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The Korean Journal of Physiology &... Jul 2024Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and...
Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.
PubMed: 38926838
DOI: 10.4196/kjpp.2024.28.4.303 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jun 2024To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear...
OBJECTIVES
To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice.
METHODS
Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 μg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues.
RESULTS
Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (<0.05), whereas Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (>0.05).
CONCLUSIONS
Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.
Topics: Animals; Airway Remodeling; Asthma; Male; Mice; Toll-Like Receptor 4; Mice, Inbred BALB C; HMGB1 Protein; NF-kappa B; Signal Transduction
PubMed: 38926382
DOI: 10.7499/j.issn.1008-8830.2312023 -
Oral and Maxillofacial Surgery Jun 2024To evaluate and compare the effect of dexamethasone, ketoprofen and cold compress on the quality of life (QoL) following surgical removal of impacted lower third molars...
Comparison of the effect of dexamethasone, ketoprofen and cold compress on postoperative quality of life following impacted lower third molar surgery: a randomized clinical trial.
OBJECTIVES
To evaluate and compare the effect of dexamethasone, ketoprofen and cold compress on the quality of life (QoL) following surgical removal of impacted lower third molars (ILTMs).
MATERIALS AND METHODS
Eligible patients requiring ILTM extraction with a modified Pederson difficulty index score of 5-6 were recruited. The patients were randomly allocated into Groups A, B and C. Groups A and C received 100 mg of ketoprofen and 8 mg of dexamethasone per-oral respectively, preoperatively. Subjects in group B applied a pre-standardized ice pack over the angle of the mandible for 6 h postoperatively. The QoL questionnaire was administered on postoperative days 1, 2 and 7.
RESULTS
In total, seventy-eight subjects completed the study: 46 (59%) were male and had a mean age of 27.8 ± 4.9 years. The groups were similar sociodemographically. The overall QoL and appearance domain score were significantly better in patients on oral dexamethasone on postoperative day 1 than in the other groups.
CONCLUSIONS
Oral dexamethasone demonstrates better improvement in postoperative QoL and appearance on day 1 following ILTM surgery compared to ice packs and ketoprofen. Although ice packs are readily available, can be used repeatedly and are a low-cost option, more research is necessary to determine their optimum therapeutic use in outpatient settings.
CLINICAL RELEVANCE
Oral dexamethasone is superior to ice pack compress and ketoprofen in improving the postoperative QoL in ILTM surgery.
TRIAL REGISTRY REGISTRATION NUMBER
PACTR202005593102009 at Pan African Clinical Trial Registry.
PubMed: 38926204
DOI: 10.1007/s10006-024-01268-5 -
Ceska a Slovenska Oftalmologie :... 2024The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to...
OBJECTIVE
The aim of this study was to evaluate the outcomes of Ozurdex® (DEX) implant in patients with diabetic macular edema (DME) in real-world clinical practice, and to determine the correlation between known OCT biomarkers and the effect of treatment.
MATERIAL AND METHODS
This retrospective study included 42 eyes of 33 patients (16 women, 17 men) treated with DEX at the Department of Ophthalmology, Faculty of Medicine and Dentistry of Palacký University and University Hospital Olomouc for DME indication between 2020 and 2023. Follow-up examinations were conducted at 1, 3, and 6 months after the first DEX application. The main assessed parameters were: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central retinal thickness (CRT), OCT biomarkers. The results were subsequently statistically evaluated.
RESULTS
At the first follow-up after DEX application, there was an average decrease in CRT of 186 ±146µm and a gain of 3 ±7 letters. Positive morphological and functional responses were observed in 39 eyes (92.9%) and 23 eyes (54.8%) respectively. The disorganization of retinal inner layers (DRIL) biomarker was initially present in 41 eyes (97.6%), with reduction or disappearance observed in 13 eyes (31%) post-application. Eyes with ellipsoid zone disruption (EZ disruption) had an average initial BCVA of 49.6 letters, compared to 57.8 letters in the group without this biomarker. The mean gain in BCVA was +8.7 letters in treatment-naive eyes and +2.1 letters in previously treated eyes. Chronic DME was less frequent in treatment-naive (n = 1, 14.3%) compared to previously treated eyes (n = 28, 84.8%). All these results were statistically significant (p < 0.05). An increase in IOP post-DEX application occurred in 9 patients (21.4%).
CONCLUSION
Our results confirm DEX as a safe and effective treatment option for DME. Treatment-naive patients achieved better functional outcomes. We confirmed ellipsoid zone disruption (EZ disruption) as a negative biomarker. Additionally, we demonstrated the capacity of DEX to reduce disorganization of the retinal inner layers (DRIL).
Topics: Humans; Macular Edema; Male; Female; Diabetic Retinopathy; Dexamethasone; Retrospective Studies; Middle Aged; Aged; Intravitreal Injections; Drug Implants; Visual Acuity; Glucocorticoids; Tomography, Optical Coherence
PubMed: 38925895
DOI: 10.31348/2024/29 -
European Journal of Pharmacology Jun 2024The CFTR modulator Trikafta has markedly improved lung disease for Cystic Fibrosis (CF) patients carrying the common delta F508 (F508del-CFTR) CFTR mutation....
