High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.

Dexamethasone in coronavirus disease 2019 care:Dosage and utilization insights

Coronavirus disease 2019(COVID-19)is a contagious disease caused by severe acute respiratory syndrome coronavirus 2.It was declared a global pandemic on March 11,2020,by the World Health Organization.An excessive inflammatory response is a severe respiratory manifestation of COVID-19,which becomes predominant in later stages.Due to its immunosuppressive and anti-inflammatory properties,dexamethasone is the first systemic glucocorticoid to treat severe COVID-19 patients.This editorial reviews the efficacy and safety of highdose vs low-dose dexamethasone in patients with COVID-19.Findings indicate that using low-dose dexamethasone is beneficial and emphasize the need for additional research on the use of high-dose dexamethasone.While the study provides a robust evidence base,it is limited by the lack of long-term data,focus on specific outcomes and heterogeneity of the included studies.Future research should focus on the long-term effects of dexamethasone and its impact across varying disease severities and patient populations to refine treatment strategies and improve patient care.

Revisiting dexamethasone dosage in COVID-19 management

The ongoing coronavirus disease 2019(COVID-19)pandemic has necessitated rapid advancements in therapeutic strategies,with dexamethasone emerging as a key treatment for severe cases.This editorial discusses the systematic review conducted by Sethi et al,published in the World Journal of Virology.The review critically examines the efficacy and safety of varying dosages of dexamethasone in severe COVID-19 patients,providing a comprehensive meta-analysis that underscores the current clinical recommendations favoring a low-dose regimen.Despite these findings,the review highlights the potential benefits of tailored dosages for specific patient subgroups,suggesting a need for personalized treatment approaches.This editorial expands on the implications of these findings,advocating for the integration of evolving clinical data into treatment protocols and calling for further research into patient-specific responses to therapy.It emphasizes the importance of adaptability and precision in pandemic response,urging the medical community to consider both the robustness of existing evidence and the potential for innovative approaches to enhance patient outcomes in the face of global health challenges.

Effects of chronic dexamethasone administration on hyperglycemia and insulin release in goats

Background: Dexamethasone(Dex), a synthetic glucocorticoid, is among the most commonly used drugs worldwide in animals and humans as an anti-inflammatory and immunosuppressive agent. GC has profound effects on plasma glucose level and other metabolic conditions. However, the effect of prolonged use of Dex on glucose metabolism in ruminants is still unclear.Results: Ten goats were randomly assigned to two groups: the control goats were injected with saline, and the Dex-treated goats were intramuscularly injected daily for 21 d with 0.2 mg/kg Dex. The results showed that plasma glucose and insulin concentrations were significantly increased after Dex administration(P < 0.05). Additionally, the content of hepatic glycogen was also markedly increased in Dex-treated goats(P < 0.01), while the content of glycogen in dorsal longissimus was unchanged by Dex(P > 0.05). The expression of several key genes, involved in blood glucose regulation, was detected by real-time PCR in the small intestine, skeletal muscle and liver. The expression of glucose transporter type 2(GLUT2), sodium-glucose transporter 1(SGLT1) and sodium-potassium ATPase(Na-K/ATPase) in the small intestine were generally increased by Dex, and GLUT2 m RNA expression was significantly up-regulated(P < 0.05). In liver, the expression of genes involved in gluconeogenesis including glucose-6-phosphatase catalytic subunit(G6 PC), cytosolic form of phosphoenolpyruvate carboxykinase(PCK1) and pyruvate carboxylase(PC), were significantly down-regulated by Dex. However, the protein expression levels of PCK1 & PCK2 were significantly increased by Dex, suggesting a post-transcriptional regulation. In dorsal longissimus, the m RNA expression of genes associated with gluconeogenesis and the insulin signaling pathway were generally upregulated by Dex, but the m RNA expression of two markers of muscle atrophy, namely F-box protein 32(FBXO32/Atrogin1) and muscle RING-finger protein 1(Mu RF1), was not altered by Dex.Conclusions: Taken together, these results indicate that chronic administration of a low dosage of Dex induces hyperglycemia mainly through gluconeogenesis activation in the goat liver.

Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis

Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.

Enhancing global hepatocellular carcinoma management:Bridging Eastern and Western perspectives on dexamethasone and Nacetylcysteine before transarterial chemoembolization

This article explores the integration of Eastern and Western perspectives on the use of dexamethasone and N-acetylcysteine as premedications in transarterial chemoembolization for hepatocellular carcinoma(HCC).By examining key concerns raised by Western researchers,particularly regarding the different etiologies of liver cirrhosis,and contrasting them with robust clinical data from Asia,this article highlights the necessity for region-specific research and proposes future directions for global HCC management.

