesions induced by ethanol. Montelukast also reduced IL-1β and TNF-α levels. It was also observed that NOS inhibitor (l-NAME), methylene blue, and glibenclamide inhibited the effects of montelukast in the stomach. Moreover, the NO precursor (l-arginine), the PDE-5 inhibitor (sildenafil), and a potassium channel opener (diazoxide) before montelukast produced gastroprotective effects. In conclusion, the effect of montelukast against gastric lesions induced by ethanol is mediated, at least in part, through the pathway of the NO-cGMP-K channel.
Topics: Rats; Animals; NG-Nitroarginine Methyl Ester; Nitric Oxide; Sildenafil Citrate; Methylene Blue; Ethanol; Cyclic GMP; Glyburide; Tumor Necrosis Factor-alpha; Diazoxide; KATP Channels; Stomach; Arginine; Adenosine Triphosphate
PubMed: 37295565
DOI: 10.1016/j.alcohol.2023.05.008 -
Proceedings (Baylor University. Medical... 2023Patients with chronic kidney disease (CKD) are at increased risk for adverse drug events due to medication dosing errors. We studied the awareness and knowledge among...
BACKGROUND
Patients with chronic kidney disease (CKD) are at increased risk for adverse drug events due to medication dosing errors. We studied the awareness and knowledge among internal medicine housestaff (IMHS) of proper dose adjustment of commonly used rheumatology and allergy/immunology medications for patients with CKD.
METHODS
We surveyed 353 IMHS to evaluate their awareness of the need for medication dose adjustments for patients with CKD and knowledge for medication adjustment by level of glomerular filtration rate for common rheumatology and allergy/immunology medications.
RESULTS
There was lack of awareness and knowledge for both rheumatology and allergy/immunology medications. Incorrect awareness and knowledge were as follows: allopurinol, 21.2%, 73.4%; colchicine, 19.0%, 75.9%; diphenhydramine, 34.0%, 34.0%; loratadine, 82.2%, 93.2%; and montelukast, 34.0%, 34.0%, respectively. Exploratory logistic regression analyses showed that PGY1 residents had higher odds for lack of awareness for allopurinol (odds ratio [OR] 24.57, 95% CI [confidence interval] 4.69, 99.13, < 0.001), colchicine (OR 3.98, 95% CI 1.50, 10.51, < 0.01), diphenhydramine (OR 2.24, 95% CI 1.10, 4.54, < 0.04), and montelukast (OR 2.45, 95% CI 1.20, 5.00, < 0.05) than PGY3 residents. A nephrology rotation in medical school was associated with lower odds for incorrect knowledge for allopurinol (OR 0.46, 95% CI 0.25, 0.87, < 0.05) and montelukast (OR 0.50, 95% CI 0.27, 0.92, < 0.05).
CONCLUSION
Overall, awareness and knowledge were poor among IMHS for dose adjustments of rheumatology and allergy/immunology medications in patients with CKD. Proper education and exposure to nephrology during training may improve quality and safety of care for patients with CKD.
PubMed: 37663380
DOI: 10.1080/08998280.2023.2228172 -
Journal of Medical Case Reports Oct 2023Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite... (Review)
Review
BACKGROUND
Clopidogrel and ticagrelor are rarely reported to cause vasculitis via drug hypersensitivity reaction, largely mediated by T cells and immunoglobulin E (IgE). Despite therapeutic advances, the etiology of refractory vasculitides remains incompletely understood. Recently, (non)immunological mechanisms bypassing T cells and IgE have been proposed to explain resistance to standard immunosuppressants. Herein, we report a case of refractory drug-induced systemic small-vessel vasculitis with varied extracutaneous manifestations and incorporate multiple sources of data to provide detailed accounts of complex (non)immunological phenomena involved in this case. Study objectives are to provide an insight about rare presentations of commonly used drugs, upgrade the pathophysiological concepts of drug-induced vasculitis, raise need for further investigation to define causes and risk factors for refractory vasculitis, and discuss most of the current knowledge suggesting novel therapeutic approaches to treat this vasculitis. To our knowledge, this is the first case of the two flares of systemic small-vessel vasculitis in a single patient in response to clopidogrel and ticagrelor exposure, respectively. However, this report is limited by attribution/observer bias.
CASE PRESENTATION
We herein report a 24-year-old Caucasian male student with a medical history of mild seasonal allergic rhinoconjunctivitis, tension-type headaches, posttraumatic arterial stenosis, and previous exposure to ibuprofen, acetylsalicylic acid, and mRNA coronavirus disease 2019 (COVID-19) vaccine who suffered largely from acute urticaria and dyspnea after 20 days of acetylsalicylic acid and clopidogrel introduction. A skin punch biopsy confirmed leukocytoclastic vasculitis. Serologic antibody testing, complement analysis, microbiologic testing, and cancer biomarkers revealed no abnormalities. Regarding the patient's medical history, both acetylsalicylic acid and clopidogrel were exchanged for ticagrelor. Furthermore, the addition of naproxen, cyclosporine, bilastine, prednisolone, and montelukast resulted in complete recovery. After 7 days, diarrhea and hematuria occurred. Urinalysis and computed tomography showed reversible proteinuria with gross hematuria and hypodense changes in kidney medulla, respectively, associated with discontinuation of ticagrelor and naproxen. In addition, the patient recovered completely without any immunosuppression up-titration.
