Effects Of Dexamethasone Treatment Research Articles

Temporal trends in laboratory parameters in survivors and non‑survivors of critical COVID‑19 illness and the effect of dexamethasone treatment.

Although coronavirus disease 2019 (COVID-19)-induced changes in laboratory parameters in patients upon admission have been well-documented, information on their temporal changes is limited. The present study describes the laboratory trends and the effect of dexamethasone treatment on these parameters, in patients with COVID-19 in the intensive care unit (ICU). Routine laboratory parameters, namely white blood cell (WBC), neutrophil, lymphocyte and platelet (PLT) counts, fibrinogen, C-reactive protein (CRP), lactate dehydrogenase (LDH) and albumin concentrations, were recorded upon admission to the ICU and, thereafter, on days 3, 5, 10, 15 and 21; these values were compared between survivors and non-survivors, as well as between those who were treated with dexamethasone and those who were not. Among the 733 patients in the ICU, (mean age, 65±13 years; 68% males; ICU mortality rate 45%; 76% of patients treated with dexamethasone), the WBC and neutrophil counts were persistently high in all patients, without significant differences over the first 15 days. Initially, low lymphocyte counts exhibited increasing trends, but remained higher in survivors compared to non-survivors (P=0.01). The neutrophil-to-lymphocyte ratio (NLR) was persistently elevated in all patients, although it was significantly higher in non-survivors compared to survivors (P<0.001). The PLT count was initially increased in all patients, although it was significantly decreased in non-survivors over time. The fibrinogen and LDH values remained similarly elevated in all patients. However, the increased levels of CRP, which did not differ between patients upon admission, further increased in non-survivors compared to survivors after day 10 (P=0.001). Declining trends in albumin levels over time, overall, with a significant decrease in non-survivors compared to survivors, were observed. Dexamethasone treatment significantly affected the temporal progression of fibrinogen and CRP in survivors and that of NLR in non-survivors. On the whole, the present study demonstrates that patients in the ICU with COVID-19 present persistently abnormal laboratory findings and significant differences in laboratory trends of NLR, CRP, PLT and albumin, but not in WBC and neutrophil count, and fibrinogen and LDH levels, between survivors and non-survivors. The temporal progression of fibrinogen, CRP and NLR is affected by dexamethasone treatment.

TMIC-27. THE ROLE OF AQUAPORIN-4 IN GLIOBLASTOMA-ASSOCIATED VASOGENIC CEREBRAL EDEMA

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Vasogenic cerebral edema is a severe complication that occurs in a majority of GBM patients, leading to a significant increase in intracranial pressure, accompanying neurological deficits, and increased mortality rates. Edema in GBM patients is almost exclusively managed by the corticosteroid dexamethasone (DEX), which has recently been found to have several drawbacks, including immunosuppression and interference with radiation therapy. Thus, there is an urgent need to better understand the mechanisms of edema resolution in GBM in order to identify alternative treatment strategies. The water channel aquaporin-4 (AQP4) is a critical player in the brain's water homeostasis, with increased levels in GBM compared to the normal brain. To gain more insight into the role of AQP4 in GBM-associated edema, we used the RCAS/tv-a system to generate de novo GBM with different driver mutations in Aqp4 knockout (KO), heterozygous (HET), and wild-type (WT) mice. Multiplex IF staining combined with RNAScope of tumors showed that AQP4 expression co-localized with GFAP-positive reactive astrocytes in perivascular areas. Our results indicated that tumor-bearing mice in an Aqp4-deficient background had increased edema content and decreased survival, suggesting that AQP4 is important for edema resolution from tumors. Loss of Aqp4 also significantly decreased astrocyte coverage in the tumor core, but not in the tumor periphery. Moreover, anti-VEGFA treatment only improved vessel leakage and reduced edema in WT tumor-bearing mice. Ongoing studies are focused on characterizing the impact of Aqp4 loss on the gene expression profile of tumor core-specific astrocytes using single-cell RNA sequencing and spatial transcriptomics. We are also studying the cellular distribution of AQP4 in GBM and the effect of DEX treatment on AQP4 levels.

