HISTOMORPHOMETRIC STUDY OF SUBCHONDRAL BONE OF NECROTIC FEMORAL HEAD IN RABBITS INDUCED BY METHYLPREDNISOLONE COMBINED WITH LOW-DOSE LIPOPOLYSACCHARIDE

Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two male adult New Zealand white rabbits were used. Among them, 16 were injected with lipopolysaccharide and methylprednisolone (osteonecrosis group), and another 16 were sham-injected with saline (control group). Magnetic resonance (MR) imaging was taken for femoral heads of the rabbits in both groups at the end of 2, 4 and 6 weeks after the injection. All the rabbits were then killed 6 weeks later. The femoral heads of the rabbits were collected and processed for histological and histomorphometric analysis. Results Femoral head necrosis occurred in 14 rabbits of the osteonecrosis group which were confirmed by histological evaluation and MR imaging. Osteonecrotic femoral heads, compared to controls, were characterized by lower values of bone volume/tissue volume (P<0.01), tabecular thichness (P<0.01), osteoid surface/bone surface (P<0.05), mineralizing apposition rate (P<0.05), and bone formation rate/bone surface (P<0.05). However, tabecular separation and eroded surface/bone surface were higher in osteonecrotic femoral heads than in controls (P<0.01). Trabecular number and osteoclast surface/bone surface did not differ significantly. Conclusion The results demonstrated that osteoporosis was apparent in osteonecrotic femoral heads induced by methylprednisolone and lipopolysaccharide, due mainly to trabecular thinning rather than reduction of trabecular number. This might be due to reduced bone formation combined with increased bone resorption.     

Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease?

1. The intra-uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant 'programming' before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra-uterine triggers appear to programme the individual's metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure. 2. Over the past decade, a series of studies in sheep have focused on the perinatal and life-long consequences of glucocorticoid exposure in mid- to late-pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound-guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction. 3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow-up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age. 4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions.     

Glucocorticoid-mediated regulation of thymic dendritic cell function.

The possible effects of glucocorticoids (GC) on the biology of thymic dendritic cells (DC) have been analyzed. Both DC and GC seem to be involved in intrathymic T cell selection but possible relationships, if any, between them remain currently unknown. For the first time, we have proved the expression of GC receptors in thymic DC. Moreover, our data demonstrate that in vitro dexamethasone (Dex) treatment barely affects the viability of mature thymic DC, which are largely resistant to its apoptotic effect. Dex-treated thymic DC also show a slightly reduced surface expression of some adhesion and co-stimulatory molecules in correlation with diminished allostimulatory properties. Furthermore, the production of both IL-1beta and tumor necrosis factor (TNF)-alpha, but not that of IL-6 and IL-10, diminished in the mixed leukocyte reaction established with Dex-treated thymic DC. However, the addition of recombinant rat IL-1beta and TNF-alpha, alone or in combination, did not recover the allostimulatory capacity. Taken together, these results support certain GC-mediated regulation of the activity of thymic DC which could be relevant for the biology of the thymus gland.     

Risedronate, an effective treatment for glucocorticoid-induced bone loss in CKD patients with or without concomitant active vitamin D (PRIUS-CKD).

BACKGROUND: Recent post hoc analysis proved the efficacy and tolerability of risedronate in osteoporotic patients with renal impairment, but the combination of active vitamin D in chronic kidney disease (CKD) patients taking glucocorticoids remains unknown. METHODS: We conducted a prospective study enrolling 114 CKD patients (creatinine clearance > or =30 ml/min/1.73 m(2)) receiving glucocorticoid therapy for > or =6 months. Eighty-eight subjects who had received active vitamin D (aVD) were randomly assigned to either a group treated with aVD only (group A), or to a group also receiving risedronate 2.5 mg/day (group B). The remaining patients (group C) received risedronate only. RESULTS: After 1 year 100 subjects were analysed. Risedronate was effective on the lumbar spine, but not on the femoral neck. The lumbar bone mineral density (BMD) significantly increased by 2.8 and 2.5% in groups B and C, respectively, but decreased by 1.0% in group A. Serum N-terminal telopeptides of type I collagen (S-NTX) and bone alkaline phosphatase (ALP) fell significantly in groups B and C at 3 and 6 months, respectively, while in group A S-NTX remained unchanged and bone ALP significantly increased. There was no significant difference between groups B and C regarding BMD and bone markers. The reduction rate of S-NTX (bone ALP) at 6 months predicted the increase in lumbar BMD at 1 year with a sensitivity of 73% (34%) and a specificity of 46.2% (100%). CONCLUSIONS: Risedronate is effective in increasing BMD with or without aVD in CKD patients receiving long-term glucocorticoid therapy. Bone markers are of some use in predicting the response to anti-resorptive therapy.     

