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International Journal of Molecular... Apr 2024Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone...
Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y and P2Y receptors and K channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K (K) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K currents, and this effect was abolished with flutamide (an androgen receptor antagonist). K channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of K1.2 and K1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y signaling and K channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.
Topics: Animals; Uridine Triphosphate; Guinea Pigs; Muscle Relaxation; Male; Adenosine Triphosphate; Trachea; Testosterone; Adenylyl Cyclases; Muscle, Smooth; Potassium Channels, Voltage-Gated; Signal Transduction; Receptors, Purinergic P2
PubMed: 38731872
DOI: 10.3390/ijms25094652 -
Journal of Clinical Anesthesia Aug 2024Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the... (Review)
Review
Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.
Topics: Humans; Herb-Drug Interactions; Plant Preparations; Perioperative Period; Dietary Supplements; Perioperative Care; Anesthetics; Phytotherapy; United States; Drug Interactions
PubMed: 38613937
DOI: 10.1016/j.jclinane.2024.111473 -
Molecular Therapy. Methods & Clinical... Jun 2024Pulmonary macrophage transplantation (PMT) is a gene and cell transplantation approach in development as therapy for hereditary pulmonary alveolar proteinosis (hPAP), a...
Pulmonary macrophage transplantation (PMT) is a gene and cell transplantation approach in development as therapy for hereditary pulmonary alveolar proteinosis (hPAP), a surfactant accumulation disorder caused by mutations in (and murine homologs). We conducted a toxicology study of PMT of gene-corrected macrophages (mGM-RαMϕs) or saline-control intervention in or wild-type (WT) mice including single ascending dose and repeat ascending dose studies evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics. Lentiviral-mediated cDNA transfer restored GM-CSF signaling in mGM-RαMϕs. Following PMT, mGM-RαMϕs engrafted, remained within the lungs, and did not undergo uncontrolled proliferation or result in bronchospasm, pulmonary function abnormalities, pulmonary or systemic inflammation, anti-transgene product antibodies, or pulmonary fibrosis. Aggressive male fighting caused a similarly low rate of serious adverse events in saline- and PMT-treated mice. Transient, minor pulmonary neutrophilia and exacerbation of pre-existing hPAP-related lymphocytosis were observed 14 days after PMT of the safety margin dose but not the target dose (5,000,000 or 500,000 mGM-RαMϕs, respectively) and only in mice but not in WT mice. PMT reduced lung disease severity in mice. Results indicate PMT of mGM-RαMϕs was safe, well tolerated, and therapeutically efficacious in mice, and established a no adverse effect level and 10-fold safety margin.
PubMed: 38596536
DOI: 10.1016/j.omtm.2024.101213 -
Anales de Pediatria May 2024Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the...
INTRODUCTION AND OBJECTIVE
Several studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission.
METHODS
Retrospective cohort study including patients aged 0-18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021.
RESULTS
228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization). In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions.
CONCLUSIONS
In our study, one third of the patients were admitted with SARS-CoV-2 infection but not because of it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.
Topics: Humans; COVID-19; Retrospective Studies; Child; Infant; Child, Preschool; Male; Female; Adolescent; Spain; Hospitalization; Systemic Inflammatory Response Syndrome; Infant, Newborn; Cohort Studies; Severity of Illness Index
PubMed: 38580601
DOI: 10.1016/j.anpede.2024.03.049 -
Tuberculosis and Respiratory Diseases Apr 2024Cardiovascular comorbidity is common in individuals with Chronic obstructive pulmonary disease (COPD). These factor interferes in pharmacological treatment. The use of...
INTRODUCTION
Cardiovascular comorbidity is common in individuals with Chronic obstructive pulmonary disease (COPD). These factor interferes in pharmacological treatment. The use of beta-blockers has been proposed for their known cardioprotective effects. However, there is a reluctance to use them due to adverse reactions and the risk of causing bronchospasm.
OBJECTIVE
To summarize existing evidences on the effects of beta-blocker use in COPD associated with cardiovascular comorbidities in relation to disease severity, exacerbation and mortality outcomes.
