Search Results (131)

Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article

Background: COPD is a heterogenous disease of the respiratory tract caused by diverse genetic factors along with environmental and lifestyle-related effects such as industrial dust inhalation and, most frequently, cigarette smoking. These factors lead to airflow obstruction and chronic respiratory symptoms. Additionally, the increased risk of infections exacerbates airway inflammation in COPD patients. As a consequence of the complex pathomechanisms and difficulty in treatment, COPD is among the leading causes of mortality both in the western countries and in the developing world. Results: The management of COPD is still a challenge for the clinicians; however, alternative interventions such as smoking cessation and lifestyle changes from a sedentary life to moderate physical activity with special attention to the diet may ameliorate patients’ health. Here, we reviewed the effects of different dietary components and supplements on the conditions of COPD. Conclusions: COPD patients are continuously exposed to heavy metals, which are commonly present in cigarette smoke and polluted air. Meanwhile, they often experience significant nutrient deficiencies, which affect the detoxification of these toxic metals. This in turn can further disrupt nutritional balance by interfering with the absorption, metabolism, and utilization of essential micronutrients. Therefore, awareness and deliberate efforts should be made to check levels of micronutrients, with special attention to ensuring adequate levels of antioxidants, vitamin D, vitamin K2, magnesium, and iron, as these may be particularly important in reducing the risk of COPD development and limiting disease severity. Full article

Background and Clinical Significance: In multiple sclerosis (MS), there are many therapeutic options, but most of the available drugs can cause drug-induced liver injury (DILI) after the first infusions. A wide group of other drugs may induce liver injury, from simple anti-pyretic medication like Acetaminophen to various dietary herb supplements like Ashwagandha. Case Presentation: A 39-year-old female patient, diagnosed with MS, has been previously treated with Glatiramer Acetate and interferon-beta, and is currently undergoing immunomodulatory treatment with natalizumab (infusion no. 81). She had a recent history of an airway infection for which she took 4–5 capsules of Acetaminophen per day for 7 days, along with the consumption of dietary supplement with Ashwagandha herb. She presented with jaundice, pruritus, and lower limb ecchymoses. The laboratory results revealed higher aminotransferase levels, total bilirubin, and alkaline phosphatase. The screening for autoimmune and infectious hepatitis was negative. The scenario of toxic hepatitis induced by recently used drugs (Ashwagandha dietary herb supplement and Acetaminophen) was adequate to start therapy with oral cortisone. The clinical and laboratory results gradually improved, with normal levels of liver enzymes and bilirubin, with no further increase after the discontinuation of corticosteroid therapy and dietary herb supplements. Conclusions: This case highlights the challenges in determining the multiple etiologies and managing acute liver injury in an MS patient on natalizumab, an immunomodulatory drug that can induce liver injury after the first infusions, especially in the context of recent ingestion of hepatotoxic drugs. Full article

Background and Objectives: The primary objective of this study was to identify factors predictive of laryngeal involvement in patients with Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). The secondary objective was to observe the effect of laryngeal involvement upon short-term patient prognosis, including intensive care unit (ICU) stay and intubation rates. We present the largest cohort of patients examined for upper aerodigestive manifestations of SJS/TEN. Materials and Methods: We performed a retrospective observational analytic study of patients at a state-wide Australian Burns referral center between January 2013 to December 2022. Inclusion criteria were adult patients who underwent flexible nasendoscopy (FNE) with biopsy-proven SJS/TEN. Data collected from medical records included patient factors, aerodigestive symptoms, bedside examination, FNE findings, TEN-specific severity-of-illness score (SCORTEN) on admission, and patient outcomes such as intubation and ICU admission. Results: Fifty-four patients with biopsy-proven SJS/TEN underwent FNE, with 17 (31.5%) identified to have laryngeal involvement. Laryngeal involvement was not significantly associated with intubation, ICU stay, or mortality (p > 0.05). The presence of either aerodigestive symptoms or oral cavity involvement was highly sensitive (94.1%, 95% CI 73.0–99.7%) for laryngeal involvement. Conclusions: We did not find laryngeal involvement in SJS/TEN to significantly impact short-term outcomes, including intubation or mortality. FNE is the gold standard of upper aerodigestive assessment. Simple clinical evaluation of the oral cavity and a history of aerodigestive symptoms also provided a sensitive predictor of the laryngeal complications of SJS/TEN. Full article

