Toxicity induced by nanoparticles

Nanoparticle research is currently an area of intense scientific interest due to a wide variety of potential applications. Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. Nanoparticle can modify the physicochemical properties of the material as well as create the opportunity for increased uptake and interaction with biological tissues through inhalation, ingestion, and injection. This combination of effects can generate adverse biological effects in living cells. Nanoparticles have proved toxic to human once in the blood stream, nanoparticles, spleen, bone marrow and nervous system can be transported around the body and be taken up by organs tissue and cell cultures, resulting in increased oxidative stress, inflammatory cytokine production and cell death. Unlike larger particles, nanoparticles may be taken up by cell mitochondria and the cell nucleus studies demonstrate the potential for nanoparticles to cause DNA mutation and induce major structural damage to mitochondria, even resulting in cell death. Size is therefore a key factor in determining the potential toxicity of a particle. How these nanoparticles behave inside the body is still a major question that needs to be resolved. There is a responsibility to test and optimize these new nanomaterials early during the development process to eliminate or ameliorate identified toxic characteristics.     

The urban geography of SARS: paradoxes and dilemmas in Toronto's health care

BACKGROUND: Severe acute respiratory syndrome (SARS) has impacted heavily on both Canada's society and its health care system. Quite unexpectedly, hospitals and health care workers became facilitators of disease diffusion. This experience has demonstrated the need for a comprehensive disease control strategy. AIMS: The aims are threefold. First, to examine the subtle and changing spatial characteristics of SARS during the short but critical period of its rapid spread in the Greater Toronto Area. Second, to make salient three paradoxes, and their associated dilemmas, faced by nurses and other health care professionals challenged with caring for the sick and containing the rapid spread of the disease. Third, to propose some ways of approaching these dilemmas, as well as some broader preventative and mitigating strategies. METHODS: The crosscutting concepts of 'clinical uncertainty' and 'flow of human contacts' are used to explain disease transmission characteristics and urban spatial diffusion and to guide the particular strategies developed. Evidence for the paper comes from public health records, governmental and non-governmental health statements and the initial epidemiological research on SARS. Direct insights are also gained from recent first-hand experiences of Toronto's health care system during the crisis. DISCUSSION: The concepts of clinical uncertainty and the flow of human contacts provide in-depth insights that complement the findings of large-scale epidemiological studies, and help operationalize their general calls for enhanced control measures. The comprehensive disease control strategy proposed includes the creation of a hospital infrastructure specific to the containment of biological threats; an advisory coalition of disease control specialists; the development of a biological threat-and-containment simulation laboratory and three specific programmes in patient safety, risk assessment and community mobilization. CONCLUSION: It is argued that containment alone, while a necessary and urgent priority, cannot be seen as an end in itself and might better be understood as one possible trajectory within a comprehensive problem-solving strategy. The experiences in Toronto may offer insights to other cities and countries that currently lack such strategies and hence may be vulnerable to similar outbreaks of dangerous infectious diseases.     

Absence of hepatitis B virus DNA detected by polymerase chain reaction in blood donors who are hepatitis B surface antigen negative and antibody to hepatitis B core antigen positive from a United States population with a low prevalence of hepatitis B serologic markers

A recent study in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive blood donors from a population with a high prevalence of hepatitis B serologic markers showed the presence of hepatitis B virus DNA (HBV DNA) as detected by polymerase chain reaction (PCR) in 4 percent of these donors. A sensitive, nested PCR assay was used to assess the prevalence of HBV DNA in a population of HBsAg-negative, anti-HBc-positive blood donors from a United States population with a low prevalence of hepatitis B serologic markers. The lower limit for detection by the PCR assay was 10(-5) pg per mL of HBV DNA. There was a review of 26,492 consecutive blood donations in a 12-month period. During this time, only 1 unit (0.004%) was HBsAg positive. An additional 158 units (0.6%) were repeatably reactive for anti-HBc. These 158 HBsAg-negative, anti- HBc-positive units were given by 119 donors of blood for allogeneic and autologous use. HBV DNA was not detected by PCR in blood from 83 allogeneic blood donors (93 samples) or 36 autologous blood donors (65 samples). Anti-HBc testing is an inefficient means of screening for potential hepatitis B infectivity and is associated with low test specificity in populations with a low prevalence of hepatitis B serologic markers.     

