Different Doses Of Methylprednisolone Research Articles

Steroids use in Severe/ Life Threatening COVID-19 Pneumonia: Does the Type or Dose Matter?

Objective: To compare the effect of different doses of methylprednisolone and dexamethasone on in-hospital mortality in severe COVID-19 pneumonia Methods: This retrospective chart review was done by reviewing old medical reports of patients with severe
 disease admitted to COVID-19 Intensive Care and High Dependency Unit from October 2020 to September 2021. Those with suspected COVID-19 infection (suggestive radiological findings but negative PCR for SARSCoV- 2 on at least two occasions) were excluded. Patients requiring high flow oxygen (>6 liters per minute) or higher levels of respiratory support were classified as having severe disease. We recorded the type of steroids used and the doses. Methylprednisolone in doses up to 40mg per day, or other steroids in equivalent doses, were considered low dose. Primary outcome of interest was in- hospital mortality. Results: There were 279 patients aged 52.53± 11.31 years, including 216 (77.42%) males. Mean hospital stay was 10.18± 3.13 days. During hospital stay, 96 (34.41%) patients died. Amongst patients receiving dexamethasone, 70 (44.87%) expired, whereas 26 (21.14%) out of 123 patients who received methylprednisolone expired (p

High Dose Methylprednisolone versus Low Dose in Correction of Congenital Acyanotic Heart Disease

ABSTRACT Background A large number of pediatric patients undergoing congenital heart disease corrective procedures receive peri-operative corticosteroids, aiming to reduce post-operative inflammation and capillary leak following cardiopulmonary bypass (CPB). This study aimed to compare the effect of different doses of methylprednisolone on inflammatory mediators’ production and effect on myocardium. Methods A trial was conducted on pediatric patients undergoing surgical correction for congenital acyanotic lesion needing CPB machine. Patients were divided into 3 groups: group A patients received 10 mg/kg methylprednisolone (MP) after induction, group B received 30 mg/kg MP and group C patients received placebo. Results Serial measurement of serum troponin, IL6 and random blood sugar showed no differences in the 3 studied groups at the first measurement, and random blood glucose at ICU admission and hour-24 were highest in the high-dose group (IL6 was lowest) with P value <0.001. Troponin showed no difference at ICU admission, while at hour-24, it was lowest in the high-dose group with p value<0.001, followed by the low-dose group and the highest in control. The ejection fraction (EF) at hour-6 was highest in the high-dose group with p value<0.001, followed by the low-dose group and lowest in control. The vasoactive inotrope score was lowest in high-dose followed by low-dose groups followed by control. As regards complications, there was no different significance between groups. Conclusion High-dose MP (30 mg/kg) given to pediatric patients undergoing surgical correction of congenital acyanotic heart disease showed better outcomes such as less elevation of inflammatory mediators, lower level of troponin, vasoactive score and higher ejection fraction, with no additional complications recorded.

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies

BackgroundThe optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients.MethodsALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRβ and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate.ResultsIn animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRβ and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected.ConclusionsThis study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.

Effects of different doses of methylprednisolone on clinical outcomes in patients with severe community-acquired pneumonia: a study protocol for a randomized controlled trial

BackgroundThe specific use of methylprednisolone in severe community-acquired pneumonia (SCAP) has not yet formed a consensus. It is not clear whether the clinical efficacy of methylprednisolone in SCAP is dose-dependent, and how to balance the best efficacy with the least complications. The aim of this study is to evaluate the efficacy and safety of different doses of methylprednisolone in the adjuvant treatment for patients with SCAP.Methods/designThis is a prospective, randomized, double-blind, parallel group, placebo-controlled trial to evaluate the efficacy and safety of different doses of methylprednisolone in the adjuvant treatment for patients with SCAP. Patients with diagnosed SCAP are randomized to the following four groups at a 1:1:1:1 ratio: group 1 (control group)—standard ICU patient care+100ml of normal saline once a day for 5 days; group 2—standard ICU patient care+40mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days; group 3—standard ICU patient care+80mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days; and group 4—standard ICU patient care+120mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days. The primary outcome is PaO2/FiO2 ratio at day 5 following randomization. The secondary outcomes are 28-day mortality, ventilator-free days at 28 days, mechanical ventilation duration at 28 days, endotracheal intubation rate, time for temperature recovery, duration of vasopressors use, serum CRP and interleukin-6 level at day 5 following randomization, hospital stay, frequency of nosocomial infections, gastrointestinal hemorrhage, and hyperglycemia.DiscussionThe results of our study may find the optimal dose of glucocorticoid in the adjuvant treatment of SCAP and provide evidence-based proof for clinicians to treat patients with SCAP. Since coronavirus disease 2019 (COVID-19) also belongs to community-acquired pneumonia, perhaps the results of our study will help to determine the appropriate dose of methylprednisolone in COVID-19 treatment.Trial registrationChinese Clinical Trial Registry ChiCTR2100045056. Registered on 4 April 2021.