Comparative studies on mannan and imiquimod induced experimental plaque psoriasis inflammation in inbred mice.

Psoriasis is a genetically determined, environmentally triggered, immune system-mediated autoimmune disease. Different animal models are needed to investigate the complex pathological mechanisms underlying this disease. Therefore, we established mannan-induced psoriasis model and compared with the most commonly used imiquimod-induced psoriasis in terms of disease, induction of innate immune cells, expression of cytokines, and the effect of dexamethasone treatment. Mannan significantly induced more severe psoriasis with better disease relapsing feature than imiquimod (IMQ). As determined by immunohistochemistry, IMQ induced significantly more infiltration of CD11c+ and F4/80+ cells than mannan in the skin. However, cytometric analysis showed a significant increase in the percentage of Gr-1+ neutrophils in the spleen and lymph nodes as well as F4/80+ macrophages in the spleen after mannan exposure. Variation in the percentage of significantly increased Vγ4 T cells was also found to be dependent on the lymphoid organs tested. However, there is a clear difference between these models in terms of expression of certain cytokine genes: IL-22, IL-23, IL-17E, and IL-17F were expressed more predominantly in mannan-induced inflammation, while IL-6 and IL-17A expressions were significantly higher in IMQ model. Interestingly, dexamethasone treatment strongly reduced epidermal thickness and histological scores induced by mannan than IMQ. Despite inducing psoriasis-like inflammation, certain differences and similarities were observed in the immune responses induced by mannan and IMQ. However, mannan-induced psoriasis model is relatively more simple, economical and less harmful to mice with an increased possibility to develop a chronic psoriasis model by exposing mice to mannan.

The Effect of Dexamethasone Treatment on COVID-19 Prognosis in Cancer Patients.

Background: Dexamethasone is used to treat cancer, relieve chemotherapy-induced nausea and vomiting, enhance cancer patients’ appetites, and treat COVID-19 patients. There is little evidence of the impact of a dexamethasone treatment plan on the severity of COVID-19 infections in cancer patients. This study explores whether dexamethasone treatment plan influences the severity of COVID-19 in dexamethasone-treated cancer patients. Methods: The medical records of 108 cancer patients receiving dexamethasone at King Hussein Cancer Center with a COVID-19 infection and 343 without corticosteroid treatment were reviewed. Patients on dexamethasone within seven days before infection, after infection, or both were included. Ventilation support, hospitalization, and mortality within 28 days of a COVID-19 diagnosis were key severity factors. Results: We found that dexamethasone before a COVID-19 infection increased the risk of requiring ventilation assistance and mortality within 28 days by a factor of 5.8 (2.8−12.0) relative to control (p < 0.005). Continuing dexamethasone treatment after a COVID-19 infection, or starting it after infection, had a risk factor equivalent to control. Conclusion: Our data showed that dexamethasone therapy protocol affected COVID-19 prognoses in cancer patients, and it is preferable to not discontinue therapy after infection. A rigorous prospective comparison between early and late dexamethasone dosing is needed to determine the best protocol for treatment.

The Effects of Dexamethasone Treatment and Dietary Fat Composition on Liver Lipid Metabolism in Mice Consuming High Fat Diets

