Different Doses Of Dexamethasone Research Articles

Efficacy of Different Doses of Dexamethasone as Pre-emptive Analgesia in Patients Undergoing Total Abdominal Hysterectomy under General Anaesthesia: A Prospective Non Randomised Placebo Controlled Study

Introduction: Pre-emptive analgesia reduces postoperative analgesic requirement, avoiding side-effects that occur with parenteral narcotics. Dexamethasone, a long acting synthetic corticosteroid with predominantly glucocorticoid activity is one of the entities used for pre-emptive analgesia. The optimum dose of dexamethasone for pre-emptive analgesia is not defined. Aim: To study the efficiency of different (low, intermediate and high) doses of dexamethasone as pre-emptive analgesia in patients undergoing total abdominal hysterectomy under general anaesthesia. Materials and Methods: The prospective non randomised placebo controlled dose range study was conducted in the Department of Anaesthesiology, at a tertiary care institute at Srinagar, Jammu and Kashmir, India, over a period of two years from July 2017 to June 2019. Eighty female patients (age 40-65 years, American Society of Anaesthesiologists (ASA) I and II) scheduled for total abdominal hysterectomy were divided into four groups (Groups A, B, C and D) on the basis of dexamethasone dose. Group A with low dose (0.1 mg/kg), group B with intermediate dose (0.12-2 mg/ kg), group C with high dose (>0.2 mg/Kg) and group D with no dexamethasone. Early and late acute postoperative pain {Visual Analog Scale (VAS) score}, cumulative analgesic consumption upto 24 hours, intraoperative blood sugar levels, Postoperative Nausea and Vomiting (PONV), and adverse events were recorded. Analysis of variance (ANOVA) was used for intergroup comparison of means and Chi-square test was used for categorical variables. Results: The mean age (years) of group A was 52.3±8.87, group B was 48.3±5.23, group C was 49.8±6.85 and group D was 51.7±4.46. Postoperative VAS score for 0 hour, 1 hour, 2 hour, 3 hour, 4 hour was more in patients who had not received dexamethasone pre-emptively (p-value <0.05). VAS score at 6 hour, 12 hour, 24 hour was more in patients who had not received dexamethasone pre- emptively. There was a statistically significant difference in VAS score at 6, 12, 24 hours when low dose dexamethasone group was compared with intermediate and high dose dexamethasone groups (p-value <0.05). Rescue analgesia consumption was significantly less in patients who received intermediate to high dose dexamethasone. Blood sugar levels increased significantly in patients receiving dexamethasone, but returned to baseline after 24 hours. The incidence of nausea and vomiting and the need for rescue antiemetic was significantly less in patients receiving dexamethasone (p-value <0.05). The incidence of postoperative adverse effects was not different among these groups (p-value >0.05). Conclusion: Intermediate and high dose dexamethasone, given preoperatively in patients undergoing abdominal hyster-ectomy produces better postoperative analgesia with added antiemetic benefit.

Preoperative dexamethasone for pain relief after total knee arthroplasty: A randomised controlled trial.

