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Medicine Jun 2024It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study,... (Observational Study)
Observational Study Randomized Controlled Trial
It aims to study the efficacy and safety of low-concentration Atropine combined with orthokeratology (OK) lens in delaying juvenile myopia. This is a prospective study, 172 adolescents aged 8 to 12 years who were admitted to the diopter department of Hengshui People Hospital from April 2021 to May 2022 were selected. According to the equivalent spherical diopter measured at the time of initial diagnosis, myopic patients were randomly divided into low myopia group (group A) and moderate myopia group (group B). At the same time, according to the different treatment methods, the patients were divided into the group wearing frame glasses alone (group c), the group wearing frame glasses with low-concentration Atropine (group d), the group wearing corneal shaping glasses alone at night (group e), and the group wearing corneal shaping glasses at night with low-concentration Atropine (group f). The control effect of myopia development and axial elongation in group f was better than that in groups d and e (P < .05). The effect of controlling myopia development and axial elongation in group f is with P > .05. The probability of postoperative adverse reactions in group f was lower and lower than that in the other groups. Low-concentration atropine combined with OK lens could effectively delay the development of juvenile myopia, and had a high safety. Low-concentration of Atropine would not have a significant impact on the basic tear secretion and tear film stability. Nightwear of OK lens also had no significant impact, but it would significantly reduce the tear film rupture time in the first 3 months, and at the same time, the tear film rupture time would be the same after 6 months as before treatment.
Topics: Humans; Atropine; Child; Myopia; Male; Female; Orthokeratologic Procedures; Prospective Studies; Mydriatics; Treatment Outcome; Ophthalmic Solutions; Contact Lenses
PubMed: 38875374
DOI: 10.1097/MD.0000000000038384 -
Frontiers in Molecular Biosciences 2024The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing...
The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing lipopolysaccharide (LPS)-elevated proinflammatory cytokines in RAW 264.7 murine macrophage cultures which we showed earlier to occur via cholinergic anti-inflammatory pathway (CAP) activation. To this end, we investigated the possible suppressive capacity of varenicline on LPS-regulated cyclooxygenase (COX-1 and COX-2) via α7 nicotinic acetylcholine receptor (α7nAChR) activation using the same model. In order to test anti-inflammatory effectiveness of varenicline, the levels of COX isoforms and products (PGE2, 6-keto PGF1α, a stable analog of PGI2, and TXA2) altered after LPS administration were determined by Enzyme Linked Immunosorbent Assay (ELISA). The antioxidant effects of varenicline were assessed by measuring reductions in reactive oxygen species (ROS) using a f intracellular a. We further investigated the contribution of nAChR subtypes by using non-selective and/or selective α7nAChR antagonists. The results were compared with that of conventional anti-inflammatory medications, such as ibuprofen, celecoxib and dexamethasone. Varenicline significantly reduced LPS-induced COX-1, COX-2 and prostaglandin levels and ROS to an extent similar to that observed with anti-inflammatory agents used. Significant downregulation in LPS-induced COX isoforms and associated decreases in PGE2, 6-keto PGF1α, and TXA2 levels along with reduction in ROS may be partly mediated via varenicline-activated α7nAChRs.
PubMed: 38859932
DOI: 10.3389/fmolb.2024.1392689 -
PloS One 2024This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used...
This study aimed to define real-world prescription patterns in Korea and compare the effectiveness of chronic obstructive pulmonary disease (COPD) medications. We used national claims data provided by the Health Insurance Review and Assessment Service in Korea and examined patients who were first diagnosed with COPD and started treatment between May 1, 2017, and April 30, 2018, with no change in drug regimen. Among 30,784 patients with COPD, long-acting β2 agonist (LABA) combined with long-acting muscarinic antagonist (LAMA) (32.7%), inhaled corticosteroid-LABA (ICS-LABA) (25.6%), LAMA (18.3%), ICS (5.8%), or LABA (4.6%) were prescribed as the first-choice inhalers. The use of LABA-LAMA (hazard ratio [HR], 0.248-0.584), LAMA (HR, 0.320-0.641), ICS-LABA (HR, 0.325-0.643), and xanthine (HR, 0.563-0.828) significantly reduced the total and severe exacerbation rates compared with no use of each medication. However, the use of ICS or LABA individually did not yield such effects. The continued use of LABA-LAMA, LAMA, and ICS-LABA showed a significant effect on exacerbation rate, whereas the long-term use of ICS, LABA, and xanthine did not. Moreover, some high doses of ICS-LABA did not show significant effects. This real-world study revealed that LAMA and/or LABA could be the first choice of therapy, as recommended by recent guidelines. However, ICS, xanthine, and high-dose ICS-LABA are still being prescribed frequently as first-line drugs in Korea.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Male; Female; Retrospective Studies; Aged; Middle Aged; Muscarinic Antagonists; Republic of Korea; Adrenergic beta-2 Receptor Agonists; Administration, Inhalation; Adrenal Cortex Hormones; Practice Patterns, Physicians'; Treatment Outcome; Bronchodilator Agents; Drug Prescriptions; Adult
PubMed: 38857214
DOI: 10.1371/journal.pone.0304362 -
Hepatology Communications Jun 2024Smoking is a risk factor for liver cirrhosis; however, the underlying mechanisms remain largely unexplored. The α7 nicotinic acetylcholine receptor (α7nAChR) has...