人工髓核假体置入治疗腰椎间盘突出症的疗效分析

目的：观察已在临床初步开展起来的人工髓核置换术治疗腰椎间盘突出症的中、远期临床疗效及并发症,分析其对策。 方法：纳入2002-02/2004-08南方医科大学附属南方医院脊柱骨病外科采用单枚人工髓核假体置换术治疗单节段腰椎间盘突出症患者98例,获得24～48个月随访患者75例,按平均随访时间达24,36,48个月,分为24个月组（n=30）,36个月组（n=23）,48个月组（n=22）。选同期采用单纯椎间盘髓核摘除术患者30例作为对照组,评估各组术后临床疗效,主观症状采用Oswestry功能障碍指数问卷表（0%表示正常,越接近100%则功能障碍越严重）和Prolo功能评分表（小于或等于5分为差,6～7分为中等,8～10为优）评价,分析术后影像学检查并测量手术节段活动度和椎间隙高度变化情况,同时观察假体位置情况,腰椎MRI观察假体位置和软骨终板的信号变化情况。腰椎活动度=（腰椎中立角度-前屈角度）＋（后伸角度-腰椎中立角度）=后伸角度-前屈角度;为消除X射线放大率的影响,椎间隙高度变化情况采用病变椎间隙后缘高度与上位椎体中部矢状径的比值表示。 结果：75例获得24～48个月随访者,全部进入结果分析。①48个月组2例、36个月组1例发生假体脱出,二次手术取出。其余患者术后临床症状均明显缓解,疼痛消失。②24,36,48个月组及对照组术后末次Oswestry功能障碍指数均较术前降低,差异有显著性意义（14.2%,52.1%;15.5%,55.2%;15.1%,53.6%;15.5%,51.5%;P〈0.05）。③24,36,48个月组及对照组术后末次Prolo能评分均较术前升高,差异有显著性意义（8.5,4.6分;8.6,4.5分;8.7,4.3分;8.4,4.2分;P〈0.05）。④24,36,48个月组同期手术节段腰椎活动度均高于对照组,差异有显著意义（P〈0.05）。⑤24个月组手术节段椎间高度较术前降低约4%、36个月组降低约12%、48个月组降低约18%、对照组较术前降低约25%,各组术前和术后椎间隙高度比值比较,差异具有显著性意义（P〈0.05）。⑥主要并发症：早期出现术后一过性腰痛24例,假体脱出3例。中、远期发现假体下沉32例,软骨终板损伤39例。 结论：单枚人工髓核假体置换治疗腰椎间盘突出症中、远期随访临床疗效肯定,但存在较严重并发症,应慎重开展此项手术。     

换液频率对骨髓间充质干细胞生物学特性的影响

目的:培养条件是影响骨髓间充质干细胞生物学特性的重要因素。实验考察换液频率对兔骨髓间充质干细胞增殖分化及代谢特性等的影响。方法:实验于2005-03/2005-06在华东理工大学生物反应器工程国家重点实验室完成。①实验材料:1月龄新西兰大白兔购自上海市淞江车墩实验动物良种场。实验过程中对动物处置符合动物伦理学标准。②实验方法:采用密度梯度离心法从兔股骨骨髓中分离得到骨髓间充质干细胞,体外培养扩增后,取生长良好的第3代细胞分别以24,48,72h时间间隔进行换液培养。③实验评估:观察细胞形态学变化,测定细胞生长曲线同时进行乳酸和氨代谢分析,并对几种条件下收获的细胞进行集落形成和成骨分化检测。结果:①每24h换液的细胞最早进入对数生长期,第5天达到增殖顶点,最大细胞数目可达3.44×105,分别是48h和72h换液频率的1.43倍和1.71倍。②每48h换液条件下收获的细胞具有最强的集落形成能力,明显高于每24h和每72h换液条件下收获的细胞。③3种换液频率条件下收获的细胞经成骨诱导后茜素红染色均为阳性,其中每48h换液的细胞胞外钙基质分泌最高。④3种换液频率条件下细胞的代谢曲线无明显差异,乳酸和氨均维持较低浓度,分别在5mmol/L和2mmol/L以下。结论:①换液频率对骨髓间充质干细胞的影响具有双向性。提高换液频率促进骨髓间充质干细胞的增殖,同时也加速了干细胞特性的丢失,导致集落形成能力和成骨分化能力下降。②普遍采用的三四天换液不能提供适合骨髓间充质干细胞生长同时利于干细胞特性维持的营养环境,提示可通过常规培养条件的优化使其有利于骨髓间充质干细胞执行对称的细胞分裂。     

Evaluation of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid in the inhibition of rouleaux formation