The relationship between indoor air quality and public health remains under-researched. WellHome is a transdisciplinary community-based study that will engage with residents to co-design feasible and acceptable research to quantify air pollution exposure in 100 homes in West London and examine its potential to exacerbate asthma symptoms in children. Sampling strategies such as using air quality monitors and passive samplers placed in kitchens, children’s bedrooms, and living rooms, will be developed in collaboration with local ambassadors and participating households to measure multiple physical, chemical, microplastic, and biological contaminants. This will provide a comprehensive understanding of indoor air quality across the city’s socio-economic gradient. Other data collected will include housing types and tenure, ventilation practices, occupant behaviours, time-activity, and airway symptoms. Epidemiological analysis will examine air pollution exposure impacts on children’s respiratory health. The particulate mixture’s relative hazard will be evaluated in toxicity studies based on source profiles and activity patterns of participants, focusing on asthma exacerbation related pathways. The study’s findings will be communicated to participants through co-designed reports and inform evidence-based recommendations for reducing indoor air pollution in London and urban areas worldwide. By raising awareness and providing actionable insights, WellHome seeks to contribute to global efforts to improve the health and well-being of vulnerable communities. Full article

Background/Objectives: Lauric acid (LA), a medium-chain fatty acid, is a promising drug for asthma treatment. This study evaluated the toxicity of repeated doses and the effect of LA on pulmonary ventilation and tracheal reactivity in asthmatic Wistar rats and identified possible molecular targets of LA action in silico. Methods: The rats were divided into control (CG) and LA-treated groups at 100 mg/kg (AL100G) for toxicity analysis. Pulmonary ventilation and tracheal reactivity were assessed in the control (CG), asthmatic (AG), asthmatic treated with LA at 25, 50, or 100 mg/kg (AAL25G, AAL50G, and AAL100G), and dexamethasone-treated groups (ADEXAG). Results: The results showed that LA at a dose of 100 mg/kg did not cause death or toxicity. A pulmonary ventilation analysis indicated that AG had reduced minute volume, which was prevented in AAL25G. LA at all doses prevented carbachol-induced tracheal hyper-responsiveness and reduced the relaxing effect of aminophylline, as observed in AG. An in silico analysis revealed that LA had a good affinity for nine proteins (β₂-adrenergic receptor, Ca_V, BK_Ca, K_ATP, adenylyl cyclase, PKG, eNOS, iNOS, and COX-2). Conclusions: LA at 100 mg/kg has low toxicity, prevents hyper-responsiveness in an asthma model in rats, and acts as a multitarget compound with a good affinity for proteins related to airway hyper-responsiveness. Full article

Methanol is a widely used industrial and household alcohol that poses significant health risks upon exposure. Despite its extensive use, methanol poisoning remains a critical public health concern globally, often resulting from accidental or intentional ingestion and outbreaks linked to contaminated beverages. Methanol toxicity stems from its metabolic conversion to formaldehyde and formic acid, leading to severe metabolic acidosis and multiorgan damage, including profound CNS effects and visual impairments. Epidemiological data underscore the widespread impact of methanol poisoning, with alarming case fatality rates reported in various countries. Comprehensive prevention and effective management strategies are urgently needed to address the significant morbidity and mortality associated with methanol poisoning. The clinical manifestations of methanol toxicity vary between adult and pediatric populations and between acute and chronic exposure. Adults typically present with gastrointestinal and neurological symptoms, whereas pediatric patients often exhibit more severe outcomes due to differences in metabolism and body weight. The diagnosis of methanol poisoning involves a combination of clinical evaluation, laboratory testing, and advanced diagnostic techniques. The identification of metabolic acidosis, elevated anion and osmolal gaps, and confirmation through methanol and formate levels are critical for accurate diagnosis. Timely intervention is crucial, and the management of methanol poisoning includes securing the airway, breathing, and circulation; addressing metabolic acidosis with sodium bicarbonate; administering antidotes such as fomepizole or ethanol; and administering hemodialysis, which plays a pivotal role in eliminating methanol and its toxic metabolites, especially in severe cases. The complexity of methanol poisoning necessitates a comprehensive approach encompassing early recognition, prompt intervention, and coordinated care among healthcare providers. Increased awareness, effective prevention strategies, and timely treatment protocols are essential to mitigate severe health consequences and improve patient survival and recovery. Full article

