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Frontiers in Immunology 2024Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature...
Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1 mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.
Topics: Animals; Receptors, Leukotriene; Mice; Disease Models, Animal; Cyclopropanes; Acetates; Sulfides; Schistosomiasis mansoni; Mice, Knockout; Quinolines; Female; Schistosoma mansoni; Chronic Disease; Leukotriene Antagonists; Liver; Mice, Inbred C57BL; Praziquantel; T-Lymphocytes, Regulatory
PubMed: 38840916
DOI: 10.3389/fimmu.2024.1279043 -
Qatar Medical Journal 2023Obstructive sleep apnea (OSA) affects 1% to 5% of all children, with the most significant prevalence between ages 2 and 8. Correlations between OSA and Adenoid...
BACKGROUND
Obstructive sleep apnea (OSA) affects 1% to 5% of all children, with the most significant prevalence between ages 2 and 8. Correlations between OSA and Adenoid hypertrophy (AH) have been well-demonstrated in children. If untreated, OSA can cause growth impairment, neuro-cognitive and behavioral problems, and cardiovascular complications. Allergy was reported to be a vital risk factor for AH, among other inflammatory processes mentioned.
OBJECTIVES
To demonstrate that the combination of nasal steroids and ani leukotriene reduces the number of adenectomies in children with OSA and adenoid hypertrophy in Saudi children.To demonstrate the positive Correlation between allergic sensitization and OSA caused by adenoid hypertrophy Methods: This retrospective study included 60 children with moderate/severe OSA attending a Pediatric Allergy Clinic in Saudi Arabia diagnosed using Sleep-Related Breathing Disorder Scale (pediatrics-related items). We had children with adenoid hypertrophy confirmed by soft neck tissue x-ray or both; children who suffer from obesity were excluded. Sensitization was defined as positive specific IgE and/or skin prick for food and/or inhaled allergens; allergic comorbidities were enumerated.
RESULTS
Combination of nasal steroid and anti-leukotriene reduces adenectomy by 58.3 % in children with OSA caused by AH. 71.7% of Them were sensitized to inhaled food or both allergens.
CONCLUSION
Anti-inflammatory treatment with a combination of nasal steroids and anti-leukotriene remarkably reduces the adenectomy rate in children with OSA caused by AH. Our findings suggest that allergic sensitization, regardless of the allergen, increases children's susceptibility to AH through the inflammatory process. This may be why nasonex and montelukast are effective treatments for OSA in children with AH.
PubMed: 38025327
DOI: 10.5339/qmj.2023.sqac.31 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Opioid may cause undue risk after surgical procedures like orthognathic surgeries. The present study was aimed to determine how the preoperative administration of oral...
INTRODUCTION
Opioid may cause undue risk after surgical procedures like orthognathic surgeries. The present study was aimed to determine how the preoperative administration of oral montelukast affected the degree of postoperative discomfort following bimaxillary orthognathic surgery (BOS).
METHODOLOGY
This study included all skeletal class III subjects scheduled for BOS. The participants were split into placebo and montelukast groups at random. Every patient received a 10-mL serving of apple juice an hour prior to the surgery; however, for the intervention group, a montelukast 10 mg pill was dissolved in the juice. The same surgical team and general anesthetic guidelines were used for all procedures. The visual analog scale (VAS) was used to calculate postoperative pain at designated intervals. The significance level for the statistical analysis was determined using the Statistical Package for the Social Sciences (SPSS) version 23.
RESULTS
The control subjects had a higher level of pain at all the intervals than the intended drug test group. Also, the control group needed more analgesics than the test group. There was one observation made that the length of the surgery had an impact on the postoperative pain.
CONCLUSION
Preoperative montelukast medication may be useful in minimizing postoperative discomfort following bimaxillary orthognathic surgery. More research is required for greater relevance.
PubMed: 37654356
DOI: 10.4103/jpbs.jpbs_432_22 -
The Journal of Pediatric Pharmacology... 2024
PubMed: 38332955
DOI: 10.5863/1551-6776-29.1.90 -
Journal of Epidemiology and Global... Apr 2024This study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is...
BACKGROUND
This study examines incidence, mortality, medical expenditure and prescription patterns for asthma on a national scale, particularly in Asian countries for asthma is limited. Our aim is to investigate incidence, mortality, prescription patterns and provide a comprehensive overview of healthcare utilization trends for asthma from 2009 to 2018.