BACKGROUND: DIDS (4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid) inhibits the formation of serum-or plasma-induced rouleaux through its ability to bind to band 3 on red cell membranes. This property of DIDS was evaluated in the serologic testing of specimens exhibiting rouleaux. STUDY DESIGN and METHODS: Optimal test conditions for DIDS treatment of reagent red cells were determined by varying the volume and concentration of DIDS solution and the incubation temperature and duration and comparing the results of antibody screening procedures using specimens that exhibit macroscopically visible rouleaux. Blind titration studies compared untreated and DIDS-treated red cells to evaluate the maintenance of antigen integrity. The use of DIDS-treated red cells for antibody detection and identification was evaluated by comparing the results in donor specimens containing antibodies with those in untreated and DIDS-treated selected panel cells. In addition, 4-percent (wt/vol) dextran in serum was used to induce rouleaux formation as a way of determining the capability of DIDS to resolve ABO serum grouping discrepancies. RESULTS: Complete inhibition of rouleaux formation occurred when reagent red cells were treated by incubation at 37 degrees C for 10 minutes with 150 microliter (approx. 5 drops) of 0.05 mg per mL of DIDS in 0.9-percent NaCl. There were no significant differences in titration scores of untreated and DIDS-treated red cells tested with the 19 antisera used to assess antigen integrity. Antibody identification studies showed that DIDS-treated reagent red cells reacted similarly to untreated reagent red cells. In addition, DIDS resolved dextran-induced ABO serum grouping discrepancies. CONCLUSION: DIDS effectively resolved the serologic problems associated with the presence of rouleaux, without affecting the results of the test system itself. Implementation of this method to inhibit the rouleaux-forming properties of serum and plasma specimens can be useful in serologic testing.     

Adverse reactions in patients transfused with cryopreserved marrow

Marrow is cryopreserved for use in autologous bone marrow transplants, but little is known of the incidence of reactions in patients transfused with these cryopreserved marrows. Reactions in patients transfused during a 4-year period with 134 autologous marrows cryopreserved in dimethyl sulfoxide (DMSO) were compared with those in patients transfused with marrow that had been collected from HLA-compatible donors and that had not been cryopreserved. Patients transfused with cryopreserved marrow had significantly more nausea (44.8 vs. 14.1%; p less than 0.0005), vomiting (23.9 vs. 8.5%; p less than 0.01), chills (31.3 vs. 1.4%; p less than 0.0005), and fever (17.9 vs. 0%; p less than 0.005) than patients transfused with fresh allogeneic marrow. The incidence of emesis correlated with the dose of DMSO received, but that of nausea did not. All cryopreserved marrows were cultured for bacteria at the time of transfusion and 17 (12.7%) were found to be positive. Only 1 of the 17 patients transfused with culture-positive marrow developed sepsis during the transplant course with the same organism that was present in the transfused marrow. Although the reactions in donors transfused with cryopreserved marrow were readily treated, this study suggests that the incidence of some reactions might be decreased by reducing the dose of DMSO transfused. Bacterial contamination of transfused marrow was a worrisome complication, and efforts should be made to improve marrow collection and processing techniques to minimize that risk.     

Does the urinary tract infection caused by carbapenem‐resistant Gram‐negative bacilli impact the outcome of kidney transplant recipients?

The incidence of urinary tract infection (UTI) after kidney transplantation (KT) caused by multidrug‐resistant (MDR) bacteria is growing. The aim of this study was to analyze the impact of UTI caused by carbapenem‐resistant Gram‐negative bacteria (CR‐GNB) in the survival of graft and recipients following KT. This was a retrospective cohort study involving patients who underwent KT between 2013 and 2016. Patients were followed since the day of the KT until loss of graft, death or end of the follow‐up period (31th December 2016). The outcomes measured were UTI by MDR following KT and graft and patient survival. Analyses were performed using Cox regression; for the graft and patient survival analysis, we used a propensity score for UTI by CR‐GNB to matching a control group. UTI was diagnosed in 178 (23.9%) of 781 patients, who developed 352 UTI episodes. 44.6% of the UTI cases were caused by MDR bacteria. Identified risk factors for UTI by MDR bacteria were DM, urologic disease as the cause of end‐stage renal failure, insertion of ureteral stent, carbapenem use, and delayed graft function (DGF). Risk factors for death during the follow‐up period were female gender, patients over 60 years old at the time of KT, DM, body mass index over 31.8, UTI caused by CR‐GNB. In conclusion, UTIs caused by CR‐GNB have great impact on patients’ survival after KT.