Dexamethasone implant in naive versus refractory patients with diabetic macular edema:a Meta-analysis

AIM:To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema(DME).METHODS:PubMed,Embase,Web of Science,and Medline databases were searched.The main outcomes were best-corrected visual acuity(BCVA)and central retinal thickness(CRT).The secondary outcomes included mean number of injections,intraoperative or postoperative complications including intraocular pressure(IOP)elevation and cataract.RESULTS:Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected.The postoperative BCVA in the naive group was significantly better than in the refractory group[mean difference(MD)-0.11,95% confidence interval(CI)-0.17 to-0.05,P=0.0003;MD 8.69,95%CI 5.08 to 12.30,P<0.00001].Additionally,the naive group got greater improvement of BCVA change as well as more gains of BCVA letters than the refractory group[MD 7.71,95%CI 2.02 to 13.40,P=0.008;odds ratio(OR)2.99,95%CI 2.05 to 4.37,P<0.00001].The subgroup analysis revealed that the naive group had significantly higher BCVA gains of≥5,≥10,and≥15 letters compared to the refractory group(P=0.002,0.0001,0.003,respectively).No significant difference was detected between the two groups in either postoperative CRT(MD-22.36,95%CI-46.39 to 1.66,P=0.07)or the overall mean number of injections(MD-0.08,95%CI-0.38 to 0.22,P=0.61).Intraoperative and postoperative complications including the elevation of IOP(OR 0.47,95%CI 0.20 to 1.13,P=0.09)and cataract(OR 1.78,95%CI 0.97 to 3.24,P=0.06)showed no significant differences between the two groups during the follow-up time.CONCLUSION:Intravitreal dexamethasone implants for DME can improve anatomical and functional outcomes in both naive and refractory eyes and have a well-acceptable safety profile.Moreover,naive eyes maintain better visual outcomes than refractory eyes.It provides further evidence of better visual response when used for naive eyes as firstline therapy.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

AIM:To evaluate the efficacy,timing of retreatment and safety of dexamethasone(DEX)implant on macular edema(ME)secondary to diabetic retinopathy(DME)and retinal vein occlusion(RVO-ME)patients who were refractory to anti-vascular endothelial growth factor(VEGF)treatment.METHODS:This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1,2019,and January 1,2023.These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness(CRT).The best corrected visual acuity(BCVA)and CRT were measured at baseline,and at 1,3,4 and 6mo post-DEX implant injection.Adverse events such as elevated intraocular pressure(IOP)and cataract were recorded.RESULTS:For RVO cases(n=22),there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection(P<0.05)and CRT decreased from 472.1±90.6 to 240.5±39.0μm at 6mo(P<0.0001).DME cases(n=15)experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection(P=0.0098),with CRT reducing from 445.7±55.7 to 271.7±34.1μm at 6mo(P<0.0001).Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications.No cases of cataract or other adverse events were reported.CONCLUSION:DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME.Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Effects of Dexamethasone, Clonidine, Tramadol and Nalbuphine on Fentanyl-Induced Hyperalgesia in Rats

Opioids are drugs used to alleviate pain. However, studies have demonstrated that these drugs can cause an increase in pain sensitivity, which is called opioid-induced hyperalgesia. The objective of this study was to describe the effects of dexamethasone, clonidine, tramadol and nalbuphine on fentanyl-induced hyperalgesia in rats. After obtaining approval from the Committee for the Ethical Use of Animals (CEUA), 36 male Wistar rats were divided into 6 groups: Group 1 (GCSSL) wherein the rats received 1 ml 0.9% saline solution in two injections;Group 2 (GFTSL), received fentanyl at a dose of 100 ug·kg-1 followed by 1 ml 0.9% saline solution via intraperitoneal;the remaining groups (3, 4, 5, 6) received fentanyl at a dose of 100 ug·kg-1 following doses via intraperitoneal: Group 3 (GFTDX), dexamethasone at a dose of 1.0 mg·kg-1;Group 4 (GFTCL), clonidine at a dose of 20 mg·kg-1;Group 5 (GFTTR), tramadol at a dose of 50 mg·kg-1, and Group 6 (GFTNB), nalbuphine at a dose of 5 mg·kg-1. Under general anestesia using isoflurane, the animals were submitted to a surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments at 2 hours after the incision and on the 1st, 3rd and 5th days afterward. At 2 hours after the surgical procedure, there was lower intensity of pain in the fentanyl group (GFTSL) compared to the other groups, and on the fifth day there were no significant differences for pain intensity between groups. The results suggest the presence of fentanyl-induced hyperalgesia and efficacy in its reduction by dexamethasone, clonidine, tramadol and nalbuphine.