MATERIAL AND METHODS
EMBASE, Medline, Lilacs, Cochrane Library and Science Direct databases were used. Study selection and data extraction, observational studies were included that evaluated the effects of beta-blockers in individuals with COPD and cardiovascular comorbidities, and related disease severity, exacerbations, or mortality to outcomes. Studies that did not present important information about the sample and pharmacological treatment were excluded. Twenty studies were included.
RESULTS
Relevance to patient care and clinical practice: The use of beta-blockers in individuals with COPD and cardiovascular disease caused positive effects on mortality and exacerbations outcomes compared with the results of individuals who did not use them. The severity of the disease caused a slight change in FEV1. The OR for mortality was 0.50 (95 % CI: 0.39-0.63; p-value <0.00001) and for exacerbations 0.76 (95 % CI: 0.62-0.92; p -value = 0.005), being favorable to the group that used beta-blockers.
CONCLUSION
Further studies are needed to study the effect of using a specific beta-blocker in COPD associated with a specific cardiovascular comorbidity.
PubMed: 38575301
DOI: 10.4046/trd.2024.0013 -
Children (Basel, Switzerland) Mar 2024The use of laryngeal masks in the surgical treatment of infantile lacrimal duct stenosis is controversial due to the potential risk of aspiration. This study...
The use of laryngeal masks in the surgical treatment of infantile lacrimal duct stenosis is controversial due to the potential risk of aspiration. This study investigates airway procedures in children aged <6 years for surgery of lacrimal duct stenosis in a tertiary care university hospital. After institutional approval, airway procedures, duration of anesthesiological measures, and airway-related complications were retrospectively analyzed. Patients were divided into two groups according to the airway procedures used (endotracheal tube [ET] vs. laryngeal mask [LMA] airway). Associations were calculated using the Chi-square test or Mann-Whitney U-test. Clinical data of 84 patients (ET = 36 [42.9%] vs. LMA = 48 [57.1%]) were analyzed. There were no significant differences in surgical treatment, age distribution, and pre-existing conditions between the groups. None of the patients showed evidence of tracheal aspiration or changes in measured oxygen saturation. LMA airway shortened time for anesthesia induction ( = 0.006) and time for recovery/emergence period ( = 0.03). In contrast, the time to discharge from the recovery room was significantly prolonged using LMA ( = 0.001). A total of 7 adverse events were recorded. Five of these were directly or indirectly related to ET (laryngo-/bronchospasm; muscle relaxant residual). LMA airway for infantile lacrimal duct stenosis seems to be a safe procedure and should be used in appropriate pediatric patients due to its lower invasiveness, low complication rate, and time savings.
PubMed: 38539355
DOI: 10.3390/children11030320 -
Journal of Fungi (Basel, Switzerland) Mar 2024Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a...
Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/μL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, : 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.
PubMed: 38535200
DOI: 10.3390/jof10030191 -
Cureus Feb 2024Benzylisoquinolinium neuromuscular blocking agents can precipitate bronchospasm either through allergy/anaphylaxis or isolated stimulation of mast cell histamine...
Benzylisoquinolinium neuromuscular blocking agents can precipitate bronchospasm either through allergy/anaphylaxis or isolated stimulation of mast cell histamine release. This report presents a 75-year-old female who attended the day surgery unit for a rigid cystoscopy under general anaesthesia. She had a hyper-reactive airway history of mild historic asthma and sensitivity to aerosols. After administration of atracurium at induction of anaesthesia, ventilation became challenging with no chest rise and a flat CO trace. Repeat video laryngoscopy confirmed correct endotracheal tube position. The patient remained cardiovascularly stable with no mucocutaneous signs of anaphylaxis. Administration of high flow oxygen, sevoflurane, salbutamol and magnesium sulfate led to gradual improvement and normalisation of respiratory parameters. Surgery was postponed. This report highlights atracurium as an important trigger of bronchospasm at induction of anaesthesia, and illustrates that in rare cases a flat capnograph does not always indicate a mispositioned airway device. Several aspects of the anaesthetic plan for this patient were suboptimal given her respiratory history, namely, the choice of mode of anaesthesia and choice of neuromuscular blocking agent. These factors are discussed in the context of anaesthetic planning for patients presenting with features suggesting high bronchospastic risk.
PubMed: 38496062
DOI: 10.7759/cureus.54251