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Methylprednisolone
Kinds of Methylprednisolone Terms modified by Methylprednisolone Selected AbstractsMethylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytesGLIA, Issue 13 2008Wei-Lin Liu Abstract Reactive gliosis caused by post-traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti-inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using ,-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA-treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR-mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. © 2008 Wiley-Liss, Inc. [source] Systematic review of randomized controlled trials of pharmacological interventions to reduce ischaemia-reperfusion injury in elective liver resection with vascular occlusionHPB, Issue 1 2010Mahmoud Abu-Amara Abstract Background:, Vascular occlusion during liver resection results in ischaemia-reperfusion (IR) injury, which can lead to liver dysfunction. We performed a systematic review and meta-analysis to assess the benefits and harms of using various pharmacological agents to decrease IR injury during liver resection with vascular occlusion. Methods:, Randomized clinical trials (RCTs) evaluating pharmacological agents in liver resections conducted under vascular occlusion were identified. Two independent reviewers extracted data on population characteristics and risk of bias in the trials, and on outcomes such as postoperative morbidity, hospital stay and liver function. Results:, A total of 18 RCTs evaluating 17 different pharmacological interventions were identified. There was no significant difference in perioperative mortality, liver failure or postoperative morbidity between the intervention and control groups in any of the comparisons. A significant improvement in liver function was seen with methylprednisolone use. Hospital and intensive therapy unit stay were significantly shortened with trimetazidine and vitamin E use, respectively. Markers of liver parenchymal injury were significantly lower in the methylprednisolone, trimetazidine, dextrose and ulinastatin groups compared with their respective controls (placebo or no intervention). Discussion:, Methylprednisolone, trimetazidine, dextrose and ulinastatin may have protective roles against IR injury in liver resection. However, based on the current evidence, they cannot be recommended for routine use and their application should be restricted to RCTs. [source] Profile of opportunistic infections among patients on immunosuppressive medicationINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006Srinivas REDDY Abstract Background:, The widespread use of immunosuppressives in treating systemic autoimmune disorders has resulted in opportunistic infections (OIs) following such therapy. Current data regarding the possibility of infection due to these drugs or from the primary disease, per se, is conflicting. Objectives:, We aimed to analyse the profile of patients requiring hospitalization for OIs among those being treated with glucocorticoids and other immunosuppressive agents as part of management of systemic autoimmune disorders and to analyse the host factors in relation to OIs. Method:, In this descriptive analysis, all patients hospitalized the Postgraduate Institute of Medical Education and Research, Chandigarh, India, under medicinal units for OIs that occurred following and during treatment with corticosteroids and other immunosuppressive agents for treatment of systemic autoimmune disorders from February 2002 to January 2003, were studied. All hospitalized patients received antibiotics according to the nature of infection and sensitivity reports. All relevant clinical details were recorded in a standard pro forma. Descriptive statistics were used. The Institute Ethics Committee's permission was secured prior to study commencement. Results:, Nineteen patients (16 female) were admitted because of OIs. Their mean age (± SD) was 37.32 (± 19.9) years. Ten patients had systemic lupus erythematosus (SLE), two had SLE with overlap, five had rheumatoid arthritis, and one each had vasculitis and scleroderma with polymyositis. There were 28 infections. One (5.3%) patient had four infections, one (5.3%) had three, six (31.6%) had two, nine (47.4%) had one, and in two (10.5%) patients the infection was not localized. Of the 19 cases, 10 (52.6%) received > 10 mg of prednisolone each day (median = 1130 mg). The remaining nine (47.4%) were on < 10 mg prednisolone each day (median = 880 mg). Methylprednisolone was given to two (6.3%) patients. Bacteria accounted for most of the infections. There were two fungal infections and one patient each with tuberculosis and peritonitis. Infections occurred predominantly in the chest, urine and skin. Septicemia was diagnosed in three patients. There were two deaths, one each with SLE and rheumatoid arthritis. Conclusion:, Since infections can occur at low doses of corticosteroids, we suggest that these disorders may be, per se, responsible for an increased risk of infection. [source] Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009M. CAN Background: