Clinical outcome of a protocol to produce immunosuppression in rhesus monkeys (Macaca mulatta): application to infectious disease and gene therapy studies

Induced immunosuppression is required for a number of studies using rhesus monkeys (Macaca mulatta). This report describes the clinical outcome and safety of a dose-finding experiment that determined doses of cyclophosphamide and prednisone that could be used to induce a state of immunosuppression in rhesus monkeys. After determining the optimum dose of immunosuppressive agents, the protocol was then used on animals participating in infectious disease and gene therapy studies. Splenectomy was performed in some animals to increase the severity of immunosuppression. The onset, duration, and severity of lymphopenia and leukopenia were consistent in all animals. In most animals, physical examination findings and clinical serum chemistry profiles demonstrated only transient abnormalities. With proper clinical monitoring, combination treatment with cyclophosphamide and prednisone is an effective and safe method for inducing immunosuppression in rhesus monkeys.     

氯雷他定联合甲基强的松冲击治疗小儿过敏性紫癜的临床疗效

目的:观察氯雷他定联合甲基强的松冲击疗法治疗小儿过敏性紫癜的疗效,及其对患儿血清免疫学指标的影响。方法:将180例过敏性紫癜患儿随机分为对照组和观察组,每组各90例。所有患者均接受包括氯雷他定的基础治疗,观察组在此基础上加用甲基强的松冲击治疗。观察并比较两组的临床疗效、临床症状消失时间及治疗前后血清免疫学指标的变化情况。结果:观察组患儿治愈率和总有效率显著高于对照组,差异具有统计学意义(P0.05);观察组临床症状消失时间显著短于对照组,差异具有统计学意义(P0.05);治疗后,观察组患儿血清Ig A、C3、TNF-α及IL-10水平显著低于对照组,差异具有统计学意义(P0.05)。结论:氯雷他定联合甲基强的松龙能有效抑制炎症反应,调节免疫平衡,在小儿过敏性紫癜治疗中具有积极意义。     

Development of prednisone: Polyethylene glycol 6000 fast-release tablets from solid dispersions: Solid-state characterization, dissolution behavior, and formulation parameters

The aim of the current study was to design oral fast-release polymeric tablets of prednisone and to optimize the drug dissolution profile by modifying the carrier concentration. Solid dispersions were prepared by the solvent evaporation method at different drug:polymer ratios (wt/wt). The physical state and drug:carrier interactions were analyzed by X-ray diffraction, infrared spectroscopy, and scanning electron microscopy. The dissolution rate of prednisone from solid dispersions was markedly enhanced by increasing the polymer concentration. The tablets were prepared from solid dispersion systems using polyethylene glycol (PEG) 6000 as a carrier at low and high concentration. The results showed that PEG 6000-based tablets exhibited a significantly higher prednisone dissolution (80% within 30 minutes) than did conventional tablets prepared without PEG 6000 (<25% within 30 minutes). In addition, the good disintegration and very good dissolution performance of the developed tablets without the addition of superdisintegrant highlighted the suitability of these formulated dosage forms. The stability studies performed in normal and accelerated conditions during 12 months showed that prednisone exhibited high stability in PEG 6000 solid dispersion powders and tablets. The X-ray diffraction showed that the degree of crystallinity of prednisone in solid dispersions decreased when the ratio of the polymer increased, suggesting that the drug is present inside the samples in different physical states. The Fourier transform infrared spectroscopic studies showed the stability of prednisone and the absence of well-defined drug:polymer interactions. Scanning electron microscopy images showed a novel morphology of the dispersed systems in comparison with the pure components.     

Hyperglycemic hyperosmolar state in a chimpanzee (Pan troglodytes)

A 19-year-old female chimpanzee (Pan troglodytes) presented for cachexia, acute weakness, hyporexia, icterus, and polyuria. The animal was diagnosed with a hyperglycemic hyperosmolar state, which is a well-recognized syndrome in diabetic humans that is rarely diagnosed in animals. This case documents an important and likely under-reported syndrome in non-human primates.     

