Effects Of Methylprednisolone Sodium Succinate Research Articles

Clinical Evaluation of the Effect of Methylprednisolone Sodium Succinate and Meloxicam in Experimental Acute Spinal Cord Injury

Background: Central nervous system (CNS) has limited repair capacity, and any spinal cord injury (SCI) can cause persistent disability in motor, sensory, and autonomic functions. The harmful reactions around the lesion must be stopped to prevent this consequence. Objectives: The present study compares the clinical effects of methylprednisolone sodium succinate (MPSS) and meloxicam in acute spinal cord injury in an animal model of rats. Methods: We randomly divided 24 male Wistar rats into 4 groups: 1) sham, 2) placebo, 3) SCI+MPSS (30 mg/kg, IV), and 4) SCI+meloxicam (1 mg/kg, SC). We used a Fogarty embolectomy catheter to induce a compression injury to the rats’ T8-T9 spinal cord segment. The drugs were injected one hour after surgery. Neurological evaluation was performed using BBB (Basso, Beattie, and Bresnahan) test immediately after recovery and then once a week for up to 6 weeks. Results: According to the BBB test results, single-dose administration of MPSS one hour after injury improved motor function significantly compared to placebo. But, there was no significant difference between MPSS and meloxicam groups and between meloxicam and placebo groups (P>0.01). Conclusion: In clinical evaluation, single-dose administration of MPSS one hour after injury improved motor function compared to meloxicam.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6h after the occurrence of facial paralysis and peaked after 2days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia.

The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy-cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P less than 0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P less than 0.05). CLL cells showed a variable dose-related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10(-5)-10(-6)M). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in-vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

Modeling of Acute Spinal Cord Injury in the Rat: Neuroprotection and Enhanced Recovery with Methylprednisolone, U-74006F and YM-14673

We used a new injury device that produces consistent spinal cord contusion injuries (T8) in rats to compare the behavioral and histologic effects of methylprednisolone sodium succinate (MPSS) administration, the clinical standard of therapy after acute spinal cord injury (ASCI), with the 21-aminosteroid, U-74006F (U74), and the TRH analogue, YM-14673 (YM), at different trauma doses. Three sequential experiments were conducted: Experiment 1 . U74 (3.0/1.5/1.5 mg/kg; 10/5/5 mg/kg; 30/15/15 mg/kg), MPSS (30/15/15 mg/kg), or vehicle were administered intravenously (iv) at 5 min, 2 and 6 h after the injury (n = 8/group). U74 (10/5/5 mg/kg) and MPSS animals scored better than controls (Days 8-43) in open field walking (OFW); no other differences were seen between groups. Experiment 2. Dose-response evaluation of MPSS determined more effective doses. Groups (n = 16) receiving 30/30/30/30 mg/kg and 60/60/60/60 mg/kg iv at 5 min and 2, 4, and 6 h after the injury had better OFW scores than controls (Days 8-29; Day 29). Both groups performed better than controls (Days 8-29) on inclined plane (IP); 30 mg/kg animals scored higher on Day 29. Percentage tissue spared (%TS) at the lesion center was greater for 60 mg/kg animals (23.4%) than controls (17.3%). Experiment 3. Compounds were administered as in experiment 2 (n = 15/group); MPSS (60/30/30/30 mg/kg) and YM (1/1/1/1 mg/kg and 1 mg/kg/day ip) were most effective. YM and MPSS combination produced no additive effects. YM animals scored better than MPSS and control animals in OFW (Days 8-29) and better than controls on IP (Days 8-29; Day 29) and grid walking (Day 29), MPSS animals scored better than controls on IP (Days 8-29 ). YM and MPSS groups had greater %TS than controls.This series of experiments demonstrates the utility of this injury model and simple behavioral measures for preclinical assessment of pharmacologic agents. Under these experimental conditions, U74 demonstrated equivalent efficacy to MPSS, and YM demonstrated greater efficacy than MPSS in the treatment of ASCI.

Effects of methylprednisolone sodium succinate on the growth of hard tissues in the young rat.