The aim of this study was to compare the anti-inflammatory response of methylprednisolone and the ,2-agonist dexmedetomidine in spinal cord injury (SCI). Methods: Twenty-four male adult Wistar albino rats, weight 200,250 g, were included in the study. The rats were divided into four groups as follows: the control group (n: 6) received only laminectomy; the SCI group (n: 6) with trauma alone; the SCI+methylprednisolone group (n: 6) with trauma and 30 mg/kg methylprednisolone, followed by a maintenance dose of 5.4 mg/kg/h; and the SCI+dexmedetomidine group (n: 6) with trauma and 10 ,g/kg dexmedetomidine treatment intraperitoneally. Twenty-four hours after the trauma, spinal cord samples were taken for histopathological examination and serum samples were collected for interleukin-6 (IL-6) and tumor necrosis factor (TNF)-, measurement. Results: TNF-, (P=0.009) and IL-6 (P=0.009) levels were significantly increased in the SCI group. TNF-, and IL-6 levels were significantly decreased with methylprednisolone (P=0.002, 0.002) and dexmedetomidine (P=0.002, 0.009) treatment, respectively. Methylprednisolone and dexmedetomidine treatment reduced neutrophils' infiltration in SCI. Conclusions: The current study does not clarify the definitive mechanism by which dexmedetomidine decreases inflammatory cytokines but it is the first study to report the anti-inflammatory effect of dexmedetomidine in SCI. Further studies are required to elucidate the effects of dexmedetomidine on the inflammatory response. [source] Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon-to-Bone Healing and Opposed Corticosteroid AggravationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006Andrija Krivic Abstract Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 µg, 10 ng, 10 pg), 6,-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6,-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6,-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Methylprednisolone exacerbates axonal loss following optic nerve trauma in ratsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2002KD Steinsapir PURPOSE: This study investigates the clinical dogma that very high doses of methylprednisolone helpful in spinal cord injury are also helpful in optic nerve trauma. Methods: The right optic nerve of 29 male rats received a 5 second traumatic crush followed 30 minutes later by one of five intravenous treatments (methylprednisolone 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or saline). Treatment was continued for three additional administrations at 6 hour intervals. Untreated sham controls (n = 7) were also prepared. Six weeks after injury, animals were sacrificed, perfused and optic nerves systematically counted. RESULTS: Axon counts (means +/, s.e.m.) were as follows: Saline = 16,670 +/, 8,900 (n = 5); Methylprednisolone: 30 mg/kg = 8,098 +/, 4,741 (n = 5); 60 mg/kg = 6,925 +/, 6,517 (n = 4); 90 mg/kg = 2,663 +/, 2,653 (n = 4); 120 mg/kg = 6,149 +/, 3,487 (n = 6). Consequently, the data revealed that saline treated animals retained more axons than those that were administered methylprednisolone (p < 0.02). CONCLUSIONS: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma. [source] Comparative Effectiveness of Methylprednisolone and Zero-balance Ultrafiltration on Inflammatory Response After Pediatric Cardiopulmonary BypassARTIFICIAL ORGANS, Issue 7 2007Jinping Liu Abstract:, Studies have demonstrated that systemic inflammatory response syndrome (SIRS) remains one of the major causes of cardiopulmonary bypass (CPB)-associated organ injury during pediatric cardiac surgery. The purpose of this investigation was to compare the effectiveness of methylprednisolone (MP) and zero-balance ultrafiltration (ZBUF) on SIRS during pediatric CPB. Thirty infants undergoing open-heart surgeries were randomized to receive either MP in the priming solution (group M, n = 15) or ZBUF during CPB (group Z, n = 15). All the patients survived. Plasma levels of tumor necrosis factor-, (TNF-,), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10) were measured before CPB (T1), 5 min after the start of CPB (T2), at the termination of CPB (T3), the fourth hour (T4), and the eighth hour (T5) postoperatively. The results showed that the plasma concentrations of TNF-, in the Z group were significantly less than those in the M group at T4 and T5 (P < 0.05), and the plasma concentrations of IL-6 were significantly less than those in the M group at T4 (P < 0.05); the plasma concentrations of IL-8 in the Z group were significantly less than those in the M group at T5 (P < 0.05). There was no difference between two groups on the plasma concentrations of IL-10. The duration of postoperative mechanical ventilation was (9.6 ± 0.8 h) in the M group and (7.8 ± 0.4 h) in the Z group (P < 0.05). This study showed that application of ZBUF is more effective to decrease the level of inflammatory mediators including TNF-,, IL-6, and IL-8 than administration of MP after pediatric CPB. [source] Concentration of methylprednisolone in the centrodistal joint after administration of methylprednisolone acetate in the