METHODS
We included patients diagnosed with asthma between 2009 and 2018. We excluded patients with missing demographic data. Our analysis covered comorbidities, including diabetes mellitus, hypertension, allergic rhinitis, eczema, atopic dermatitis, coronary artery disease, congestive heart failure, chronic kidney disease, chronic hepatitis, stroke, and cancer. Investigated medications comprised oral and intravenous steroids, short-acting beta-agonists, inhaled corticosteroids (ICS), combinations of ICS and long-acting beta-agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists montelukast. We also assessed the number of outpatient visits, emergency visits, and hospitalizations per year, as well as the average length of hospitalization and average medical costs.
RESULTS
The study included a final count of 88,244 subjects from 1,998,311 randomly selected samples between 2000 and 2019. Over the past decade, there was a gradual decline in newly diagnosed asthma patients per year, from 10,140 to 6,487. The mean age annually increased from 47.59 in 2009 to 53.41 in 2018. Over 55% of the patients were female. Eczema was diagnosed in over 55% of the patients. Around 90% of the patients used oral steroids, with a peak of 97.29% in 2018, while the usage of ICS varied between 86.20% and 91.75%. Intravenous steroids use rose from 40.94% in 2009 to 54.14% in 2018. The average annual hospital stay ranged from 9 to 12 days, with a maximum of 12.26 days in 2013. Lastly, the average medical expenses per year ranged from New Taiwan dollars 5558 to 7921.
CONCLUSIONS
In summary, both asthma incidence and all-cause mortality rates decreased in Taiwan from 2009 to 2018. Further analysis of medical expenses in patients with asthma who required multiple hospitalizations annually revealed an increase in outpatient and emergency visits and hospitalizations, along with longer hospital stays and higher medical costs.
PubMed: 38656730
DOI: 10.1007/s44197-024-00230-8 -
Cureus Aug 2023Eosinophilic enteritis is a rare subset of eosinophilic gastrointestinal disorders. It typically presents with chronic symptoms of abdominal pain, nausea, vomiting,...
Eosinophilic enteritis is a rare subset of eosinophilic gastrointestinal disorders. It typically presents with chronic symptoms of abdominal pain, nausea, vomiting, diarrhea, and ascites. However, the clinical presentation can vary due to acute flare-ups. Here, we present a case of eosinophilic enteritis in a young female patient with intractable vomiting and diarrhea, mimicking acute gastroenteritis in the absence of other gastrointestinal symptoms. This case illustrates the challenge of diagnosing acute and diverse presentations of eosinophilic enteritis. It also highlights the importance of promptly treating and confirming the diagnosis through urgent tissue histopathology in adolescents with unexplained vomiting and diarrhea.
PubMed: 37767271
DOI: 10.7759/cureus.44199 -
Qatar Medical Journal 2023Bronchial asthma affects about 20% of Qatar's population. The impact of asthma on COVID-19 outcomes is controversial. The aim of this study was to explore the impact of...
BACKGROUND
Bronchial asthma affects about 20% of Qatar's population. The impact of asthma on COVID-19 outcomes is controversial. The aim of this study was to explore the impact of asthma on COVID-19 outcomes and the predictors of COVID-19-related morbidity and mortality in a cohort of asthma patients infected by COVID-19.
METHODS
This is a retrospective cohort study of adult patients with asthma infected with COVID-19, who were recruited from Hamad Medical Corporation (HMC), the main healthcare system in Qatar. Patients were matched to a control group of non-asthmatic COVID-19 patients (1:2) based on sex, age, and other comorbidities.
RESULTS
Between March and August 2020, 616 patients with asthma met the inclusion criteria. The need for hospitalization among patients with asthma was independently associated with older age (adjusted odds ratio [aOR] for 10 years, 1.32; 95% confidence interval [CI], 1.13-1.54; = 0.001) and hypertension (aOR, 2.4; 95% CI, 1.43-3.93; = 0.001) but not with the use of inhaled corticosteroids (ICS), long-acting beta2 agonists, montelukast, or tiotropium. Patients with asthma required less hospitalization for COVID-19 than non-asthmatic patients (28.2% vs. 37.3%, respectively; aOR, 0.59; 95% CI, 0.77-0.90; < 0.001). However, admission to the intensive care unit (ICU) was comparable between both groups (3.3% vs. 2.2%; aOR, 1.64; 95% CI, 0.78-3.43; = 0.193). No difference in mortality rate was observed between the two groups.