Omega‐3 fatty acids are essential fats that the body cannot produce on its own and play a very integral role in the body in regard to inflammation and hormone production. Glucocorticoids are hormones that are also effective in inflammation reduction and suppressing the immune system; however, often have many detrimental side effects such as adipose accumulation, muscle atrophy and metabolic dysfunction. The purpose of this research experiment was to examine the effects dexamethasone treatment in combination with diets high in either omega‐3 fatty acids or omega‐6 fatty acids on markers of lipid metabolism in the liver. For a span of 4 weeks, two groups of mice were placed on a diet consisting of 45% fat containing either high omega‐3 or omega‐6 fatty acids. On the fifth week mice were randomized to two groups per diet and received either PBS placebo or Dexamethasone (Dex) injections daily. We hypothesized that Dex treatment would induce liver lipid accumulation and an omega‐3 rich diet would prevent this. At the completion of the 5 weeks, tissue was harvested and liver triglycerides were measured. There was a main effect of omega‐3 diet to have lower liver triglyceride levels (p=0.01). Fasn, Crat, Hsl, Cd36, and Fabp mRNA levels were measured in liver tissue. The resulted show that CratmRNA (p=.0153) and HslmRNA (p=.0417) was increased with omega‐3 rich diet, but there was no effect of Dex treatment. The Cd36 (p=.0495) and Fabp(p=.0229) mRNA increased in omega‐6 rich diets treated with Dex and omega‐3 high fat diet attenuated this increase. It can be concluded that one week of Dexamethasone treatment altered liver lipid signaling primarily by increasing lipid import and transport regulators, and omega‐3 high fat diet was able to prevent this increase. Additionally, omega‐3 high fat diet increase markers of lipid metabolism that were unaltered with one week of dex. These data suggest that omega‐3 fatty acids may help prevent the detrimental side effects of glucocorticoid treatment.

Effect of dexamethasone treatment at variable therapeutic windows in reversing nitrogen mustard-induced corneal injuries in rabbit ocular in vivo model

Nitrogen mustard (NM) is an analogue of the potent vesicating agent sulfur mustard, with well-established ocular injury models in rabbit eyes to study vesicant-induced ocular toxicity. The effects of NM-exposure to eyes may include irritation, redness, inflammation, fibrosis, epithelial degradation, blurred vision, partial/complete blindness, which may be temporary or permanent, depending on the route, duration, and dosage of exposure. Effective countermeasures against vesicant exposure are presently not available and are warranted in case of any terrorist activity or accidental leakage from stockpiles. Herein, our focus was to evaluate whether dexamethasone (DEX), an FDA approved potent corticosteroid with documented anti-inflammatory activities, could be an effective treatment modality. Accordingly, utilizing NM-induced corneal injuries in rabbit ocular in vivo model, we examined and compared the efficacy of DEX treatments when administration was started at early (2 h), intermediate (4 h), and late (6 h) therapeutic windows of intervention after NM-exposure and administered every 8 h thereafter. The effects of NM-exposure and DEX treatments were evaluated on clinical (corneal opacity, ulceration, and neovascularization), biological (epithelial thickness, epithelial-stromal separation, blood vessels density, and inflammatory cell and keratocyte counts) and molecular (COX-2 and VEGF expression) parameters, at day 1, 3, 7 and 14. Results indicated that DEX treatment markedly and effectively reversed the NM-induced injury markers in rabbit corneas. Early administration of DEX at 2 h was found to be most effective in reversing NM-induced corneal injuries, followed by DEX 4 h and DEX 6 h administration initiation, indicating that DEX has best efficacy at the early therapeutic window in our study model.

The profile of dexamethasone combined with transcranial direct current stimulation in rats submitted to an arthritis model

ABSTRACT BACKGROUND AND OBJECTIVES: To pursue safer and more effective treatments for rheumatoid arthritis, the effect of dexamethasone treatment (DEX, 0.25mg/kg) combined with transcranial direct current stimulation (tDCS) in the behavior and neurochemical parameters of arthritic rats was evaluated. METHODS: Thirty-six Wistar rats were divided into four groups: control+DEX (CTRL+DEX), arthritis+DEX (RA+DEX), arthritis+DEX+sham-tDCS (RA+DEX+sham-tDCS) and arthritis+DEX+tDCS (RA+DEX+tDCS). The arthritic model (RA) was induced by complete Freund’s adjuvant (CFA) paw administration. Paw edema and mechanical allodynia were assessed by plethysmometer and von Frey apparatus, respectively. Fourteen days after the CFA injection, rats received the treatment for eight days (DEX and/or tDCS). Behavioral parameters were measured with the Open-Field test. ELISA was used to evaluate hippocampal and spinal cord tumor necrosis factor (TNF-α) levels, cerebral cortex and brainstem BDNF levels. RESULTS: In pre-treatment measurements, arthritic rats presented an increase in joint swelling and mechanical allodynia when compared to the control group, confirming chronic pain establishment. A slight antinociceptive effect of dexamethasone combined with tDCS in the pain model was observed. The pain model significantly induced an increase in the grooming behavior and a reduction in the spinal cord and hippocampal TNF-α levels; these effects were reverted in the sham- and active-tDCS-treated rats. However, no effects of DEX or tDCS were observed in the BDNF levels in the cerebral cortex and brainstem. CONCLUSION: Despite the small effect observed, tDCS treatment cannot be discarded as a non-pharmacological adjuvant technique for inflammatory chronic pain treatment.