tarsometatarsal jointEQUINE VETERINARY JOURNAL, Issue 2 2005A. SERENA Summary Reasons for performing study: The centrodistal (CD) and tarsometatarsal (TMT) joints are often injected individually with a corticosteroid to resolve lameness caused by osteoarthritis (OA). There are no data available regarding diffusion of methylprednisolone (MP) from the TMT joint to the CD joint. Hypothesis: A therapeutic concentration of MP diffuses into the CD joint after methylprednisolone acetate (MPA) is administered into the TMT joint. Objective: To measure the concentration of MP in the CD joint after MPA was administered into the TMT joint. Methods: MPA was administered into a TMT joint of 16 horses. At different times, the ipsilateral CD joint of these horses was injected with a small amount of saline and recovered saline was measured for concentration of MP using high performance liquid chromatography. Results: Six hours after administration of MPA into the TMT joint, a therapeutic concentration of MP was found in all 10 CD joints sampled at this time. Conclusions: Horses with pain arising from the distal 2 joints of the hock can be treated by administering MPA into the TMT joint alone. Potential relevance: Administering MPA into the TMT joint only, to treat OA of the distal 2 hock joints, reduces the difficulties and risks associated with centesis of the CD joint. [source] Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004H.-C. Tillmann Abstract Background, Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge. Methods, Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry. Results, Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone). Conclusion, This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect. [source] Over-expression of CCL3,,MIP-1, in a blastoid mantle cell lymphoma with hypercalcemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2010Norimichi Hattori Abstract We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels of interleukin-6 (IL-6), tumor necrosis factor-, (TNF-,), macrophage inflammatory protein-1, (MIP-1,), and type I collagen telopeptide, but not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse transcription polymerase chain reaction (RT-PCR) analysis, we found predominant expression of mRNA for MIP-1, in addition to those for receptor-activator of nuclear-factor kappa B ligand (RANKL), TNF-,, and IL-6 in lymphoma cells obtained from the patient. Furthermore, recombinant MIP-1, significantly stimulated 3H-thymidine uptake by isolated MCL cells in vitro. Treatment with intravenous fluids, bisphosphonate, and methylprednisolone followed by combination chemotherapy promptly corrects the hypercalcemia and successfully induced complete remission, which was accompanied by a decrease of these cytokines in the serum, including MIP-1,. In the present case, MIP-1,, an osteoclast-activating factor produced by mantle lymphoma cells, may contribute to the development of hypercalcemia. It likely acts through RANKL expression in tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1, is also involved in the development of an aggressive phenotype on MCL by stimulating proliferation of these lymphoma cells. In summary, the present study demonstrated that MIP-1, is an important factor in the development of both hypercalcemia and an aggressive phenotype in some types of B-cell lymphoma. [source] The corticosteroid-induced inhibitory effect on NK cell function reflects down-regulation and/or dysfunction of triggering receptors involved in natural cytotoxicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2004Chiara Vitale Abstract Corticosteroids are known to inhibit NK cell functions. However no information is available on whether such inhibition may affect the expression and/or the function of receptors involved in NK cell activation. In an attempt to analyze this point, we studied peripheral blood NK cells isolated from pediatric patients undergoing allogeneic BM transplantation. NK cells were analyzed before, during and after methylprednisolone administration to treat acute graft-versus-host disease. In NK cells freshly isolated from peripheral blood during methylprednisolone treatment, the surface expression of activating receptors, particularly NKp46 and NKp30, was consistently reduced. Such impaired expression could also be detected after 5,days of culture in IL-2. Such cultured NK cells also failed to express the IL-2-inducible NKp44 receptor. Accordingly, cytotoxicity against different tumor target cell lines was sharply reduced. The effect on NK cells isolated from healthy individuals and cultured in the presence of methylprednisolone was also analyzed. A similar inhibitory effect occurred in the expression of activating NK receptors. In addition, a sharp impairment of NK cytotoxicity against different tumor target cell lines or immature DC was detected. [source] EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapsesEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2005F. Sellebjerg Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS. [source] Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2005M. Zorzon