OBJECTIVE: To explore the effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats. METHODS: Twenty female Sprague-Dawley rats (3.5 months old) were randomly assigned to two groups: a treatment group and a control group (n=10 per group). The treatment group was subcutaneously injected with methylprednisolone 3.5 mg/(kg.d) while the control group was subcutaneously injected with same volume of vehicle (saline). Rats were sacrificed at 9 weeks after the treatments. Before the sacrifice, the body weight and total bone mineral density (BMD) were measured. The right forelimb was separated through humeral shoulder and then single axial fatigue loading was performed on the right ulna. After fatigue load, the middle ulna section was bulkstained in basic fuchsin. Bone histomorphometry and microdamage analysis were performed on the middle ulna section. RESULTS: Compared with the control group, the body weight, total bone BMD and ulnas BMD in the treatment group were decreased by 15%, 6.4% and 4.3% respectively (all P<0.05); the ulna inner perimeter and marrow area in the treatment group were increased by 23.3% and 32%, respectively (both P<0.05), while the outer perimeter were decreased by 3.1% (P>0.05). There was no significant difference in the cortical and total area between the 2 groups (both P>0.05). The number of microcrack, microcrack density and microcrack surface density in the treatment group were increased by 43%, 48% and 50%, respectively, compared with those in the control group (all P<0.05), but there was no significant difference in the mean length of microcrack between the 2 groups (P>0.05). CONCLUSION Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.
Animals ; Bone Density ; drug effects ; Female ; Methylprednisolone ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ulna ; drug effects ; pathology

OBJECTIVE: To determine the influence of stress on myocardial apoptosis in ischemic preconditioning group (IPC). METHODS: Twenty-four Japanese white rabbits were randomly divided into 4 groups (n=6): an etomidate group (the Etom group) of depressed stress established by intravenous etomidate, an IPC group, an ischemic reperfusion group (the IR group) and a methylprednisolone group (the MP group). Myocardial apoptosis was examined by DNA-laddering, in situ nick-end labeling (TUNEL) and Hoechst dyeing. RESULTS: The DNA ladder increased in the Etom group. The percentage of apoptosis by TUNEL method was 1.7%±0.2% in the IPC group, 2.3%±0.8% in the MP group, 3.8%±1.3% in the IR group and 3.0%±0.4% in the Etom group. Hoechst dying was 4.1%±0.9% in the IPC group, 3.5%±0.4% in the MP group, 6.2%±1.6% in the IR group and 7.6%±0.4% in the Etom group. There was significant difference between the IPC group and the Etom group or IR group, and also between the MP group and the IR group. CONCLUSION A depressed stress response impairs the inhibition on myocardial apoptosis in ischemic preconditioning. Methylprednisolone may inhibit myocardial apoptosis.
Animals ; Apoptosis ; Etomidate ; pharmacology ; Heart ; drug effects ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Methylprednisolone ; pharmacology ; Myocardium ; pathology ; Rabbits

OBJECTIVETo study the effects of a Gold Belt (GB, a traditional Chinese herbal medicine) combined with methyl-prednisolone (MP) on the motor function and brain-derived neurotrophic factor (BDNF) expression in rats with contusive spinal cord injury (SCI).

METHODSThirty adult female SD rats were randomly divided into 5 equal groups, namely the sham-operated group, SCI group, SCI with MP treatment group (MP group, with intramuscular injection of 50 mg/kg MP within 8 hours after SCI and then dosage reduced 10 mg/kg daily), SCI with GB treatment group (GB group, with intragastric gavage of GB 50 mg/kg once daily for 7 days), and combined GB and MP treatment group. The Basso, Beattie and Bresnahan (BBB) locomotor scale was used to evaluate the hindlimb motor function of the rats on days 1, 3, 7, 14, 21 and 28 after the injury. After the last evaluation the rats were sacrificed for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of spinal cord.

RESULTSBDNF were distributed mainly in neurons in the spinal cord grey matter ventral horn and dorsal horn of the rats. The number of BDNF-positive neurons and BBB scores in the combined treatment group were significantly higher than those in the other 4 groups (P<0.05).

