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PloS One 2024Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to...
Coronary microvascular dysfunction (CMD) is a critical pathogenesis of cardiovascular diseases. Lower endothelial nitric oxide synthase (eNOS) phosphorylation leads to reduced endothelium-derived relaxing factor nitric oxide (NO) generation, causing and accelerating CMD. Endoplasmic reticulum stress (ER stress) has been shown to reduce NO production in umbilical vein endothelial cells. Oxidized low-density lipoprotein (ox-LDL) damages endothelial cell function. However, the relationship between ox-LDL and coronary microcirculation has yet to be assessed. Short-chain fatty acid (SCFA), a fermentation product of the gut microbiome, could improve endothelial-dependent vasodilation in human adipose arterioles, but the effect of SCFA on coronary microcirculation is unclear. In this study, we found ox-LDL stimulated expression of ER chaperone GRP78. Further, we activated downstream PERK/eIF2a, IRE1/JNK, and ATF6 signaling pathways, decreasing eNOS phosphorylation and NO production in human cardiac microvascular endothelial. Furthermore, SCFA-propionate can inhibit ox-LDL-induced eNOS phosphorylation reduction and raise NO production; the mechanism is related to the inhibition of ER stress and downstream signaling pathways PERK/eIF2a, IRE1/JNK, and ATF6. In summary, we demonstrate that ox-LDL induced CMD by activating ER stress, propionate can effectively counteract the adverse effects of ox-LDL and protect coronary microcirculation function via inhibiting ER stress.
Topics: Humans; Endoplasmic Reticulum Stress; Lipoproteins, LDL; Nitric Oxide Synthase Type III; Endoplasmic Reticulum Chaperone BiP; Propionates; Nitric Oxide; Signal Transduction; Phosphorylation; Endothelial Cells; Coronary Vessels; Fatty Acids, Volatile; eIF-2 Kinase; Activating Transcription Factor 6; Microcirculation; Heat-Shock Proteins
PubMed: 38814895
DOI: 10.1371/journal.pone.0304551 -
International Journal of Chronic... 2024Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the... (Observational Study)
Observational Study
PURPOSE
Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data.
PATIENTS AND METHODS
Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori).
RESULTS
Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period.
CONCLUSION
The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Primary Health Care; Treatment Outcome; Bronchodilator Agents; Middle Aged; Time Factors; Adrenergic beta-2 Receptor Agonists; United Kingdom; Glycopyrrolate; Databases, Factual; Budesonide, Formoterol Fumarate Drug Combination; Lung; Muscarinic Antagonists; Drug Combinations; Retrospective Studies; Glucocorticoids; Aged, 80 and over
PubMed: 38813078
DOI: 10.2147/COPD.S452624 -
Turkish Journal of Medical Sciences 2024We aimed to search the relationship between the preoperative PVI (pleth variability index) and intraoperative respiratory parameters to reveal whether PVI can be used as...
BACKGROUND/AIM
We aimed to search the relationship between the preoperative PVI (pleth variability index) and intraoperative respiratory parameters to reveal whether PVI can be used as a prediction tool in bariatric surgery.
MATERIALS AND METHODS
Forty patients undergoing bariatric surgery were included. Noninvasive pleth variability index measured via finger probe before induction of general anesthesia. Following intubation each patient was ventilated in controlled mode. Intraoperative blood pressure, peak airway pressure, end-tidal CO, SpO, PEEP, and FiO were recorded every 5 min for the first 10 min and then every 10 min until extubation. Steroid and bronchodilator requirements were recorded.
RESULTS
The systolic pressure-PVI, oxygen saturation-PVI relationship was statistically significant (p = 0.03, p = 0.013). A relationship was found between pleth variability index and peak airway pressure (p = 0.002). No correlation was detected between end-tidal CO and pleth variability index. The relationship between steroid, bronchodilator use, and PVI was significant (p = 0.05, p = 0.01). A positive correlation between PEEP and PVI was detected at varying time points. A positive correlation was found between FiO-PVI.
CONCLUSION
A relationship was found between PVI and intraoperative peak airway pressures, oxygen saturation, PEEP, bronchodilatator, and steroid usage. This result may be inspiring to conduct larger studies addressing the issue of predicting intraoperative respiratory problems in bariatric surgeries.