Background: At present, there is a paucity of data in the literature pertaining to the impact of radiotherapy (RT) on the success of tracheal intubation in patients with nasopharyngeal cancer (NPC). The aim of this study is to investigate the frequency of difficult tracheal intubation in patients with NPC following RT. Methods: Patients with NPC who underwent RT followed by surgery between 2012 and April 2024 at the University Hospital Heidelberg were retrospectively analyzed. Results: Twenty-three patients, predominantly males (73.9%) with a mean age of 52.9 years, were enrolled. Overall, 65.2% of the patients had an American Society of Anesthesiologists (ASA) class of III. The mean total laryngeal dose was 53.5 Gy for the main and boost plan, and the maximum total laryngeal dose was 66.61 Gy. Direct laryngoscopy was performed in 69.6% of cases, followed by 26.1% videolaryngoscopy, and 4.2% required fiberoptic intubation. In total, 47.8% of the patients had a Cormack/Lehane grade of I, followed by 43.5% with grade II and 8.7% with grade III. Overall, 87% of patients were successfully intubated on the first attempt. Conclusions: It has been demonstrated by previous studies that RT has the potential to enhance complications and difficulties encountered during airway management. While the results must be interpreted with caution, our study provides no evidence of severe impairment in advanced airway management in patients with nasopharyngeal cancer who have undergone radiotherapy. Full article

Copper oxide nanoparticles (CuO NPs) have seen increasing use across various industries, raising significant concerns about their potential toxicity and the exacerbation of pre-existing conditions like asthma. Asthma, a chronic inflammatory condition of the airways, can be triggered or worsened by environmental factors such as allergens, air pollutants, and chemicals, including nanoparticles. This study aimed to investigate the pulmonary toxicity induced by CuO NPs and their impact on asthma, with a particular focus on the role of thioredoxin-interacting protein (TXNIP). Using an ovalbumin (OVA)-induced asthma model, we found that CuO NP exposure led to significant increases in inflammatory cell infiltration, cytokine production, airway hyperresponsiveness, OVA-specific immunoglobulin (Ig)E levels, and mucus production. These pathological changes were closely associated with the upregulation of TXNIP-related signaling pathways, including phosphorylated apoptosis signal-regulating kinase (p-ASK)1, the Bax/Bcl-2 ratio, and cleaved caspase-3 activation. Complementary in vitro experiments using NCI-H292 respiratory epithelial cells showed that CuO NP treatment enhanced TXNIP signaling and increased mRNA expression and the production of inflammatory cytokines. Notably, TXNIP knockdown significantly attenuated these CuO NP-induced effects. In conclusion, our findings suggest that CuO NP exposure not only induces pulmonary toxicity but also exacerbates asthma, primarily through the activation of the TXNIP signaling pathway. Full article

Asian sand dust (ASD), generated from the deserts of China and Mongolia, affects Korea and Japan during spring and autumn, causing harmful effects on various bio-organs, including the respiratory system, due to its irritants such as fine dust, chemicals, and toxic materials. Here, we investigated the therapeutic effects of silibinin against ASD-induced airway inflammation using mouse macrophage-like cell line RAW264.7 and a murine model. ASD was intranasally administered to mice three times a week and silibinin was administered for 6 days by oral gavage. In ASD-stimulated RAW264.7 cells, silibinin treatment decreased tumor necrosis factor-α production and reduced the expression of p-p65NF-κB, p-p38, and cyclooxygenase (COX)-2, while increasing heme oxygenase (HO)-1 expression. In ASD-exposed mice, silibinin administration reduced inflammatory cell count and cytokines in bronchoalveolar lavage fluid and decreased inflammatory cell infiltration in lung tissue. Additionally, silibinin lowered oxidative stress, as evidenced by decreased 8-hydroxy-2’-deoxyguanosin (8-OHdG) expression and increased HO-1 expression. The expression of inflammatory-related proteins, including p-p65NF-κB, COX-2, and p-p38, was markedly reduced by silibinin administration. Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation. Full article