Corticosteroids can reduce pain but the optimal dose and safety profiles are still uncertain. This study aimed to evaluate two different doses of dexamethasone for pain management and their side effects after total knee arthroplasty. A prospective randomised, controlled trial. A tertiary teaching hospital in Hong Kong. One hundred and forty-six patients were randomly allocated to one of three study groups. Before operation, patients in group D8, D16 and P received dexamethasone 8 mg, dexamethasone 16 mg and placebo (0.9% saline), respectively. The primary outcome was postoperative pain score. Secondary outcomes were opioid consumption, physical parameters of the knees and side effects of dexamethasone. Compared with placebo, group D16 patients had significantly less pain during maximal active flexion on postoperative day 3 [-1.3 (95% CI, -2.2 to -0.31), P = 0.005]. There was also a significant dose-dependent trend between pain scores and dexamethasone dose (P = 0.002). Compared with placebo, patients in group D16 consumed significantly less opioid [-6.4 mg (95% CI, -11.6 to -1.2), P = 0.025] and had stronger quadriceps power on the first three postoperative days (all P < 0.05). They also had significantly longer walking distance on postoperative day 1 [7.8 m ([95% CI, 0.85 to 14.7), P = 0.023] with less assistance during walking on the first two postoperative days (all P < 0.029) and significantly better quality-of-recovery scores on postoperative day 1 (P = 0.018). There were significant dose-dependent trends between all the above parameters and dexamethasone dose (all P < 0.05). No significant differences were found in the incidence of chronic pain or knee function 3, 6 and 12 months postoperatively. Dexamethasone 16 mg given before total knee arthroplasty led to a reduction in postoperative pain, less opioid consumption, stronger quadriceps muscle power, better mobilisation and better overall quality-of-recovery after operation. No long-term improvement in reduction in pain and function of the knee was found. ClinicalTrials.gov identifier: NCT02767882.

Shifts in the gut microbiota of mice in response to dexamethasone administration.

Glucocorticoids (GCs) are an important anti-inflammatory drug, used widely, regardless of its side effects. GCs can affect intestinal flora directly or indirectly, though few studies have focused on the changes of gut microbiota composition. In this study, ICR mice were randomly divided into three groups, gavage administration with saline, and different doses of dexamethasone (DEX): 0.1mg/kg and 1mg/kg. Five days later, the microbial diversity of the colon contents was analyzed. A significant loss in weight was observed in the DEX1.0 group as compared with the control group (P = 0.011). The gut microbiota richness (ACE, P = 0.01; Chao, P = 0.013) and diversity (Shannon, P = 0.035; Simpson, P = 0.032) were decreased in DEX group. The proportions of genus Butyricicoccus, Oscillibacter, Anaerotruncus, Ruminiclostridium, Ruminococcaceae, and Lachnospiraceae were the most abundant and predominant followed by Lactobacillus, Pseudomonas, and Enterorhabdus. Dex administration led to changes in the liver/body ratio and spleen/body ratio. The results obtained from our study indicate that DEX can decrease the level of WBC and change the structure of the gut microbiota composition; moreover, the results of this study provide new insight into alleviating the clinical side effects of GC therapy.

Effect of different doses of dexamethasone on labor in Santa Inês ewes and its influence on the onset of labor and the expulsion of fetal membranes

ABSTRACT: The induction of labor aims to concentrate births to follow up better the parturient and the first care to the neonates. However, even if the labor induction technique with dexamethasone administration has been successfully described since the late 1970s, few studies report the technique of birth development and neonatal vitality in Santa Inês sheep. This study aimed to evaluate the efficiency of dexamethasone use in two doses (8 and 16mg) in labor induction of Santa Inês ewes at 145 days of gestation and to evaluate its effects on the birth characteristics. In this study, 58 ewes were used, raised in an extensive system in the experimental farms of UFBA, with confirmation pregnancy after fixed-time artificial insemination or controlled breeding. These female ewes were separated into three groups according to the dose of dexamethasone administered (G1 = 0mg, G2 = 8mg, and G3 = 16mg). From these births, 79 lambs were born. This study analyzed the period from induction of labor to birth, fetal presentation at birth, the weight of the placenta, and the period for placenta expulsion. The data were analyzed by the Statistical Analysis System (SAS v.9.1.3®, 2002), and the significance level considered for all analyzes was 5%. Births of induced groups occurred on average at 48.4±22.17 hours after induction, while the females with non-induced labor gave birth 131.96±41.9 hours on average after the placebo application (P&lt;0.05), confirming the efficiency of both doses for induction of labor. The period from induction to birth did not differ (P&gt;0.05) between the doses used. There were no differences in delivery about the fetal static relation, time to placental attachment, and weight. With this study, it can be concluded that the induction at 145 days of gestation with eight or 16mg of dexamethasone is a useful technique and does not alter the labor in Santa Inês sheep.

