Knee replacement surgery significantly elevates the urinary inflammatory biomarkers neopterin and 7,8-dihydroneopterin

ContextKnee arthroplasty surgery is significant trauma, leading to an activated immune system causing inflammation and oxidative stress. Many current biomarkers are invasive, costly, and often slow to analyse, limiting their use for rapid inflammatory measurements.ObjectivesWe have examined the use of urinary neopterin and total neopterin in knee arthroplasty patients to non-invasively measure oxidative stress and inflammation from immune system activation. We aim to validate the use of these biomarkers for quick, cost effective and predictive measurements of post-surgical inflammation assessment.Methodology19 Knee arthroplasty patients were analysed pre-operatively and for a defined post-operative period to determine the urinary levels of neopterin and total neopterin (neopterin +7,8-dihydroneopterin) using high performance liquid chromatography with fluorescence detection. These results were then compared to a control group of 20 participants with normal knee function.Results7,8-Dihydroneopterin was stable in urine over 12 h when refrigerated. Knee arthritis was associated with an increase in pre-operative neopterin (oxidative stress) and total neopterin (inflammation). The subsequent arthroplasty surgery generated a significant increase neopterin and total neopterin. Both biomarkers were reduced immediately post-operatively, before becoming elevated on the following days. There was no clear evidence of an association between initial neopterin and total neopterin levels and a patient's level of inflammation during in-hospital recovery.ConclusionsThe stability of 7,8-dihydroneopterin in urine allows for its use as an inflammatory marker. Urinary neopterin and total neopterin provided a fast, non-invasive, and simple measure of oxidative stress and inflammation after knee arthroplasty.     

Osteoporosis and sarcopenia in older age

Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition.This article is part of a Special Issue entitled “Muscle Bone Interactions”.     

Effect of Chronic Administration of PDE5 Combined with Glycemic Control on Erectile Function in Streptozotocin‐Induced Diabetic Rats

IntroductionChronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes‐induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED.AimsWe evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED.MethodsSprague‐Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM‐I), DM treated with PDE5 (DM‐P), and DM treated with insulin and PDE5 (DM‐I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM‐I group was treated with a daily injection of neutral protamine Hagedorn, and the DM‐P group was treated with a daily dosage of 20 mg/kg PDE5 (DA‐8159) for 4 weeks. The DM‐I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed.Main Outcome MeasuresErectile function and histological and biochemical markers in corporal tissue.ResultsRats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM‐I and DM‐P groups showed intermediate erectile function between the DM and C groups. Rats in the DM‐I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM‐I = DM‐P < DM‐I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order.ConclusionsChronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5. Choi WS, Kwon OS, Cho SY, Paick J‐S, and Kim SW. Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin‐induced diabetic rats. J Sex Med 2015;12:600–610.     

High-intensity interval exercise lowers postprandial glucose concentrations more in obese adults than lean adults

AimsTo compare postprandial glucose responses to high-intensity interval exercise (HIE) between obese and lean individuals.MethodsThirty healthy young adult males (15 obese, 15 lean) ate a standardised meal, then performed HIE (4 × 30-s Wingate cycling/4-min rest) or a no-exercise control trial (CON). Blood glucose was measured preprandially and up to 150 min postprandially.ResultsCompared to CON, HIE reduced postprandial glucose concentrations at 120–150 min in obese (p < 0.001) and lean men (p < 0.05), with greater reductions in obese than lean subjects at 120 (−27.0% vs. −8.3%), 135 (−31.9% vs. −15.7%), and 150 min (−21.8% vs. −10.6%). The total glucose area under the curve (AUC) for the testing period was lower with HIE than CON among obese men (p < 0.05), but not lean men (p > 0.05). We found moderate correlations between body mass and postprandial glucose changes (r = 0.39–0.44, p < 0.05), and between glucose AUC and body mass and fat free mass (r = 0.39–0.48, p < 0.05).ConclusionsOur findings suggest that HIE may act as a time-efficient lifestyle intervention strategy for improving obesity-related diabetes risk factors, and might play a role in primary diabetes prevention for the healthy but sedentary population.     

Alemtuzumab in renal transplantation. Reviews of literature and usage in the United Kingdom

Kidney transplantation has evolved over the years from transplants between identically matched donors and recipients to successfully transplanting allografts across virtually any degree of donor-recipient human leukocyte antigen mismatch and ABO-incompatibility. Integral to these improved outcomes has been the development and deployment of a range of immunosuppressive agents. The addition of monoclonal and polyclonal antibodies as a standard part of overall immunosuppression has led to the improved outcomes by providing a robust and focused protection during the first few months of transplantation when allografts are most vulnerable to immune-mediated injury.Alemtuzumab is a recombinant anti-CD52 pan-lymphocyte depleting monoclonal antibody that has been in use for kidney transplantation since the late 1990s.Despite the many years of experience with alemtuzumab, its utilisation in the UK has remained relatively restrained. This may be due to a lack of high-level evidence to support its safety and efficacy in transplantation. Also, long-term outcomes have not been addressed by existing studies.Nevertheless, available evidence suggests that alemtuzumab is associated with a lower risk of acute rejection within the first year of transplantation while exhibiting a comparable safety profile to non-lymphocyte depleting agents. Despite the current economic advantages of alemtuzumab (available free of cost on a named transplant recipient basis), its use in UK transplant centres has remained limited, variating from non-use, through usage in selected high immunologic risk subjects, to use as routine induction immunosuppression.This review discusses the current use of alemtuzumab for immunosuppression induction in kidney transplantation. It describes its evolution from development to its present application in kidney transplantation and reviews the evidence underpinning its utilisation. The role of alemtuzumab in the immunosuppressive protocols individual UK kidney transplant centres is also described.     

25-羟维生素D_3治疗2型糖尿病患者早期肾损害的临床观察

目的观察25-羟维生素D3(Vit D3)对2型糖尿病(T2DM)患者早期肾损害的临床疗效。方法纳入T2DM早期肾损伤患者80例,采用随机数字表法等分为治疗组与对照组,对照组继续原有降糖方案,治疗组在既往用药基础上,肌肉注射Vit D3注射液,疗程均为10个月,治疗结束后进行疗效评价。结果 1与治疗前相比,治疗组糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)水平上调,微量白蛋白(MA)、β2-微球蛋白(β2-M)及肾脏损伤分子-1(KIM-1)水平下调,治疗组低于对照组差异有统计学意义(P<0.05)。2与治疗前相比,治疗组治疗后Vit D3水平上调,治疗组高于对照组差异有统计学意义(P<0.01)。3T2DM患者Vit D3水平与MA(r=-0.432),β2-M(r=-0.615),及KIM-1(r=-0.763)水平均呈负相关(P<0.05)。结论 Vit D3可有效减轻T2DM患者的早期肾损害,对肾脏具有保护作用。