Dexamethasone Treatment Group Research Articles

Hydrogel Matrix Containing Microcarriers for Dexamethasone Delivery to Protect Against Cisplatin-Induced Hearing Loss.

A functional hydrogel containing biopolymer microcarriers loaded with dexamethasone was developed to address the hearing loss that results from cisplatin ototoxicity. The drug delivery platform was tested both in vitro in the HEI-OC1 inner ear cell line and in vivo in a rat animal model. The newly described formula offered prolonged release of the contained dexamethasone for up to six days and transformed into a solid state at body temperature, thus counteracting its clearing through the Eustachian tube when injected into the middle ear. When tested in vitro, the inner ear cells exposed to cisplatin showed significantly higher viability at 48 hours when seeded on hydrogel containing dexamethasone-loaded microparticles than the cells treated with free dexamethasone. In the rat in vivo model, the ears of the rats treated with the hydrogel formulation presented better hearing thresholds after cisplatin administration than contralateral ears treated with free dexamethasone. The ears of the rats treated with microcarriers without inclusion in the functional hydrogel obtained better results than the dexamethasone treatment group but not as good as the hydrogel-containing microcarrier group. Histological assessment of the rats' inner ears showed better integrity of the structures and lower apoptosis in the microcarrier-treated groups than in the control group. Overall, the newly described microcarrier of dexamethasone offers better protection against cisplatin-induced hearing loss than free dexamethasone, especially when contained in a functional hydrogel formulation.

The impact of different corticosteroids in hospitalised patients with severe COVID-19 pneumonia: a retrospective observational study

Background: The COVID-19 pandemic created havoc on health care systems and economies worldwide. Corticosteroids have been shown to be effective in the management of COVID-19. Methods: A retrospective observational study was conducted on 311 patients meeting the inclusion criteria at the Augustus Long Hospital, Trinidad and Tobago between July-December 2021. Data was classified into three treatment groups: low dose dexamethasone, high dose dexamethasone and methylprednisolone pulse therapy. The primary outcomes were the 28-day mortality and need for invasive mechanical ventilation and the secondary outcome was the length of hospital stay. The patient cohort was also classified into simple oxygen and high flow oxygen groups and a subgroup analysis was also performed. Results: There were no significant statistical differences between age, gender, vaccination status and co-morbidities between the treatment groups. However, there were significant differences in the ethnic ratios amongst the high dose dexamethasone and methylprednisolone treatment groups (East Indians to Africans; 61.7%vs. 37%; 72.9% vs.25.4% respectively; p=0.02). In patients receiving simple oxygen on admission, those who were treated with low dose dexamethasone when compared to high dose dexamethasone and methylprednisolone, had the lowest 28-day mortality (15.3% vs. 40.9% vs. 40% respectively; p< 0.001), lowest need for IMV (0.7% vs. 9.1% vs. 40% respectively; p< 0.001) and the shortest length of hospital stay (median [IQR] days; 7[12-5], 11[22-7], 16[27-14] respectively; p< 0.001). In patients receiving high flow oxygen, those treated with methylprednisolone had the lowest 28-day mortality (45.8%), when compared to the high dose dexamethasone (59.5%) and low dose dexamethasone (81%) groups; however, these results were not statistically significant (p = 0.053). Conclusion: In our study, patients receiving simple oxygen had better clinical outcomes when treated with low dose dexamethasone compared to higher dose corticosteroids. Methylprednisolone pulse therapy may be beneficial in patients requiring high flow oxygen; but further studies are needed.

Dexamethasone relieves the inflammatory response caused by inguinal hernia meshes through miR-155.