CONCLUSIONS
In Qatar, adult patients with asthma do not appear to be at higher risk of COVID-19-related hospitalization or ICU admission compared to the general adult COVID-19-infected population. Older age and hypertension were the only significant predictors of COVID-19-related hospitalization among patients with asthma. Further larger studies are required to confirm such an association.
PubMed: 37565045
DOI: 10.5339/qmj.2023.15 -
Pakistan Journal of Medical Sciences 2023To observe the efficacy of Montelukast combined with sublingual immunotherapy (SLIT) in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS)...
Efficacy of Montelukast combined with Sublingual Immunotherapy in the treatment of children with Obstructive Sleep Apnea Hypopnea Syndrome Complicated with allergic rhinitis.
OBJECTIVE
To observe the efficacy of Montelukast combined with sublingual immunotherapy (SLIT) in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with allergic rhinitis (AR).
METHODS
This is a prospective study. A total of 102 children with OSAHS complicated with allergic rhinitis admitted to Hunan Children's Hospital from April 2020 to April 2021 were selected and randomly divided into two groups: sublingual group and two-drug combination group. Children in the sublingual group were treated with standardized dust mite drops Nos. 1-4 for SLIT, while those in the two-drug combination group were treated with Montelukast on top of the sublingual group. Statistical analysis and comparison were made between the two groups of children in terms of Sleep apnea hypopnea index (AHI), Hypoxic saturation (Lsao), interleukin-4, Il-4), interleukin-17 (IL-17), OSA-18 Snoring Symptom Scale for Children (OSA-18), allergic rhinitis symptom scale (TNSS), efficacy, occurrence of adverse reactions, etc.
RESULTS
After treatment, the AHI index of the two-drug combination group was significantly decreased, and the Lsao index was significantly increased compared with the sublingual group (P<0.05). Compared with the sublingual group, the levels of IL-4 and IL-17 in the two-drug combination group were significantly decreased (P<0.05), the OSA-18 score and TNSS score were significantly lower (P<0.05). Moreover, compared with the sublingual group, the efficacy of the two-drug combination group was significantly increased (P<0.05), the incidence of adverse reactions was significantly lower (P<0.05).
CONCLUSION
Montelukast combined with sublingual immunotherapy offers many advantages, such as effectively controlling nasal allergy symptoms in children with OSAHS complicated with allergic rhinitis and improving OSAHS symptoms.
PubMed: 37680839
DOI: 10.12669/pjms.39.5.6985 -
Animal Models and Experimental Medicine Apr 2024Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid...
BACKGROUND
Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH.
METHODS
An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.
RESULTS
Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement.
CONCLUSION
The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.
PubMed: 38572767
DOI: 10.1002/ame2.12396 -
Journal of Orthopaedic Translation Jan 2024Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This...
BACKGROUND
Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This devastating complication may cause consistent pain and dramatically reduction of functionality. Unfortunately, the conservative treatments to prevent the AF in the early stage are largely unknown due to the lack of specific biomarkers and reliable therapeutic targets.
METHODS
In this study, we extracted1782 fibrosis related genes (FRGs) from 373,461published literature based on the large natural language processing models (ChatGPT) and intersected with the 2750 differential expressed genes (DEGs) from mRNA microarray (GSE135854). A total of 311 potential AF biomarker genes (PABGs) were obtained and functional analysis were performed including gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, we accomplished validation in AF animal models with immobilization of the unilateral knee joints of 16 rabbits for 1-week, 2-weeks, 3-weeks and 4-weeks. Finally, we tested the biomarkers in a retrospective cohort enrolled 35 AF patients and 35 control group patients.
RESULTS
We identified G-protein-coupled receptor 17 (GPR17) as a reliable therapeutic biomarker for AF diagnosis with higher AUC (0.819) in the ROC curve. A total of 21 potential drugs targeted to GPR17 were screened. Among them, pranlukast and montelukast have achieved therapeutic effect in animal models. In addition, we established an online AF database for data integration (https://chenxi2023.shinyapps.io/afdbv1).
CONCLUSIONS
These results unveiling therapeutic biomarkers for AF diagnosis, and provide potential drugs for clinical treatment.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF.
PubMed: 38304615
DOI: 10.1016/j.jot.2023.11.002