Dexamethasone causes calcium deposition and degeneration in human anterior cruciate ligament cells through endoplasmic reticulum stress

BackgroundDexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. ObjectiveThis study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. ResultsIn vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. ConclusionDexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.

P23 - Effect of dexamethasone treatment on cytochrome P450 3A-UDP-glucuronosyltransferase 1A interactions in rat liver

P23 - Effect of dexamethasone treatment on cytochrome P450 3A-UDP-glucuronosyltransferase 1A interactions in rat liver

Effects of dexamethasone treatment on serous retinal detachment in ranibizumab-resistant diabetic macular edema.

Purpose:To evaluate outcome of intravitreal dexamethasone implant (IDI) treatment on serous retinal detachment (SRD) in patients with ranibizumab-resistant diabetic macular edema (DME).Materials and methods:Forty-eight eyes of 48 patients with DME resistant to ranibizumab were enrolled in this retrospective and comparative study. Patients were divided into two groups according to presence of serous retinal detachment: (1) SRD or (2) non-SRD groups. All patients had at least three monthly ranibizumab injections, after which they were treated with IDI. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), use of antiglaucomatous drugs, and presence of cataract progression were noted at 1, 3, and 6 months post-IDI treatment.Results:There was not any statistically significant difference in terms of baseline characteristics of the patients. The mean CRT was declined in both groups at 1, 3, and 6 months (p < 0.001). After IDI treatment, the mean BCVA was improved in both groups at 1, 3, and 6 months (p < 0.001). When groups were compared, the change in CRT was higher in the SRD group (p = 0.018), while there was no statistically significant difference between groups in terms of BCVA changes (p = 0.448).Conclusion:The presence of SRD resulted in higher anatomical gain. SRD had no effects on visual changes after dexamethasone treatment in patients with ranibizumab-resistant DME.

Differential gene expression and gene-set enrichment analysis in Caco-2 monolayers during a 30-day timeline with Dexamethasone exposure

ABSTRACTGlucocorticoid hormones affect gene expression via activation of glucocorticoid receptor NR3C1, causing modulation of inflammation and autoimmune activation. The glucocorticoid Dexamethasone is an important pharmaceutical for the treatment of colitis and other inflammatory bowel diseases. While suppressive effects of glucocorticoids on activated immune cells is significant, their effects upon epithelial cells are less well studied. Previous research shows that the effects of Dexamethasone treatment on polarized Caco-2 cell layer permeability is delayed for >10 treatment days (as measured by transepithelial electrical resistance). In vivo intestinal epithelial cells turn over every 3–5 days; we therefore hypothesized that culture age may produce marked effects on gene expression, potentially acting as a confounding variable. To investigate this issue, we cultured polarized Caco-2 monolayers during a 30-day timecourse with ~15 days of continuous Dexamethasone exposure. We collected samples during the timecourse and tested differential expression using a 250-plex gene expression panel and Nanostring nCounter® system. Our custom panel was selectively enriched for KEGG annotations for tight-junction, actin cytoskeleton regulation, and colorectal cancer-associated genes, allowing for focused gene ontology-based pathway enrichment analyses. To test for confounding effects of time and Dexamethasone variables, we used the Nanostring nSolver differential expression data model which includes a mixturenegative binomial modelwith optimization. We identified a time-associated “EMT-like” signature with differential expression seen in important actomyosin cytoskeleton, tight junction, integrin, and cell cycle pathway genes. Dexamethasone treatment resulted in a subtle yet significant counter-signal showing suppression of actomyosin genes and differential expression of various growth factor receptors.

Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a spectrum of endotypes. TH2- and TH17-related cytokines are 2 central regulators involved in the inflammation associated with CRSwNP. We sought to investigate the interregulation of TH2 and TH17 pathways in Chinese patients with CRSwNP. Levels of key TH2- and TH17-related factors were measured in homogenates of polyp tissue obtained from patients with CRSwNP. The relationship of these factors and their expression in groups classified according to tissue IL-5 and IL-17 concentrations were analyzed. Cross-regulation of TH2 and TH17 cytokines and the effects of dexamethasone treatment were studied in dispersed nasal polyp cells. Associations between TH2- and TH17 related factors and comorbid atopic status and asthma, disease recurrence, and edema scores were also explored. Four CRSwNP groups were classified based on expression or nonexpression of mutually exclusive TH2- and TH17-related factors. The TH2 cytokines IL-4 and IL-13 inhibited expression of TH17-related factors, whereas the TH17 cytokines IL-17 and TGF-β1 enhanced expression of TH2-related factors. Dexamethasone treatment inhibited both the TH2 and TH17 pathways. Apatient's atopic status was related to their TH2 immune response. Edema scores were positively correlated with the TH2 pathway and negatively correlated with the TH17 pathway. The TH2 and TH17 pathways are mutually exclusive and regulate each other, favoring the development of a TH2 immune response in Chinese patients with CRSwNP.

The Effects of Ocimum basilicum Extract and Its Constituent, Rosmarinic Acid on Total and Differential Blood WBC, Serum Levels of NO, MDA, Thiol, SOD, and CAT in Ovalbumin Sensitized Rats.

The effects of Ocimum basilicum (O. basilicum) and its constituent, rosmarinic acid, on total and differential blood WBC, serum levels of NO2, NO3, MDA, thiol, SOD, and CAT in sensitized rats were examined. The study was performed in control animals (group C) and eight groups of sensitized rats to ovalbumin which were given drinking water alone (group S), drinking water containing three concentrations of O. basilicum (O; 0.75, 1.5 and 3.0 mg/mL), three concentrations of rosmarinic acid (R; 0.125, 0.25 and 0.5 mg/mL) and dexamethasone (1.25 μg/mL), (n = 6 for R treated and n = 8 for other groups). Total and differential WBC as well as serum concentrations of oxidant and antioxidant biomarkers were measured in all groups. Serum levels of oxidant biomarkers, total WBC count, percentages of eosinophils and neutrophils were significantly increased but other measured parameters except monocytes were significantly decreased in group S compared to group C. Serum levels of oxidant biomarkers, total WBC count, percentages of eosinophils, neutrophils and monocytes were significantly decreased but other measured parameters were significantly increased in treated S groups with dexamethasone, extract, and rosmarinic acid compared to group S. The effects of the extract and rosmarinic acid on some measured variables were significantly higher than the effect of dexamethasone treatment. These results showed the effect of O. basilicum and its constituent, rosmarinic acid on inflammatory and oxidant parameters in sensitized rats which was comparable or even more potent than dexamethasone at used concentrations.

Training Attenuated Hypertension in Dexamethasone‐Treated Wistar Rats and SHR Through Different Mechanisms