Transcriptome Responses to Dexamethasone Depending on Dose and Glucocorticoid Receptor Sensitivity in the Liver.

Tissue sensitivity to glucocorticoids is a key factor dictating outcome of their homeostatic and therapeutic action, whereby liver represents one of the major peripheral targets. Here, we used pigs carrying a natural gain-of-function glucocorticoid receptor (GR) variant Ala610Val (GRAla610Val) as a model to identify genes and pathways related to differential glucocorticoid sensitivity. Animals with different GRAla610Val genotypes were treated either with saline or two different doses of dexamethasone. Genome-wide transcriptional responses depending on treatment, genotype, and their interaction in the liver were investigated using mRNA sequencing. Dexamethasone induced vast transcriptional responses, with more than 30% of present genes being affected. Functional annotation of genes differentially expressed due to dexamethasone treatment suggested that genes related to inflammation respond more sensitively, despite absence of an immune stimulus. In contrast, genes involved in glucose metabolism and cancer appeared to be less sensitive. Analysis of genotype and genotype × treatment interaction revealed that clustered protocadherins, particularly PCDHB7, are most prominently affected by GRAla610Val, mainly depending on dose. GRAla610Val influenced also expression of a set of glucose metabolism related genes, including PPARGC1A and CEBPB, in the absence of dexamethasone though no differences in basal plasma glucose level were observed. This might represent an adaptive response, keeping balance between receptor sensitivity, and level of circulating endogenous glucocorticoids. Administration of low dexamethasone dose changed their expression pattern and induced higher glucose response in carriers of the hypersensitive Val receptor. Our findings suggest that GRAla610Val modulates tissue responses to glucocorticoids dynamically, depending on their circulating level.

Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer

BackgroundPerioperative dexamethasone is associated with attenuation of the postoperative systemic inflammatory response and fewer postoperative complications following elective surgery for colorectal cancer.This study examined the impact of different doses of dexamethasone, given to reduce postoperative nausea and vomiting (PONV) after elective colonic resection for cancer, on the postoperative Glasgow Prognostic Score (poGPS) and morbidity. MethodsPatients from a single centre were included if they underwent potentially curative resection of colonic cancer from 2008 to 2017 (n = 480). Patients received no dexamethasone (209, 44%), or either 4 mg (166, 35%), or 8 mg (105, 21%), intravenously during anaesthesia, at the discretion of the anaesthetist. The postoperative Glasgow Prognostic Score (poGPS) on day 3 and 4, and complication rate at discharge were recorded. ResultsWhen patients were grouped by surgical approach (open or laparoscopic) and dexamethasone dose (0 mg, 4 mg or 8 mg), there was a statistically significant linear trend toward a lower postoperative systemic inflammatory response (day 3 poGPS) with the use of minimally invasive surgery and higher doses of dexamethasone (p < 0.001). Furthermore, this combination of laparoscopic surgery and higher doses of dexamethasone was significantly associated with a lower proportion of postoperative complications (p < 0.001).At multivariate Cox regression, dexamethasone was not significantly associated with either improved or poorer cancer specific or overall survival. ConclusionsHigher doses of perioperative dexamethasone are associated with greater reduction in postoperative systemic inflammation and complications following surgery for colonic cancer without negative impact on survival.

Effects of different doses of dexamethasone on immune thrombocytopenia and regulatory T cells

