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Biomolecules Jun 2023Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. At the present time, nothing can reliably halt labor once it begins. The... (Review)
Review
Preterm labor leading to preterm birth is the leading cause of infant morbidity and mortality. At the present time, nothing can reliably halt labor once it begins. The knowledge that agonists of the β2 adrenergic receptor relax airway smooth muscle and are effective in the treatment of asthma led to the notion that β2 mimetics would prevent preterm birth by relaxing uterine smooth muscle. The activation of cAMP-dependent protein kinase by β2 receptors is unable to provide meaningful tocolysis. The failure of β2 agonists such as ritodrine and terbutaline to prevent preterm birth suggests that the regulation of uterine smooth muscle is disparate from that of airway. Other smooth muscle quiescent-mediating molecules, such as nitric oxide, relax vascular smooth muscle in a cGMP-protein kinase G-dependent manner; however, nitric oxide activation of protein kinase G fails to explain the relaxation of the myometrium to nitric oxide. Moreover, nitric oxide-mediated relaxation is blunted in preterm labor, and thus, for this reason and because of the fall in maternal blood pressure, nitric oxide cannot be employed as a tocolytic. The β3 adrenergic receptor-mediated relaxation of the human myometrium is claimed to be cAMP-dependent protein kinase-dependent. This is scientifically displeasing given the failure of β2 agonists as tocolytics and suggests a non-canonical signaling role for β3AR in myometrium. The addition of the β3 agonist mirabegron to pregnant human myometrial strips in the tissue bath relaxes oxytocin-induced contractions. Mirabegron stimulates nitric oxide production in myometrial microvascular endothelial cells, and the relaxation of uterine tissue in vitro is partially blocked by the addition of the endothelial nitric oxide synthase blocker Nω-Nitro-L-arginine. Recent data suggest that both endothelial and smooth muscle cells respond to β3 stimulation and contribute to relaxation through disparate signaling pathways. The repurposing of approved medications such as mirabegron (Mybetriq™) tested in human myometrium as uterine tocolytics can advance the prevention of preterm birth.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Myometrium; Tocolytic Agents; Premature Birth; Nitric Oxide; Endothelial Cells; Obstetric Labor, Premature; Cyclic AMP-Dependent Protein Kinases; Receptors, Adrenergic
PubMed: 37371585
DOI: 10.3390/biom13061005 -
Molecules (Basel, Switzerland) Dec 2023Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol...
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC > 100,000 nM, IC = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol. These compounds could be used to discover novel specific BChE inhibitors for the treatment of Alzheimer's disease.
Topics: Humans; Rivastigmine; Butyrylcholinesterase; Alzheimer Disease; Cholinesterase Inhibitors; Pain; Terbutaline
PubMed: 38202655
DOI: 10.3390/molecules29010072 -
Internal Medicine (Tokyo, Japan) Jul 2023A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days... (Review)
Review
A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days after receiving a second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, 1 year after the third episode. After fluid therapy and albumin administration, we initiated terbutaline and theophylline prophylaxis for SCLS. A literature review revealed that SCLS attacks often occur 1-2 days after the second COVID-19 vaccination. Patients with a history of SCLS should avoid COVID-19 vaccination and be carefully monitored for 1-2 days if they receive the vaccine.
Topics: Humans; Male; BNT162 Vaccine; Capillary Leak Syndrome; COVID-19; COVID-19 Vaccines; Terbutaline
PubMed: 37081683
DOI: 10.2169/internalmedicine.1682-23 -
World Journal of Clinical Cases Dec 2023Bronchiolitis is a common lower respiratory tract infection in infants and young children. Severe cases may be accompanied by obvious dyspnea and oxygen saturation...
BACKGROUND
Bronchiolitis is a common lower respiratory tract infection in infants and young children. Severe cases may be accompanied by obvious dyspnea and oxygen saturation decline.
AIM
To summarize the clinical features, standard diagnosis, and treatment of bronchiolitis.
METHODS
This is a retrospective analysis of 114 pediatric patients (74 males, 40 females) who were first diagnosed as having bronchioles at the Department of Pediatrics of Tongling Maternal and Child Health Hospital from January 2019 to December 2019. The clinical features, imaging features, treatment, and other clinical data were recorded and analyzed.
RESULTS
The age of onset of the disease was mainly from 1 mo to 6 mo (75.4%), and the time to hospital visit was mostly from the 2 day to the 4 day of the course of the disease (75.4%). Lung imaging examination showed increase in lung texture, fuzzy (93.8%). The main treatment was atomization therapy: Budesonide combined with terbutaline (45.6%) and budesonide combined with salbutamol (38.5%). The average hospitalization time was 7.1 ± 2.4 d, and the overall cure rate was 94.7%. In patients without bacterial infection, the use of antibiotics significantly prolonged the length of hospital stay (7.8 ± 2.5 d 5.7 ± 1.8 d) and improved the cure rate (98.3% 87.9%, < 0.05).
CONCLUSION
Infants with bronchiolitis are mainly male and tend to have a good prognosis. However, the unneeded use of antibiotics may prolong the length of hospital stay significantly, which imposes the burden both on the patients and hospital system.
PubMed: 38130614
DOI: 10.12998/wjcc.v11.i35.8284 -
Brazilian Journal of Anesthesiology... 2024Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during... (Comparative Study)
Comparative Study
BACKGROUND
Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as β2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair.
METHODS
Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery.
RESULTS
Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL vs. 13.06 ± 6.35 mg.dL, for atosiban, p = 0.001) levels.