The present study was performed to obtain direct eviden ce of MPNSS (methylprednisolone sodium succinate) on the growth retardation of hard tissues in rats. For this purpose, different doses of MPNSS were injected intraperitoneally to the rat (daily administration of 2.0 mg/kg, 14 times and alternate-day administration of 10.0 mg/kg, 14 times). To the age-matched control animals, 0.9 % NaCl solution was injected. The body weight was measured daily. Wet weight of the adrenal gland was measured and the lengths of upper jaw (diastema) and tibia were also measured with dial calipers. In addition, the rate of the incisal dentine formation was measured with a chronological-labelling method using tetracycline. The right tibia was used for measuring the defatted -dry weight and the ash weight. To detect changes in calcium homeostasis, contents of calcium and phosphorus in the plasma were analysed. Following treatment with MPNSS, the weight loss, atrophy of the adrenal gland and retardation of bone growth were detected in both experimental groups.On the other hand, osteoporosis could not be recognized by contact-microradiography. It was confirmed that reduction of the growth rates was greater in the daily injected group than in the alternate-day injected one. In conclusion, the present study showed a direct inhibitory effect of MPNSS on bone growth in growing young rats. It is suggested that a larger dose of glucocorticoids could be given more effectively with less side effects of the drug by an alternate-day administration.

Methylprednisolone affects inhibitors of the complement and the contact systems; functional and immunochemical studies on α2-macroglobulin and C1 inhibitor

The effects of methylprednisolone sodium succinate (MP) on main inhibitors of the classical pathway of complement and on the contact system were studied in citrated pool plasma. Endotoxin (2·10 9 ng/l,lipopolysaccharide B, E. coli 026: B6 Difco Laboratories, Detroit, Michigan, USA) and/or MP in doses of 0.1, 1, 5 and 10 mg/ml were incubated with plasma at 37°C. Plasma samples were obtained at timed intervals up to 24 hours for determination of Cl inhibitor (Clinh) and α 2-macroglobulin ( α 2M) values using both functional and immunochemical assays. Plasma containing endotoxin without MP revealed decreases of Clinh and α 2M values after 12 hours. Addition of MP in high doses (10 mg/ml) gave an additive effect on the endotoxin-induced decreases of Clinh and α 2M values, evident 1 and 12 hours after the beginning of incubation, respectively. When MP alone was added to plasma (5 and 10 mg/ml) also significant decreases in Clinh and α 2M values were seen. MP in low doses (0.1 and 1 mg/ml) did not either influence the endotoxin-induced changes in the protease inhibitor functions, or induce significant changes in Clinh and α 2M values when incubated in plasma without endotoxin. This study demonstrates that MP in high doses induces marked decreases in plasma Clinh and α 2M inhibitory functions and that MP has an additive effect on the endotoxin-induced decreases of these inhibitors.

Steroid-induced enhancement of functional recovery of postischemic, reperfused myocardium in conscious dogs

The effects of methylprednisolone sodium succinate (20 mg/kg, intravenously administered) on the time course of functional recovery of myocardium following a 15-minute coronary artery occlusion period and subsequent 5 hour reperfusion period were studied in chronically instrumented, conscious dogs. In comparison to a control group, animals receiving methylprednisolone 90 minutes prior to coronary occlusion demonstrated less depression of regional segment shortening following 15 minutes of reperfusion (52 ± 13% vs control levels of 23 ± 7% of preocclusion values) and improved recovery at 5 hours postreperfusion (106 ± 6% vs control levels of 54 ± 4% of preocclusion values). In animals receiving methylprednisolone immediately prior to reperfusion, there was also similar recovery of segment shortening at 5 hours (97 ± 3%). In contrast, dogs receiving methylprednisolone 15 minutes after the onset of reperfusion or sodium succinate (5.5 mg/kg, intravenously administered) 90 minutes prior to occlusion demonstrated no improvement in recovery of function. Experiments in dogs not subjected to coronary occlusion documented that methylprednisolone sodium succinate lacked inotropic and vasodilator properties. The results suggest that methylprednisolone administered prior to or during coronary artery occlusion but not after reperfusion enhances the functional recovery of hypokinetic, postischemic, reperfused myocardium. These effects are unrelated to any direct hemodynamic action of steroids or to the sodium succinate salt.