The Comparison of the effect of two different doses of methylprednisolone on pain, swelling and trismus after 3rd molar surgery.

Objective The aim of this study was to compare the effects of intravenous administration of 1.5mg/kg and 3mg/kg of methylprednisolone sodium succinate on pain, swelling and trismus after third molar surgery.&#x0D; Study Design. Twenty five healthy patients with bilaterally symmetrical impacted mandibular third molars were included in this study. Either 1.5mg/kg or 3mg/kg of methylprednisolone was administered by intravenous route 1 hour before the operation. At the second operation the other dose was applied. Facial swelling was evaluated by using cotton sutures. Trismus was determined by measuring maximum interincisal opening. Pain was determined by using visual analogue scale.&#x0D; Results. There was no statistically significant difference in pain swelling and trismus between the two groups.&#x0D; Conclusion. No significant benefit of higher dose of methylprednisolone administered.&#x0D;

Effects of glucocorticoids on the proliferation of CD19 CAR-T cells targeting B-cell tumor cell lines

目的评估糖皮质激素对CD19嵌合抗原受体T细胞（CAR-T细胞）靶向杀瘤过程中增殖的影响。方法健康志愿者的外周血单个核细胞（PBMC）作为T细胞来源，经CD3磁珠分选及CD19 CAR慢病毒转染制备CD19 CAR-T细胞；采用流式细胞术（FCM）测定CD19 CAR-T细胞转染率及其在培养体系中所占比例；采用CFDA SE细胞增殖示踪荧光探针试剂标记CD19 CAR-T细胞后测定其荧光强度；LDH细胞毒性检测方法检测不同浓度的糖皮质激素对B细胞肿瘤细胞株杀伤活性的影响。结果①CD19 CAR-T细胞CD19 CAR转染率为（51.34±5.28）％。②24 h后不同剂量甲泼尼龙对Nalm6、Pfeiffer及U2932细胞的杀伤活性高于地塞米松，48 h后低浓度（4 mg/ml）甲泼尼龙对Nalm6、Pfeiffer、U2932细胞杀伤活性高于低浓度（0.75 mg/ml）地塞米松，而高浓度（12 mg/ml）甲泼尼龙杀伤活性低于高浓度（2.25 mg/ml）地塞米松。但各个时间不同剂量甲泼尼龙组对EHEB细胞的杀伤活性均低于对应时间、剂量的地塞米松。③CD19 CAR-T细胞在不同浓度糖皮质激素作用下的比例及平均荧光强度比较，地塞米松对CD-19 CAR-T细胞的增殖抑制作用强于甲泼尼龙，两种糖皮质激素的高浓度组较低浓度组对CD19 CAR-T细胞的增殖抑制作用更明显。④CD19 CAR-T细胞与不同肿瘤细胞共培养体系中，其比例及平均荧光强度比较，地塞米松对CD19 CAR-T细胞的增殖抑制作用强于甲泼尼龙，两种糖皮质激素的高浓度组较低浓度组对CD19 CAR-T细胞的增殖抑制更明显。结论CD19 CAR-T细胞靶向不同肿瘤细胞株过程中地塞米松对CD19 CAR-T细胞的扩增和增殖抑制作用大于甲泼尼龙，高剂量组该抑制作用更加明显。

Comparison of the effect of two different intravenous methylprednisolone doses on the occurrence time of biphasic reaction