目的 探讨不同剂量地塞米松对免疫性血小板减少症(ITP)疗效及调节性T细胞的影响。 方法 选取2017年2月至2018年6月山西医科大学第二医院诊治的ITP患者68例为研究对象，根据随机数字表法分为观察组和对照组各34例。观察组应用大剂量地塞米松治疗(40 mg/d)，对照组应用标准剂量地塞米松治疗(10～15 mg)，观察两组治疗效果，治疗后血小板计数以及调节性T细胞水平。 结果 两组患者治疗后血小板计数较治疗前明显上升，且观察组治疗后1周[(52.64±20.05)×109/L比(30.17±18.61)×109/L]、2周[(71.08±28.38)×109/L比(45.22±22.42)×109/L]和4周[(122.15±38.17)×109/L比(92.08±38.64)×109/L]血小板水平明显高于对照组，差异均有统计学意义(t＝6.325、8.532、9.851，均P<0.05)。观察组与对照组治疗效果比较，差异有统计学意义(Z＝3.846，P<0.05)。其中，观察组显效率(52.94%比8.82%)以及总有效率(97.06%比82.35%)均明显高于对照组，差异均有统计学意义(χ2＝6.257、3.981，均P<0.05)。患者术后CD4＋CD25＋T淋巴细胞表达水平明显高于治疗前，且术后7 d及14 d观察组CD4＋CD25＋T淋巴细胞表达水平明显高于对照组[(5.36±1.48)%比(4.88±1.12)%]、[(9.37±2.04)%比(6.82±2.08)%]，差异均有统计学意义(t＝4.335、6.358，均P<0.05)。 结论 大剂量地塞米松对ITP患者疗效好，患者治疗后血小板和外周血CD4＋CD25＋调节性T淋巴细胞上升明显。

Study the Effect of Dexamethasone on the External morphology features at different Embryonic Developmental stages in the Swiss Albino Mice Embryos.

The current study was conducted for the period from September 2015 until August 2016 in college of Education for Pure Sciences - University of Thi- Qar, this study aimed to fallow the changes on the External morphology features at different Embryonic Developmental stages when the pregnant mice treated with different doses of Dexamethasone (Dex). Use In the current study, sixty pregnant mice were randomly divided into four groups and each group of 15 pregnant mice. Given the members of each group specific dose of Dex and at different time periods, while the control group injected with a solution of Normal Saline 0.9%, all animals received doses used by tail intravenous injection until the end of the time periods specified. The treatment of animals under the same conditions were determined dose based on body weight, according to what is stated in the pharmaceutical constitutions. The results of statistical analysis at the level of probability (p<0.05) to different doses Dexamethasone show there is an negative effects on mice embryo's body weights and the lengths increase with increasing of number and doses concentrations. using of different doses of Dex showed various changes on general external morphological features and congenital malformation in embryos of treated mothers included: Death of embryos , Letter C Shape Embryos , Head hemorrhage , placenta damage , Neural Tube Defect, Trunk Torsion, curved head , Brain hypertrophy , Liver Hypertrophy , swelling , Short nostril and limbs, Convoluted Tail, Oedema ,Wrinkled skin, absent fingers and eyelids, Crooked pave, Short toes, Seal legs appearance , Tail congestion , Bulging eyes.

Two regimens of dexamethasone versus prednisolone for acute exacerbations in asthmatic Egyptian children

IntroductionAsthma is one of the most prevalent chronic respiratory diseases, which often leads to an emergency department visit. Prednisolone is the most commonly used corticosteroid in treatment of asthma exacerbation....

Comparison of 4 mg dexamethasone versus 8 mg dexamethasone as an adjuvant to levobupivacaine in fascia iliaca block-a prospective study.

BackgroundTo compare the effects of adding two different doses of dexamethasone on the duration and quality of the fascia iliaca block in patients undergoing proximal femoral fracture surgery.MethodsA total of 60 patients (age 18–70 years) undergoing proximal femoral nailing surgery under spinal anesthesia were given fascia iliaca block after random assignment to one of the two groups: Group H received an injection of levobupivacaine (0.5%) 28 ml with 2 ml (8 mg) dexamethasone, and Group L received an injection of levobupivacaine (0.5%) 28 ml with dexamethasone 1 ml (4 mg) with 1 ml normal saline. Assessment of the duration of analgesia and the total tramadol requirement over 48 hours were noted after a successful block.ResultsThe duration of analgesia was found to be significantly longer in Group H (17.02 ± 0.45 h) than in the Group L patients (14.29 ± 0.45 h) with a p-value of 0.000. Postoperative analgesic requirement (amount of tramadol in mg) was significantly higher in Group L (Q2: 200.0; IQR: 100.0, 200.0) as compared to Group H (Q2: 100.0; IQR: 100.0, 200.0) with a p-value of 0.034. No patient showed any sign of neurotoxicity.ConclusionsDexamethasone, in a dose of 8 mg, is superior to 4 mg when used as an adjuvant with levobupivacaine in the FIB. Though both prolonged analgesia and were effective in reducing oral/intravenous analgesics, 8 mg dexamethasone can be recommended as a more efficacious adjuvant to local anesthetics in the FIB.