To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = ,0.31, P =0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone. [source] Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving combined therapy with oral cyclosporine and steroidsEXPERIMENTAL DERMATOLOGY, Issue 2 2010Deborah Lee Please cite this paper as: Serum levels of IL-18 and sIL-2R in patients with alopecia areata receiving combined therapy with oral cyclosporine and steroids. Experimental Dermatology 2010; 19: 145,147. Abstract:, This study was to determine which immunologic factors contribute to the prognosis of patients with alopecia areata (AA) who were receiving oral cyclosporine A and methylprednisolone. Patients with >25% hair regrowth were defined as responders, and patients exhibiting ,25% regrowth were poor-responders. The serum levels of IL-18 and soluble IL-2 receptor (sIL-2R) were measured at baseline in 21 patients with AA and 22 control subjects. The mean serum level of IL-18 in the patients with extensive AA was significantly higher than that in the control subjects. The mean serum concentration of sIL-2R in the AA patients significantly decreased after 1 month of treatment. The mean basal serum level of IL-18 was highest in the responder, whereas the baseline level of sIL-2R was significantly higher in the poor-responder group than other groups. In conclusion, increased serum sIL-2R level and lower IL-18 level at baseline was associated with a poor prognosis in patients with AA. [source] Pemphigus mouse model as a tool to evaluate various immunosuppressive therapiesEXPERIMENTAL DERMATOLOGY, Issue 3 2009Yujiro Takae Abstract:, Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by immunoglobulin G (IgG) autoantibodies against desmoglein 3 (Dsg3). We have generated an active disease mouse model for PV by adoptive transfer of Dsg3,/, lymphocytes. In this study, we investigated the benefits and limitations of this model as a tool to evaluate various immunosuppressive therapeutic strategies. We used the following three measurements to evaluate the effects of the drugs during the time course: Dsg3 enzyme-linked immunosorbent assay scores that represent the level of production of anti-Dsg3 IgG, body weight loss that reflects the severity of oral erosions and PV score that reflects the extent of skin lesions. We examined various immunosuppressive agents currently used to treat patients with PV model mice in preventive protocol. Cyclophosphamide almost completely suppressed the production of anti-Dsg3 IgG, development of body weight loss and the appearance of the PV phenotype in contrast with the control group without the drug. Azathioprine, cyclosporin A and tacrolimus hydrate also showed suppressive effects to various degrees. However, methylprednisolone and dexamethasone failed to show significant effects in contrast to the findings reported in humans. Knowing the advantages and limitations of this model will provide an important foundation for the future evaluation and development of novel therapeutic strategies. [source] High-dose methylprednisolone influences the physiology and virulence of Candida albicans ambiguously and enhances the candidacidal activity of the polyene antibiotic amphotericin B and the superoxide-generating agent menadioneFEMS YEAST RESEARCH, Issue 2 2007Ágnes Gyetvai Abstract Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid,polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids. [source] Systematic review of randomized controlled trials of pharmacological interventions to reduce ischaemia-reperfusion injury in elective liver resection with vascular occlusionHPB, Issue 1 2010Mahmoud Abu-Amara Abstract Background:, Vascular occlusion during liver resection results in ischaemia-reperfusion (IR) injury, which can lead to liver dysfunction. We performed a systematic review and meta-analysis to assess the benefits and harms of using various pharmacological agents to decrease IR injury during liver resection with vascular occlusion. Methods:, Randomized clinical trials (RCTs) evaluating pharmacological agents in liver resections conducted under vascular occlusion were identified. Two independent reviewers extracted data on population characteristics and risk of bias in the trials, and on outcomes such as postoperative morbidity, hospital stay and liver function. Results:, A total of 18 RCTs evaluating 17 different pharmacological interventions were identified. There was no significant difference in perioperative mortality, liver failure or postoperative morbidity between the intervention and control groups in any of the comparisons. A significant improvement in liver function was seen with methylprednisolone use. Hospital and intensive therapy unit stay were significantly shortened with trimetazidine and vitamin E use, respectively. Markers of liver parenchymal injury were significantly lower in the methylprednisolone, trimetazidine, dextrose and ulinastatin groups compared with their respective controls (placebo or no intervention). Discussion:, Methylprednisolone, trimetazidine, dextrose and ulinastatin may have protective roles