Inguinal hernia is a relatively common condition. Most patients with inguinal hernia require surgery. At present, mesh repair is one of the most effective methods to treat inguinal hernia, but insertion of the mesh can cause inflammation. Dexamethasone (DEX) can treat inflammation, but the mechanism by which DEX alleviates inflammation caused by inguinal hernia mesh placement remains unclear. We randomly divided rats into groups: negative control (NC), inguinal hernia (IH), polypropylene mesh (PM), DEX treatment, and miR-155 treatment groups. RT-qPCR was performed to determine the expression of miR-155. ELISA was implemented to determine the secretion of IL-1β, IL-6, and IL-18. Western blotting was used to detect caspase-1, JAK1, p-JAK1, STAT3, and p-STAT3 expression. A dual-luciferase reporter gene array identified a connection between miR-155 and JAK1. The results revealed that the expression of miR-155, IL-1β, IL-6, and IL-18 was upregulated in the PM group. After DEX treatment, the secretion of miR-155, caspase-1, IL-1β, IL-6, and IL-18 decreased. Dual luciferase results confirmed that miR-155 induced the targeted downregulation of JAK1, while a miR-155 mimic reversed the therapeutic effect of DEX, and the expression levels of p-JAK1 and p-STAT3 increased. DEX regulates the JAK1/STAT3 signaling pathway through miR-155 to relieve inflammation caused by inguinal hernia meshes.

Comparison between low-volume local anesthetic with intravenous dexamethasone and conventional volume without dexamethasone for superior trunk block after arthroscopic shoulder surgery: a randomized controlled non-inferiority trial

IntroductionThis study aimed to investigate whether low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while maintaining the analgesic duration compared with conventional volume of local...

Biochemical and histopathological evidence for beneficial effects of Empagliflozin pretreatment on acetic acid-induced colitis in rats

BackgroundUlcerative Colitis (UC) is a disorder which oxidative stress plays a critical role in its pathogenesis. Empagliflozin (EMPA) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been shown to have anti-inflammatory and antioxidative effects. The aim of this study was to investigate the protective effects of EMPA on acetic acid (AA) induced colitis in rats.MethodsA total of twenty-four rats were divided into four groups (six animals in each group) as follows: (1) Control group; (2) acetic acid (AA)-induced colitis group (AA); (3) EMPA treatment group (AA + EMPA); (4) Dexamethasone (Dexa) treatment group (AA + Dexa). Animals in pre-treatment groups received EMPA (10 mg/kg, i.p.) or dexamethasone (4 mg/kg, i.p. as reference drug) for four consecutive days before induction of colitis by intra-rectal acetic acid (4% v/v) administration. Twenty-four hours after AA administration, rats were sacrificed and the colon tissues were removed for histopathological and biochemical evaluations.ResultsPretreatment with EMPA significantly decreased colon weight/length ratio (81.00 ± 5.28 mg/cm vs. 108.80 ± 5.51 mg/cm) as well as, macroscopic (2.50 ± 0.57 vs. 3.75 ± 0.25) and histological scores (3.3 ± 0.14 vs. 1.98 ± 0.14) compared to the AA-induced colitis group (p < 0.01). Pretreatment with EMPA significantly reduced malondialdehyde (MDA) (324.0 ± 15.93 vs. 476.7 ± 32.26 nmol/mg p < 0.001) and increased glutathione level (117.5 ± 4.48 vs. 94.38 ± 3.950 µmol/mg, p < 0.01) in comparison to the AA-induced colitis group. Furthermore, a significant increase in catalase (44.60 ± 4.02 vs.14.59 ± 2.03 U/mg, P < 0.01), superoxide dismutase (283.9 ± 18.11 vs. 156.4 ± 7.92 U/mg, p < 0.001), and glutathione peroxidase (10.38 ± 1.45 vs. 2.508 ± 0.37, p < 0.01) activities were observed by EMPA pretreatment when compared to the AA-induced colitis group. These results were in line with those of the reference drug.ConclusionsIt is concluded that EMPA could effectively reduce the severity of tissue injury in experimental colitis. This protective effect may be related to the antioxidative effects of EMPA drug.

