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Naunyn-Schmiedeberg's Archives of... Feb 2024The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial... (Review)
Review
The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.
Topics: Humans; Anti-Asthmatic Agents; Microbiota; Asthma; Lung; Bacteria
PubMed: 37650889
DOI: 10.1007/s00210-023-02681-5 -
Iranian Journal of Kidney Diseases Jul 2023Rhabdomyolysis is a clinical syndrome accompanied with biochemical changes that is diagnosed in some patients with acute chemical or drug poisoning. In this regard, the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Rhabdomyolysis is a clinical syndrome accompanied with biochemical changes that is diagnosed in some patients with acute chemical or drug poisoning. In this regard, the present study aimed to evaluate the effects of Montelukast in the treatment of intoxication-induced rhabdomyolysis.
METHODS
This single-blind randomized clinical trial study was conducted in Loghman Hakim Hospital from March 2021 to March 2022. The study participants were 60 individuals evenly distributed into experimental and control groups. The experimental group received Montelukast plus routine treatment and the control group Creatine phosphokinase (CPK), urea, creatinine, aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were monitored daily in both groups for seven days. The variables of age, gender and history of diabetes mellitus and kidney diseases were recorded.
RESULTS
The mean age was 39.9 ± 16.87 and 38.2 ± 16.3 years in the control and intervention groups, respectively. Montelukast significantly (P < .05) reduced CPK levels on days five and seven, urea on days three, four, five and seven, and creatinine on days two to seven. The AST and ALT levels, unlike the control group which has a decreasing trend, increased first in the Montelukast group and then decreased on the sixth and seventh days.
CONCLUSION
The results showed that Montelukast effectively reduced CPK, urea and creatinine levels, as well as the recovery time in patients with poison-induced rhabdomyolysis. In other words, Montelukast is effective in the treatment of rhabdomyolysis. DOI: 10.52547/ijkd.7222.
Topics: Humans; Young Adult; Adult; Middle Aged; Creatinine; Single-Blind Method; Acetates; Cyclopropanes
PubMed: 37634246
DOI: No ID Found -
Children (Basel, Switzerland) Jul 2023Drug-induced neuropsychiatric effects are important for disease management. We aim to evaluate the neuropsychiatric effects of montelukast-levocetirizine combination...
Drug-induced neuropsychiatric effects are important for disease management. We aim to evaluate the neuropsychiatric effects of montelukast-levocetirizine combination therapy in children. This descriptive study was conducted with children aged 2-5 years, diagnosed with asthma and allergic rhinitis, who began to receive montelukast and levocetirizine combination therapy. The respiratory and asthma control test for children (TRACK), Rhino Conjunctivitis Scoring System (RCSS), and common neuropsychiatric effects (irritable behavior, hallucinations, headaches, nightmares, sleep disorders, behavioral and mood disorder, restlessness, depression) were ascertained by the questionnaire applied before and 4 weeks after the treatment. Parents answered on behalf of their children. The most common finding before and after treatment was irritable behavior. While irritable behavior was observed in 82.4% ( = 56) of children before the treatment, this percentage was 63.2% ( = 43) after the treatment ( = 0.004). The percentage of children who developed at least one neuropsychiatric symptom after treatment was 22.1% ( = 15). There was no significant effect of age, gender, RCSS, TRACK, or allergy test positivity on the development of neuropsychiatric symptoms ( > 0.05). According to the results, at least one neuropsychiatric finding developed in approximately one in five children. Identifying risk factors will enable more careful treatment or consideration of alternative treatments for children at higher risk in the clinical follow-up period.
PubMed: 37628300
DOI: 10.3390/children10081301 -
Cureus Jul 2023Eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of disorders including eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis....
Eosinophilic gastrointestinal disorders (EGIDs) are a spectrum of disorders including eosinophilic esophagitis, eosinophilic gastroenteritis, and eosinophilic colitis. We report a case of EGID involving the esophagus, small intestine, and large intestine simultaneously. A 38-year-old male patient presented with chronic diarrhea, abdominal pain, and unquantified weight loss for the last two months, which not improving with routine empirical treatment. Endoscopy revealed erosions in the stomach, duodenum, terminal ileum, and proximal colon. Biopsy revealed eosinophilic infiltration in the esophagus, terminal ileum, and proximal colon. Contrast-enhanced CT showed multiple skip areas of short- and long-segment circumferential mural thickening with enhancement in the jejunum and ileal loops, causing mild luminal narrowing with pelvic ascites, indicating involvement of muscular and probably serosal layer to a lesser degree (absence of obstructive symptoms with minimal ascites) along with predominant mucosal involvement (responsible for clinical symptoms). The patient was treated with elimination diet, systemic corticosteroids, and montelukast. Diarrheal episodes decreased, and the treatment was shifted to oral budesonide. We believe it to be one of the first reports to show a simultaneous involvement of the esophagus, small intestine, and large intestine, along with mucosal and mural involvement. It strengthens the fact that a common underlying pathogenesis causes EGIDs and an underlying muscular layer involvement in patients with predominant mucosal disease.