BACKGROUND
Smoking is a risk factor for liver cirrhosis; however, the underlying mechanisms remain largely unexplored. The α7 nicotinic acetylcholine receptor (α7nAChR) has recently been detected in nonimmune cells possessing immunoregulatory functions. We aimed to verify whether nicotine promotes liver fibrosis via α7nAChR.
METHODS
We used osmotic pumps to administer nicotine and carbon tetrachloride to induce liver fibrosis in wild-type and α7nAChR-deficient mice. The severity of fibrosis was evaluated using Masson trichrome staining, hydroxyproline assays, and real-time PCR for profibrotic genes. Furthermore, we evaluated the cell proliferative capacity and COL1A1 mRNA expression in human HSCs line LX-2 and primary rat HSCs treated with nicotine and an α7nAChR antagonist, methyllycaconitine citrate.
RESULTS
Nicotine exacerbated carbon tetrachloride-induced liver fibrosis in mice (+42.4% in hydroxyproline assay). This effect of nicotine was abolished in α7nAChR-deficient mice, indicating nicotine promotes liver fibrosis via α7nAChR. To confirm the direct involvement of α7nAChRs in liver fibrosis, we investigated the effects of genetic suppression of α7nAChR expression on carbon tetrachloride-induced liver fibrosis without nicotine treatment. Profibrotic gene expression at 1.5 weeks was significantly suppressed in α7nAChR-deficient mice (-83.8% in Acta2, -80.6% in Col1a1, -66.8% in Tgfb1), and collagen content was decreased at 4 weeks (-22.3% in hydroxyproline assay). The in vitro analysis showed α7nAChR expression in activated but not in quiescent HSCs. Treatment of LX-2 cells with nicotine increased COL1A1 expression (+116%) and cell proliferation (+10.9%). These effects were attenuated by methyllycaconitine citrate, indicating the profibrotic effects of nicotine via α7nAChR.
CONCLUSIONS
Nicotine aggravates liver fibrosis induced by other factors by activating α7nAChR on HSCs, thereby increasing their collagen-producing capacity. We suggest the profibrotic effect of nicotine is mediated through α7nAChRs.
Topics: Animals; alpha7 Nicotinic Acetylcholine Receptor; Hepatic Stellate Cells; Nicotine; Mice; Liver Cirrhosis; Humans; Collagen Type I; Collagen Type I, alpha 1 Chain; Carbon Tetrachloride; Rats; Male; Cell Proliferation; Aconitine; Cell Line; Mice, Inbred C57BL; Transforming Growth Factor beta1; Mice, Knockout; Nicotinic Agonists
PubMed: 38836815
DOI: 10.1097/HC9.0000000000000457 -
Food Research International (Ottawa,... Jul 2024Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC)...
Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.
Topics: Edible Grain; Hydrogen-Ion Concentration; Infant Food; Tandem Mass Spectrometry; Food Contamination; Tropanes; Temperature; Alkaloids; Humans; Food Handling; Hot Temperature; Atropine; Infant; Chromatography, High Pressure Liquid
PubMed: 38823829
DOI: 10.1016/j.foodres.2024.114439 -
Biomedicine & Pharmacotherapy =... May 2024Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine...
Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.
PubMed: 38823278
DOI: 10.1016/j.biopha.2024.116821 -
Respiratory Research May 2024COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study...
BACKGROUND
COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD.
METHODS
A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded.
RESULTS
Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86-3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01-1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01-1.39), along with older age and male sex, were independently associated with the development of lung cancer.
CONCLUSION
Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.
Topics: Humans; Male; Female; Lung Neoplasms; Middle Aged; Retrospective Studies; Aged; Pulmonary Disease, Chronic Obstructive; Republic of Korea; Administration, Inhalation; Nebulizers and Vaporizers; Adult; Cohort Studies; Adrenal Cortex Hormones; Population Surveillance; Adrenergic beta-2 Receptor Agonists; Muscarinic Antagonists
PubMed: 38822332
DOI: 10.1186/s12931-024-02838-7 -
Experimental Gerontology Aug 2024Chronic stress (CS) is critically involved in the Alzheimer's disease (AD) pathogenesis resulting in cognitive disturbance. Also, amyloid precursor protein (APP) related...