Aim: The aim of this study is to determine the effect of two different doses of methylprednisolone administered in our emergency department (ED) on the elapsed time in biphasic or recurrent anaphylaxis cases.Materials and Methods: The patients with anaphylaxis admitted to the ED were retrospectively analyzed. A total of 82 patients who received methylprednisolone in combination with epinephrine in the ED due to anaphylaxis and who developed biphasic reaction within 48 h after discharge were included in the study. The patients were classified into two groups according to the dose of methylprednisolone administered: 80 mg (Group 1, low-dose) and 120 mg (Group 2, high-dose). The effect of different doses of methylprednisolone on the development time of biphasic reaction was evaluated.Results: Two different doses of IV methylprednisolone administered in the ED did not affect the development time of biphasic reaction (p = 0.24). The biphasic reaction development times were 335 (IQR, 212–950) min in the low-dose group and 520 (IQR, 265–1150) min in the high-dose group. The earliest development time of biphasic reaction was 125 min (low-dose group) and the latest development time was 2270 min (high-dose group). The relationship between dose and biphasic reaction development times was evaluated using Kaplan–Meier curve. No significant difference was observed between the two groups (p = 0.28). Upon comparing the symptoms in patients’ second admission to the ED due to biphasic reaction, no statistically significant difference was observed in patient symptoms with respect to the dose administered (p > 0.05).Conclusions: Corticosteroids are often used in ED, although there is no definitive evidence that they prevent biphasic reactions. The administration of two different doses of methylprednisolone has no effect on biphasic reaction development time.

Efficacy of methylprednisolone on pain, trismus and quality of life following surgical removal of mandibular third molars: a double-blind, split-mouth, randomised controlled trial.

Background The objective of the present study was to compare the efficacy of different doses of methylprednisolone on postoperative sequelae and quality of life (QoL) following surgical removal of mandibular third molars (SRM3). Material and Methods Fifty-two patients (16 men and 36 women, mean age 25.9 years, range: 18-39) with bilateral impacted mandibular third molars were randomly allocated into intraoperative muscular injection of either 20mg, 30mg, 40mg methylprednisolone or saline injection. Baseline measurements were obtained preoperatively and compared with assessment after one day, three days, seven days and one month. Pain and trismus were estimated by visual analog scale score and interincisal mouth opening, respectively. Subjective assessment of QoL included Oral Health Impact Profile (OHIP-14). Descriptive and generalized estimating equation analyses were made and expressed as mean values with a 95% confidence interval. Results Methylprednisolone revealed no significant differences in pain, trismus and QoL compared with placebo. Higher prevalence of postoperative pain and worsening in QoL were observed with increased age (P=0.00). Smoking and increased time of surgery decreased mouth opening in the early healing phase (P=0.00). Conclusions The present study revealed no significant improvement of methylprednisolone on postoperative sequelae and QoL following SRM3 compared with placebo. Key words:Corticosteroids, dentistry, mandible, methylprednisolone, pain, third molar, trismus.

Short-term Haematological Parameters Following Surgical Removal of Mandibular Third Molars with Different Doses of Methylprednisolone Compared with Placebo. A Randomized Controlled Trial.

ABSTRACTObjectivesTo evaluate the influence of a single intraoperative injection of methylprednisolone on short-term haematological parameters following surgical removal of mandibular third molars.Material and MethodsFifty-two patients with indications for surgical removal of bilateral impacted mandibular third molars were included in a randomized, split-mouth and double-blinded study design. Each molar were randomly allocated into one of following four groups: 20 mg methylprednisolone, 30 mg methylprednisolone, 40 mg methylprednisolone and placebo. Peripheral blood samples were obtained before and three days after surgery. Haematological parameters involving haemoglobin, white blood cell count and C-reactive protein (CRP) were evaluated and expressed as mean changes. Level of significance was 0.05. Furthermore, outcomes were correlated for age, sex, smoking and time of surgery.ResultsThere were no significant differences in postoperative haematological parameters with different doses of methylprednisolone compared with placebo. Peripheral blood samples revealed decreased level of haemoglobin and increased level of leucocytes and CRP in each group. Smokers displayed a significant lower level of haemoglobin and CRP compared with non-smokers (P < 0.05) and level of eosinophils decreased significantly with increasing age (P < 0.05).ConclusionsThis study indicates that a single intraoperative injection of methylprednisolone seems not to cause suppression of short-term haematological parameters compared with placebo following surgical removal of mandibular third molars.