Clinical Efficacy and Safety of Different Doses of Dexamethasone Combined with Bortezomib and Thalidomide for Treating Patients with Multiple Myeloma

To study the clinical efficacy and safety of dexamethasone of different doses combined with bortezomib and thalidomide for treatment of primary multiple myeloma. Ninety-six patients with multiple myeloma from January 2013 to January 2014 were randomly divided into group A (high-dose dexamethasone + bortezomib + thalidomide, 32 cases), group B (low-dose dexamethasone + bortezomib + thalidomide, 32 cases) and group C (placebo + bortezomib + thalidomide, 32 cases). The clinical efficacy and safety of patients was compared among 3 groups. The overall remission rate (ORR) in group A and B was significantly higher than that in group C (P<0.05), but the ORR was not significant difference between group A and group B (P>0.05). After treatment, the KPS and RNS score in 3 groups were significantly higher and lower than those before treatment, respectively; the KPS score in group A and B was significantly higher than that in group C (P<0.05), the RNS score in group A and B was significantly lower C (P<0.05). After treatment, the positive expression rates of CD38, CD56 and CD138 as well as small residual lesion (SRL) positive rate in 3 grops were significantly lower than those before treatment, but the positive expression rate of CD19 was significantly higher that before treatment; the positive expression rates of CD38, CD56 and CD138 as well as SRL positive rate in group A and B were significantly lower thant those in group C, while the positive expression rate of CD19 was significantly higher that in group C (P<0.05), but the positive expression rates of CD19, CD38, CD56 and CD138 as well as SRL positive rate were not significantly different between group A and B (P>0.05). The incidence of fatigue, rash, peripheral neuropathy, anlmia, granulocyte deficiance and so on in group B and C was significantly lower than that in group A(P<0.05), but the difference in group B and C was not significant (P>0.05). The therapeutic efficacy of different doses of dexamethasone combined with bortezomib and thalidomide for patients with multiple myeloma is similar, can obviously enhance remission rate, prolong the survival time, promote life quality, but the incidence of adverse reactions in low dose dexamethason rigemen is significantly reduced, and the safety is better.

Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and Viscoelastic Properties: Aspects of Aging

ObjectivesThe purpose of this study was to estimate the state of tension (tone) and the biomechanical and viscoelastic properties of skeletal muscle in aging rats during the administration of different doses of dexamethasone and to find the relationships among the state of muscle atrophy, muscle strength, and the abovementioned muscle properties. MethodsMuscle state of tension, biomechanical (elasticity, dynamic stiffness) and viscoelastic (mechanical stress relaxation time, Deborah number) properties (using MyotonPRO, Myoton Ltd, Tallinn, Estonia), lean body mass (BM), and hind limb grip strength were measured before and after the administration of a 10-day treatment with dexamethasone 100 μg/100 g BM (young and old group) and 50 μg/100 g BM (old group). ResultsMuscle elasticity (logarithmic decrement) was lower in old animals (1.86 ± 0.03) in comparison with young adult rats (1.38 ± 0.04) (P < .01). After the 10-day treatment with dexamethasone 100 μg/100 g BM, young adult rats had 10% lower muscle elasticity (P < .01). The same dose of dexamethasone in old rats increased tone (frequency of natural oscillation) from 29.13 ± 0.51 Hz to 38.50 ± 0.95 Hz (P < .001). There were dose-dependent differences in dynamic stiffness and tone of muscle; changes in elasticity were independent of the dose in old animals. In old rats, the muscle’s viscoelastic properties decreased after dexamethasone administration. Significant correlation was found between changes in muscle logarithmic decrement and stiffness (rs = 0.90; P < .05) in old animals. ConclusionsBiomechanical and viscoelastic properties of skeletal muscle indicate changes in the main function of muscle during glucocorticoid-induced muscle atrophy and are in agreement with changes in hind limb strength. The myometric measurements indicate the direction and magnitude of change in muscle tissue after different doses of dexamethasone administration easily and quickly.