Mycotoxins have the potential to increase the risk of airway or intestinal infection due to their effects on epithelial integrity and function. The bacterium Streptococcus suis (S. suis) is often carried in pigs and can cause outbreaks of invasive disease, leading to sepsis and meningitis in postweaning piglets. In this study, we tested the effect of two Fusarium mycotoxins (deoxynivalenol (DON) and T-2) on the integrity of the intestinal epithelium and their interaction with S. suis. Porcine ileal organoids were exposed to DON and T-2 individually or in combination and co-cultured with or without S. suis. Both DON and T-2 were toxic for ileal organoid monolayers at a concentration of 1 µM but not S. suis, even at a higher concentration of 4 µM. To mimic sub-clinical exposures on farms, DON was tested at a concentration of 0.1 µM and T-2 at a concentration of 0.01 µM. The mycotoxins alone did not affect cell permeability, but in combination with S. suis there was an increase in epithelial permeability. Furthermore, DON and T-2 together decreased the transepithelial electrical resistance and increased bacterial translocation. Full article

Hypertensive disorders of pregnancy affect approximately 5% to 10% of pregnant women. Eclampsia is a serious hypertensive disorder that is primarily characterized by the onset of grand mal seizure activity in the absence of other causative conditions. While eclampsia is diagnosed clinically, laboratory tests are recommended to assess for complications. Treatment strategies for eclampsia focus on controlling seizures and managing hypertension. Acute care during a seizure is critical because of the need for immediate medical interventions, including the management of the airway, breathing, and circulation, as well as ensuring the safety of the patient during convulsions. Magnesium sulfate is the preferred anticonvulsant drug. Care must be taken during administration to prevent magnesium toxicity. Antihypertensive drugs used in eclampsia include labetalol, hydralazine and nifedipine. The definitive treatment of eclampsia is delivery. Close monitoring of both mother and fetus is important to identify any indications for delivery. The timing and mode of delivery depend on obstetric indications, the severity of eclampsia, the gestational age of the fetus, and the overall clinical status of the patient. Neuraxial anesthesia is the anesthesia of choice for conscious, seizure-free, and with stable vital signs women undergoing cesarean section. Full article

Fine inhalable particulate matter (PM) triggers an inflammatory response in the airways and activates mononuclear cells, mediators of tissue homeostasis, and tumour-promoting inflammation. We have assessed ex vivo responses of human monocytes and monocyte-derived macrophages to standardised air pollutants: carbon black, urban dust, and nanoparticulate carbon black, focusing on their pro-inflammatory and DNA-damaging properties. None of the PM (100 μg/mL/24 h) was significantly toxic to the cells, aside from inducing oxidative stress, fractional DNA damage, and inhibiting phagocytosis. TNFα was only slightly increased. PM nanoparticles increase the expression and activate DNA-damage–related histone H2A.X as well as pro-inflammatory NF-κB. We have shown that the urban dust stimulates the pathway of DNA damage/repair via the selective post-translational phosphorylation of H2A.X while nanoparticulate carbon black increases inflammation via activation of NF-κB. Moreover, the inflammatory response to lipopolysaccharide was significantly stronger in macrophages pre-exposed to urban dust or nanoparticulate carbon black. Our data show that airborne nanoparticles induce PM-specific, epigenetic alterations in the subsets of cultured mononuclear cells, which may be quantified using binary fluorescence scatterplots. Such changes intercede with inflammatory signalling and highlight important molecular and cell-specific epigenetic mechanisms of tumour-promoting inflammation. Full article

Titanium dioxide nanoparticles (TiO₂NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO₂NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO₂NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO₂NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO₂NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO₂NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO₂NP-induced pulmonary toxicity. Full article

The production of nanoparticles has recently surged due to their varied applications in the biomedical, pharmaceutical, textile, and electronic sectors. However, this rapid increase in nanoparticle manufacturing has raised concerns about environmental pollution, particularly its potential adverse effects on human health. Among the various concerns, inhalation exposure to nanoparticles poses significant risks, especially affecting the respiratory system. Airway epithelial cells play a crucial role as the primary defense against inhaled particulate matter and pathogens. Studies have shown that nanoparticles can disrupt the airway epithelial barrier, triggering inflammatory responses, generating reactive oxygen species, and compromising cell viability. However, our understanding of how different types of nanoparticles specifically impact the airway epithelial barrier remains limited. Both in vitro cell culture and in vivo murine models are commonly utilized to investigate nanoparticle-induced cellular responses and barrier dysfunction. This review discusses the methodologies frequently employed to assess nanoparticle toxicity and barrier disruption. Furthermore, we analyze and compare the distinct effects of various nanoparticle types on the airway epithelial barrier. By elucidating the diverse responses elicited by different nanoparticles, we aim to provide insights that can guide future research endeavors in assessing and mitigating the potential risks associated with nanoparticle exposure. Full article