Effects of caspase recruitment domain protein 9 gene knockout on airway inflammation in C57BL/6 mice with steroid resistant asthma

Objective: To investigate the role of caspase recruitment domain protein 9 (CARD9) in airway injury and inflammation of steroid resistant asthma in C57BL/6 mice. Methods: C57BL/6 mice were divided into A group (control group), B group (model group) and C group (dexamethasone treatment group), with 6 mouse in each group using random number table. The mouse asthma model was established in B and C group by subcutaneous injection of ovalbumin (OVA)/complete Freund adjuvant (CFA) in the abdomen and OVA aerosol challenge, the pathological change and cell count in broncho alveolar lavage fluid (BALF) were detected in order to confirm the model as steroid resistant asthma, and the lung tissue inflammatory infiltration was scored. Western blot was used to detect the changes of CARD9 protein between the group A and B; then wild-type and CARD9 knockout mice were divided into D group (wild-type control group), E group (wild-type model group), F group (CARD9 knockout control group) and G group (CARD9 knockout model group), the following indicators were observed and compared after establishing steroid resistant asthma model separately: HE staining was used to observe the pathological changes of lung tissue, ELISA was used to detect the protein levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-17(IL-17) in BALF, and RT-PCR was used to detect the mRNA levels of CXC motif chemokine ligand-10 (CXCL-10) and IL-17 in lung. Results: The inflammatory score (3.33±0.82 vs 0.67±0.52) and BALF total cell count [(10.13±4.83) ×105/ml vs (3.76±0.84) ×105/ml] in B group were higher than those in the A group with statistical significance (P<0.05). There was no significant difference between group C and group B in inflammatory infiltration score (2.83±0.75 vs 3.33±0.82) and BALF total cell count [(9.80±3.19) ×105/ml vs (10.13±4.83) ×105/ml] (P>0.05). Moreover the protein level of CARD9 was increased in the B group than A group (0.245±0.090 vs 0.047±0.014, P=0.004). Compared to E group and F group, more obviously inflammatory cells, neutrophils, eosinophils infiltration and tissue injury were observed in G group (P<0.05), so did the expression of IL-4 (P<0.05), IL-5 and IL-17. Meanwhile the mRNA expression levels of IL-17 and CXCL-10 also increased in lung tissue (P<0.05) of G group. Conclusion: CARD9 gene deletion may aggravate the steroid resistant of asthma by increasing neutrophil chemokines, such as IL-17 and CXCL-10, therefore increasing infiltration of neutrophils in C57BL/6 mice asthma model.

For better or worse: Dexamethasone versus methylprednisolone among patients with COVID-19 pneumonia.

Objective: The aim of this study was to compare the outcome of dexamethasone and methylprednisolone among patients suffering with COVID-19 pneumonia. Study Design: Quantitative Retrospective Comparative study. Setting: Department of Medicine, Allied Hospital, Faisalabad. Period: February to September 2021. Material &amp; Methods: Data included archival record of 120 diagnosed cases of COVID-19 pneumonia during July 2020 to December 2020. Data was retrospectively collected by researchers using a predesigned study proforma and analyzed through SPSS software 25.0. Results: Out of 120 reported cases of COVID-19 pneumonia, 76 (63.3%) were males, and 44(36.7%) were females (p= 0.097). There were 67 patients (55.8%) prescribed with dexamethasone treatment (Group A) and 53 patients (44.2%) with methylprednisolone treatment (Group B). Mean duration of hospital stay was 3.48 + 3.0 days in Group A and 3.45 + 3.0 days in Group B. Six patients were lost for follow-up Out of 114 patients, 63 patients (55.26%) had mortality within 30 days of study while 51 patients (44.74%) survived. Conclusion: There is no statistical difference in the outcomes of COVID-19 pneumonia when treated with dexamethasone as compared to methylprednisolone in terms of outcome related to duration of hospitalization, need for ICU admission and reported mortality within 30 days. More studies are warranted with larger sample size.

