Rutile TiO₂ particles exert size and surface coating dependent retention and lesions on the murine brain

The rising commercial use and large-scale production of engineered nanoparticles (NPs) may lead to unintended exposure to humans. The central nervous system (CNS) is a potential susceptible target of the inhaled NPs, but so far the amount of studies on this aspect is limited. Here, we focus on the potential neurological lesion in the brain induced by the intranasally instilled titanium dioxide (TiO₂) particles in rutile phase and of various sizes and surface coatings. Female mice were intranasally instilled with four different types of TiO₂ particles (i.e. two types of hydrophobic particles in micro- and nano-sized without coating and two types of water-soluble hydrophilic nano-sized particles with silica surface coating) every other day for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the titanium contents in the sub-brain regions. Then, the pathological examination of brain tissues and measurements of the monoamine neurotransmitter levels in the sub-brain regions were performed. We found significant up-regulation of Ti contents in the cerebral cortex and striatum after intranasal instillation of hydrophilic TiO₂ NPs. Moreover, TiO₂ NPs exposure, in particular the hydrophilic NPs, caused obvious morphological changes of neurons in the cerebral cortex and significant disturbance of the monoamine neurotransmitter levels in the sub-brain regions studied. Thus, our results indicate that the surface modification of the NPs plays an important role on their effects on the brain. In addition, the difference in neurotoxicity of the two types of hydrophilic NPs may be induced by the shape differences of the materials. The present results suggest that physicochemical properties like size, shape and surface modification of the nanomaterials should be considered when evaluating their neurological effects.     

钬激光联合吡柔比星灌注治疗浅表性膀胱癌

目的 探讨经尿道钬激光切除联合吡柔比星即刻灌注治疗浅表性膀胱癌的临床疗效.方法 51例浅表性膀胱癌患者按随机数字表法分为两组,治疗组26例行经尿道膀胱肿瘤钬激光切除,术后即刻予以膀胱内保留灌注无菌蒸馏水50 ml+吡柔比星30 mg,1次;对照组25例行经尿道膀胱肿瘤电切治疗,两组术后拔除尿管时灌注1次,以后每周1次,共8次,后改为每月1次,持续至术后1年以上,随访15～39个月.结果 治疗组手术时间20～53 min,平均(31.6 ±8.9) min,无膀胱穿孔发生,术后留置导尿管1～5d,平均(2.7±0.6)d,4例复发;对照组手术时间13 ～47 min,平均(29.8±8.3)min,1例术中膀胱穿孔,术后留置导尿管3～11d,平均(4.6±1.1)d,11例复发.两组平均手术时间、膀胱穿孔例数差异均无统计学意义(均P＞0.05),治疗组术后导尿管留置时间、肿瘤复发例数均低于对照组(均P＜0.05).结论 经尿道钬激光切除联合吡柔比星灌注治疗浅表性膀胱肿瘤疗效优于电切治疗,术后恢复快.     

Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): a trial of the Eastern Cooperative Oncology Group

ObjectiveTo assess the safety and effectiveness of AD32, a doxorubicin analogue with little systemic exposure when administered intravesically, in patients with recurrent or refractory superficial urothelial carcinoma (formerly called transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed prior BCG-based immunotherapy.MethodsEligible patients received six weekly doses (800 mg) of intravesical AD32 and were evaluated at 12-week intervals for 24 months or until date of worsening disease. Primary analysis was the proportion of all patients recurrence-free at 12 months. Treatment-related and GU-specific toxicities were also examined. All participating institutions submitted the protocol for Institutional Review Board (IRB) approval.ResultsThe study was halted due to unavailability of study drug after accrual of 48 of a planned 64 patients; 42 were included in the analysis. Of these, 28 (67%) were still alive after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients with complete response (CR), 3 (60%) experienced disease recurrence; (median time to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20% (90% CI, 7.8%, 36.1%) and 15% (90 CI, 4.9%, 30.2%), respectively, for patients with TCC and 80% (90% CI, 31.4%, 95.8%) at both intervals for CIS patients with CR. Infection was the most common treatment-related toxicity; no grade 4 or higher toxicity was observed. The most common GU-specific toxicity was increased frequency/urgency.ConclusionsAD32 is safe and active for treatment of recurrent or refractory superficial bladder carcinoma. The agent awaits more complete characterization when drug production problems can be solved.     

Oxidative Damage to Lung Tissue and Peripheral Blood in Endotracheal PM2.5-treated Rats

Objective To investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats. Methods PM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase （GSH-Px） and concentration of malondialdehyde （MDA） were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length （μm） and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. Results The activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length （μm） and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. Conclusion PM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length （μm） and rate of tail are simple and valuable biomarkers of PM2 5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.     

沙培林联合羟基喜树碱膀胱灌注与单独灌注预防膀胱癌术后复发疗效对比观察

目的：评价联合应用沙培林（OK-432）和羟基喜树碱（HCPT）膀胱腔内灌注及单独应用预防膀胱癌复发的疗效。方法：128例膀胱乳头状移行细胞癌患者行经尿道电切术和膀胱部分切除术后,随机分为3组：联合治疗组36例,OK-432组42例,HCPT、组50例。膀胱癌切除术后开始灌注,每周1次,共8周;以后每月1次,随访18个月。每2个月复查1次膀胱镜和尿细胞学检查。结果：联合应用组无复发,OK-432组3例复发,复发率7．14％（3／42）,HCPT组5例复发、复发率10．00％（5／50）。OK-432组与HCPT组比较差异无统计学意义（P〉0．05）;但二者与联合组比较,组间差异有统计学意义（P〈0．05）。三组均无严重不良反应和并发症。结论：联合应用OK-432、HCPT疗效优于单独应用,预防复发疗效好,不良反应不明显,有较高临床应用价值。     

EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder

CONTEXT AND OBJECTIVE: To present the updated version of 2008 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer. EVIDENCE ACQUISITION: A systematic review of the recent literature on the diagnosis and treatment of non-muscle-invasive bladder cancer was performed. The guidelines were updated and the level of evidence and grade of recommendation were assigned. EVIDENCE SYNTHESIS: The diagnosis of bladder cancer depends on cystoscopy and histologic evaluation of the resected tissue. A complete and correct transurethral resection (TUR) is essential for the prognosis of the patient. When the initial resection is incomplete or when a high-grade or T1 tumour is detected, a second TUR within 2-6 wk should be performed. The short- and long-term risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients to low, intermediate, and high-risk groups-separately for recurrence and progression-represents the cornerstone for indication of adjuvant treatment. In patients at low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is strongly recommended. In those at an intermediate or high risk of recurrence and an intermediate risk of progression, one immediate instillation of chemotherapy should be followed by further instillations of chemotherapy or a minimum of 1 yr of bacillus Calmette-Guerin (BCG). In patients at high risk of tumour progression, after an immediate instillation of chemotherapy, intravesical BCG for at least 1 yr is indicated. Immediate cystectomy may be offered to the highest risk patients and in patients with BCG failure. The long version of the guidelines is available on www.uroweb.org. CONCLUSIONS: These EAU guidelines present the updated information about the diagnosis and treatment of non-muscle-invasive bladder cancer and offer the recent findings for the routine clinical application.     

Comparative study of pathological lesions induced by multiwalled carbon nanotubes in lungs of mice by intratracheal instillation and inhalation

The pathological lesions induced by multiwalled carbon nanotubes (MWCNTs) in bronchi and alveoli of mice were studied by intratracheal instillation and inhalation. In instillation groups, the dose was 0.05 mg MWCNTs/mouse. Similar size clumps of MWCNTs were distributed in bronchi and alveoli. The clumps led to inflammation to the lining wall of bronchi and severe destruction to alveolar netted structure around them. In the inhalation groups, the mice were exposed to aerosolized MWCNTs with mean concentration of 32.61 mg/m(3), the intralung deposition dose were roughly 0.07, 0.14, and 0.21 mg in the 8-day group, 16-day group, and 24-day group, respectively. Most of aggregations of MWCNTs in the alveoli were smaller than that in bronchi. The aggregations induced proliferation and thickening of alveolar walls. With the exception of these moderate pathological lesions, the general alveolar structure was still remained. The preliminary study demonstrated a difference in lung pathological lesions induced by instilled MWCNTs and inhaled ones, which may be due to the different size and distribution of aggregations of MWCNTs in lung.     

Ketamine-associated bladder dysfunction

Objective:   To assess the impact of ketamine abuse on genitourinary tract dysfunction.
Methods:   Eleven patients with urinary tract symptoms and a history of ketamine abuse in recent years were studied. Urinalysis, urine culture, renal function tests, abdominal sonography and urodynamic studies were done. Bladder biopsies were carried out in selected cases.
Results:   The most common complaints were lower urinary tract symptoms, including dysuria, frequency, urgency and gross hematuria. Urinalyses showed nonbacterial pyuria and were negative for tuberculosis. All biopsy specimens showed infiltrations of granulocytes (mostly eosinophils) and mast cells within the bladder tissue. Medications produced only slight clinical improvements. Intravesical instillation of hyaluronan solution was performed for some patients and a significant improvement of lower urinary tract symptoms was observed.
Conclusions:   Although the dosage and duration of ketamine abuse causing severe side-effects are still unclear, some patients develop irreversible histological changes in the urinary tract. Therefore, clinicians should be aware of the negative effects of ketamine abuse on genitourinary tract function.     

Intravesical Instillation in Pure Line LEW Rats and Nude Mice

In order to study bladder intravesical instillation methods in pure line LEW rats and nude mice, female LEW rats and nude mice aged 2 to 4 weeks were sacrificed. Their urethra and bladder were observed under anatomical microscopy. A trochar was prepared according to the outline and an- gle of the urethra. Ink was poured into female rats and nude mice bladder though urethra. Filling and staining of bladder were observed and evaluated under anatomical microscopy. Status and urethral injury of rats and mice were observed. The results showed that urethra anatomic structure of rats and nude mice was different from that of human urethra. When bladder was filled with ink and became blue, liquid was not seen to leak out. The success rate of intubation was high (100%). Living activi- ties of animals weren’t influenced by intravesical instillation. It was concluded that bladder irrigation might be a kind of valid and utilizable method in pure line rat and nude mouse empirical study. The model may be a more effective tool for study of bladder tumor.     

输卵管通液治疗不孕症的疗效观察

目的：为进一步探讨不孕症的原因，对不孕症病人实施输卵管通液术的诊断治疗以观察通畅后的受孕情况。方法：对509例不孕症病人进行输卵管通液术，随机分两组加入不同药液自宫颈管注入，观察输卵管通畅情况对比2个疗程后的受孕率。结果：造成继发不孕的原因首位是人工流产刮宫术，其次是放置IUD，少数为盆腔炎而造成不同程度的输卵管粘连有关，A组296例不孕症中经第二疗程卵管通畅218例（73．64％），半年受孕285例，受孕率达96．30％，B组213例不孕症中经第二疗程输卵管通畅92例（43．20％），半年受孕58例，受孕27．23％（P＜0．01）有显差异，结论：通过输卵管通液术和加入不同药液防止输卵管术中痉挛，避免术后再次粘连及预防术中，术后感染是治疗不孕症，提高受孕率的重要环节。