Prednisolone and prednisone neo-formation in bovine urine after sampling

The rise in the frequency of detecting prednisolone in bovine urine from northern Italy has come into focus of attention in recent years. The possibility that neo-formation of prednisolone or that prednisone may occur in urine after collection of samples was therefore investigated. Cow urine collected for official routine controls in Lombardy containing more than 80 ng/ml cortisol, and prednisolone and prednisone below the decision limit (CCα) of the method (0.4 and 0.5 ng/ml, respectively) was used. The C1-2 dehydrogenation of naturally present cortisol and cortisone was checked by incubating urine, both contaminated and uncontaminated with faeces, at 37°C and by collecting samples at 0, 1, 2, 4, 6 and 24 h. The influence of Helix pomatia juice was also investigated in order to determine whether deconjugation could influence the reliability of the results. All samples were analysed by HPLC-MS3 for the presence of cortisol, cortisone, prednisolone and prednisone in negative electrospray ionisation mode, utilising the consecutive reaction monitoring of product ions derived from the formate molecular adduct ([M+HCOO]-). The observed neo-formation of prednisolone shows that inappropriate temperatures in sample storage and processing can result in an incorrect accusation of non-compliance. The faecal contamination of urine, performed with the aim to mimic a collection conducted without the necessary care, moreover, evoked a high increase in prednisolone concentration in two out of seven animals. Moreover, H. pomatia juice had no significant effect on the prednisolone concentration, indicating that this corticosteroid is present in its free form in cow urine.     

Insulin Dosing and Glycemic Outcomes Among Steroid-treated Hospitalized Patients

ObjectiveTo determine the optimal insulin-to-steroid dose ratio for the attainment of glycemic control in hospitalized patients.MethodsWe retrospectively studied data collected from the electronic health records within an academic medical center from 18 599 patient-days where patients were treated concurrently with insulin and steroids. Multivariate logistic regression analyses, which included demographic and clinical variables, were performed to assess the relationships between the exposures of total and basal insulin-to-steroid ratios and the outcomes of glycemic control (all blood glucose readings on the following patient-day were >70 and ≤180 mg/dL) and hypoglycemia within 3 subgroups of steroid dosing: low (≤10-mg prednisone equivalent dose [PED]), medium (from >10-mg to ≤40-mg PED), and high (>40-mg PED).ResultsIncreased insulin-to-steroid ratio was associated with increased odds of both glycemic control and hypoglycemia. The optimal total insulin-to-steroid ratio for attaining glycemic control was 0.294 U/kg/10-mg PED in the low-dose subgroup, 0.257 U/kg/10-mg PED in the medium-dose subgroup, and 0.085 U/kg/10-mg PED in the high-dose subgroup. The optimal basal insulin-to-steroid ratio was 0.215 U/kg/10-mg PED in the low-dose subgroup, 0.126 U/kg/10-mg PED in the medium-dose subgroup, and 0.036 U/kg/10-mg PED in the high-dose subgroup.ConclusionIncreasing insulin-to-steroid ratios are positively associated with glycemic control and hypoglycemia. Our study suggests that approximately 0.3 U/kg/10-mg PED is an optimal dose for low- and medium-dose steroids, whereas approximately 0.1 U/kg/10-mg PED is an optimal dose for high-dose steroids. Further prospective studies are needed to identify insulin regimens that will optimize glycemic control in steroid-treated patients while minimizing the risk of hypoglycemia.     

Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in clinical diagnosis and treatment

Over half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured by standard R-CHOP treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). However, the remaining patients are refractory and ultimately succumb to progressive or relapsed disease. During the past decade, there has been significant progress in the understanding of molecular mechanisms in DLBCL, largely owing to collaborative efforts in large-scale gene expression profiling and deep sequencing, which have identified genetic alterations critical in lymphomagenesis through activation of key signaling transduction pathways in DLBCL. These discoveries have not only led to the development of targeted therapies, including several currently in clinical trials, but also laid a solid foundation for the future identification of more effective therapies for patients not curable by R-CHOP. This review summarizes the recent advances in our understanding of the molecular characterization and pathogenesis of DLBCL and new treatment directions.