Optical Coherence Tomography (OCT) Feature Identifying Niche for Dexamethasone (FIND) Intravitreal Implant in the Treatment of Anti-VEGF Slow Responders with Diabetic Macular Edema

This paper raises the question if intravitreal dexamethasone implant deserves to be utilized more effectively in a select subset of eyes with diabetic macular edema (DME). If so, what is the OCT morphology of such eyes? A retrospective consecutive case series is employed to answer these questions. Twenty consecutive eyes were studied: ten that have been treated with intravitreal anti-VEGF (Group A) injections and ten which have been treated with the steroidal implant (Group O) because they failed or were slow to respond to multiple injections of anti-VEGF medications. Specifically, 1) macular edema in the eyes were categorized for the type of OCT morphology and 2) their response to the respective treatments in terms of the resolution of the OCT morphology was determined. Results show that the OCT morphology of eyes that were in Group O predominantly (7/10) had the feature of posterior retinal leakage (subretinal fluid and large outer retinal cysts);this feature was rare in Group A (2/10). Further, each of these eyes (7/7) in Group O had a complete resolution of the macular edema after a single treatment with the dexamethasone intravitreal implant whereas neither eye with this feature (0/2) responded to the (anti-VEGF) treatment in Group A. This leads to the conclusion that there exists an OCT Feature that Identifies a Niche for Dexamethasone Intravitreal implant (FIND) in the treatment of anti-VEGF slow responders in DME. The clinical significance of the study is that selecting eyes with a priori FIND morphology on the OCT for treatment with dexamethasone implant prior to, or at the outset of, a series of anti-VEGF treatment may resolve DME promptly and lower the treatment burden for patients and cost to society.

Simultaneous Intravitreal Ranibizumab and Dexamethasone Implant Administration at the Same Setting in Eyes with Severe Diabetic Macular Edema

Aim: To share our experience in eyes with severe DME (exhibiting serous retinal detachment or large cysts) treated with simultaneous intravitreal ranibizumab and dexamethasone implant administration at the same setting as the first treatment step. Subjects and Results: Five eyes of three patients with DME who were either treatment naive or relatively undertreated were presented in this report. As optical coherence tomography exhibited serous retinal detachment or severe cystoid edema with large cysts, intravitreal ranibizumab and dexamethasone implant were simultaneously employed at the same setting as the first treatment step in those eyes. Panretinal photocoagulation was also commenced bilaterally a week after the start of injections when at least one eye had retinal neovascularization. Subsequent treatments of intravitreal ranibizumab and/or dexamethasone implant were administered. Patients were followed up for seven, eight and 13 months respectively. All five eyes achieved a relative anatomic stability and experienced visual improvement at the end of follow-up. Conclusion: In some cases with severe DME with or without proliferative diabetic retinopathy, simultaneous intravitreal ranibizumab and dexamethasone implant administration at the same setting may be a better option to initiate the treatment over mono ranibizumab treatment. A randomized study comparing the mono anti-VEGF therapy and mono dexamethasone implant administration with simultaneous treatment may outline the place of this type of therapy in the treatment armamentarium of severe DME.

Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.

A Triterpenoid Inhibited Hormone-Induced Adipocyte Differentiation and Alleviated Dexamethasone-Induced Insulin Resistance in 3T3-L1 adipocytes

6a-Hydroxylup-20(29)-en-3-on-28-oic acid(1),a natural triterpenoid,was found to possess the ability in a dose-dependent manner inhibiting hormone-induced adipocyte differentiation in 3T3-L1 preadipocytes,and restoring glucose consuming ability in dexamethasone(DXM)-induced insulin resistant 3T3-L1 adipocytes.Compound 1 was also found to ameliorate DXM-induced adipocyte dysfunction in lipolysis and adipokine secretion.Mechanistic studies revealed that 1 inhibited adipocyte differentiation in 3T3-L1 preadipocytes via down-regulating hormone-stimulated gene transcription of peroxisome proliferator-activated receptor c and CCAAT-enhancer-binding protein alpha which are key factors in lipogenesis,and restored DXM-impaired glucose consuming ability in differentiated 3T3-L1 adipocytes via repairing insulin signaling pathway and activating down-stream signaling transduction by phosphorylation of signaling molecules PI3K/p85,Akt2 and AS160,thus leading to increased translocation of glucose transporter type 4 and transportation of glucose.

Dexamethasone-Loaded PLGA Microspheres Incorporated PLLA/PLGA/PCL Composite Scaffold for Bone Tissue Engineering

The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.