Topics: Humans; Bariatric Surgery; Female; Male; Adult; Middle Aged; Predictive Value of Tests; Intraoperative Complications; Plethysmography
PubMed: 38812625
DOI: 10.55730/1300-0144.5771 -
Frontiers in Bioscience (Landmark... May 2024Nitric oxide synthases (NOS) are essential regulators of vascular function, and their role in ocular blood vessels is of paramount importance for maintaining ocular... (Review)
Review
Nitric oxide synthases (NOS) are essential regulators of vascular function, and their role in ocular blood vessels is of paramount importance for maintaining ocular homeostasis. Three isoforms of NOS-endothelial (eNOS), neuronal (nNOS), and inducible (iNOS)-contribute to nitric oxide production in ocular tissues, exerting multifaceted effects on vascular tone, blood flow, and overall ocular homeostasis. Endothelial NOS, primarily located in endothelial cells, is pivotal for mediating vasodilation and regulating blood flow. Neuronal NOS, abundantly found in nerve terminals, contributes to neurotransmitter release and vascular tone modulation in the ocular microvasculature. Inducible NOS, expressed under inflammatory conditions, plays a role in response to pathological stimuli. Understanding the distinctive contributions of these NOS isoforms in retinal blood vessels is vital to unravel the mechanisms underlying various ocular diseases, such diabetic retinopathy. This article delves into the unique contributions of NOS isoforms within the complex vascular network of the retina, elucidating their significance as potential therapeutic targets for addressing pathological conditions.
Topics: Humans; Retinal Vessels; Animals; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitric Oxide Synthase Type I; Nitric Oxide; Diabetic Retinopathy; Nitric Oxide Synthase Type II
PubMed: 38812321
DOI: 10.31083/j.fbl2905190 -
Revista Paulista de Pediatria : Orgao... 2024To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis.
OBJECTIVE
To investigate the effect of bronchodilator on the respiratory mechanics and pulmonary function of children and adolescents with cystic fibrosis.
METHODS
Cross-sectional study on clinically stable children and adolescents with cystic fibrosis aged from six to 15 years. Participants underwent impulse oscillometry and spirometry evaluations before and 15 minutes after bronchodilator inhalation. The Kolmogorov-Smirnov test was applied to verify the sample distribution, and the Student's t-test and Wilcoxon test were used to compare the data before and after bronchodilator inhalation.
RESULTS
The study included 54 individuals with a mean age of 9.7±2.8 years. The analysis showed a statistically significant improvement in impulse oscillometry and spirometry parameters after bronchodilator inhalation. However, according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommendations (2020 and 2021), this improvement was not sufficient to classify it as a bronchodilator response.
CONCLUSIONS
The use of bronchodilator medication improved respiratory mechanics and pulmonary function parameters of children and adolescents with cystic fibrosis; however, most patients did not show bronchodilator response according to ATS/ERS recommendations.
Topics: Humans; Cystic Fibrosis; Child; Adolescent; Cross-Sectional Studies; Spirometry; Female; Male; Oscillometry; Bronchodilator Agents; Respiratory Mechanics; Respiratory Function Tests
PubMed: 38808869
DOI: 10.1590/1984-0462/2024/42/2023162 -
World Journal of Clinical Cases May 2024We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory...
BACKGROUND
We described a case of a patient with a meningioma in the posterior fossa presenting atypically with an isolated unilateral vocal cord palsy causing severe respiratory distress. This is of interest as the patient had no other symptomatology, especially given the size of the mass, which would typically cause a pressure effect leading to neurological and auditory symptoms.
CASE SUMMARY
This case report described a 48-year-old male who was married with two children and employed as a car guard. He had a medical history of asthma for the past 10 years controlled with an as-needed beta 2 agonist metered dose inhaler. He initially presented to our facility with severe respiratory distress. He reported a 1-wk history of shortness of breath and wheezing that was not relieved by his bronchodilator. He had no constitutional symptoms or impairment of hearing. On clinical examination, the patient's chest was "silent." Our initial assessment was status asthmaticus with type 2 respiratory failure, based on the history of asthma, a "silent chest," and the arterial blood gas results.
CONCLUSION
A posterior fossa meningioma of such a large size and with extensive infiltration rarely presents with an isolated unilateral vocal cord palsy. The patient's chief presenting feature was severe respiratory distress, which combined with his background medical history of asthma, was misleading. Clinicians should thus consider meningioma as a differential diagnosis for a unilateral vocal cord palsy even without audiology involvement.
PubMed: 38808343
DOI: 10.12998/wjcc.v12.i13.2281 -
Plant Cell Reports May 2024Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide,...
Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide, hydrogen sulfide, and antioxidant systems for enhanced drought tolerance. While nitric oxide (NO), a signalling molecule, enhances plant tolerance to abiotic stresses, its precise contribution to improving tomato tolerance to drought stress (DS) through modulating oxide-nitrosative processes is not yet fully understood. We aimed to examine the interaction of NO and nitrosative signaling, revealing how sodium nitroprusside (SNP) could mitigate the effects of DS on tomatoes. DS-seedlings endured 12% polyethylene glycol (PEG) in a 10% nutrient solution (NS) for 2 days, then transitioned to half-strength NS for 10 days alongside control plants. DS reduced total plant dry weight, chlorophyll a and b, Fv/Fm, leaf water potential (Ψ), and relative water content, but improved hydrogen peroxide (HO), proline, and NO content. The SNP reduced the DS-induced HO generation by reducing thiol (-SH) and the carbonyl (-CO) groups. SNP increased not only NO but also the activity of L-cysteine desulfhydrase (L-DES), leading to the generation of HS. Decreases in S-nitrosoglutathione reductase (GSNOR) and NADPH oxidase (NOX) suggest a potential regulatory mechanism in which -nitrosylation [formation of S-nitrosothiol (SNO)] may influence protein function and signaling pathways during DS. Moreover, SNP improved ascorbate (AsA) and glutathione (GSH) and reduced oxidized glutathione (GSSG) levels in tomato plants under drought. Furthermore, the interaction of NO and HS, mediated by L-DES activity, may serve as a vital cross-talk mechanism impacting plant responses to DS. Understanding these signaling interactions is crucial for developing innovative drought-tolerance strategies in crops.