Effects of glucocorticoid receptor agonists on hyperalgesia of rats with neuropathic pain and its mechanisms

To investigate the effects of glucocorticoid receptor agonists on hyperalgesia in rats with neuropathic pain (NPP) by regulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) pathway and its mechanisms. Forty SD rats were divided into control group, NPP model group, NPP treated with NLRP3 inhibitor group and dexamethasone treatment group with 10 rats in each group. The NPP rat model was induced by vincristine. The model group was established according to the above method, the NLRP3 inhibitor group was treated with NLRP3 inhibitor (MCC950) after the NPP model was established, and the treatment group was treated with glucocorticoid receptor agonist (dexamethasone) after the model was established according to the design. The rats of the control group were given the same amount of normal saline. After 7 days of intervention, the mechanical pain threshold, thermal pain threshold, morphological changes of spinal dorsal horn, pain factors (prostaglandin E2 (PGE2), substance P (SP), 5-hydroxytryptamine (5-HT)), inflammatory factors (interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6)), and NLRP3/IL-1β protein expressions were determined and compared among the four groups. Compared with the model group, the pathological changes of spinal dorsal horn neurons in NLRP3 inhibitor group and treatment group were alleviated significantly, the arrangement of neurons was tended to be close, the number of neurons was gradually returned to normal, and the pyknosis of neurons was decreased. Compared with the control group, the mechanical pain threshold and thermal pain threshold of the model group were decreased significantly (P＜0.05), and the expressions of inflammatory factors, pain factors and NLRP3, IL-1β protein were increased significantly (P＜0.05); compared with the model group, the mechanical pain threshold and thermal pain threshold of the NLRP3 inhibitor group and the dexamethasone treatment group were increased significantly (P＜0.05), and the expressions of inflammatory factors, pain factors and NLRP3, IL-1β protein were decreased significantly (P＜ 0.05). The difference between NLRP3 inhibitor group and treatment group was not statistically significant (P＞0.05). Glucocorticoid receptor agonists may reduce the hyperalgesia of neuropathic pain rat model by down regulating NLRP3/IL-1β pathway, which may be the mechanism of dexamethasone on antiinflammatory of analgesia in early stage of NPP.

Protective effects of intranasal curcumin on silica-induced lung damage

ObjectiveBeing anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. Materials and methodsMice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. ResultsPresent study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung.Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. ConclusionsPresent study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae against myocardial injury in septic mice

To evaluate the protective effect of excretory-secretory proteins from Trichinella spiralis muscle larvae (Ts-MES) on sepsis-induced myocardial injury in mice. Eighty male BALB/C mice were randomized equally into sham-operated group, myocardial injury group, Ts-MES treatment group and dexamethasone treatment group. In the latter 3 groups, sepsis-induced myocardial injury models were established by cecal ligation and perforation; the sham operation was performed by exposure of the cecum without ligation or perforation. Forty minutes after the operation, the mice were given intraperitoneal injections 150 μL PBS, 20 μg TS-MES or 0.3 mg/kg dexamethasone as indicated. At 12 h after the operation, 6 mice were randomly selected from each group for echocardiography, and 8 mice were used for observing the survival rate within 72 h. The remaining 6 mice were examined for myocardial pathologies with HE staining and serum levels of NTPro-BNP and cTnI with ELISA; the expressions of TNF-α, IL-6, IL-10 and TGF-β in the serum and myocardial tissue were detected using ELISA and qRT-PCR. Compared with the sham-operated mice, the septic mice showed significantly decreased cardiac function indexes (LVEF, LVFS, and E/A) with lowered survival rate within 72 h (P < 0.001) and significantly higher myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.01). Treatment with TS-MES significantly improved the cardiac function and 72-h survival rate (P < 0.05) and lowered the myocardial injury scores and serum levels of NTPro-BNP and cTnI (P < 0.05) in the septic mice. Compared with the sham-operated mice, the septic mice had obviously increased TNF-α and IL-6 levels in the serum and myocardial tissue (P < 0.001), which were significantly lowered by treatment with TS-MES (P < 0.05). TS-MES and dexamethasone both increased the levels of IL-10 and TGF-β in the septic mice, but the changes were significant only in TS-MES-treated mice (P < 0.05). Ts-MES are capable of protecting against myocardial injury in septic mice by reducing the production of pro-inflammatory cytokines and enhancing the levels of regulatory cytokines.

High-dose dexamethasone injection disordered metabolism and multiple protein kinases expression in the mouse kidney.