The CFTR modulator Trikafta has markedly improved lung disease for Cystic Fibrosis (CF) patients carrying the common delta F508 (F508del-CFTR) CFTR mutation. F508del-CFTR results in an apical trafficking defect and loss of function in CFTR-expressing epithelial cells. However, Trikafta has not resulted in improved gastrointestinal function in CF patients. A humanized mouse model of F508del-CFTR was recently generated to evaluate CFTR modulators and other compounds to treat human F508del-CFTR CF intestinal disease. Short-term (4h) treatment of rats with Dexamethasone (Dex) potently activates serum glucocorticoid kinase 1 (SGK1) and increases CFTR apical traffic and ion transport in the native intestine. This study examined CFTR localization and ion transport in intestinal segments from humanized F508del-CFTR mice following treatment with Dex in the presence/absence of Trikafta. Dex treatment improved apical CFTR localization and function but was inconsistent along intestinal segments. Combined treatment with Dex and Trikafta was superior to Dex alone but inconsistently improved CFTR localization and function. These data suggest further optimization of humanized CF mouse models will be necessary to test the efficacy of compounds to treat human CF intestinal disease.
PubMed: 38925289
DOI: 10.1016/j.ejphar.2024.176771 -
The New England Journal of Medicine Jun 2024
Topics: Humans; Brain Neoplasms; Glioblastoma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Clinical Trials, Phase I as Topic; Brain Diseases; Dexamethasone; Bevacizumab
PubMed: 38924746
DOI: 10.1056/NEJMc2405721 -
The New England Journal of Medicine Jun 2024
Topics: Humans; Male; Brain Neoplasms; Glioblastoma; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Clinical Trials, Phase I as Topic; Bevacizumab; Dexamethasone
PubMed: 38924745
DOI: 10.1056/NEJMc2405721 -
Head & Neck Jun 2024Corticosteroid therapy is commonly recommended for acute facial nerve weakness; however, its effectiveness in treating traumatic nerve injuries remains controversial....
BACKGROUND
Corticosteroid therapy is commonly recommended for acute facial nerve weakness; however, its effectiveness in treating traumatic nerve injuries remains controversial. This study investigated the functional recovery and cellular effects of systemic dexamethasone administration after facial nerve injury.
METHODS
C57BL/6 mice were assigned to two groups by intraperitoneal injection: the phosphate-buffered saline group and the dexamethasone group. Facial nerve crush injury was induced, followed by the functional grading of recovery. Cellular effects were investigated using transmission electron microscopy, flow cytometry, immunofluorescence, and intravital imaging.
RESULTS
Macrophage infiltration into the facial nerves was significantly inhibited by systemic dexamethasone administration. However, dexamethasone group slightly delayed the functional recovery of the facial nerve compared to the PBS group. In addition, the morphological changes in the nerve were not significantly different between the two groups at 14 days post-injury. Macrophage migration analysis in the intravital imaging also showed no difference between groups.
CONCLUSIONS
In summary, systemic dexamethasone successfully inhibited leukocyte infiltration; however, functional recovery was delayed compared to the PBS control group. Clinically, these findings indicate that more evidence and research are required to use steroid pulse therapy for the treatment of traumatic facial nerve injuries.
PubMed: 38924195
DOI: 10.1002/hed.27855 -
British Journal of Haematology Jun 2024Steroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant...
Steroids are a mainstay in the treatment of acute lymphoblastic leukaemia (ALL) in children and adolescents; however, their use can cause clinically significant steroid-related neuropsychiatric symptoms (SRNS). As current knowledge on SRNS during ALL treatment is limited, we mapped the phenotypes, occurrence and treatment strategies using a database created by the international Ponte di Legno Neurotoxicity Working Group including data on toxicity in the central nervous system (CNS) in patients treated with frontline ALL protocols between 2000 and 2017. Ninety-four of 1813 patients in the CNS toxicity database (5.2%) experienced clinically significant SRNS with two peaks: one during induction and one during intensification phase. Dexamethasone was implicated in 86% of SRNS episodes. The most common symptoms were psychosis (52%), agitation (44%) and aggression (31%). Pharmacological treatment, mainly antipsychotics and benzodiazepines, was given to 87% of patients while 38% were hospitalised due to their symptoms. Recurrence of symptoms was reported in 29% of patients and two previously healthy patients required ongoing pharmacological treatment at the last follow up. Awareness of SRNS during ALL treatment and recommendation on treatment strategies merit further studies and consensus.
PubMed: 38924051
DOI: 10.1111/bjh.19610 -
American Journal of Reproductive... Jun 2024
Authors' reply: Commentary on "Intrauterine perfusion of dexamethasone improves pregnancy outcomes in recurrent reproductive failure patients with elevated uterine natural killer cells. A retrospective cohort study".
Topics: Humans; Female; Pregnancy; Dexamethasone; Killer Cells, Natural; Uterus; Pregnancy Outcome; Retrospective Studies; Perfusion; Abortion, Habitual
PubMed: 38923191
DOI: 10.1111/aji.13866