CONCLUSIONS
Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair.
Topics: Humans; Retrospective Studies; Terbutaline; Female; Meningomyelocele; Adult; Tocolytic Agents; Pregnancy; Vasotocin; Cohort Studies; Blood Gas Analysis
PubMed: 38521500
DOI: 10.1016/j.bjane.2024.844495 -
RSC Advances Dec 2023The objective of this study was to establish a novel method for the detection of lean meat powder (salbutamol sulfate and terbutaline sulfate) residues in commercially...
The objective of this study was to establish a novel method for the detection of lean meat powder (salbutamol sulfate and terbutaline sulfate) residues in commercially available pig liver based on diazo coupling reaction by combining thin layer chromatography (TLC) with surface-enhanced resonance Raman scattering (SERRS). TLC was used to separate samples; after determining the spots of each component, diazo coupling reaction was carried out on the spots in situ to generate azo compounds, and then the spots of azo compounds mixed with silver sol on the TLC plate were qualitatively detected by SERRS. The limit of detection (LOD) of salbutamol sulfate was as low as 0.14 μg kg, and that of terbutaline sulfate was as low as 0.04 μg kg. The influence of the sample matrix in TLC-SERRS detection of salbutamol sulfate and terbutaline sulfate was investigated by experiment on a simulated positive sample, and salbutamol sulfate and terbutaline sulfate in commercially available pig liver were detected. Compared with the reported method (HPLC-MS/MS), this method has the advantages of strong specificity, high sensitivity, rapidity and low cost. It provides a new reference method for establishing and perfecting the safety system of veterinary drug residues.
PubMed: 38090098
DOI: 10.1039/d3ra07202a -
Frontiers in Bioscience (Landmark... Jul 2023Early identification of sepsis improves the survival rate; however, it is one of the most challenging tasks for physicians, especially since symptoms are easily confused...
BACKGROUND
Early identification of sepsis improves the survival rate; however, it is one of the most challenging tasks for physicians, especially since symptoms are easily confused with those of systemic inflammatory response syndrome (SIRS). Our aim was to explore biomarkers for early identification of sepsis that would aid in its differential diagnosis.
METHODS
Eight patients with SIRS, eight with sepsis, and eight healthy controls were included in this study. Metabolites were screened using gas chromatography-mass spectrometry (GC-MS). Metabolism profiles were analyzed using the untargeted database of GC-MS from Lumingbio (LUG) database, and metabolic pathways were enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The S-plot was used to screen the potential biomarkers distinguishing between patients with SIRS, sepsis, and healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate potential biomarkers between SIRS and sepsis patients. Correlation analysis was used to measure the degree of correlation between differential metabolites. Correlation analysis between 2-deoxy-d-erythro-pentofuranose-5-phosphate and clinical indicators was performed.
RESULTS
There were 51 metabolites that were distributed in the SIRS group, and they were enriched with 18 metabolic pathways compared with healthy controls. Moreover, 63 metabolites in the sepsis group were significantly distinguishable compared to the healthy controls, and were associated with 21 metabolic pathways. Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine were found to be candidate biomarkers for distinguishing between SIRS, sepsis, and healthy controls using the S-plot model. Only four differential metabolites, including 2-deoxy-d-erythro-pentofuranose-5-phosphate, terbutaline, allantoic acid, and homovanillic acid (HVA), were enriched in the dopaminergic synapse and tyrosine metabolism pathways when sepsis patients were compared with SIRS patients. The Area Under Curve (AUC) of 2-deoxy-d-erythro-pentofuranose-5-phosphate was 0.9297, indicating a strong diagnostic ability for sepsis. A significant negative correlation was identified between 2-deoxy-d-erythro-pentofuranose-5-phosphate and lactate (r = -0.8756, = 0.0044).
CONCLUSIONS
Methyl 3-o-acetyl-d-galactopyranoside and N-acetylputrescine may be used as candidate biomarkers to distinguish SIRS and sepsis patients from healthy controls using GC-MS. 2-deoxy-d-erythro-pentofuranose-5-phosphate may be the candidate biomarker to distinguish sepsis from SIRS. Our study explored candidate biomarkers for the early identification of sepsis, which is vital for improving its prognosis.
PubMed: 37525905
DOI: 10.31083/j.fbl2807145 -
Heliyon Dec 2023Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with β-mimetic terbutaline in an isolated organ bath and to perform in...
AIMS
Our aims were to investigate the uterus relaxant effect of sildenafil alone and co-administered with β-mimetic terbutaline in an isolated organ bath and to perform in vivo smooth muscle electromyographic studies in pregnant rats. The modifications in uterine cAMP/cGMP levels were also detected.
MAIN METHODS
Contractions of non-pregnant and 5/15/18/20/22-day pregnant uterine rings were measured in an isolated organ bath system in the presence of sildenafil alone or with terbutaline. The uterine levels of cAMP and cGMP were determined by commercial ELISA assays. The in vivo efficacy of the combination was measured by smooth muscle electromyography.
KEY FINDINGS
Sildenafil reduced uterine contractions in vitro and in vivo; additionally, terbutaline significantly increased the uterorelaxant effect of sildenafil in the lower concentration or dose ranges. Terbutaline enhanced the cGMP level increasing effect of sildenafil.
SIGNIFICANCE
The co-administration of sildenafil and terbutaline could be a promising tocolytic combination to reduce maternal and foetal adverse events and increase efficacy.
PubMed: 38046168
DOI: 10.1016/j.heliyon.2023.e22488