Inhibition of A&#946;(1-42)Oligomerization, Fibrillization and Acetylcholinesterase Activity by Some Anti-Inflammatory Drugs: An in vitro Study.

Number of contradictory reports are available on the effects of antiinflammatory drugs on Alzheimer's disease (AD) including beneficial, adverse and stage dependent effects. We provide insights of the effects exerted by some anti-inflammatory drugs on the chemistry of AD. Three different doses of dexamethasone (0.015, 0.030, 0.060 μM), piroxicam (5, 7.5, 10 μM), indomethacin (1, 1.25, 1.50 μM), diclofenac (0.6, 0.8, 1.0 μM), aspirin (90, 120, 150 μM) and celecoxib (30, 45, 60 μM) were used. Rivastigmine, methylene blue and butylated hydroxyanisole were used as standard drug, oligomerization inhibitor and antioxidant, respectively. Oligomerization and fibrillization reactions were performed using Aβ1-42 peptides. Results-Indomethacin and aspirin mainly inhibited oligomerization, while rivastigmine and piroxicam inhibited fibrillization. Diclofenac and celecoxib inhibited both oligomerization and fibrillization almost equally. Dexamethasone showed poor efficiency on both the processes, but exert comparably more inhibition of oligomerization than fibrillization. Inhibition of acetylcholinesterase activity was also potent and was in the following order: celecoxib> piroxicam> diclofenac> aspirin> indomethacin> dexamethasone. Strong radical scavenging (More than 50%) activity was showed by indomethacin and aspirin for NO radicals. Present study consistently revealed that anti-inflammatory drugs have potential to Modulate chemistry of AD progression. Inclusion of anti-inflammatory drugs in low doses along with routine therapies may provide therapeutically and economically more efficient therapies for AD. However, further studies are warranted, because the overall therapeutic effect seems to be the function of stage of disease, dose of drug, main underlying mechanism of action(s).

Neurokinin-1 Receptor Antagonist-Based Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting: A Network Meta-Analysis.

Neurokinin-1 receptor antagonists (NK-1RAs) are widely used for chemotherapy-induced nausea and vomiting (CINV) control in patients with highly emetogenic chemotherapy (HEC) and/or moderately emetogenic chemotherapy (MEC). Whether the efficacy and toxicity of antiemesis are different among various NK-1RA-based triple regimens is unknown. Data of complete responses (CRs) in the acute, delayed, and overall phases and treatment-related adverse events (TRAEs) were extracted from electronic databases. Efficacy and toxicity were integrated by pairwise and network meta-analyses. Thirty-six trials involving 18 889 patients using triple regimens (NK-1RA+serotonin receptor antagonists [5HT3RA] + dexamethasone) or duplex regimen (5HT3RA+dexamethasone) to control CINV were included in the analysis. Different NK-1RA-based triple regimens shared equivalent effect on CRs. In patients with HEC, almost all triple regimens showed statistically significantly higher CRs than duplex regimen (odds ratio [OR]duplex/triple = 0.47-0.66). However, in patients with MEC, only aprepitant-based triple regimen showed better effect than duplex regimen statistically significantly in CRs (ORduplex/triple = 0.52, 95% confidence interval [CI] = 0.34 to 0.68). No statistically significant difference of TRAEs was found among different triple regimens. Palonosetron-based triple regimens were equivalent to first-generation 5HT3RAs-based triple regimens for CRs. Moreover, different doses of dexamethasone plus NK-1RA and 5HT3RA showed no statistically significant difference in CRs. Different NK-1RAs-based triple regimens shared equivalent effect on CINV control. Various triple regimens had superior antiemetic effect than duplex regimen in patients with HEC. Only aprepitant-based triple regimen showed better CINV control compared with duplex regimen in patients receiving MEC. Palonosetron and first-generation 5HT3RAs might share equivalent CINV control in the combination of NK-1RAs and dexamethasone. Lower doses of dexamethasone might be applied when used with NK-1RAs and 5HT3RAs.

Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice.

The mechanism of cleft palate induction by dexamethasone is not fully known. Bone morphogenetic protein-2 (BMP-2) has been associated with dexamethasone-induced osteoporosis. In this study, the authors induced cleft palate models in Institute of Cancer Research mice by dexamethasone to investigate the role of BMP-2 and its transcriptional element GATA-6. The authors injected different doses of dexamethasone into pregnant mice (E13), and assessed the histology of the palatal shelf and the expression levels of BMP-2, GATA-6, and specific apoptosis-related proteins. The results showed that cleft palate formation was dependent on dexamethasone dosage, with high incidence (50.55%) at high concentration (50 mg/kg) compared with the low doses (6 mg/kg, 38.10%). Transmission electron microscopy revealed significant cellular changes of the cleft palate shelf, including loose cell connection, cellular swelling, as well as reduced extracellular matrix and mitochondria. Following exposure to dexamethasone, the apoptotic rate in the palate increased with elevated dosage. Western blotting analysis indicated that the expression levels of GATA-6 and BMP-2 were reduced, while the levels of apoptotic proteins bax and caspase-3 were increased. The results of authors' study suggested that dexamethasone-induced cleft palate formation involved apoptosis occurred in a dose-dependent manner. BMP-2 and GATA-6 mediated dexamethasone-induced cleft palate formation.

A Novel Model of Dexamethasone-Induced Hypertension: Use in Investigating the Role of Tyrosine Hydroxylase.

Our objective was to study hypertension induced by chronic administration of synthetic glucocorticoid, dexamethasone (DEX), under nonstressful conditions and examine the role of catecholamine biosynthesis. To achieve this, we did the following: 1) used radiotelemetry to record mean arterial pressure (MAP) and heart rate (HR) in freely moving rats, and 2) administered different doses of DEX in drinking water. To evaluate the involvement of tyrosine hydroxylase (TH), the rate-limiting step in catecholamine biosynthesis, we treated rats with the TH inhibitor, α-methyl-para-tyrosine (α-MPT), for 3 days prior to administration of DEX and assessed TH mRNA and protein expression by quantitative real-time polymerase chain reaction and Western blot in the adrenal medulla. We observed a dose-dependent elevation in blood pressure with a DEX dose of 0.3 mg/kg administered for 10 days, significantly increasing MAP by +15.0 ± 1.1 mm Hg, while concomitantly reducing HR. Although this DEX treatment also significantly decreased body weight, pair-fed animals that showed similar decreases in body weight due to lowered food intake were not hypertensive, suggesting that body weight changes may not account for DEX-induced hypertension. Chronic DEX treatment significantly increased the TH mRNA and protein levels in the adrenal medulla, and α-MPT administration not only reduced DEX pressor effects, but also inhibited TH (serine(40)) phosphorylation. Our study thus validates a novel model to study hypertension induced by chronic intake of DEX in freely moving rats not subject to the confounding factors of previous models and establishes its dependence on concomitant activation of peripheral catecholamine biosynthesis.

Relationship Between Pneumocystis carinii Burden and the Degree of Host Immunosuppression in an Airborne Transmission Experimental Model.