against IR injury in liver resection. However, based on the current evidence, they cannot be recommended for routine use and their application should be restricted to RCTs. [source] Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves' ophthalmopathyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2007. Aktaran Summary A prospective, randomised and single blind clinical trial was designed to compare intravenous methylprednisolone pulse (IVGC) with oral methylprednisolone (OGC) monotherapy in terms of effectiveness and tolerability in Graves' ophthalmopathy (GO). Fifty-two consecutive patients with untreated, moderately severe and active GO were randomly treated with either IVGC or OGC therapy for 12 weeks. IVGC therapy achieved a more rapid and significant improvement than OGC therapy according to clinical activity score (p < 0.01), proptosis (p < 0.038), lid width (p < 0.0001), extraocular muscle changes (p < 0.02), optic neuropathy. (p < 0.001), intraocular pressure (p < 0.04), visual acuity (p < 0.03), quality of life (p < 0.0001) and treatment response (p < 0.001). Diplopia was significantly improved in two groups but there was no difference between them (p < 0.6). Heavy smokers indicated alteration of ophthalmic signs with increased thyroid stimulating hormone (TSH)-receptor antibody during the therapy. In conclusion, IVGC therapy was more effective and better tolerated than OGC therapy in the management of GO. [source] Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndromeINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2007Raquel Cardoso MD Background, A 31-year-old woman presented with a 5-year history of painful ulcerations, palpable purpura, porcelain-white atrophic scars of the malleolar region and dorsal aspect of the feet, livedo reticularis on the limbs, arthralgia, xerophthalmia, and xerostomia. Methods, Skin biopsy revealed vessel wall hyalinization and thrombosis of the microvasculature with a very scarce dermal inflammatory infiltrate. Biopsy of the oral mucosa showed mononuclear infiltration of an intralobular duct of a salivary gland. Results, Laboratory studies, including autoantibodies and inflammation markers, were normal, except for a positive rheumatoid factor. Coagulation screening revealed C677T methylenetetrahydrofolate reductase (MTHFR) mutation, with a normal serum homocysteine. The patient was treated with oral methylprednisolone (32 mg/day with progressive reduction) and enoxaparin (20 mg/day subcutaneously), with complete ulcer healing within 4 months. Conclusion, Livedoid vasculitis or vasculopathy has not been referred to previously in association with Sjögren's syndrome, but may be associated with other autoimmune disorders and anomalies of coagulation, namely factor V Leiden mutation, protein C deficiency, and MTHFR mutation, associated or not with hyperhomocysteinemia, a condition that seems to confer an increased risk of recurrent arterial and venous thrombosis. We stress the importance of anticoagulant therapy for ulcer healing and for the prevention of other thrombotic events. [source] Chronic lymphocytic leukemia presenting as cutaneous and bone involvementINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2001Maria P. Stefanidou MD An 84-year-old man had a 3-year history of a progressive, painless, papulonodular eruption, that was particularly prominent on the face and extremities. Physical examination revealed firm, bluish-red nodules and plaques, located on the tip of the nose, the cheeks, ears, and distal digits. Skin lesions produced a leonine facies (Fig. 1), deformities of the fingers and toes, finger clubbing, and onyxis. An identical lesion was seen on a postoperational scar on the left cheek. The mucous membranes were spared. The patient had anterior and posterior cervical and bilateral axillary lymphadenopathy and splenomegaly. Figure 1. Leonine facies On admission, the peripheral blood count revealed 260,000/mm3 leukocytes (lymphocytes 97%, neutrophils 2%, and monocytes 1%), a hemoglobin level of 9.5 g/dL, and platelet count of 100,000/mm3. Hypogammaglobulinemia with reduction of immunoglobulin G (IgG) and IgM was found. Radiography of the fingers showed multiple osteolytic lesions of the phalanges and phalangette destruction of the left median finger (Fig. 2a,b). Computed tomography of the chest and abdomen revealed bilateral axillary, mediastinal, and para-aortic lymphadenopathy and spleen enlargement. Figure 2. X-Ray of the hands: (a) ,multiple osteolytic lesions of the phalanges and (b) ,partial destruction of the left median phalangette Skin biopsy specimens from the ear and finger lesions showed a massive nonepidermal leukemic infiltration in the papillary and reticular dermis, with a grenz zone consisting of small lymphocytes (Fig. 3). Figure 3. Skin biopsy (hematoxylin and eosin, ×,250). Massive leukemic infiltration consisting of small lymphocytes. Subepidermally, a grenz zone of connective tissue is noted Biopsy of the enlarged cervical lymph node showed a diffuse infiltration with lymphocytes. Tissue biopsy from a finger lytic lesion revealed infiltration of