Meta-analysis of the Clinical Efficacy and Safety of High- and Low-dose Methylprednisolone in the Treatment of Children With Severe Mycoplasma Pneumoniae Pneumonia.

Mycoplasma pneumoniae pneumonia is generally a self-limiting disease, but it can develop into severe Mycoplasma pneumoniae pneumonia (SMPP). Immunologic mechanisms are thought to play an important role in the pathogenesis of SMPP. Therefore, the use of systemic glucocorticoids may have beneficial effects. However, to date, the use of glucocorticoid therapy in SMPP is limited to small case series, and the glucocorticoid dosage for children with SMPP has not been established. Here, we used a meta-analysis method to collect data from randomized control trials of different doses of methylprednisolone in SMPP to assess the safety and efficacy of treatment with low- versus high-dose methylprednisolone in children with SMPP. We included 13 Chinese randomized control trials that included 1049 children. The high- and low-dose groups were comprised of 524 and 525 children, respectively. The high-dose group was significantly more effective than the low-dose group in clinical efficacy [risk ratio = 1.30, 95% confidence interval (CI) (1.23, 1.38), P < 0.05]. In addition, compared with low-dose methylprednisolone, high-dose methylprednisolone significantly shortened hospital stays and antipyretic therapy, pulmonary rales disappearance, cough disappearance and pulmonary shadow absorption times. There was no significant difference in adverse events between the high- and low-dose groups: risk ratio= 0.85, 95% CI (0.53, 1.36), P > 0.05. We conclude that high-dose methylprednisolone is effective in the treatment of SMPP without increasing the incidence of adverse reactions.

The Efficacy of Risk Score System Establishment and Methylprednisolone Stratification Treatment for Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Retrospective (development) and a Prospective (validation) Study

Introduction Pre-engraftment syndrome (PES) is a common immune reaction prior to neutrophil engraftment after unrelated cord blood transplantation (UCBT), with a unique clinical manifestation of non-infectious fever and skin rash. The reported incidence of PES ranges from 20% to 78%. Although many researchers believe that PES is associated with a high incidence of acute graft-versus-host disease (GVHD) but not with transplant-related mortality (TRM) , relapse, or overall survival (OS), they did not stratify the risk factors of PES, and how to carry out different doses of methylprednisolone (MP) stratified intervention therapy still remains unknown. Method s First, 136 hematological malignancy patients treated with UCBT from April 2000 to February 2012 in our transplantation center were retrospectively analysis. Among them, 92 patients occurred PES. High-risk factors for 180-day TRM in PES patients were established by univariate and multivariate analysis. Then, from January 2013 to August 2016, 221 PES patients were scored according to the risk scoring system and stratified treated with different doses of MP. Finally, in order to validate the efficacy of MP stratification treatment, we conducted a prospective, open label and non-randomized clinical trial including 240 PES patients who underwent UCBT from September 2016 to December 2018. This trial is registered at www.chictr.org.cn as ChiCTR-ONC-16009013. Results The cumulative incidence of neutrophil and platelet engraftment was significantly higher in PES group than non-PES group (97.8% vs 70.5%, P&lt;0.001; 75.0% vs 54.5%, P=0.05). In 92 PES patients, multivariate analysis showed that failed MP treatment, multiple clinical symptoms and early onset of PES were independent high risk factors affecting180-day TRM. One high risk factor was scored as 1. The 92 PES patients were divided into PES-0, PES-1,PES-2 and PES-3, and the higher the score, the higher the TRM (17.7% vs 21.9% vs 62.5% vs 100%,respectively; P&lt;0.001), and the lower the OS (68.3% vs 56.2% vs 25.0% vs 0%, respectively; P&lt;0.001). Then, from January 2013 to August 2016, 221 PES patients were scored as PES-0, PES-1 and PES-2 according to the following two high risk factors (multiple clinical symptoms and early onset of PES) and stratified treated with different doses of MP (0.5mg/kg/d for PES-0, 1mg/kg/d for PES-1 and 2mg/kg/d for PES-2). Compared to the previous PES patients with the same risk score, the 180-day TRM of PES-1 and PES-2 patients was significantly reduced and the OS, disease free survival (DFS), and GVHD-free and Relapse-free survival (GRFS) were significantly increased after stratified treatment. The results in the prospective trial were similar to the retrospective study. In addition, although stratified therapy could significantly improve the prognosis of PES-2 patients cohort, the cumulative incidence of acute GVHD and GRFS are still the worst compared with other risk score patients. Therefore, how to improve the outcomes of PES-2 patients remains to be further studied. Conclusion s PES after UCBT is benefit for engraftment, but should be graded according the risk scoring system. Different doses of MP stratified intervention therapy can significantly improve the prognosis of severe PES patients. The risk scoring system of PES after UCBT and MP stratification treatment are worthy of clinical application. But the cumulative incidence of acute GVHD and GRFS in severe PES patients still need to be ameliorated in the further study. Disclosures No relevant conflicts of interest to declare.