Glucocorticoids (GCs) have been widely used in clinical treatment as anti-inflammatory, anti-shock and immunosuppressive medicines. However, the effect of excessive GCs on immune response and metabolism of kidney remains unclear. Here, we profiled the gene expression of kidney from mice with high-dose dexamethasone (DEX) treatment. A total of 1193 differentially expressed genes (DEGs) were screened in DEX treatment group compared with the saline group, including 715 down- regulated and 478 up-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of these DEGs showed extracellular matrix (ECM)–receptor interaction, cell adhesion molecules signaling pathway were significantly enriched, and that the vast majority of DEGs were involved in monocarboxylic acid metabolism, leukocyte cell–cell adhesion and fatty acid metabolism. Gene set enrichment analysis (GSEA) revealed that DEGs were strongly associated with immune-response and cell adhesion gene sets, such as Fc γ R-mediated phagocytosis, leukocyte transendothelial migration, T-cell receptor signaling pathway, cell adhesion, ECM–receptor interaction and focal adhesion-associated pathways. KEGG pathway analysis of differentially expressed kinases (DEKs) showed T-cell receptor and forkhead box class O signaling pathway were enriched. Furthermore, we found multiple protein kinases expression were dysregulated greatly after dexamethasone treatment, including classical effector of GCs stimulation-serum and GC-regulated kinase. These protein kinases are involved in multiple signaling pathways in mice kidney, such as mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. We profiled the gene expression of the kidney from high-dose dexamethasone-treated mice and provided important information for further study the mechanism of side effects of GCs in clinical therapy.

Anti-inflammatory effect of pregabalin on acetic acid-induced colitis in the rats.

Background and purpose:Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease characterized by the inflammation of the intestine. The available medicinal treatments for IBD are not efficacious enough since they exert various adverse effects. Therefore, the search for new therapeutic agents should be continued. The present study aimed to assess the anti-inflammatory effects of pregabalin on acetic acid-induced colitis in rats.Experimental approach:Using 2 mL of 3% acetic acid solution, colitis was intra-rectally induced in rats. Animals were randomly divided into 6 groups including the normal group, colitis control group, pregabalin treatment groups (30, 50, and 100 mg/kg; i.p., respectively), and dexamethasone treatment group (1 mg/kg; i.p.). Macroscopic, microscopic, and biochemical (myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) examinations were used to evaluate the efficacy of pregabalin in the inflamed colon.Findings/Results:All the applied doses of pregabalin significantly decreased the severity of macroscopic and microscopic colonic damages including ulcer severity, ulcer area, percentage of necrosis, and total colitis index compared to the colitis control group. These results were confirmed by the reduced colonic concentration of tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, and myeloperoxidase activity.Conclusion and implications:Results of this study indicated that pregabalin administration has beneficial effects upon the treatment of experimental colitis, which might be partly due to its anti-inflammatory properties.

Functional Analysis of Injectable Substance Treatment on Surgically Injured Rabbit Vocal Folds

The objective of this study was to evaluate the efficacy of immediate injection treatments of dexamethasone, hyaluronic acid (HA)/gelatin (Ge) hydrogel and glycol-chitosan solution on the phonatory function of rabbit larynges at 42 days after surgical injury of the vocal folds, piloting a novel ex vivo phonatory functional analysis protocol. A modified microflap procedure was performed on the left vocal fold of 12 rabbits to induce an acute injury. Animals were randomized into one of four treatment groups with 0.1 mL injections of dexamethasone, HA/Ge hydrogel, glycol-chitosan or saline as control. The left mid vocal fold lamina propria was injected immediately following injury. The right vocal fold served as an uninjured control. Larynges were harvested at Day 42 after injection, then were subjected to airflow-bench evaluation. Acoustic, aerodynamic and laryngeal high-speed videoendoscopy (HSV) analyses were performed. HSV segments of the vibrating vocal folds were rated by three expert laryngologists. Six parameters related to vocal fold vibratory characteristics were evaluated on a Likert scale. The fundamental frequency, one possible surrogate of vocal fold stiffness and scarring, was lower in the dexamethasone and HA/Ge hydrogel treatment groups compared to that of the saline control (411.52±11.63 Hz). The lowest fundamental frequency value was observed in the dexamethasone group (348.79±14.99 Hz). Expert visual ratings of the HSV segments indicated an overall positive outcome in the dexamethasone treatment group, though the impacts were below statistical significance. Dexamethasone injections might be used as an adjunctive option for iatrogenic vocal fold scarring. An increased sample size, histological correlate, and experimental method improvements will be needed to confirm this finding. Results suggested a promising use of HSV and acoustic analysis techniques to identify and monitor post-surgical vocal fold repair and scarring, providing a useful tool for future studies of vocal fold scar treatments.