bone trabecular and fibrous tissue with a dense population of small- and medium-sized lymphocytes. Immunohistochemical study of cutaneous and bone lesions showed that the infiltrate in both biopsies consisted mainly of B lymphocytes (CD20+, CD45R+, CD45Ro,, OPD4,). Peripheral blood smear had a B-cell phenotype (CD19 98%, CD20 97%, CD23 99%, CD25 40%, CD5 90%, HLA-DR 100%). Bone marrow smear and immunophenotyping surface marker analysis found a diffuse pattern of B-lymphocytic infiltration. A diagnosis of B-cell chronic lymphocytic leukemia stage C (Binet staging system), with specific cutaneous and bone lesions, was established. The patient received chemotherapy with chlorambucil and methylprednisolone, which resulted in improvement of the hematologic profile. Two years later, the cutaneous lesions showed partial remission. [source] Severe antibody-mediated agranulocytosisINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2008H. JOHNSEN Summary A 56-year-old female with Crohn's disease was admitted to the hospital with malaise, fever, and a low white blood cell count (0.8 × 109/l) with no granulocytes or myeloid precursor cells in the bone marrow. The leucopenia was initially thought to be the result of an infection and she was treated with antibiotics and granulocyte colony-stimulating factor (G-CSF, filgrastim). However, the bacterial cultures and viral tests were all negative. The patient's condition deteriorated and she became morbidly ill, but recovered after high dose steroid treatment. Six weeks later she relapsed whilst receiving 7.5 mg daily dose of prednisolone. She recovered quickly after being given high dose methylprednisolone in combination with filgrastim. A high maintenance dose of prednisolone was tapered over 5 months. She has not relapsed since and is currently well. Antibodies to the human neutrophil antigen (HNA)-3a were detected, but these antibodies could not easily explain her agranulocytosis as she had a HNA-3a negative phenotype. It seems plausible that her agranulocytosis was immune mediated through autoantibodies directed towards the early myeloid cells. [source] HLA-haploidentical nonmyeloablative stem cell transplantation: induction to tolerance without passing through mixed chimaerismINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2005K. IKEGAME Summary There are few reports of unmanipulated HLA-haploidentical nonmyeloablative stem cell transplantation (NST) using only pharmacological acute graft- vs. -host disease (GVHD) prophylaxis. We present here a successful case of unmanipulated HLA-haploidentical NST for mediastinal large B cell lymphoma that was resistant to autologous peripheral blood stem cell transplantation (PBSCT). The conditioning regimen consisted of fludarabine, busulfan and rabbit anti-T-lymphocyte globulin (ATG) in addition to rituximab. GVHD prophylaxis was performed using tacrolimus and methylprednisolone 1 mg/kg. The patient had rapid engraftment, with 100% donor chimaerism in the lineages of both T cells and granulocytes on day +12, but developed no GVHD clinically. The patient is still in complete remission past day +1020, with no sign of chronic GVHD without receiving immunosuppressive agents. HLA-haploidentical NST may be performed without utilizing mixed chimaerism. [source] Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized studyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 3 2005Intravenöse Dexamethason-Cyclophosphamid-Pulstherapie im Vergleich zu einer oralen Methylprednisolon-Azathioprin-Therapie bei Patienten mit Pemphigus-Erkrankungen: Ergebnisse einer multizentrischen, prospektiven, randomisierten Studie Azathioprin; Cyclophosphamid; Pemphigus; Pulstherapie Summary Background: Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22,patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11,patients of the M/A group were treated with daily doses of methylprednisolone (initially 2,mg/kg body weight) and azathioprine (2,,,2,5,mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11,patients consisted of intravenous administration of 100,mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500,mg) on day one. Pulses were initially repeated every 2,,,4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50,mg) was given daily for 6,months. Results: Within 24,months after treatment initiation, 5/11,patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3,patients) and 6/11,patients had a progression. In the M/A group, there were remissions in 9/11,patients (complete remissions after discontinuation of therapy in 3,patients) and progression in 1/11,patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy. Zusammenfassung Hintergrund: Pemphiguserkrankungen sind potentiell lebensbedrohliche blasenbildende Autoimmunerkrankungen, die üblicherweise mit hochdosierten Kortikosteroiden in Kombination mit Immunsuppressiva behandelt werden. In einer multizentrischen, prospektiven, randomisierten Studie verglichen wir die Wirksamkeit und Nebenwirkungen einer Dexamethason-Cyclophosphamid (D/C)-Pulstherapie mit einer Methylprednisolon-Azathioprin (M/A)-Therapie bei 22,Patienten