How can methylprednisolone work on epileptic spasms with malformation of cortical development?

Although steroids are suggested as the treatment of choice for infantile spasms, the mechanism of action is still unclear. Using a rat model of malformation of cortical development with refractory infantile spasms, we evaluated the efficacy of methylprednisolone on spasms susceptibility and behaviors. Additionally, we investigated the in vivo electrophysiological and neurochemical changes of the brain after methylprednisolone treatment. Infant rats with prenatal exposure of methylazoxymethanol at gestational day 15 were used. After a single dose of methylprednisolone or three different doses of methylprednisolone for 3days, spasms were triggered by intraperitoneal injection of N-methyl-d-aspartic acid. In rats with 3days of methylprednisolone pretreatment and their controls, behavioral testing was performed at postnatal day 15. In vivo magnetic resonance imaging was conducted at postnatal day 15 after 3days of methylprednisolone treatment. The rats with single methylprednisolone pretreatment showed significantly delayed onset of spasms and multiple doses of methylprednisolone significantly suppressed the development of spasms in a dose-dependent manner. After multiple methylprednisolone pretreatment and a cluster of N-methyl-d-aspartic acid-induced spasms, the rats showed significantly increased freezing behaviors to conditioned stimuli. Glutamate-weighted chemical exchange saturation transfer revealed significant elevation of glutamate concentration in the cortices of the rats with multiple methylprednisolone pretreatments. Methylprednisolone pretreatment could attenuate N-methyl-d-aspartic acid-induced spasms with in vivo neurochemical and electrophysiological changes, which indicates this steroid's action on the brain and in epilepsy.

Therapeutic effects of different doses of methylprednisolone on smoke inhalation-induced acute lung injury in rats