CONCLUSIONGB combined with MP produces better therapeutic effects for treating SCI than GB or MP used alone, and such effects are probably related with enhanced BDNF expression in the spinal cord.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Methylprednisolone ; pharmacology ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; metabolism

OBJECTIVETo investigate the effects of methylprednisolone pretreatment on pulmonary lung permeability index and the content of the pulmonary surfactant dipalmitoylphosphatidylcholine (DPPC) in a rabbit model of reexpansion pulmonary edema.

METHODSTwenty-one male New Zealand white rabbits were randomly divided into control group, reexpansion, and reexpansion+methylprednisolone pretreatment groups. The rabbit model of reexpansion pulmonary edema was established using Sakaos method. A bolus dosage of methylprednisolone (3 mg/kg) in reexpansion+methylprednisolone group group or 2.0 ml/kg normal saline in the other two groups was administered intravenously 20 min before reexpansion pulmonary edema. Bronchoalveolar lavage fluid (BALF) and arterial blood samples were collected for measurement of the total protein (TP) and DPPC contents 4 h after reexpansion, and the pulmonary permeability index was calculated.

RESULTSThe pulmonary permeability index in methylprednisolone pretreatment group was significantly lower than that in the reexpansion group (0.007∓0.002 vs 0.177∓0.004, P<0.05). Methylprednisolone pretreatment significantly increased DPPC concentration in the BALF as compared with saline treatment in the reexpansion group (61.815∓28.307 vs 101.955∓24.544 µg/ml, P<0.05).

CONCLUSIONMethylprednisolone pretreatment can increase pulmonary surfactant content and improve pulmonary permeability in the rabbit model of reexpansion pulmonary edema.

1,2-Dipalmitoylphosphatidylcholine ; analysis ; Animals ; Bronchoalveolar Lavage Fluid ; Capillary Permeability ; drug effects ; Male ; Methylprednisolone ; pharmacology ; Permeability ; Pulmonary Edema ; metabolism ; physiopathology ; Pulmonary Surfactants ; metabolism ; Rabbits

Dexamethasone ; therapeutic use ; Glucocorticoids ; pharmacology ; therapeutic use ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; drug therapy ; physiopathology ; Methylprednisolone ; therapeutic use ; Prednisolone ; therapeutic use

Using computerized vitreous fluorophotometry (VFP, Fluorotron(TM)), we examined the effect of cryotherapy on the blood retinal barrier (BRB) and the effect of subtenon injection of methylprednisolone acetate (Depomedrol(R)). In experiment 1, the right eyes of the 13 pigmented rabbits were treated with heavy cryotherapy after baseline VFP readings. The freezes were applied at 6 places in each quadrant around the equator are in two rows, a total of 24 places circumferentially. The left eyes were reserved as controls. In 6 rabbits (cryo with steroid group), Depomedrol(R) 10 mg of Depomedrol was injected into subtenon space after cryotherapy. The other 7 rabbits were treated with cryotherapy only (cryo only group). The VFP readings were taken 1, 3, 5, and 7 days, 2, 3, 5, and 7 weeks after cryotherapy. Cryotherapy increased the breakdown of BRB significantly. The peak VFP readings were obtained 5 days after cryotherapy in the cryo only group and 7 days after cryotherapy in the cryo with steroid group. In the cryo only group, the severity of the breakdown of BRB was higher than in the cryo with steroid group, and the increased VFP readings could not be normalized until 7 weeks after cryotherapy. In experiment 2, both eyes of the 8 pigmented rabbits were treated with medium cryotherapy after baseline VFP readings. The freezes were applied at 3 places in the superior temporal quadrant and at 3 places in the superior nasal quadrant, a total of 6 places. Depomedrol(R) 10 mg was injected into subtenon space after cryotherapy in the right eyes only. The VFP readings were taken 1, 3, 5, 7, 10, and 14 days after cryotherapy. In this experiment, cryotherapy did not increase the breakdown of BRB. But in the right eye, the severity of the breakdown of BRB was significantly lower than in the left eye 7 and 10 days after cryotherapy. These results suggest that Depomedrol(R) can decrease the severity of the breakdown of BRB after cryotherapy, and may be useful in the prevention of proliferative vitreoretinopathy (PVR).
Animals ; Anti-Inflammatory Agents/*pharmacology ; Blood-Retinal Barrier/*drug effects ; Capillary Permeability ; *Cryosurgery/adverse effects ; Fascia ; Fluorophotometry ; Injections ; Methylprednisolone/*analogs & derivatives/pharmacology ; Orbit ; Rabbits ; Retina/*drug effects/surgery ; Vitreoretinopathy, Proliferative/prevention & control