To quantitatively assess the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed rat hosts, we developed an animal model, where rats went through different doses of dexamethasone. Then, natural and aerial transmission of Pneumocystis carinii occurred during cohousing of the rats undergoing gradual ID levels (receivers) with nude rats developing pneumocystosis (seeders). Following contact between receiver and seeder rats, the P. carinii burden of receiver rats was determined by toluidine blue ortho staining and by qPCR targeting the dhfr monocopy gene of this fungus. In this rat model, the level of circulating CD4(+) and CD8(+) T lymphocytes remained significantly stable and different for each dose of dexamethasone tested, thus reaching the goal of a new stable and gradual ID rat model. In addition, an inverse relationship between the P. carinii burden and the level of circulating CD4(+) or CD8(+) T lymphocytes was evidenced. This rat model may be used to study other opportunistic pathogens or even co-infections in a context of gradual ID.

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

Comparative analgesic efficacy of different doses of dexamethasone during infraumbilical surgery: A Randomized controlled trial.

Background:Postoperative pain is a common complaint and despite the availability of various drugs, is still not managed well. Analgesic effects of glucocorticoids are still to be substantially established. Hence, we designed randomized, double-blind, placebo-controlled trial to compare the effect of two different doses of dexamethasone on postoperative pain in patients undergoing infra-umbilical surgeries under spinal anesthesia.Methods:Ninety American Society of Anesthesiologists Grade I and II patients were randomized to receive injection dexamethasone 8 mg (Group DI), dexamethasone 16 mg (Group DII) or placebo (Group C) prior to performance of intrathecal block. Outcome studied was postoperative pain on the rest and motion and nausea and vomiting.Result:There was no difference in Visual Analog Scale (VAS) scores during rest in all the three groups. However, VAS scores on motion showed a significant decrease in Group DII at 24 and 36 h when compared to Group C (95% confidence interval [CI] of mean at 24 h for Group C = 5.6093–7.1049 and Group DII = 4.8709–5.9567, P = 0.04; 95% CI of mean at 36 h for Group C = 4.5868–5.8418 and Group DII = 3.5388–4.7378, P = 0.01). There was no significant difference in the incidence of postoperative nausea and vomiting or additional analgesic requirements.Conclusion:Dexamethasone 16 mg reduces postoperative pain on motion at 24 and 36 h. It has no effect on postoperative pain at rest or on nausea and vomiting.

Levels of interleukin-8, interleukin-4 and tumor necrosis factor-α of neonatal mouse with systemic inflammatory response syndrome treated by different doses of dexamethasone

Objective To observe the expression levels of IL-8, IL-4, TNF-α of neonatal mouse with systemic inflammatory response syndrome (SIRS) treated by different doses of dexamethasone. Methods A total of 50 neonatal mice were randomly divided into five groups: blank control group, saline control group and treatment group A, B, C. The saline control group and treatment groups were established into SIRS models, treatment group A: a single high-dose of dexamethasone (2 mg/kg), subcutaneous injection (SC); treatment group B: two doses of dexamethasone (1 mg/kg, q12 h, total 2 mg/kg, SC); treatment group C: four doses of dexamethasone (0.5 mg/kg, q12 h, total 2 mg/kg, SC); saline control group: saline of the same volume (0.4 ml/kg, SC). All mice were detected IL-4, IL-8, TNF-α by ELISA 72 hours after animal models being completed. Results The levels of IL-4, IL-8, TNF-α in saline control group and treatment group A, B, C were higher than those in blank control group respectively (P 0.05). Conclusion Dexamethasone could lower the expressions of pro-inflammatory cytokines IL-8, TNF-α and anti-inflammatory factor IL-8 of neonatal mouse with SIRS, and the effect of multiple low-doses of dexamethasone on SIRS is significantly better than a single high dose. Key words: Systemic inflammatory response syndrome; Dexamethasone; Cytokine