Experimental posttraumatic pulmonary microembolism. Effects of methylprednisolone on its development.

The effects of methylprednisolone sodium succinate on the course of posttraumatic pulmonary microembolism were studied in pigs submitted to a reproducible high-energy trauma of the limb and then observed under long-term anesthesia. Methylprednisolone sodium succinate (30 mg/kg of body weight) was given one hour after trauma and thereafter every eighth hour during a 72-hour observation period. Intrapulmonary microembolism was quantitatively measured by repeated external detection of chromium 51-labeled platelets and iodine 125-labeled fibrinogen, sequential chest roentgenograms, and morphologic examination of the lungs post mortem. Methylprednisolone delayed the onset of pulmonary roentgenogram changes and modulated Pao2 and platelet count reductions, but, at the end of the observation period, the signs of microembolism changes were as pronounced as in the nontreated traumatized pigs. Methylprednisolone thus did not prevent posttraumatic pulmonary microembolism in this experimental situation.

Effects of methylprednisolone on resolution of acid-aspiration pneumonitis.

We studied the effects of methylprednisolone sodium succinate on the pulmonary function of unanesthetized dogs for four days after aspiration of 1.5 to 2.0 mL/kg of 0.1N hydrochloric acid. Methylprednisolone sodium succinate (30 mg/kg) was administered to nine dogs at 2, 8, and 24 hours after acid aspiration. Nine animals were untreated after aspiration and served as controls. Acid aspiration caused significant increases in venous admixture and reductions in Pao2 in both groups of animals. These changes persisted for 96 hours after aspiration. There were no differences in cardiac output, venous admixture, and blood gas values between treated and untreated animals at any time. At death there were no differences between groups in amounts of lung water or histologic characteristics. We concluded that methylprednisolone administered after hydrochloric acid aspiration does not affect resolution of the injury.

A Double Blind Controlled Study on the Clinical Effects of Methylprednisolone Sodium Succinate in Shock as Compared with Hydrocortisone Sodium Succinate

The effects of methylprednisolone sodium succinate (Solu-Medrole®) in shock were studied by the double blind technique at 32 medical centers, using hydrocor. tisone sodium succinate (Solu-Cortef®) as the active control drug. Either methylprednisolone sodium succinate or hydrocortisone sodium succinate was administered in an initial dose of 20-30 mg per kg of body weight to each of 135 patients. Any patients who failed to respond well to the initial doses were given additional doses. The effects of the steroids used were evaluated within 12 hours following the final doses.The results obtained are as follows:1. The general improvement rate was higher for the methylprednisolone sodium succinate group than for the hydrocortisone sodium succinate group.2. The global utility rate was greater for the methylrednisolone sodium succinate group than for the hydrocortisone sodium succinate group.3. Methylprednisolone sodium succinate group showed a greater improvement than the hydrocoritsone sodium succinate group in the post-treatment measurements of shock score, systolic blood pressure, pulse pressure, shock index, urinary output, arterial blood pH and Base Excess.

Acute effects of methylprednisolone sodium succinate on spinal reflexes

The acute effects of single intravenous doses of methylprednisolone sodium succinate (30, 60, or 90 mg/kg) on segmental spinal cord function were examined by stimulating the triceps surae nerves and recording the monosynaptic (2N) and polysynaptic discharges at ventral root L7. Five to ten seconds after injection, an intense but short-lived, spontaneous discharge concomitant with a dose-related reduction in the stimulus-evoked 2N response occurred. This was rapidly followed by enhancement in the 2N discharge amplitude which peaked by 45 s after administration. The duration of the 2N increase was 10 to 60 min. Polysynaptic discharge was augmented to a lesser extent and for a shorter time. The reflex enhancement was reproducible in preparations in which the distally transected dorsal roots were stimulated. All drug-induced responses were prevented by preadministration of 2.5 to 10.0 mg/kg Na pentobarbital i.v. These results indicate that i.v. glucocorticoid enhances mainly monosynaptic transmission perhaps by an action on the primary afferent terminals which augments their spontaneous and evoked transmitter release. Furthermore, they provide additional support for the view that the beneficial effects of glucocorticoids in central nervous system trauma and stroke may in part reflect an improved synaptic function.