To investigate the therapeutic effect of different doses of methylprednisolone (MP) in smoke inhalation-induced acute lung injury (SI-ALI). Adult male Sprague-Dawley (SD) rats were divided into control group (group A, n = 6), smoke inhalation group (group B, smoke inhalation 30 minutes, n = 30) and smoke + MP 40, 4, 0.4 mg/kg intervention group (groups C, D, E; intraperitoneal injection of MP at 1 hour before smoke inhalation, n = 30) according to random number table method. The survival status of rats in each group was observed at 24 hours, and murine smoke inhalation induced trauma score (MSITS) according to the symptoms and signs of rats at 3 hours after smoke inhalation were scored. The blood of abdominal aorta of rats was collected. Then the rats were sacrificed to harvest bronchoalveolar lavage fluid (BALF) and lung tissue. The levels of interleukin (IL-6, IL-17a) in plasma and BALF were detected by enzyme linked immunosorbent assay (ELISA); the total number of white blood cells and the proportion of leukocytes or macrophages in BALF were calculated; the histopathological changes of lung were observed and the lung injury score was given; the expression of myeloperoxidase (MPO) and high mobility group protein B1 (HMGB1) in lung tissue were detected by Western Blot. The 24-hour survival rate of group B rats was 33.67%. The survival rate of groups C, D and E (65.73%, 85.17%, 60.07%) were significantly higher than that of group B (all P < 0.05), and the survival rate of group D was significantly higher than that of groups C and E. Diffuse inflammatory cell infiltration, intra-alveolar hemorrhage and a large amount of edema fluid were seen in the lung tissue of group B; and the lung injury score was significantly higher than that of group A. Compared with group B, the lung injury in different doses of MP group were decreased to different degrees, while the lung injury scores in groups C and D were significantly decreased (3.31±1.37, 2.62±0.98 vs. 5.52±0.97, both P < 0.01); correlation analysis showed that MSITS score was significantly and positively correlated with lung injury score (r = 0.862, P < 0.001). The levels of plasma inflammatory factors and BALF protein, inflammatory cells and inflammatory factors, and the expression of MPO, HMGB1 in group B were significantly higher than those in group A. Compared with group B, the levels of inflammatory factors in plasma, and protein content, inflammatory cells and inflammatory factors in BALF in different doses of MP group were decreased to different degrees, with significant differences in groups C and D [plasma: IL-17a (pg/L): 49.28±27.12, 36.57±16.52 vs. 191.79±88.21; IL-6 (ng/L): 206.47±109.96, 197.52±113.86 vs. 669.00±299.60; BALF: protein content (mg/L): 892.0±164.5, 566.1±120.9 vs. 1 838.0±145.8; white blood cell count (×109/L): 5.40±1.67, 2.81±1.20 vs. 9.02±2.06; neutrophil ratio: 0.315±0.081, 0.273±0.080 vs. 0.590±0.096; IL-17a (ng/L): 22.63±8.62, 18.92±8.43 vs. 43.31±19.17; IL-6 (ng/L): 156.49±46.94, 123.66±64.91 vs. 253.43±80.03; all P < 0.01]; in addition, the expression of MPO and HMGB1 protein in lung tissues of MP groups with different doses were significantly decreased, the expression of MPO in group D was significantly lower than that in group E [MPO/β-actin (fold increase from group A): 2.14±0.97 vs. 4.35±0.87, P < 0.01], the expression of HMGB1 in groups C and D were significantly lower than that in group E [HMGB1/β-actin (fold increase from group A): 1.77±0.73, 1.23±0.67 vs. 3.65±1.08, both P < 0.05]. MP can significantly improve the survival rate of SI-ALI rats and reduce the acute pulmonary and systemic inflammatory response. The MP effect of 4 mg/kg was better than 40 mg/kg and 0.4 mg/kg.

An experimental study to evaluate the antiosteoporotic effect of Panchatikta Ghrita in a steroid-induced osteoporosis rat model

Objective:The study was conducted to develop the glucocorticoid-induced osteoporosis (GIO) model in Sprague-Dawley weanling rats using different doses of methylprednisolone (MP) and evaluate the antiosteoporotic effect of a classical ayurvedic formulation, Panchatikta Ghrita (PG), in this model.Materials and Methods:Institutional Animal Ethics Committee approval was obtained. Development of model was done by subcutaneous injection of 2 doses of MP (14 and 28 mg/kg/week) for 4 weeks in 21-day old weanlings. Following confirmation of the dose of MP that induced osteoporosis, the antiosteoporotic effect of PG was tested in this model in comparison to a known antiosteoporotic agent, alendronate. Both alendronate (2.9 mg/kg/day) and PG (1.35 g/kg/day) were administered orally 2 weeks after MP - 14 mg/kg/week injection and continued for 4 weeks. Serum and urine calcium and inorganic phosphate were analyzed at weekly intervals. Animals were sacrificed after 6 weeks, and femur bones were processed to measure bone hardness and elasticity and for histological studies.Results:Rats treated with MP - 14 mg/kg/week showed optimum osteoporotic effect with no mortality as compared to MP - 28 mg/kg/week; hence, this dose of MP was used further for the efficacy study. Osteoporotic rats treated with PG 1.35 g/kg showed increase in serum calcium and inorganic phosphate levels, whereas urine calcium and phosphate levels were significantly reduced. A significant decrease in a number of osteoclasts, whereas an increase in bone hardness and elasticity was observed as compared to diseased group demonstrating antiosteoporotic effect of PG.Conclusion:PG has an antiosteoporotic effect in GIO rat model.

