Assessment of Hemodialysis Adequacy by Ionic Dialysance: Comparison to Standard Method of Urea Removal

Background. The hemodialysis adequacy is one of the most important issues influencing the survival of patients on maintenance hemodialysis (HD). Assessment of measuring the delivered dialysis dose using clearance × time/volume (Kt/V) index requires multiple blood sampling. New methods for assessment of dialysis dose based on ionic dialysance (ID) have been suggested. Online conductivity monitoring (using sodium flux as a surrogate for urea) allows the repeated noninvasive measurement of Kt/V on each HD treatment. In this study we have compared this method with the standard method of estimating Kt/V. Methods. We studied 24 established HD patients over a 4 week time period. Patients were dialyzed using Fresenius 4008S dialysis monitors, equipped with modules to measure ID. Data were manually collected and analyzed using the appropriate statistical software. Urea removal (UR) was measured once a week by a two-pool calculation, estimating an eKt/V. Results. The Kt/V measured by ID highly correlated with the one derived from the measurement of the UR (r = 0.8959, p< 0.0001). The ID underestimated UR by the mean of 6%. The ID varied greatly within individual patients with a median of 1.29 ± 0.22. If the eKt/V ≥ 1.2 is considered adequate, 33% of the patients would have been inadequately dialyzed. The mean HD duration to achieve an adequate dialysis was 4 hours and 47 minutes with high interpatient variability. Conclusion. The ID seems to be an easily obtained measure of the delivered dialysis dose, correlating well with standard UR method. Substantial individual variations imply that repeated measures (ideally for all treatments) are necessary to obtain a real answer to the mean treatment dose being delivered to the patients.     

传统尸体供肾与心脏死亡器官捐献供肾肾移植效果的比较

目的比较心脏死亡器官捐献（donation after cardiac death,DCD）供肾与传统尸体供肾肾移植的临床效果。方法回顾性分析2012年1月至2013年2月在郑州人民医院实施肾移植的70例患者的临床资料。根据供肾来源分为DCD供肾组（DCD组,22例）和传统尸体供肾组（传统组,48例）。患者均签署知情同意书,符合医学伦理学规定。比较两组患者术后7、14、28d肾功能指标血尿素氮（BUN）和血清肌酐（Scr）水平差异。比较两组患者术后1个月内并发症发生情况及预后情况。结果DCD组术后7、14d的BUN和Scr水平均明显高于传统组（均为P〈0．01）;DCD组术后28d的scr水平亦明显高于传统组（P〈0．05）,两组BUN水平差异无统计学意义（P〉0．05）。与传统组比较,DCD组的移植物功能延迟恢复（DGF）、急性排斥反应（AR）、感染、移植肾切除的发生率及死亡率明显增高,差异有统计学意义（均为P〈0．01）。结论DCD供。肾肾移植术后早期肾功能恢复情况不如传统尸体供肾,且围手术期内各种并发症的发生率及死亡率也明显高于传统尸体供肾肾移植。     

An update on the use of benzoate,phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease

Introduction: Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal.

Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease.

Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.     

Development of a Tissue‐Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema

Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re‐establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue‐engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane‐poly(carbonate‐urea)urethane (POSS‐PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS‐PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re‐establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P < 0.001), favorable kink resistance, and excellent suture retention property (casted vs. coagulated, P < 0.05). Cytocompatibility study showed that the POSS‐PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue‐engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

The relationship between dental caries status and dental plaque urease activity

INTRODUCTION: Ammonia production from the metabolism of urea by urease enzymes of oral bacteria moderates plaque acidification and may inhibit dental caries, as suggested by in vitro studies and indirect clinical observations. The objective of this study was to examine the relationship of urease activity with dental caries at the clinical level. METHODS: Urease activity was measured in dental plaque and saliva samples from 25 caries-free subjects (CF) and in eight subjects with six or more open caries lesions (CA). Plaque and saliva collection was repeated for each subject 1 week later using identical procedures. RESULTS: Urease-specific activity in the dental plaque of CF subjects was significantly higher compared to that in the subjects with caries. The association of low plaque urease levels with increased caries was further supported by odds ratio analysis using different plaque urease cut-off points. Using a receiver operating characteristic curve it was estimated that there was an approximately 85% probability of correctly classifying the subjects as CA or CF based on the relative ordering of their plaque urease activity levels. No statistically significant differences were observed in salivary urease activity. CONCLUSION: This study suggests that loss of alkali-generating potential of tooth biofilms via the urease pathway has a positive relationship to dental caries.     