CONCLUSIONS
This case highlights the role of clopidogrel and ticagrelor as possible triggering agents for systemic small-vessel vasculitis and offers an insight into novel therapeutic strategies for refractory vasculitides. Further research is needed to build on the findings of a current report.
Topics: Humans; Male; Young Adult; Aspirin; Clopidogrel; Hematuria; Immunoglobulin E; Naproxen; Ticagrelor; Vasculitis
PubMed: 37885023
DOI: 10.1186/s13256-023-04174-8 -
Brain Research Feb 2024Clinical studies have shown that asthma is a risk factor for dementia or Alzheimer's disease (AD). To investigate whether asthma aggravates AD in APP/PS1 mice and...
Clinical studies have shown that asthma is a risk factor for dementia or Alzheimer's disease (AD). To investigate whether asthma aggravates AD in APP/PS1 mice and explore the potential mechanisms, an asthma model was established using six-month-old APP/PS1 mice, and montelukast was used as a therapeutic agent in APP/PS1 mice with asthma. The Morris water maze test showed that asthma aggravates spatial learning and memory abilities. Asthma also upregulates the NF-κB inflammatory pathway in APP/PS1 mice and promotes the expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), amyloid-β (Aβ) deposition, neuronal damage, synaptic plasticity deficiency, activation of microglia and astrocytes. The level of LTD4 and its receptor CysLT1R in the hippocampus of APP/PS1 mice after the asthma modeling was established was higher than that in APP/PS1 mice, suggesting that asthma may affect the pathology of AD through LTD4 and its receptor Cys-LT1R. Montelukast ameliorates these pathological changes and cognitive impairment. These results suggest that asthma aggravates AD pathology and cognitive impairment of APP/PS1 mice via upregulation of the NF-κB inflammatory pathway, and montelukast ameliorates these pathological changes.
Topics: Mice; Animals; Alzheimer Disease; NF-kappa B; Amyloid Precursor Protein Secretases; Leukotriene D4; Amyloid beta-Protein Precursor; Mice, Transgenic; Aspartic Acid Endopeptidases; Amyloid beta-Peptides; Cognitive Dysfunction; Signal Transduction; Disease Models, Animal; Presenilin-1; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38092296
DOI: 10.1016/j.brainres.2023.148711 -
Iranian Journal of Otorhinolaryngology Mar 2024Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications...
INTRODUCTION
Adenoid hypertrophy is a common childhood disease; its standard treatment is adenoidectomy. The desire for medical management is increasing due to fewer complications and more convenience. The present study investigated the effect of adding oral montelukast to mometasone nasal spray in treating adenoid hypertrophy.
MATERIALS AND METHODS
This was a randomized, double-blind, placebo-controlled study conducted at a referral teaching hospital (Tehran, Iran) from September 2020 to September 2021. Children aged 2 to 14 years with clinical and radiological findings of adenoid hypertrophy were enrolled. Patients were randomly divided into two groups: mometasone nasal spray with oral montelukast (case group) or mometasone with placebo (control group). Then, the clinical scores were compared before and two months after the intervention.
RESULTS
Ninety-six patients completed the study [62.5% male (n=60)]. Of these, 51 were in the case and 45 in the control group. The clinical score in each group decreased significantly after the intervention (P<0.001), but the decrease in clinical score in the case group was not significantly different from the control (p=0.576).
CONCLUSION
The results showed that the combination therapy with mometasone and montelukast has the same efficacy as mometasone and placebo in treating adenoid hypertrophy. Adding montelukast to mometasone has no additional effect.
PubMed: 38476566
DOI: 10.22038/IJORL.2024.73906.3490 -
Plastic and Reconstructive Surgery Sep 2023
Topics: Humans; Cromolyn Sodium; Breast Implants; Contracture; Implant Capsular Contracture
PubMed: 37224195
DOI: 10.1097/PRS.0000000000010540 -
The Journal of Asthma : Official... Apr 2024Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids...
OBJECTIVE
Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment.
METHODS
Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 ( = 1182) and 2015 ( = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi-test. Odds ratios (ORs) were calculated using logistic regression.
RESULTS
Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% ( = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, < 0.001), while SABA use decreased (46.4- 41.8%, = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use.
CONCLUSIONS
The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.
Topics: Adult; Humans; Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Drug Therapy, Combination; Quinolines; Sulfides; Sweden; Male; Female
PubMed: 37910450
DOI: 10.1080/02770903.2023.2272798 -
The Journal of Asthma : Official... Jul 2024Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma...
BACKGROUND
Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS).
METHODS
Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps.
RESULTS
Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses.
CONCLUSION
Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.
Topics: Humans; Acetates; Male; Female; International Classification of Diseases; Cyclopropanes; Adult; Sulfides; Quinolines; Middle Aged; Adolescent; Child; Asthma; Young Adult; Self-Injurious Behavior; Anti-Asthmatic Agents; Suicide, Attempted; Aged; Cohort Studies; Risk Assessment; Adrenal Cortex Hormones
PubMed: 38064517
DOI: 10.1080/02770903.2023.2293064 -
Indian Journal of Endocrinology and... 2024Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its...
BACKGROUND
Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy.
METHODS
40 Wistar rats of either sex were randomly divided into four groups . 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study.
RESULTS
Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group.
CONCLUSION
Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.
PubMed: 38533280
DOI: 10.4103/ijem.ijem_414_22