Topical Cardiac Hypothermia: The Effect of Methylprednisolone Sodium Succinate

We evaluated the effects of methylprednisolone sodium succinate (MPSS) on 60 minutes of myocardial ischemia during profound (5°C) topical cardiac hypothermia (ice chips) in a canine right heart bypass preparation. The ventricular function curve shifted to the right and downward, but not significantly, after ischemia, and stroke work declined significantly for both control and treated dogs. Contractility (rate of rise of left ventricular pressure and maximum velocity of the contractile element) declined for both groups but not significantly. Total coronary flow, oxygen consumption, and metabolism of lactate and pyruvate were not different for control and treated dogs. Ultrastructure of the outer and inner myocardium did not demonstrate benefit from MPSS. Intracellular and extracellular edema of moderate severity was slightly worse in the subendocardium, and reversible mitochondrial injury of a mild to moderate degree was symmetrically present. Ice-related injury was not noted. We were unable to demonstrate that pretreatment with MPSS favorably alters cardiodynamics or ultrastructure after 60 minutes of profound topical cardiac hypothermia.

Experimental Herpes Simplex Virus Encephalitis

The effects of methylprednisolone sodium succinate and cytarabine have been examined in an experimental herpes simplex virus-induced encephalitis in rabbits. In this model herpes simplex virus (HSV) is normally cleared from the brains of untreated animals. Infected animals treated with large doses of methylprednisolone showed a slight delay in the rate of clearance of virus, and a minimal reduction in the inflammatory process, but did not otherwise differ from untreated controls. Animals treated with cytarabine displayed a notable rise in viral titers in brain at a time when virus had been cleared from untreated controls. Cytarabine-treated animals also showed persistence of intranuclear inclusions in the lesions, and moderate diminution in the extent of inflammatory response. Thus, while methylprednisolone appears to have little adverse effect on the encephalitic process, cytarabine, perhaps because of its immunosuppressive properties, results in a failure of normal clearance of virus from nervous system lesions.

Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia

The metabolic and hemodynamic effects of methylprednisolone sodium succinate (40 mg/kg body weight) after acute myocardial ischemia were determined in 24 heparinized mongrel dogs. Myocardial ischemia was produced by ligation of the left anterior descending coronary artery. Catheters in the coronary sinus and the vein draining the left anterior descending coronary arterial area were used to collect blood samples from nonischemic and ischemic myocardium. Lactate, pyruvate, glucose, free fatty acids and oxygen were measured in arterial and venous blood from ischemic and nonischemic areas before and 3, 30 and 60 minutes after myocardial ischemia in animals with (Group II) and without (Group I) steroid treatment. In both Groups I and II glucose, lactate, free fatty acids, oxygen and coronary blood flow in nonischemic areas were not significantly changed, whereas glucose uptake in ischemic areas was significantly increased with myocardial ischemia and remained elevated. In Group I lactate uptake in ischemic areas became negative after coronary arterial ligation and remained so; in Group II, it increased after 30 (70 percent) and 60 (111 percent) minutes. Free fatty acid uptake in ischemic areas was reduced after myocardial ischemia in Group I, but in Group II it increased after 30 (224 percent) and 60 minutes (173 percent), and there was a concomitant increase in oxygen uptake. Pyruvate uptake in nonischemic areas decreased after 60 minutes in Group I, whereas it was reduced after 30 (68 percent) and 60 minutes (513 percent) in Group II. The changes were similar in ischemic myocardium. There were no significant changes in hemodynamic indexes. Coronary blood flow in ischemic areas decreased in Group I after myocardial ischemia and further after 30 and 60 minutes, but in Group II it increased after 30 (82 percent) and 60 minutes (53 percent). The data indicate that administration of methylprednisolone results in improved collateral blood flow into the infarcted area and a significantly improved metabolic response of ischemic myocardium. The glucocorticoid may also have a direct benefical effect on carbohydrate metabolism and cause the increased pyruvate neccesary to maintain the generation of energy-producing substrates. The results also suggest that methylprednisolone increases cell survival time and results in greater salvage of ischemic myocardium.