PubMed: 37621796
DOI: 10.7759/cureus.42349 -
Frontiers in Aging Neuroscience 2023Aging is in general associated with a decline in cognitive functions. Looking more closely, there is a huge heterogeneity in the extent of cognitive (dys-)abilities in...
INTRODUCTION
Aging is in general associated with a decline in cognitive functions. Looking more closely, there is a huge heterogeneity in the extent of cognitive (dys-)abilities in the aged population. It ranges from the population of resistant, resilient, cognitively unimpaired individuals to patients with severe forms of dementias. Besides the known genetic, environmental and life style factors that shape the cognitive (dys-)abilities in aging, the underlying molecular mechanisms and signals related to cognitive heterogeneity are completely unknown. One putative mechanism underlying cognitive heterogeneity might be neuroinflammation, exerted through microglia, the brain's innate immune cells, as neuroinflammation is central to brain aging and neurodegenerative diseases. Recently, leukotrienes (LTs), i.e., small lipid mediators of inflammation produced by microglia along aging and neurodegeneration, got in the focus of geroscience as they might determine cognitive dysfunctions in aging.
METHODS
Here, we analyzed the brain's expression of key components of the LT synthesis pathway, i.e., the expression of 5-lipoxygenase (5-Lox), the key enzyme in LT production, and 5-lipoxygenase-activating protein (FLAP) in young and aged rats. More specifically, we used a cohort of rats, which, although grown up and housed under identical conditions, developed into aged cognitively unimpaired and aged cognitively impaired traits.
RESULTS
Expression of 5-Lox was increased within the brain of aged rats with the highest levels detected in cognitively impaired animals. The number of microglia cells was higher in the aged compared to the young brains with, again, the highest numbers of 5-Lox expressing microglia in the aged cognitively impaired rats. Remarkably, lower cognitive scores in the aged rats associated with higher numbers of 5-Lox positive microglia in the animals. Similar data were obtained for FLAP, at least in the cortex. Our data indicate elevated levels of the LT system in the brain of cognitively impaired animals.
DISCUSSION
We conclude that 5-Lox expressing microglia potentially contribute to the age-related cognitive decline in the brain, while low levels of the LT system might indicate and foster higher cognitive functions and eventually cognitive reserve and resilience in aging.
PubMed: 37600518
DOI: 10.3389/fnagi.2023.1140708 -
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 -
Iranian Journal of Immunology : IJI Sep 2023Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do... (Review)
Review
Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do we consider complement inhibitors in therapeutic protocols?". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms "COVID-19", "Complement", "Complement inhibitor", "SARS-CoV-2", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in "KEGG pathway database". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; SARS-CoV-2; Complement Activation; Complement Inactivating Agents; Immunologic Factors
PubMed: 37545318
DOI: 10.22034/iji.2023.97585.2522 -
Minerva Medica Aug 2023
PubMed: 37534834
DOI: 10.23736/S0026-4806.23.08711-6 -
Pharmaceutics Jul 2023Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their...
Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their efficacy against emerging Variants of Concern (VOCs) such as Omicron. Our research fills this gap by investigating these drugs' impact on VOCs, a topic that current scientific literature has largely overlooked. We employed computational methodologies, including molecular mechanics and machine learning tools, to identify drugs that could potentially disrupt the SARS-CoV-2 spike RBD-ACE2 protein interaction. This led to the identification of two FDA-approved small molecule drugs, M and T, conventionally used for treating asthma and hypertension, respectively. Our study presents an additional potential use for these drugs as antivirals. Our results show that both M and T can inhibit not only the WT SARS-CoV-2 but also, in the case of M, the Omicron variant, without reaching cytotoxic concentrations. This novel finding fills an existing gap in the literature and introduces the possibility of repurposing these drugs for SARS-CoV-2 VOCs, an essential step in responding to the evolving global pandemic.
PubMed: 37514075
DOI: 10.3390/pharmaceutics15071891