Machine Learning Supports Clinical Decision in Optimized Treatment for COVID-19 Patients

Background: It has been difficult to distinguish between mild, moderate, and severe cases at an early stage for COVID-19 patients, making it challenging to decide an optimized treatment for each patient. This machine learning system could predict the clinical course and be used to develop a novel method to provide optimal treatment based on risk. Method: We applied machine learning techniques to international clinical data from a large cohort of patients with COVID-19 at 15 hospitals in Japan and three hospitals in New York City from January 1, 2020 to March 30, 2021. We analyzed clinical information of over 2000 COVID-19 patients comprising various races and ethnicities and built a severity and mortality prediction model. Furthermore, using a severity index with machine learning allowed early detection of patients most at-risk for developing severe illness to support the decision for the patient to receive optimized therapy. Findings: We developed an international COVID-19 early prediction model for use at the time of hospital admission that predicts disease severity and mortality with high accuracy, 0.88 (AUC). Using the novel method of severity-matched analysis to assess treatment effectiveness, in the high-risk group, the Kaplan–Meier estimates of mortality by Day 30 were 26% in the dexamethasone treatment group and 63% in the non-treatment group. The Kaplan–Meier estimates of mortality were low at 3% with remdesivir and dexamethasone in combination and 49% with no remdesivir and dexamethasone treatment by Day 30. There may be an add-on effect of remdesivir to conventional dexamethasone. Interpretation: The severity prediction index can be calculated, which can assist with an optimized treatment for COVID-19 patients in each risk group. The severity-matched treatment system could support the recommendation of optimized treatments, such as dexamethasone, remdesivir, or heparin, in high-risk groups by calculating the severity index predicted at the time of the first visit.Trial Registration Details: The trial registration number was 2020142NI. Funding Information: K.T., K.I., and Y.D. received funding from the Japan Agency for Medical Research and Development (AMED) (19fk0108153h0001). K.T. received funding from AMED (19jm0610015h0001). K.T. received funding from the Healthy Longevity Global Grand Challenge, Catalyst Award.Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study protocol was centrally reviewed by the Institutional Review Board of Tokyo University. The requirement for consent was waived given the retrospective and non-interventional nature of the study.

The effect of diallyl sulfide on the lung tissue of rats poisoned by paraquat

Objective: To investigate the mechanism of diallyl sulfide (DAS) on paraquat (PQ) - induced acute lung injury in rats. Methods: In May 2016, 32 adult male Wistar rats were randomly divided into control group, model (PQ) group, DAS treatment group and dexamethasone (DXM) treatment group, with 8 rats in each group. PQ poisoning model was established by intragastric administration of PQ solution (70 mg/kg) . 100 mg/kg DAS (DAS treatment group) , normal saline (control group and PQ group) and 1 mg/kg DXM (DXM treatment group) were injected intraperitoneally before and after modeling. After 24 hours, the rats were killed and the degree of lung injury was observed. The expression of inducible nitric oxide synthase (iNOS) in lung tissue was measured. Alveolar macrophages were isolated and cultured. The supernatant was taken to determine the content of NO, and the expressions of iNOS mRNA in alveolar macrophages were detected. Results: Compared with the control group, the pathological injury score and the expression of iNOS in the lung tissue of PQ group were significantly increased, and the content of NO secreted by alveolar macrophages and the expression of iNOS mRNA were significantly increased (P<0.05) . Compared with PQ group, the pathological injury scores and the expressions of iNOS in lung tissue of rats in DAS treatment group and DXM treatment group were significantly decreased, and the contents of NO secreted by alveolar macrophages and the expressions of iNOS mRNA were significantly decreased (P<0.05) . There was no significant difference between DXM group and DAS group (P>0.05) . Conclusion: DAS may have protective effect on acute lung injury induced by PQ in rats.