Inadequacy of steroids in the treatment of severe hemorrhagic shock

Massive doses of methylprednisolone were given to dogs prior to severe, lethal, hemorrhagic shock. An untreated group of dogs subjected to hemorrhagic shock served as controls. No persistent significant differences were seen in cardiac output, mean arterial blood pressure, superior mesenteric artery flow, and survival. Calculated total peripheral resistance tended to be lower in the treated dogs and was significantly lower after reinfusion of shed blood. Pretreatment with methylprednisolone did not prevent plasma elevations of the lysosomal enzymes, cathepsin D and β-glucuronidase. Stabilization of hepatic lysosomes in treated dogs subjected to hemorrhagic shock was not evident. The results failed to indicate significant salutary effects of methylprednisolone sodium succinate in this lethal hemorrhagic shock model.

EFFECTS OF METHYLPREDNISOLONE SODIUM SUCCINATE ON OPERANT BEHAVIORS IN RATS

Effects of methylprednisolone sodium succinate, a water soluble corticosteroid, on conditioned behaviors in fixed ratio (FR 30) and fixed interval (FI 60sec.) schedules of food reinforcement, as well as in Sidman's and discriminated avoidance schedules were investigated in rats.The effects on conditioned suppression (CER) which was developed by warning stimulus associated with electric shock in FR and FI schedules, were also observed after the steroid.These conditioned responses did not exhibit marked change following the administration of the steroid (10-40 mg/kg). However, correct response rate increased with decreasing of total responses in discriminated avoidance schedule. Such phenomena became rather prominent 24 hours after the administration; thus the mechanism was probably caused by the inhibition of ACTH-release rather than by the direct central-action of the steroid.

Clinical Cardiogenic Shock. Vasopressor Versus Corticoid Therapy.

Meeting Abstracts1 May 1972Clinical Cardiogenic Shock. Vasopressor Versus Corticoid Therapy.Leonard S. Schultz, M.D., Ronald H. Dietzman, M.D., George J. Motsay, M.D., Lloyde Romero, M.D., Charles Beckman, M.D., Richard C. Lillehei, M.D., Ph.D.Leonard S. Schultz, M.D.Search for more papers by this author, Ronald H. Dietzman, M.D.Search for more papers by this author, George J. Motsay, M.D.Search for more papers by this author, Lloyde Romero, M.D.Search for more papers by this author, Charles Beckman, M.D.Search for more papers by this author, Richard C. Lillehei, M.D., Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-867_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNinety-five patients in clinical cardiogenic shock (Group I: cardiac index, ≤ 2 litre/min·m2body surface area; systolic blood pressure, ≤ 90 mm Hg) and 20 in impending cardiogenic shock (Group II: cardiac index, ≤ 3.0 litres/min·m2body surface area; systolic blood pressure, ≤ 90 mm Hg) were studied. Sixty-seven patients in Group I were given massive corticoid treatment (methylprednisolone (M-P), intravenously, mg/kg body weight) as primary therapy, whereas the rest received methylprednisolone with a vasopressor infusion of levarteranol, 4 μg/kg body weight·min. Therapy was either randomly selected or specifically requested by the patient's personal physician. Group II was given intravenous... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Minneapolis, Minn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBeneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia 1 May 1972Volume 76, Issue 5Page: 867-868KeywordsBlood pressureBody surface areaBody weightShockSystolic pressureVasopressors Issue Published: 1 May 1972 PDF downloadLoading ...

Endotoxin Shock in the Subhuman Primate

The circulatory and biochemical effects of methylprednisolone sodium succinate (Solu-Medrol) in endotoxin shock were studied. The two most important effects of methylprednisolone in endotoxin shock appeared to be a decrease in peripheral resistance and the prevention of a drop in plasma volume. In the group receiving endotoxin alone, the aortic pressure, renal artery flow, cardiac output, and stroke volume showed a gradual decline but with methylprednisolone administration they were less pronounced. A rise in the blood lactic acid level was a consistent finding whether the animals received the steroid or not. This study suggests that glucocorticoids in pharmacologic doses appear to improve the cardiovascular status of the subhuman primate subjected to endotoxin shock.