Outcome Values of Adding Sodium Bicarbonate, Dexamethasone and Fentanyl to Local Anesthetic in Peribulbar Block during Vitreoretinal Surgeries. A Randomized Prospective Study

Background and aims: we aimed to detect the outcome values of adding fentanyl, dexamethasone and sodium bicarbonate to mixture of local anesthetic in peribulbar block for vitreoretinal surgery. Methods: 120 adult ASA I & II patients, admitted for vitreoretinal surgery under peribulbar block were included in this comparative study. This study included 4 groups: Group I: (30) patients using a mixture of 1 ml normal saline, 4 ml lidocaine 2% plus 4 ml from bupivacaine 0.5% 20 ml vial containing hyaluronidase 1500 IU. Group II: (30) patients using a mixture of 1 ml of sodium bicarbonate (from 1 ml sodium bicarbonate 8.4% diluted in 10 ml normal saline), 4 ml lidocaine 2% plus 4 ml from bupivacaine 0.5% 20 ml vial containing hyaluronidase 1500 IU. Group III: (30) patients using a mixture of 1 ml fentanyl 20 μg (from a mixture of fentanyl 100 μg diluted in 5 ml normal saline), 4 ml lidocaine 2% plus 4 ml from bupivacaine 0.5% 20 ml vial containing hyaluronidase 1500 IU. Group IV: (30) patients using a mixture of 1 ml of 4 mg dexamethasone (1 ampoule = 8 mg/2 ml), 4 ml lidocaine 2% plus 4 ml from bupivacaine 0.5% 20 ml vial containing hyaluronidase 1500 IU. We measured the onset and duration of anesthesia, IOP, eyelid and global akinesia, postoperative pain by numerical pain rating scale, first analgesic requirement and postoperative side effects. Results: No significant differences were detected among the four groups as respect to age, sex and the intraocular pressure (IOP) before the anesthesia block. While the intraocular pressure (IOP) after the anesthesia block there was a significant difference, as IOP was markedly decreased postoperatively in group II compared with other groups. As regard to the onset & duration of anesthesia there was significant difference among all groups, there was rapid onset and prolonged duration of anesthesia in group III compared with other groups (1.77 ± 0.63 & 5.03 ± 0.89) respectively. As regard the onset of lid akinesia there was significant difference among the four groups with better outcome in group III, as in group III represented the most rapid onset of lid akinesia. As respecting to the onset of global akinesia there was significant difference among the four groups. There was better outcome in group III as it represented more rapid onset of global akinesia compared with other groups. There were significant differences among the four groups as regard postoperative pain all over 6 hours, better results were in group III (0.27 ± 0.69) compared with group I (2.23 ± 1.17), group II (2.00 ± 1.70), group IV (0.67 ± 0.71). As regarding to the first time for analgesic requirement there were significant differences among groups, there was no request for analgesia with better outcome in group III with increasing need to the analgesic medication in group I compared to group II and group IV. As regard side effects postoperatively there were few side effects in all groups with few numbers of cases in groups III only one patient. Although these differences in number of patients are not significant among the four groups. Conclusion: Addition of sodium bicarbonate to local anesthetic mixture was the best way in lowering the IOP other than other groups and addition of fentanyl to local anesthesia provided more rapid onset and duration of anesthesia, more rapid onset and duration for lid and global akinesia, less pain, less analgesic requirement and minimal side effects than the other groups.

Dexamethasone treatment alters kinetics properties of liver mitochondrial F₀.F₁-ATPase and membrane lipid profiles in developing and adult rats

Dexamethasone—a potent synthetic glucocorticoid—has multiple diagnostic and therapeutic applications in wide range of age groups. However, the side-effects of dexamethasone (Dex) treatment including those on development are becoming increasingly apparent. Since the developmental processes are energy-dependent, we examined the effects of chronic Dex treatment on kinetics properties of liver mitochondrial F0.F1-ATPase and mitochondrial membrane lipid profiles in rats belonging to different developmental age groups (2, 3, 4 and 5 weeks) and in adults (~8 weeks). The animals were treated with a subcutaneous dose of 2 mg of Dex/kg body weight (or saline as vehicle) for three alternative days (at around 7.00 A.M.) prior to the day of sacrifice. Dex treatment resulted in significant reduction in F0.F1-ATPase activity in developmental age groups and in adults as compared to their age-matched vehicle-treated control group. The substrate kinetics analysis of F0.F1-ATPase resolved Km and Vmax values in 3 components in all the control age groups;whereas Dex treatment significantly altered the Km and Vmax values or abolished the entire components in age-specific manner. Dex treatment significantly lowered the energy of activation and altered phase transition temperature (TtoC) in all the developmental age groups and in adults. Dex treatment significantly increased the contents of total phospholipid (TPL), individual phospholipids classes and cholesterol (CHL) in all the developmental age groups whereas opposite pattern was observed in adults. The mitochondrial membrane became more fluidized in the developing age groups (2, 4 and 5 weeks);whereas no change was observed in 3-week and adult groups following Dex treatment. In present study, our data demonstrate comprehensive deleterious effects of chronic Dex treatment on liver mitochondrial membrane structure and F0.F1-ATPase functional properties with respect to energy metabolism. At the same time, our data also warns against excessive repeated use of antenatal DEX in treatments in growing and adult human patients.