Effect of methylprednisolone use on the rotator cuff in rats: biomechanical and histological study

ObjectiveTo evaluate the influence of treatment with different doses of methylprednisolone on the mechanical resistance and possible histological alterations of the rotator cuff tendon in rats. MethodsMale Wistar rats were divided randomly into four treatment groups: sham, vehicle or 0.6mg/kg or 6.0mg/kg of methylprednisolone. Changes to mechanical resistance (in N) and histological parameters (fibrillar appearance, presence of collagen, edema and vascular proliferation) of the rotator cuff tendon were evaluated. The analyses were conducted after administration of one treatment (24h afterwards), two treatments (7 days afterward) or three treatments (14 days afterwards), into the subacromial space. ResultsSeven and fourteen days after the treatments were started, it was found that in a dose-dependent manner, methylprednisolone reduced the mechanical resistance of the rotator cuff tendon (p<0.05 in relation to the vehicle group). Modifications to the histological parameters were observed on the 7th and 14th days after the first infiltration, especially regarding the presence of collagen and vascular proliferation, for the dose of 0.6mg/kg of methylprednisolone, and also regarding the presence of collagen, edema and vascular proliferation for the dose of 6.0mg/kg of corticoid. ConclusionThe results obtained demonstrated a relationship between methylprednisolone use through infiltration into the subacromial space and reduction of the mechanical resistance of and histological modifications to the rotator cuff tendon in rats.

Efeito do uso da metilprednisolona no manguito rotador em ratos. Estudo biomecânico e histológico

ObjectiveTo evaluate the influence of treatment with different doses of methylprednisolone on the mechanical resistance and possible histological alterations of the rotator cuff tendon in rats. MethodsMale Wistar rats were divided randomly into four treatment groups: sham, vehicle or 0.6mg/kg or 6.0mg/kg of methylprednisolone. Changes to mechanical resistance (in N) and histological parameters (fibrillar appearance, presence of collagen, edema and vascular proliferation) of the rotator cuff tendon were evaluated. The analyses were conducted after administration of one treatment (24h afterwards), two treatments (7 days afterward) or three treatments (14 days afterwards), into the subacromial space. ResultsSeven and fourteen days after the treatments were started, it was found that in a dose‐dependent manner, methylprednisolone reduced the mechanical resistance of the rotator cuff tendon (p<0.05 in relation to the vehicle group). Modifications to the histological parameters were observed on the 7th and 14th days after the first infiltration, especially regarding the presence of collagen and vascular proliferation, for the dose of 0.6mg/kg of methylprednisolone, and also regarding the presence of collagen, edema and vascular proliferation for the dose of 6.0mg/kg of corticoid. ConclusionThe results obtained demonstrated a relationship between methylprednisolone use through infiltration into the subacromial space and reduction of the mechanical resistance of and histological modifications to the rotator cuff tendon in rats.

The harmful effect of prolonged high-dose methylprednisolone in acute lung injury

Although many literatures have shown that prolonged high-dose administration of corticosteroids is hazardous and not indicated to therapy acute lung injury (ALI), there is little information on the harmful effect of prolonged high-dose corticosteroids in acute lung injury. In this study, we aimed to investigate the effect of prolonged high-dose methylprednisolone (MPL) on ALI and improve knowledge regarding the appropriate use of corticosteroids in ALI. The different doses of MPL (3, 30, 180mg·kg−1) were given via tail vein injection 1h after the first time LPS administration and were daily administrated for 14days. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements at 12h, 7days and 14days after LPS administration. Single administration of 180mg·kg−1 MPL decreased the lung injury score, wet-to-dry ratio, the total cell numbers and level of procollagen type III in BALF at 12h after LPS challenge. However, prolonged therapy with 180mg·kg −1 MPL for 7days and 14days decreased the number of AMs in BALF and increased the above-mentioned indexes. These results suggested that the prolonged high-dose MPL has harmful effects to treat LPS-induced ALI in rats.

Avascular necrosis of the femoral head in multiple sclerosis: report of five patients

Osteonecrosis of the femoral head is a severe complication of corticosteroids, which may lead to more disability in multiple sclerosis (MS) patients because of delayed diagnosis. The exact dose and risk period of steroids which cause the necrosis are not clearly known. The aim of the study was to enhance the attention of clinicians to leg pain in MS patients with regard to steroid therapies. We report five MS patients with femoral head necrosis who had relapsing remitting MS and received different doses of methyl prednisolone. Our young cases consist of three females and two males. The duration of disease varied between 1 and 3 years. The least interval between the last pulse of prednisolone and diagnosis of avascular necrosis was 6 months. Two of them received one pulse of 5 g of methyl prednisolone. All five patients had delayed diagnosis because the signs and symptoms were attributed to MS, which indicate the necessity of further focusing attention to early evaluations.