Quercetin ameliorates cognitive deficit, expression of amyloid precursor gene, and pro-inflammatory cytokines in an experimental models of Alzheimer's disease in Wistar rats.
Chronic stress (CS) is critically involved in the Alzheimer's disease (AD) pathogenesis resulting in cognitive disturbance. Also, amyloid precursor protein (APP) related gens, pro-inflammatory cytokines, and stress increases AD-related pathogenesis through increasing APP, all are important players in the development of AD. Herein, we explore the possible neuroprotective and anti-amnestic effect of quercetin (QUER) on cognitive deficits induced by scopolamine (SCOP) in stressed rats. Stress induction was performed by exposed of rats to 2-h chronic restraint stress for 10 days. Then rats were supplemented with QUER (25 mg/kg/day oral gavage, for 1 month). Ratswere submitted to intraperitoneal (i.p.) injection of SCOP (1 mg/kg) during the final 9 days of QUER supplementation to induce dementia like condition. Following the interventions, behavioral tests [elevated plus maze (EPM) and novel object recognition memory (NORM)] was examined to analysis the cognitive functions. Meanwhile, prefrontal cortex (PFC) and hippocampus of brain were used for gene expression and biochemical studies. Also, the plasma corticosterone (CORT) level was measured. We established that administration of QUER ameliorated the SCOP-related memory impairment. Also, QUER decreased stress related anxiety like behaviors in the EPM. QUER also altered the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in both PFC and hippocampus of SCOP treated rats in stress and non-stress conditions. We found that QUER increased APP and amyloid precursor-like protein 2 (APLP2) mRNA expression in both non-stress and stressed rats. Also, our findings imply that QUER suppress the effect of SCOP on cognitive functions. Moreover, decreased APP mRNA expression in the hippocampus were observed following pretreatment of rats with QUER in both stress and non-stress groups. Given that decreased amyloid beta (Aβ) expression in the hippocampus of stressed rats, it can be proposed that elevations in APP mRNA expression by QUER activates non-amyloidogenic pathways leading to reduction in Aβ levels. However, our findings indicate that QUER can be a therapeutic candidate, which exerts an anti-amnesic property against SCOP-induced memory decline. On the other hand, prior QUER administration in stress condition could be a promising approach against AD prevention.
Topics: Animals; Quercetin; Alzheimer Disease; Rats, Wistar; Male; Disease Models, Animal; Rats; Cytokines; Hippocampus; Amyloid beta-Protein Precursor; Stress, Psychological; Cognitive Dysfunction; Scopolamine; Neuroprotective Agents; Corticosterone; Prefrontal Cortex; Cognition
PubMed: 38821324
DOI: 10.1016/j.exger.2024.112466 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024This study investigates the 10-year trend in the sedative and anticholinergic burden among older adults in Slovenia, with the aim of identifying opportunities to...
This study investigates the 10-year trend in the sedative and anticholinergic burden among older adults in Slovenia, with the aim of identifying opportunities to optimize pharmacotherapy in this population. A retrospective drug utilization analysis was conducted based on a national anonymized database of dispensed prescriptions from 2009 to 2019. The study employed the sedative load model and the anticholinergic cognitive burden scale to assess the sedative and anti cholinergic burden, respectively. The findings indicate that in 2019, 45.6 % and 40.8 % of older adults (≥ 65 years) used sedative and anticholinergic medications, respectively. A high sedative load and a clinically significant anticholinergic burden were observed in a considerable proportion of older adults (13.2 % and 11.2 %, respectively, in 2019). The age-standardized prevalence of sedative load and anti-cholinergic burden significantly decreased over the 10-year study period by 5.6 % and 1.7 %, respectively (absolute difference), while the prevalence of clinically significant anticholinergic burden remained stable. Notably, the age groups 85-89 years and above 90 years had an increase in the proportion of individuals with a clinically significant anticholinergic burden over the years. These results emphasize the need for targeted interventions, particularly in the oldest age groups, to promote safe and effective medication use among older adults.
Topics: Humans; Cholinergic Antagonists; Slovenia; Aged; Aged, 80 and over; Male; Retrospective Studies; Female; Hypnotics and Sedatives; Drug Utilization; Databases, Factual; Age Factors; Prevalence
PubMed: 38815203
DOI: 10.2478/acph-2024-0017