Topics: Nitroprusside; Solanum lycopersicum; Hydrogen Peroxide; Droughts; Nitric Oxide; Glutathione; Antioxidants; Oxidation-Reduction; Oxidative Stress; Stress, Physiological; Seedlings; Plant Leaves; Nitrosation; Chlorophyll
PubMed: 38806834
DOI: 10.1007/s00299-024-03238-3 -
Farmacia Hospitalaria : Organo Oficial... May 2024To identify the administration characteristics and connection methods of bronchodilators by pressurized inhalers to the ventilatory circuit of patients under invasive... (Review)
Review
OBJECTIVE
To identify the administration characteristics and connection methods of bronchodilators by pressurized inhalers to the ventilatory circuit of patients under invasive mechanical ventilation.
METHODS
A scope review was conducted following the PRISMA for Scoping Review, using the PubMed, Embase Elsevier, Cochrane Library, and Lilacs databases without language restrictions, up to July 2023. Eligible sources included reviews and consensuses (based on clinical studies), experimental and observational studies involving adult patients admitted to the intensive care unit and undergoing invasive mechanical ventilation, regardless of the underlying condition, who used bronchodilator drugs contained in pressurized inhalers. Information regarding inhalation technique, pressurized inhalers connection mode to the circuit, and patient care were collected by 2 researchers independently, with discrepancies resolved by a third reviewer. Studies involving bronchodilators combined with other pharmacological classes in the same device, as well as reviews containing preclinical studies, were excluded.
RESULTS
In total, 23 publications were included, comprising 19 clinical trials and 4 non-randomized experimental studies. Salbutamol (albuterol) was the bronchodilator of study in the majority of the articles (n=18), and the spacer device was the most commonly used to connect the pressurized inhaler to the circuit (n=15), followed by an in-line adapter (n=3), and a direct-acting device without chamber (n=3). Concerning the pressurized inhaler placement in the circuit, 18 studies positioned it in the inspiratory limb, and 19 studies synchronized the jet actuation with the start of the inspiratory phase. Agitation of the pressurized inhaler before each actuation, waiting time between actuations, airway suction before administration, and semi-recumbent patient positioning were the most commonly described measures across the studies.
CONCLUSIONS
This review provided insights into the aspects related to inhalation technique in mechanically ventilated patients, as well as the most prevalent findings and the existing gaps in knowledge regarding bronchodilator administration in this context. The evidence indicates the need for further research on this subject.
PubMed: 38806364
DOI: 10.1016/j.farma.2024.03.012 -
Therapeutic Advances in Respiratory... 2024Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is... (Observational Study)
Observational Study
BACKGROUND
Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear.
OBJECTIVES
To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1).
DESIGN
This was a single-center, retrospective, observational cohort study.
METHODS
We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)].
RESULTS
Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 ( = 2, 33.3% and = 4, 44.4%, respectively).
CONCLUSION
BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.
Topics: Humans; Male; Retrospective Studies; Female; Bronchial Thermoplasty; Asthma; Middle Aged; Forced Expiratory Volume; Treatment Outcome; Aged; Severity of Illness Index; Lung; Adult; Recovery of Function; Time Factors; Quality of Life
PubMed: 38804685
DOI: 10.1177/17534666241254980 -
International Journal of Chronic... 2024Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male... (Observational Study)
Observational Study Comparative Study
BACKGROUND
Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan.
PATIENTS AND METHODS
We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study.
RESULTS
Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p<0.01). Although there was no difference in age or forced expiratory volume in one second (FEV) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥2: p<0.01; number of exacerbations≥2: p=0.011). The mean forced vital capacity and FEV values in females were lower than those in males (p<0.0001 and p<0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p<0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males.
CONCLUSION
The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV, respiratory failure, and asthma-like conditions.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Female; Cross-Sectional Studies; Japan; Male; Aged; Forced Expiratory Volume; Middle Aged; Sex Factors; Lung; Vital Capacity; Prevalence; Healthcare Disparities; Risk Factors; Oxygen Inhalation Therapy; Disease Progression; Adrenal Cortex Hormones; Treatment Outcome; Smoking; Health Status Disparities; Aged, 80 and over; Bronchodilator Agents
PubMed: 38803411
DOI: 10.2147/COPD.S455397