Methylprednisolone dosage effects on peripheral lymphocyte subpopulations and eicosanoid synthesis.

Glucocorticoids have a major role in the treatment of glomerular diseases. Despite recent advances in understanding of their mechanism of action, very few studies have addressed the relative advantage of the wide range of different dose regimens employed in clinical practice. We studied the effects of methylprednisolone given intravenously for three consecutive days at the doses of 1 mg/kg (group 1, N = 7; group 2, N = 5), 5 mg/kg (group 3, N = 5) or 15 mg/kg (group 4, N = 6) on total blood peripheral leukocytes and on lymphocyte subsets in patients with glomerular diseases, and investigated whether such effects were a function of the drug concentration in the blood. Since glucocorticoids have an inhibitory effect on the formation of eicosanoids in different cells, we also investigated in the same patients the effect of 1 and 15 mg/kg methylprednisolone on systemic and renal eicosanoid synthesis. Results of pharmacokinetic study showed that the three different doses of methylprednisolone we used resulted in major differences in patient's exposure to the drug, and within the same dose there was a great individual variability. By contrast the three different doses of methylprednisolone induced a comparable drop in the absolute number of lymphocytes six hours after the first injection of methylprednisolone, while 24 hours later blood lymphocyte counts returned to the pre-injection values in all patients. Analysis of lymphocyte subsets showed a selective decrease in the number of circulating CD4+ and CD8+ cells six hours after methylprednisolone which was comparable in the four groups of patients studied. As for the effect of methylprednisolone on systemic and renal eicosanoid synthesis in patients with glomerular diseases, 1 and 15 mg/kg were equally unable to reduce thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) release by circulating polimorphonuclear cells (PMNs). By contrast, methylprednisolone partially inhibited eicosanoid synthesis by PMNs in vitro. Consistent with the data on PMNs, urinary excretion of TxA2 and prostacyclin (PGI2) metabolites were unaltered by the different doses of methylprednisolone. By contrast urinary PGE2 was markedly and significantly reduced in patients given 15 but not 1 mg/kg. We conclude that 1 mg/kg methylprednisolone given to patients with glomerular diseases has the same effect on peripheral total blood leukocyte count and lymphocyte subsets than 5 and 15 mg/kg. The same is true for eicosanoid synthesis by PMNs. Renal synthesis of PGE2 is inhibited by 15 mg/kg but not by 1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytokine release syndrome induced by the 145-2C11 anti-CD3 monoclonal antibody in mice: prevention by high doses of methylprednisolone.

The hamster mAb 145-2C11 specific for the CD3 complex of murine T lymphocytes shares many properties with OKT3, including the induction of T cell activation. In vivo, the injection of 145-2C11 entails a variety of pathologic changes in relation to the systemic release of cytokines. We tested the effects on this cytokine release syndrome of different doses of methylprednisolone (m-PDS) given at various intervals of time before the 145-2C11 mAb. The administration of high doses of m-PDS (50 mg/kg) 2 to 3 h before the mAb resulted in an almost complete inhibition of the systemic release of TNF-alpha, IL-2, and IL-6. As far as the pathologic changes are concerned, the hypothermia, the acute renal tubular necrosis, and the fatty infiltration of the liver were completely prevented whereas the hypoglycemia was only partially attenuated. The protective effect of m-PDS on the toxicity of 145-2C11 was confirmed by the reduction of the mortality rate among galactosamine-sensitized mice. The inhibition of the release of cytokines by m-PDS did not affect the immunosuppression triggered by 145-2C11 as assessed by the CTL activity against alloantigens measured 48 h after the injection of the mAb. We conclude that the administration of very high doses of glucocorticoids 2 to 3 h before 145-2C11 prevents the release of cytokines and attenuates the acute toxicity of the mAb. Similar protocols could allow mitigation of the cytokine-release syndrome induced by the OKT3 mAb in man.