外用糖皮质激素联合夫西地酸乳膏对婴儿湿疹的干预作用

目的 探讨外用糖皮质激素联合夫西地酸乳膏治疗婴儿湿疹的临床疗效.方法 收集2012年3月至2015年1月该院门诊收治的湿疹婴儿400例,将其分为观察组(220例)和对照组(180例),观察组接受外用糖皮质激素联合夫西地酸乳膏,对照组单纯外用糖皮质激素.随诊记录两组达到临床治愈所需的用药时间,以及观察期30 d内疗效维持时间及复发率.结果 30 d观察期内,共有50例婴儿退出本研究,其中观察组17例、对照组33例.观察组湿疹平均用药时间[(2.2±0.9)d]较对照组[(3.2±1.1)d]缩短,观察期内疗效维持时间[(11.7±5.4)d]较对照组[(7.2±4.0)d]延长,差异均有统计学意义(P<0.05);观察期内观察组中74.0%复发患儿表现为轻度湿疹,对照组57.8%复发患儿表现为轻度湿疹,后续无需使用糖皮质激素,观察组复发时症状改善情况优于对照组,差异有统计学意义(P<0.05).结论 外用糖皮质激素联合西地酸乳膏治疗婴儿湿疹可减少用药时间,延长疗效维持时间,减轻湿疹复发时的症状.     

Synthetic pharmacotherapy for lupus nephritis

Introduction: Lupus nephritis is a frequent complication and a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE).

Area covered: The main characteristics and mechanisms of action of the synthetic drugs more frequently used in lupus nephritis are described. Possible strategies aimed to reduce the potential adverse events without affecting efficacy are reported.

Expert opinion: Many synthetic immunosuppressive drugs used in lupus nephritis have a low therapeutic index. Good knowledge of their pharmacologic characteristics, mechanisms of action, and drug-to-drug interactions, coupled with a strategy aimed to increase immunosuppression in the active phases of SLE while reducing the dosage in quiescent periods can reduce the iatrogenic morbidity while maintaining efficacy. Biologic agent may allow to reduce the use or the dosage of synthetic immunosuppressive drugs.     

The effect of pre‐operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised,double‐blind,placebo‐controlled trial

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre‐operative dose of methylprednisolone reduced markers of early endothelial damage after fast‐track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre‐operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan‐1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE‐Selectin), and permeability by vascular endothelial growth factor, as well as C‐reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan‐1: 11.6 (1.0) ng.ml^?1 vs. 13.4 (1.1) ng.ml^?1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml^?1 vs. 5.7 (0.2) ng.ml^?1, p = 0.009; sE‐Selectin: 64.8 (1.8) ng.ml^?1 vs. 75.7 (1.9) ng.ml^?1, p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml^?1 vs. 58.5 (2.8) ng.ml^?1, p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE‐Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C‐reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l^?1 vs. 68.4 (1.1) mg.l^?1, p < 0.001. Pre‐operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C‐reactive protein) early after fast‐track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.     

糖皮质激素治疗类风湿关节炎的管理策略

在早期类风湿关节炎中,低、中剂量的激素可以预防关节损伤,低剂量的糖皮质激素可以作为类风湿关节炎的维持治疗,中、高剂量的则可作为最初的桥方案,极高剂量或冲击疗法可用于治疗急性危及生命或累及器官的并发症。同时,激素的副作用和药物相互作用也应引起重视。     

Recent advances in the diagnosis and treatment of polymyalgia rheumatica

Introduction: Polymyalgia rheumatica is one of the most common rheumatic inflammatory disorders in people older than 50 years characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdle and neck..

Areas covered: In this review, we will focus on recent advances on the diagnosis and management of PMR.

Expert commentary: Controversy exist whether PMR represent a single entity disease or is an umbrella term that comprises a clinical presentation common to a range of related conditions (polymyalgic syndrome). To date there are no specific diagnostic tests, and the diagnosis remains clinical, although ultrasonography, positron emission tomography scan and the recent ACR/EULAR classification criteria may help to confirm the clinical diagnosis. A step-wise process for the diagnosis of PMR has been proposed. Low-dose steroids are highly effective in the majority of patients and remain the mainstay of treatment, but relapses occur in about 50% of patients and glucocorticoid related adverse event are common. The steroid sparing effects of the immunosuppressive treatment evaluated to date are unclear.