杞菊地黄丸联合环丙沙星治疗慢性肾盂肾炎的疗效观察

目的探讨杞菊地黄丸联合环丙沙星治疗慢性肾盂肾炎的临床效果。方法选取日照市妇幼保健院在2015年12月—2016年12月收治的慢性肾盂肾炎患者141例,随机分成对照组(70例)和治疗组(71例)。对照组患者口服盐酸环丙沙星片,1片/1次,3次/d;治疗组在对照组的基础上口服杞菊地黄丸,8丸/次,3次/d。所有患者均经过规律治疗4周。观察两组患者临床疗效,比较治疗前后两组患者主要症状积分、肾功能指标和不良反应情况。结果治疗后,对照组患者临床总有效率为85.71%明显低于治疗组的98.59%,停药半年内对照组和治疗组的重新感染率分别为12.86%、2.82%,两组比较差异具有统计学意义(P0.05)。治疗后,两组主要症状积分明显降低(P0.05);且治疗组积分明显低于对照组(P0.05)。治疗后,两组患者的血清肌酐、血尿素氮和尿微量白蛋白水平均显著降低(P0.05);且治疗组患者肾功能指标水平明显低于对照组(P0.05)。治疗期间,治疗组患者不良反应发生率为4.23%,明显低于对照组患者的17.14%,两组比较差异具有统计学意义(P0.05)。结论杞菊地黄丸联合环丙沙星治疗慢性肾盂肾炎疗效显著,可降低停药半年内重新感染率,具有一定的临床推广应用价值。     

中药肾复舒颗粒合用阿托品对肾衰大鼠残余肾VEGF和MVD的影响

目的观察中药肾复舒颗粒合用阿托品对肾衰大鼠残余肾组织血管内皮生长因子(VEGF)的表达和微血管密度(MVD)分布与肾损伤的影响。方法将5/6肾切除SD大鼠随机分为肾复舒治疗组、肾复舒+阿托品治疗组和模型组,并设假手术组为正常对照,术后1周开始给药,连续8周后处死动物。采血检测各组用药前后血尿素氮(BUN)、血肌酐(Cr)和尿蛋白的浓度变化;并取大鼠残余肾组织切片用HE染色和免疫组化法检测肾组织VEGF表达水平及MVD、肾小球硬化指数(GSI)、肾小管间质损伤指数(TIS)。用MVD与BUN、Cr、GSI、TIS和尿蛋白作相关分析。结果两治疗组肾组织VEGF、MVD表达比对照组明显增强;VEGF与MVD成正相关;MVD与血尿素、肌酐、GSI、TIS和尿蛋白成负相关(P<0.05);且肾复舒+阿托品组改变更为明显(P<0.05)。结论肾复舒和阿托品能加强VEGF在残余肾组织的表达,增加微血管密度;降低肾小球硬化和肾小管间质损伤程度。2种药物合用作用更为明显。     

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

Objective

Benzene, as a volatile organic compound, is known as one of the main air pollutants in the environment. The aim of this review is to summarize all available evidences on non-cancerous health effects of benzene providing an overview of possible association of exposure to benzene with human chronic diseases, specially, in those regions of the world where benzene concentration is being poorly monitored.

Methodology

A bibliographic search of scientific databases including PubMed, Google Scholar, and Scirus was conducted with key words of “benzene toxic health effects”, “environmental volatile organic compounds”, “diabetes mellitus and environmental pollutants”, “breast cancer and environmental pollution”, “prevalence of lung cancer”, and “diabetes prevalence”. More than 300 peer reviewed papers were examined. Experimental and epidemiologic studies reporting health effects of benzene and volatile organic compounds were included in the study.

Results

Epidemiologic and experimental studies suggest that benzene exposure can lead to numerous non-cancerous health effects associated with functional aberration of vital systems in the body like reproductive, immune, nervous, endocrine, cardiovascular, and respiratory.

Conclusion

Chronic diseases have become a health burden of global dimension with special emphasis in regions with poor monitoring over contents of benzene in petrochemicals. Benzene is a well known carcinogen of blood and its components, but the concern of benzene exposure is more than carcinogenicity of blood components and should be evaluated in both epidemiologic and experimental studies. Aspect of interactions and mechanism of toxicity in relation to human general health problems especially endocrine disturbances with particular reference to diabetes, breast and lung cancers should be followed up.     

Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.