mit neu diagnostiziertem Pemphigus vulgaris und Pemphigus foliaceus. Patienten und Methoden: 11,Patienten der M/A-Gruppe wurden kontinuierlich oral mit Methylprednisolon (initial 2,mg/kg Körpergewicht/Tag) und Azathioprin (2,,,2,5,mg/kg Körpergewicht/Tag) behandelt; die Dosen wurden schrittweise reduziert. Die Therapie bei den 11,Patienten der D/C-Gruppe erfolgte durch intravenöse Gabe von 100,mg Dexamethason/Tag an 3 aufeinander folgenden Tagen und 500,mg Cyclophosphamid am ersten Tag. Die Pulstherapie wurde zunächst alle 2,,,4 Wochen, dann in längeren Abständen wiederholt. Im Intervall wurden 50,mg Cyclophosphamid/Tag oral für 6,Monate verabreicht. Ergebnisse: Innerhalb von 24,Monaten nach Therapiebeginn kam es bei 5 von 11,Patienten der D/C-Gruppe zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten); bei 6 der 11,Patienten verlief die Erkrankung progredient. In der M/A-Gruppe kam es bei 9 von 11,Patienten zu einer Remission (komplette Remission nach Absetzen der Therapie bei 3,Patienten) und bei einem Patienten zu einer Progression. In der M/A-Gruppe traten häufiger Rezidive nach Remission auf als in der D/C-Gruppe. Therapienebenwirkungen kamen in der M/A-Gruppe häufiger vor. Diese Unterschiede waren nicht signifikant (p > 0,05). Schlußfolgerungen: Aufgrund der hohen Anzahl von Progressionen bei Patienten der D/C-Gruppe können wir die positiven Ergebnisse früherer Berichte über die D/C-Pulstherapie nicht bestätigen. Dennoch scheint die D/C-Therapie, beim einzelnen Patienten einmal erfolgreich, seltener zu Rezidiven zu führen und möglicherweise auch besser verträglich zu sein als die M/A-Therapie. [source] Effects of dexmedetomidine or methylprednisolone on inflammatory responses in spinal cord injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009M. CAN Background: The aim of this study was to compare the anti-inflammatory response of methylprednisolone and the ,2-agonist dexmedetomidine in spinal cord injury (SCI). Methods: Twenty-four male adult Wistar albino rats, weight 200,250 g, were included in the study. The rats were divided into four groups as follows: the control group (n: 6) received only laminectomy; the SCI group (n: 6) with trauma alone; the SCI+methylprednisolone group (n: 6) with trauma and 30 mg/kg methylprednisolone, followed by a maintenance dose of 5.4 mg/kg/h; and the SCI+dexmedetomidine group (n: 6) with trauma and 10 ,g/kg dexmedetomidine treatment intraperitoneally. Twenty-four hours after the trauma, spinal cord samples were taken for histopathological examination and serum samples were collected for interleukin-6 (IL-6) and tumor necrosis factor (TNF)-, measurement. Results: TNF-, (P=0.009) and IL-6 (P=0.009) levels were significantly increased in the SCI group. TNF-, and IL-6 levels were significantly decreased with methylprednisolone (P=0.002, 0.002) and dexmedetomidine (P=0.002, 0.009) treatment, respectively. Methylprednisolone and dexmedetomidine treatment reduced neutrophils' infiltration in SCI. Conclusions: The current study does not clarify the definitive mechanism by which dexmedetomidine decreases inflammatory cytokines but it is the first study to report the anti-inflammatory effect of dexmedetomidine in SCI. Further studies are required to elucidate the effects of dexmedetomidine on the inflammatory response. [source] Combination regimen of methylprednisolone, IV immunoglobulin, and plasmapheresis early in the treatment of acute disseminated encephalomyelitisJOURNAL OF CLINICAL APHERESIS, Issue 4 2006Rommel P. Lu Abstract Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease of the central nervous system that is associated with significant morbidity and mortality. Early recognition of the disease is of paramount importance; however, treatment options are limited because only case reports and small series are available in the literature. We report a case of a 42 year-old previously healthy man, whom we treated successfully with a combination regimen of methyprednisolone, IV immunoglobulin, and plasmapheresis early in the course of the disease. J. Clin. Apheresis 21: 2006. © 2006 Wiley-Liss, Inc. [source] Estrogen as a neuroprotective agent in rat spinal cord injuryJOURNAL OF NEUROCHEMISTRY, Issue 2002N. L. Banik Spinal cord injury (SCI) is a neurological problem affecting approximately 11 000 Americans each year. Several treatment agents have been proposed; however, only methylprednisolone has limited efficacy. Estrogen is a multiactive neuroprotectant with antioxidant and anti-inflammatory properties and attenuates calcium (Ca2+) influx following neuronal injury. To examine the neuroprotective effects of estrogen in SCI, we induced SCI (40 g/cm injury) in rats. Treatment groups were sham (laminectomy only), SCI plus vehicle, and SCI plus estrogen. Injured rats were treated with either 4 mg/kg 17 ,-estradiol (estrogen group) or dimethylsulfoxide (vehicle group) at 15 min and 24 h following injury. All rats were killed at 48 h to analyze SCI segments for calpain content and Bax/Bcl-2 ratio by Western blotting. Tissue was also examined using calcium green-2 to measure intracellular [Ca2+], JC-1 to measure mitochondrial membrane potential, and double immunofluorescence for macrophages and calpain. Calpain content in the lesion penumbra, adjacent to the injury, was higher in vehicle than sham and this increase was attenuated in estrogen treated rats. In the lesion penumbra, the Bax/Bcl-2 ratio was increased in vehicle rats as compared to sham. This increase was attenuated in estrogen treated rats. Estrogen treated rats had less Ca2+ influx, less inflammatory cell infiltration, and increased maintenance of mitochondrial membrane potential compared to vehicle treated rats. Our preliminary data suggest that estrogen may be effective in decreasing Ca2+ influx, inflammatory cell infiltration, and Bax/Bcl-2 ratio following SCI. Acknowledgements:, Supported in part by grants from NIH-NINDS and South Carolina Electric and Gas. [source] Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 8 2010Eric A. Sribnick Abstract Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause paralysis. The only recommended pharmacotherapy for the treatment of SCI is high-dose methylprednisolone, and its use is controversial. We have previously shown that estrogen treatment attenuated cell death, axonal and myelin damage, calpain and caspase activities, and inflammation in acute SCI. The aim of this study was to examine whether posttreatment of SCI with estrogen would improve locomotor function by protecting cells and axons and reducing inflammation during the chronic phase following injury. Moderately severe injury (40 g · cm force) was induced in male Sprague-Dawley rats following laminectomy at T10. Three groups of animals were used: sham (laminectomy only), vehicle (dimethyl sulfoxide; DMSO)-treated injury group, and estrogen-treated injury group. Animals were treated with 4 mg/kg estrogen at 15 min and 24 hr postnjury, followed by 2 mg/kg estrogen daily for the next 5 days. After treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses. Estrogen treatment reduced COX-2 activity, blocked nuclear factor-,B translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of calpain and caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function compared with vehicle-treated animals. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. © 2010 Wiley-Liss, Inc. [source] Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2005Eric Anthony Sribnick Abstract Spinal cord injury (SCI) is a devastating neurologic injury with functional deficits for which the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen is a multiactive steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca2+ and attenuate apoptosis. For this study, male rats were divided into three groups. Sham group animals received a laminectomy at T12. Injured rats received both laminectomy and 40 g · cm force SCI. Estrogen-group rats received 4 mg/kg 17,-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle-group rats received equal volumes of dimethyl sulfoxide (vehicle). Animals were sacrificed at 48 hr post-injury, and 1-cm-long segments of the lesion, rostral penumbra, and caudal penumbra were excised. Inflammation was assessed by examining tissue edema, infiltration of macrophages/microglia, and levels of cytosolic and nuclear NF,B and inhibitor of kappa B (I,B,). Myelin integrity was examined using Luxol fast blue staining. When compared to sham, vehicle-treated animals revealed increased tissue edema, increased infiltration of inflammatory cells, decreased cytosolic levels of NF,B and I,B,, increased levels of nuclear NF,B, and increased myelin loss. Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent. Further work needs to be done, however, to elucidate the neuroprotective mechanism of estrogen. © 2005 Wiley-Liss, Inc. [source] Oral pemphigus: long term behaviour and clinical response to treatment with deflazacort in sixteen casesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2000Michele D. Mignogna Abstract: Systemic corticosteroids remain the mainstay of therapy for pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening. Sixteen patients affected by oral pemphigus vulgaris were retrospectively examined to illustrate the natural course of the disease and to describe the efficacy of the treatment we utilised. Deflazacort, used with azathioprine, is the steroid of first choice in our therapeutic protocols, while cyclophosphamide and methylprednisolone "pulse therapy" are reserved for cases unresponsive to high doses of oral corticosteroids. In addition, the literature on oral pemphigus vulgaris was reviewed with respect to clinical history, signs and symptoms, management, and treatment outcome. [source] Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon-to-Bone Healing and Opposed Corticosteroid AggravationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006Andrija Krivic Abstract Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 µg, 10 ng, 10 pg), 6,-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6,-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6,-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] | ||||||||||||||||||||||||||||||||||||||||