It has been shown that chronic treatment with dexamethasone (DEX) increase blood pressure (BP) in normotensive rats, however, nothing is known about the effects of DEX treatment in spontaneously hypertensive rats (SHR). On the other hand, exercise training (T) has been recommended as a non‐pharmacological treatment for hypertension. Thus, the aim of this study was to investigate the preventive role of T in counteracting DEX‐induced BP increase in normotensive and SHR. Rats were randomly allocated into 8 groups: Wistar sedentary control (WSC), Wistar sedentary treated with DEX (WSD), Wistar trained control (WTC), Wistar trained and treated with DEX (WTD), SHR sedentary control (SHRSC), SHR sedentary treated with DEX (SHRSD), SHR trained control (SHRTC) and SHR trained and treated with DEX (SHRTD). All groups underwent T protocol (treadmill, 60% of physical capacity, 5 days/week, 8 weeks) or were kept sedentary. Then, rats were treated with DEX or saline (0.05 mg/kg per day, s.c., 14 days). Systolic arterial pressure (SAP) was measured by carotid artery catheterization and cardiovascular autonomic modulation to the heart was evaluated by spectral analysis. In addition, tibialis anterior (TA) muscle was collected for morphometric analysis. In Wistar rats, DEX treatment increased SAP (130 ± 5 vs 106 ± 6 mmHg, for SD vs SC, respectively) associated with an increase in low‐frequency spectral power (LF) (45.1 ± 5.9 vs 18.7 ± 4.8 nu, for SD vs SC, respectively) and a decrease in high‐frequency (HF) spectral power (54.8 ± 5.9 vs 81.2 ± 4.8 nu, for SD vs SC, respectively) of pulse interval; also DEX decreased capillary‐to‐fiber ratio (C:F ratio) (0.7 ± 0.02 vs 0.9 ± 0.01, for SD vs SC, respectively) in TA muscle, without affecting wall‐to‐lumen ratio (W/L ratio). Although SHR presented higher SAP (149 ± 7 vs 106 ± 6 mmHg, for SHRSC vs WSC, respectively) and W/L ratio (0.91 ± 0.09 vs 0.58 ± 0.08, for SHRSC vs WSC, respectively) as well as lower values of C:F ratio (0.7 ± 0.04 vs 0.9 ± 0.01, for SHRSC vs WSC, respectively), compared with Wistar rats, DEX treatment did not produce any further alterations in these parameters. On the other hand, T, in Wistar rats, was able to attenuate SAP increase (122 ± 4 vs 130 ± 5 mmHg, for TD vs SD, respectively), LF increase (27.6 ± 6.2 vs 45.1 ± 5.9 nu, for TD vs SD, respectively), HF decrease (72.3 ± 6.2 vs 54.8 ± 5.9 nu, for TD vs SD, respectively) of pulse interval and also C:F ratio decrease (1.0 ± 0.02 vs 0.7 ± 0.02, for TD vs SD, respectively) in TA muscle. In addition, in SHR, T was effective to reduce SAP (121 ± 5 vs 151 ± 8 mmHg, for TD vs SD, respectively), to increase C:F ratio (1.0 ± 0.04 vs 0.7 ± 0.02, for TD vs SD, respectively) and to decrease arterioles W/L ratio (0.58 ± 0.09 vs 0.91 ± 0.08, for TD vs SD, respectively) in TA muscle. In conclusion, these results allow us to suggest that T was able to attenuate DEX‐induced BP increase in Wistar rats, associated with an improvement of cardiovascular autonomic modulation and skeletal muscle microcirculation. In addition, T was able to decrease BP in SHR, mainly through decreases in arterioles W/L ratio and improvements in microcirculation, independent of DEX treatment.Support or Funding InformationSão Paulo Research FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modulation of lung inflammation and immune markers in asthmatic rats treated by Portulaca oleracea.

Previous studies indicated anti-inflammatory effects for Portulaca oleracea in various inflammatory disorders. In this study, the effects of P. oleracea on bronchoalveolar lavage fluid (BALF) levels of total protein (TP), Phospholipase A2 (PLA2) and IgE in sensitized rats were examined. Male rats were randomly divided into six groups namely, control (group C), sensitized rats (group S), sensitized animal treated with three concentrations of the extract of P. oleracea and dexamethasone (n = 8 for each group). The levels of TP, PLA2 and IgE in BALF were measured. The levels of TP, PLA2 and IgE were significantly increased in the BALF of group S compared to group C (p<0.001 for all cases). However, treatment of S rats with all concentrations of the extract, resulted in a significant and concentration-dependent reduction in BALF levels of TP, PLA2 and IgE compared to group S (p<0.001 for all cases except for the effect of the low extract concentration on TP). Dexamethasone treatment also led to significant reduction of TP, PLA2 and IgE (p<0.001 for all cases). The effect of dexamethasone treatment on PLA2 was significantly higher than the effects of all extract concentrations (p<0.001 for all cases). However, the effect of high extract concentration on TP and IgE was significantly higher than that of dexamethasone (p<0.001 both cases). The results indicated anti-inflammatory and immunomodulatory effects of P. oleracea in sensitized rats (as an animal model of asthma) which was equal or more marked than dexamethasone at studied concentrations.

