Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.     

平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形60例报道

目的：评价平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形的疗效。方法：采用平阳霉素和泼尼松龙及鱼肝油酸钠联合病变内注射治疗60例颌面部静脉畸形患者。1周注射1次，3-5次为1个疗程，治疗结束后对疗效进行评价。结果：60例患者平均疗程3周，治疗完成后随访0．5～2a，治愈和显效率达94％，有效率为100％。结论：平阳霉素和泼尼松龙及鱼肝油酸钠联合注射治疗颌面部静脉畸形安全、廉价、高效、简便，疗程适中。     

Synergistic effect of donor pretreatment with 8-methoxypsoralen and ultraviolet irradiation of the graft plus azathioprine and prednisolone therapy in prolonging rat renal allograft survival

Summary Pretreatment of the kidney donor with 8-methoxy-psoralen (8-MOP) and direct longwave ultraviolet (UVA) irradiation of the kidney graft (PUVA therapy) significantly prolonged survival in allogeneic recipients. 40% of the recipients survived more than 100 days with normal transplant function. The addition of standard clinical immunosuppressive agents azathioprine and prednisolone (both at dosages of 15 mg/kg body weight/day for 21 days) to the PUVA therapy further improved graft survival rate, with a recipient survival rate of 62.5%. The two drugs alone were less effective in prolonging graft survival rate (28.5%). A synergistic effect of PUVA therapy and standard immunosuppressive treatment with azathioprine and prednisolone was demonstrated. This suggested a possible clinical application of this type of immunosuppression and immunoregulation.     

Effect of LS-2616 on the graft protection achieved by cyclosporin A,prednisolone, and 15-deoxyspergualin in heart-transplanted rats

The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day —1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.     

Marked increase of serum hepatitis C virus (HCV) RNA titer during treatment with high-dose prednisolone in a case of polymyositis

A 70-year-old Japanese woman with hepatitis C virus (HCV) infection was diagnosed with polymyositis and treated with high-dose prednisolone (PSL). The serum alanine aminotransferase (ALT) level increased from 78 to 345 U/l 1 week after initiating treatment, although the polymyositis settled promptly. Furthermore, the serum HCV RNA level increased markedly from 110 to 850 kIU/ml 3 weeks after starting treatment. Previously, the patient had suffered an occlusion of the left branch of the retinal vein secondary to hyperviscosity syndrome resulting from Sjögrens syndrome and low-dose PSL treatment had been commenced. The serum HCV RNA and transaminase levels had not increased during this low-dose PSL treatment. Although intensive immunosuppression is necessary as an initial treatment of several collagen diseases including polymyositis, high-dose PSL therapy may markedly augment the serum HCV RNA level and therefore careful observation is necessary in HCV-infected patients.     

Chromosome abnormalities in peripheral lymphocytes from patients with progressive systemic sclerosis

Summary Chromosomal abnormalities in cultured peripheral lymphocytes from 14 progressive systemic sclerosis (PSS) patients and 15 normal subjects were examined. No increase was observed in the frequency of chromosome aberrations in PSS patients who had not received any medical treatment. Those who had received medication showed an increased frequency of dicentrics (0.3%) although the frequency was not significantly higher than that for normal subjects. It is not clear, however, whether the increase was due to the hypersensitivity of PSS patients to agents used for therapeutic purposes.     

The effect of systemic corticosteroid therapy on the breaking strength of skin

Summary It was noted clinically that patients under long-term steroid treatment were susceptible to avulsion injuries following minor trauma. Laboratory experiment in mice revealed significant reduction in the breaking strength following steroids therapyThe authors dedicate this paper to the dear memory of Prof. Z. Neuman, M.D., F.A.C.S. former Chairman of the department of Plastic and Maxillofacial Surgery, who passed away on March 22, 1977     

Drug-protein recognition processes investigated by NMR relaxation data. A study on corticosteroid-albumin interactions

In this paper we investigated the interaction processes occurring at the protein-solvent interface for prednisolone-albumin and prednisone-albumin systems, using an approach based on the analysis of proton selective relaxation rate enhancements of the ligand in the presence of the macromolecule. The contribution from the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index[A]L(T) and the normalized affinity index [AI(N)]L(T) which removes the effects of motional anisotropies and different proton densities, and isolates the contribution due to a decrease in the ligand dynamics caused by the binding with the protein. This approach allowed the comparison of the binding ability of prednisolone and prednisone towards albumin.     

大鼠激素性股骨头坏死组织氧化应激相关基因的差异表达

 目的 通过基因芯片寻找大鼠激素性股骨头坏死（steriod-induced necrosis of femoral head,SINFH）组织中表达变化的氧化应激相关基因,探究氧化应激诱发或加重SINFH的始动因素和分子机制。
方法 20只成年健康Wistar大鼠随机分为对照组和模型组,每组10只。模型组大鼠腹腔注射大肠杆菌内毒素后,于左侧臀肌注射大剂量甲基泼尼松龙,建立SINFH模型;正常对照组大鼠腹腔注射大肠杆菌内毒素后,于左侧臀肌注射相同剂量生理盐水。6周后取两组大鼠的左侧股骨头标本进行组织病理学观察,并抽提各组大鼠股骨头组织的m RNA,经反转录获得大鼠股骨头组织c DNA,进行基因芯片检测。检测结果经荧光定量PCR验证。
结果 组织病理学观察显示模型组大鼠股骨头出现骨小梁紊乱、变细,骨细胞坏死,空骨陷窝率增加;对照组大鼠未见股骨头坏死。模型组基因芯片检测发现27条氧化应激相关基因存在差异表达,其中COX6A2、COX4I2、SOD3和DUSP1等4条基因的表达与对照组存在显著差异,且均呈下调表达。这些显著差异表达基因的功能涉及抑制活性氧自由基（ROS）生成,加速ROS清除以及保护组织免受氧化损伤等方面。
结论 大鼠SINFH组织中氧化应激相关基因的表达存在变化,初步提示COX6A2、COX4I2、SOD3和DUSP1基因是氧化应激在SINFH发生、发展过程中起作用的关键基因。     

Immunotherapy Maintenance in Acute Non-Lymphocytic Leukaemia

Abstract: Between January 1975 and December 1977, 264 adult patients with acute non-lymphocytic leukaemia entered the Australian National Leukaemia Trial. Of 251 evaluable patients, three induction regimens achieved similar complete response (CR) rates. CROP (cytosine arabinoside, daunorubicin, vincristine, prednisolone) produced CR in 41% of patients, 7 and 3 (cytosine arabinoside, daunorubicin) in 42% and 7 and 3 plus hydroxyurea in 52%. Remission duration and survival were similar when induction regimens were compared. Fortyfive patients reaching maintenance therapy were randomised to either chemo-immunotherapy (BCG plus intradermal leukaemic blast cells) or chemotherapy alone. The duration of CR in these two groups was almost identical, though patients receiving chemotherapy alone had prolonged survival (median 161 weeks) when compared to the chemo-immunotherapy group (84 weeks, p = 0.07). Institutions with less developed supportive facilities reported lower CR rates (p =0.04). Leucocytosis, (> 100 × 10⁹/I) and older age (> 50 years) were associated with shortened survival. The Trial has failed to show any advantage for this form of immunotherapy.