Sinus Bradycardia Rare but Expected Complications of Chemo Regimen Involving Dexamethasone: Case Report

Weight gain, Osteoporosis, Glucose intolerance, Hypertension, and Cataract are the common complications associated with Dexamethasone. However, here we report a case of Multiple Myeloma who received chemotherapy involving Dexamethasone. Although this patient has no previous comorbid cardiac condition, he developed Sinus Bradycardia during the latter part of chemo regimen. Ironically Sinus Bradycardia was asymptomatic in these cases. The exact mechanism of how Dexamethasone causes Sinus Bradycardia is yet not properly understood, and some of the possible mechanisms of Dexamethasone causing Sinus Bradycardia have been postulated below.

Comparison of High-Dose Dexamethasone and Prednisone for Initial Treatment of Adult Primary Immune Thrombocytopenia

Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.

Adansonia digitata aqueous leaf extract ameliorates dexamethasone-induced testicular injury in male Wistar rats

Objective:To evaluate the effects of aqueous leaf extract of Adansonia(A.)digitata L on dexamethasone-induced testicular damage in male Wistar rats.Methods:Twenty adult male Wistar rats weighing 170-190 g were divided into four groups.GroupⅠreceived 0.5 mL of phosphate buffer orally for 28 days and served as the normal control group;groupⅡreceived 10 mg/kg of dexamethasone(a synthetic glucocorticoid)intraperitoneally for 7 days and 0.5 mL of phosphate buffer orally for 21 days,groupⅢreceived 10 mg/kg of dexamethasone for 7 days and 800 mg/kg of A.digitata extract orally for 21 days;groupⅣreceived 10 mg/kg of dexamethasone for 7 days and 300 mg/kg of vitamin-E orally for 21 days.Dexamethasone was administered intra-peritoneally for 7 days and all administration lasted for 28 days.The rats were sacrificed by anesthesia with diethyl ether and the testes of each animal were harvested.The testis was homogenized in 0.25 M sucrose at 4℃for biochemical and histological analyses.Results:Administration of dexamethasone significantly decreased body weight,glucose-6-phosphate dehydrogenase(G6PDH),lactate dehydrogenase(LDH),superoxide dismutase(SOD),and glutathione peroxidase(GPx)(P<0.05),and significantly increased malondialdehyde(MDA)activities(P<0.05).The degeneration in the population of spermatogonia and vacuolation and abnormal widening of the interstitial spaces were observed in the rats treated with dexamethasone.However,administration of A.digitata significantly increased SOD,GPx,G6PDH,and LDH levels,significantly decreased MDA activities and improved the histoarchitecture of the testis(P<0.05).Conclusions:A.digitata may have an ameliorative effect on dexamethasone-induced testicular damage in Wistar rats because of its anti-inflammatory and antioxidant properties.

The Effect of Intramuscular versus Intra-Amniotic Dexamethasone Administration on Blood Glucose Level in Diabetic Pregnant Women

Background: To investigate the blood glucose level response of diabetic pregnant women when administrating antenatal dexamethasone to accelerate fetal lung maturity in different routes. Methods: This prospective cohort study included 60 pregnant women with diabetes who required promotion of fetal lung maturity in Peking University First Hospital from January 2013 to April 2015. Dexamethasone was administered by IM (n = 29) or IAC (n = 31). Blood glucose level was monitored before injection, and 1 day, 2 days and 3 days after injection. Results: In the intramuscular injection group, the preprandial and postprandial blood glucose concentration was significantly elevated in the first two days (P < 0.001), and the postprandial blood glucose level was still higher than basal level (P = 0.034) on the third day. In the intra-amniotic injection group, the preprandial and postprandial blood glucose concentration was also significantly elevated on the first day (P < 0.001), but soon returned to the basal level on the second day. No significant difference was found in the magnitude of glucose increase between the two groups. Conclusion: Blood glucose level is significantly influenced by intramuscular injection of antenatal dexamethasone rather than amniotic cavity injection.