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BMC Chemistry Jan 2024In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current...
In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 2 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.
PubMed: 38291482
DOI: 10.1186/s13065-024-01117-2 -
Archives of Medical Research Feb 2024Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a...
BACKGROUND
Chagas disease and cutaneous leishmaniasis, two parasitic diseases caused by Trypanosoma cruzi (T. cruzi) and Leishmania mexicana (L. mexicana), respectively, have a major global impact. Current pharmacological treatments for these diseases are limited and can cause severe side effects; thus, there is a need for new antiprotozoal drugs.
METHODS
Using molecular docking, this work describes a structure-based virtual screening of an FDA-approved drug library against Trypanosoma cruzi and Leishmania mexicana glycolytic enzyme triosephosphate isomerase (TIM), which is highly conserved in these parasites. The selected compounds with potential dual inhibitory activity were tested in vitro to confirm their biological activity.
RESULTS
The study showed that five compounds: nilotinib, chlorhexidine, protriptyline, cyproheptadine, and montelukast, were more active against T. cruzi, than the reference drugs, nifurtimox and benznidazole while chlorhexidine and protriptyline were the most active against L. mexicana.
CONCLUSIONS
The analysis of these compounds and their structural characteristics may provide the basis for the development of new antiprotozoal agents.
Topics: Humans; Molecular Docking Simulation; Chlorhexidine; Protriptyline; Chagas Disease; Trypanosoma cruzi; Leishmaniasis, Cutaneous; Antiprotozoal Agents
PubMed: 38290200
DOI: 10.1016/j.arcmed.2024.102958 -
BMC Chemistry Jan 2024For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous...
For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50-2000 ng mL for Montelukast sodium and 50-1000 ng mL for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.
PubMed: 38268023
DOI: 10.1186/s13065-024-01116-3 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a...
Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: -0.053; 95% CI -0.0142 to 0.0002; = 0.020). In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.
PubMed: 38256958
DOI: 10.3390/ph17010125 -
Current Hypertension Reviews 2024Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are...
BACKGROUND
Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis.
OBJECTIVE
This research aims to examine the consequence of montelukast (specific CysLT antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals.
METHODS
2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain's oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined.
RESULTS
Montelukast in doses of 5.0 and 10.0 mg kg was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension- provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction.
CONCLUSION
The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.
Topics: Animals; Sulfides; Cyclopropanes; Acetates; Quinolines; Male; Dementia, Vascular; Leukotriene Antagonists; Oxidative Stress; Hypertension, Renovascular; Disease Models, Animal; Endothelium, Vascular; Receptors, Leukotriene; Inflammation Mediators; Cognition; Rats, Wistar; Brain; Rats; Maze Learning
PubMed: 38192137
DOI: 10.2174/0115734021276985231204092425 -
American Journal of Translational... 2023This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil...
OBJECTIVE
This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil (EOS) percentage in children comorbid with allergic rhinitis (AR) and asthma.
METHODS
The medical records of 114 children comorbid with AR and asthma treated in the Guizhou Provincial People's Hospital from February 2020 to September 2022 were collected and analyzed retrospectively. Among them, 54 children treated with budesonide were assigned to a control group, and the remaining 60 children treated with montelukast sodium combined with budesonide were assigned to an observation group. The efficacy was compared between the two groups. Additionally, the changes in pulmonary function, serum IgE levels, and EOS percentage were compared between the two groups before and after treatment (one month). The adverse reactions during the treatment and the recurrence of AR within 3 months were recorded. Logistics regression was conducted to analyze the risk factors affecting the efficacy in children.
RESULTS
The observation group showed a significantly higher overall response rate than the control group (P<0.05). After treatment, the observation group showed significantly higher levels of forced expiratory volume in 1 second (FEV1)%, FEV1/forced vital capacity (FVC), and peak expiratory flow (PEF) than the control group (P<0.05), and significantly lower IgE levels and EOS percentage than the control group (P<0.05). No significant difference was found between the two groups in terms of the total incidence of adverse reactions (P>0.05). According to the follow-up results of prognosis, the observation group presented a greatly lower recurrence rate of AR within 3 months than the control group (P<0.05). Multivariate logistics regression analysis showed that therapeutic regimen, IgE, and EOS were independent risk factors affecting the efficacy in the patients (P<0.05).
CONCLUSION
Montelukast sodium combined with budesonide can substantially improve the pulmonary function in children with comorbid AR and asthma, alleviate their symptoms of asthma and rhinitis, and lower the IgE level and EOS percentage. In addition, therapeutic regimen, IgE and EOS are independent risk factors affecting the efficacy in patients.
PubMed: 38186993
DOI: No ID Found -
International Journal of Pediatric... Jan 2024We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in...
OBJECTIVE
We sought to study adenoidectomy rates in children with adenoid hypertrophy (AH) who were either treated with medical therapy or not during a 2-year follow-up period in a longitudinal population-based study.
METHODS
We retrospectively identified healthy children aged 1-18 years between 2014 and 2020 with AH diagnosis from the Clalit Health Services database, the largest healthcare maintenance organization in Israel. The main outcome was adenoidectomy alone or in combination with other procedures performed within 2 years after diagnosis. The treatment group consisted of children who received medical therapy, defined as a pharmacy purchase of montelukast, nasal steroid sprays and/or antihistamines (medical therapy aimed to reduce AH) for ≥2 consecutive months, while the control group consisted of untreated children.
RESULTS
We identified 68,356 unique children with AH, of them 56 % were boys, with a mean age of 4.9 ± 3.3 years. Of them, 5310 (7.7 %) received medical therapy. Overall, 6633 (9.7 %) underwent adenoidectomy within 2 years following diagnosis. There was no significant difference in surgery referral rates between the treatment and the control groups, 10 % vs. 9.7 %, respectively (p = 0.3). When adjusted for age and sex, the likelihood of undergoing adenoidectomy was similar in both groups (HR = 0.98, 95 % CI = 0.90-1.07, p = 0.6). Among operated children, the average time from diagnosis to surgery was statistically significantly longer in the treatment group than in the control group, 346 ± 180 vs 311 ± 175 days (p < 0.001).
CONCLUSION
Prescribing montelukast, nasal steroids and/or oral antihistamines was not associated with a reduction in adenoidectomy rates and was associated with an average surgery delay of 35 days.
Topics: Child; Male; Humans; Infant; Child, Preschool; Female; Adenoids; Retrospective Studies; Sulfides; Adenoidectomy; Nasal Sprays; Hypertrophy
PubMed: 38154416
DOI: 10.1016/j.ijporl.2023.111836 -
International Journal of Molecular... Dec 2023Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was...
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the and genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, = 2.6 × 10; R = -0.21, = 0.015) and cg21886367 (R = -0.45, = 7.3 × 10; R = -0.24, = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated . To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.
Topics: Humans; Triple Negative Breast Neoplasms; Cell Line, Tumor; Epigenomics; Receptors, Leukotriene
PubMed: 38139172
DOI: 10.3390/ijms242417343 -
Journal of Clinical Medicine Dec 2023Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this...
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.
PubMed: 38137814
DOI: 10.3390/jcm12247745