BACKGROUNDMethylprednisolone (MP), a synthetic glucocorticosteroid, has been broadly studied in experiments on endotoxin-induced shock and septic shock. This study was designed to ascertain whether glycine and MP can protect against organ injury and death caused by hemorrhagic shock, and to elucidate the underlying mechanisms of these protective effects in rats.

METHODTo establish a shock model, Wistar rats were bled to maintain mean arterial pressure at 30-50 mmHg for 1 hour and subsequently resuscitated with the shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to four groups: sham group (operation performed without inducing shock), shock group, shock + glycine group (glycine injected at the beginning of resuscitation) and shock + MP group (MP injected at the beginning of resuscitation).

RESULTS(1) Seventy-two hours after resuscitation, the survival rate of rats from the shock group had decreased to 20%, while the survival rates of rats from the shock + glycine and shock + MP groups were 77.8% and 80%, respectively. The difference was significant (P <0.05). (2) Eighteen hours after resuscitation, pathological alterations in the organs of the rats were apparent. In rats from the shock group, edema, interstitial leukocyte infiltration, and cellular degeneration occurred in the liver, lungs, kidneys, and heart. Glycine and MP reduced these pathological changes significantly. (3) Eighteen hours after resuscitation, the levels of creatine phosphokinase, transaminases, and creatine were elevated significantly in rats from the shock group, indicating injury to the heart, liver, and kidneys, while these levels were elevated only slightly in the shock + glycine and shock + MP groups. The differences were significant (P <0.01). (4) There were significant increases in intracellular calcium and production of tumor necrosis factor (TNF-alpha) by isolated Kupffer cells stimulated by endotoxin after hemorrhagic shock. These changes were completely prevented by glycine and MP (P <0.01).

CONCLUSIONGlycine and MP reduce organ injury and mortality caused by hemorrhagic shock by preventing increase of intracellular calcium levels in Kupffer cell, suppressing Kupffer cell activation, decreasing the production of TNF-alpha by Kupffer cells, and blocking systemic inflammatory responses.

Animals ; Calcium ; metabolism ; Glycine ; pharmacology ; therapeutic use ; Methylprednisolone ; pharmacology ; therapeutic use ; Multiple Organ Failure ; etiology ; Rats ; Rats, Wistar ; Shock, Hemorrhagic ; drug therapy ; mortality ; pathology ; Tumor Necrosis Factor-alpha ; biosynthesis

OBJECTIVETo study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.

METHODSTwelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.

RESULTSInfusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05).

CONCLUSIONSMP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.

Analysis of Variance ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lipid Peroxidation ; Male ; Methylprednisolone ; pharmacology ; Probability ; Random Allocation ; Reference Values ; Reperfusion Injury ; drug therapy ; physiopathology ; Sensitivity and Specificity ; Shock, Hemorrhagic ; drug therapy ; physiopathology ; Survival Rate

OBJECTIVETo observe the changes of human umbilical venous endothelial cells (HUVECs) induced by the sera from children with active Henoch-Sch-nlein purpura (HSP) and the protective effects of methylprednisolone against HUVECs injury.