Symptom trajectories during chemotherapy in patients with non-small cell lung cancer (NSCLC) and the function of prolonging low dose dexamethasone in promoting enhanced recovery after chemotherapy.

BackgroundLung cancer, mainly non‐small cell lung cancer (NSCLC), is one of the leading causes of death worldwide. Currently, chemotherapy is still the most significant treatment strategy for NSCLC. However, scant attention has been paid in previous studies to those patients who often experience various symptoms and discomfort during chemotherapy treatment cycles.MethodsThis study included 127 NSCLC patients who completed an EORTC QLQ‐C30 questionnaire and specifically designed symptom diary. Chi‐square test, factor analysis, Pearson correlation coefficient and hierarchical cluster analysis were used to perform multivariate analysis.ResultsWe identified the top five most‐frequent symptoms within the chemotherapy cycle which included fatigue, insomnia, cough and sputum, appetite loss and hypodipsia. These symptoms were at a moderate level on chemotherapy treatment days 3–7, and were then reduced to a stable and lower level in the following two weeks. A statistically significant difference in adverse events (AEs) was found between 54 patients who received dexamethasone (treatment group) and the control group: fatigue (risk ratio [RR]: 1.48; 95% confidence interval [CI]: 1.120–1.961; p = 0.006), insomnia (RR: 1.34; 95% CI: 1.016–1.778; p = 0.038), cough and sputum (RR: 2.00; 95% CI: 1.484–2.695; p < 0.001), appetite loss (RR: 1.28; 95% CI: 0.959–1.696; p = 0.095). In total, 62 patients completed the EORTC QLQ‐C30 scale. The functioning scales of the treatment group were higher than the control population within positive effect sizes (ES: 0.1–0.8). Apart from diarrhea scales, most symptom scales were lower than the control group within negative effect sizes (ES: 0.1–0.9).ConclusionsIn this study we identified the top five most frequent post‐chemotherapy AEs in a chemotherapy treatment cycle and found that dexamethasone was well tolerated by NSCLC patients who received platinum‐based chemotherapy and substantially alleviated the symptom burden and improved the health‐related quality of life (HRQOL) of patients.

Dihydroartemisinin alleviates atopic dermatitis in mice by inhibiting mast cell infiltration

To observe the therapeutic effect of different doses of dihydroartemisinin (DHA) on atopic dermatitis (AD) in mice and explore the mechanism. Forty-two C57BL/6 mice were randomly divided into 7 groups (n=6), including a blank control group, a 2, 4-dinitrochlorobenzene (DNCB)-induced AD model group, a solvent-treated group, 3 DHA treatment groups treated with 25, 75, and 125 mg/kg DHA, and a dexamethasone treatment group. The counts of skin scratches were recorded and the lesion scores were evaluated on a daily basis. After 7 consecutive days of treatment, skin tissues were sampled from the lesions on the back and ear of the mice for pathological examination with HE staining, Masson staining and toluidine blue staining. Treatment with 25, 75, and 125 mg/kg DHA and dexamethasone all alleviated AD symptoms of mice, reduced the severity scores of skin lesions, and ameliorated pathological changes of the skin tissue. DHA at 125 mg/kg produced the most obvious therapeutic effect and significantly alleviated mast cell infiltration in the lesions as compared with the other treatment groups (P < 0.05). DHA is effective for the treatment of AD in mice with an optimal dose of 125 mg/kg. The therapeutic effect of DHA is achieved probably through regulation of local immunity by inhibiting mast cell infiltration in the lesions.

Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE2 pathways

BackgroundAsthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). MethodsKorean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. ResultsKRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE2 pathways. ConclusionKRGWE is a promising drug for asthma treatment.

The therapeutic effect of carnosine combined with dexamethasone in the lung injury of seawater-drowning

Objective: To explore the therapeutic effect of carnosine and dexamethasone in lung injury caused by seawater drowning. Methods: The in vitro experiments with A549 cells were divided into 5 groups: blank control group (C), seawater injury group (S), seawater injury+dexamethasone treatment group (S+D), seawater injury+carnosine treatment group (S+C), seawater injury dexamethasone and carnosine combined therapy(S+D+C) group. The optimal therapeutic dose of drugs for the treatment of seawater drowning lung injury was tested in vitro. Based on the optimal dose, the levels of TNF-α and IL-6 in each group at different time points were detected at the cell level by ELISA. The level of apoptosis was detected by flow cytometry. The in vivo experiments with SD rats were randomly divided into 5 groups (n=8 each): blank control group (RC),seawater drowning injury group (RS),seawater drowning injury+dexamethasone treatment group (RSD),seawater drowning injury+carnosine treatment group (RSC),seawater drowning injury+dexamethasone+carnosine combined treatment group (RSDC). The animal model with seawater inhalation acute lung injury was made by intratracheal infusion (4 ml/kg). The pathological changes of the lungs were observed. The expression of superoxide dismutase (SOD) in each group was detected by Western blot. Results: The results of in vitro experiments showed significant increase of apoptosis after seawater injury. The normal cell rate in group C was 98.3% while the apoptosis rate was 1.7%. The normal cell in group S was 18.8%, and the apoptosis rate was 81% (P<0.01). TNF-α and IL-6 levels in group S increased to 180.25 ng/L and 61.56 ng/L, respectively, which were statistically significant compared with group C (P<0.01). After drug protection, apoptosis was reduced in S+D group, S+C group and S+D+C group, with apoptosis rates of 65.4%, 70.9% and 42.6%, respectively. The contents of TNF-α and IL-6 also decreased in the S+D+C group (P<0.01). The results of in vivo experiments showed obvious lung injury and disordered lung tissue structures in the RS group at 4 h after modeling. There was hemorrhage in the pulmonary interstitium and a large number of inflammatory cells. Results of western blot showed that the expression of SOD increased in the RS group. Compared with RS group, the treatment alleviated acute lung injury and decreased the expression level of SOD in RSD, RSC and RSDC groups (P<0.01). Conclusion: Dexamethasone and carnosine reduced the influence of seawater inhalation on the lung in the rat model. The positive effect of combination of these two drugs on lung injury caused by seawater inhalation was stronger than a single drug.

Quantitative evaluation of dexamethasone treatment effects in renal ischemia-reperfusion injury using contrast enhanced ultrasonography in rats.

Renal ischemia-reperfusion (I/R) injury often occurs in various clinical events, and its incidence and mortality have been increasing. To investigate the value of contrast enhanced ultrasonography (CEUS) in the monitoring of dexamethasone in the improvement of renal I/R injury in rats. Eighteen healthy male Sprague-Dawley rats were randomly divided into sham-operated, I/R, and I/R surgery plus dexamethasone treatment (Dexa) groups. In the I/R group 45-minute renal ischemia with 24 h reperfusion period was monitored. Time-intensity curve (TIC)-derived parameters, which included peak value, time to peak (TP), area under the curve (AUC), and mean transit time (MTT) were compared to the blood creatinine, urea, Caspase-1, and NLRP3 levels. The I/R group showed an increased peak value, prolonged TP and MTT, and greater AUC (P < 0.05). The Dexa group showed shorter TP and MTT, and smaller AUC (P < 0.05). Results show that the associations between (i) TP, AUC, and MTT and (ii) creatinine, urea, Caspase-1, and NLRP3 levels were significant (P < 0.05). Dexamethasone can alleviate renal I/R injury in rats, which may be related to the inhibition of NLRP3 and caspase-1. CEUS can quantitatively measure this change, in which the changes in TP, AUC and MMT values have considerable reference values.