Effects of dexamethasone treatment on insulin sensitivity, insulin, thyroxine, and triiodothyronine concentrations, and the MSH and ACTH responses to sulpiride in geldings

Two studies were conducted to determine efficacy of cabergoline for suppressing prolactin (PRL) and the possible effects on vernal transition in mares. In experiment 1, six mares each received either vehicle or cabergoline (5 mg, intramuscularly) every 10 days for 12 treatments beginning February 4, 2013. Blood samples were drawn regularly, and mares were challenged with sulpiride periodically to assess PRL suppression. Weekly hair samples were obtained to determine shedding. Prolactin was suppressed (P < .05) by cabergoline, but suppression waned in spring. There was no effect (P > .05) of treatment on day of first ovulation, luteinizing hormone, or follicle stimulating hormone. Hair shedding was generally suppressed (P = .05). In 2014 (experiment 2), eight of the same 12 mares were used in a similar experiment to determine if the rise in PRL observed in experiment 1 was due to refractoriness to cabergoline or perhaps another factor. Treatment began on April 6, 2014, corresponding to the increase in PRL in treated mares in experiment 1. Mares were treated with cabergoline or vehicle until June 5. Prolactin was suppressed (P < .05) by cabergoline, and the pattern of apparent escape from suppression was similar to year 1. We conclude that (1) cabergoline at this dose alters hair shedding but does not alter the time of first ovulation in mares and (2) relative to our previous reports of cabergoline treatment in the fall, there is a seasonal effect on the ability of this dose of cabergoline to suppress unstimulated PRL secretion.

Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers.

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers ( = 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h on d -3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d -4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at -74, -50, and -26 h; at 0.5-h intervals from -4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction ( < 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d -3 and 0, respectively. A treatment × time interaction ( < 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers ( < 0.001) yet decreased lymphocytes in CHR steers ( = 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased ( < 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosinophils were greater ( < 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction ( = 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced ( ≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed ( ≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed ( ≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.

Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers ( = 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h on d -3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d -4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at -74, -50, and -26 h; at 0.5-h intervals from -4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction ( < 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d -3 and 0, respectively. A treatment × time interaction ( < 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers ( < 0.001) yet decreased lymphocytes in CHR steers ( = 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased ( < 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosinophils were greater ( < 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction ( = 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced ( ≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed ( ≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed ( ≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.

GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis.

Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic β-cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes. However, the mechanism is not fully understood. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase and plays an important role in energy metabolism, cell growth and apoptosis. Therefore, the contribution of GSK-3β in dexamethasone-induced pancreatic β-cell apoptosis was determined in the present study. The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress (ROS), and the phosphorylation status of GSK-3β was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride (LiCl) on dexamethasone-induced β-cell apoptosis was also evaluated. Dexamethasone (0.1 μM) treatment induced INS-1 apoptosis, which was associated with increased GSK-3β activation and increased NOX4-derived ROS generation. Pretreatment of INS-1 with LiCl inhibited dexamethasone induced ROS generation and INS-1 apoptosis. This study provides a new mechanism of Dex induced pancreatic β cell apoptosis and may serve as a new therapeutic option for treating GC induced diabetes.

Toxicological effect of dexamethasone treatment on the transport of both amino-acids, tyrosine and tryptophan, across the blood brain barrier (BBB)

Toxicological effect of dexamethasone treatment on the transport of both amino-acids, tyrosine and tryptophan, across the blood brain barrier (BBB)