METHODSHUVECs were divided into four groups based on the culture conditions: blank control group, normal serum group, HSP serum group, and HSP serum plus methylprednisolone group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-8 in the supernatants of each group were detected using ELISA and the nitric oxide (NO) level by nitrate reductase determination. Moreover, the expressions of nuclear factor-kappa B (NF-κB) and Fractalkine in HUVECs were examined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively.

RESULTSThe levels of IL-8, TNF-α, and NO in the HSP serum group were significantly higher than those in the blank control and normal serum groups (P<0.05). Compared with the HSP serum group, the levels of IL-8, TNF-α, and NO in the HSP serum plus methylprednisolone group decreased significantly (P<0.05). The mRNA expression levels of NF-κB and Fractalkine in the HSP serum group were significantly higher than those in the blank control group (P<0.05). The protein expression levels of NF-κB and Fractalkine in the HSP serum group were significantly higher than those in the blank control and normal control group (P<0.05). Compared with the HSP serum group, the mRNA and protein expression levels of NF-κB and Fractalkine in the HSP serum plus methylprednisolone group decreased significantly (P<0.05).

CONCLUSIONSThe sera from children with active HSP can induce the in vitro cultured HUVECs to become activated and excrete cytokines. Methylprednisolone may inhibit NF-κB expression, reduce the production of inflammatory factors, and thus alleviate vascular inflamation.

Cells, Cultured ; Chemokine CX3CL1 ; analysis ; genetics ; Child ; Child, Preschool ; Cytokines ; blood ; Cytoprotection ; Female ; Human Umbilical Vein Endothelial Cells ; drug effects ; immunology ; metabolism ; Humans ; Male ; Methylprednisolone ; pharmacology ; NF-kappa B ; analysis ; antagonists & inhibitors ; genetics ; Nitric Oxide ; physiology ; Purpura, Schoenlein-Henoch ; blood

The aim of this study is to investigate the effects of electroacupuncture, corticosteroid, and combination of two treatments on ambulatory paresis due to spinal cord injury in dogs by comparing therapeutic effects of electroacupuncture and corticosteroid. Spinal cord injury was induced in twenty healthy dogs (2.5~7 kg and 2~4 years) by foreign body insertion which compressed about 25% of spinal cord. There was no conscious proprioception, no extensor postural thrust, and ambulatory. Dogs were divided into four groups according to the treatment; corticosteroid (group A), electroacupuncture (group B), corticosteroid and electroacupuncture (group AB), and control (group C). Neurological examination was performed everyday to evaluate the spinal cord dysfunction until motor functions were returned to normal. Somatosensory evoked potentials (SEPs) were measured for objective and accurate evaluations. The latency in measured potentials was converted into the velocity for the evaluation of spinal cord dysfunctions. Pain perceptions were normal from pre-operation to 5 weeks after operation. Recovery days of conscious proprioception in groups A, B, AB, and C were 21.2+/-8.5 days, 19.8+/-4.3 days, 8.2+/-2.6 days, and 46.6+/-3.7 days, respectively. Recovery days of extensor postural thrust in group A, group B, group AB, and group C were 12.8+/-6.8 days, 13.8+/-4.8 days, 5.4+/-1.8 days, and 38.2+/-4.2 days, respectively. There were no significant differences between group A and group B. However, recovery days of group AB was significantly shorter than that of other groups and that of group C was significantly delayed (p<0.05). Conduction velocities of each group were significantly decreased after induction of spinal cord injury on SEPs (p<0.05) and they showed a tendency to return to normal when motor functions were recovered. According to these results, it was considered that the combination of corticosteroid and electroacupuncture was the most therapeutically effective for ambulatory paresis due to spinal cord injury in dogs.
Animals ; Anti-Inflammatory Agents/*therapeutic use ; Dogs ; Electroacupuncture/*veterinary ; Evoked Potentials, Somatosensory/drug effects ; Female ; Male ; Methylprednisolone Hemisuccinate/pharmacology/*therapeutic use ; Spinal Cord/drug effects/pathology ; Spinal Cord Compression/drug therapy/*therapy/*veterinary