Characterization and Biodistribution Analysis of Oxygen-Doped Single-Walled Carbon Nanotubes Used as in Vivo Fluorescence Imaging Probes.

Single-walled carbon nanotubes (SWCNTs) show strong fluorescence in the 1000-1700 nm second near-infrared (NIR-II) wavelength range and are considered promising candidates for angiographic imaging probes. Oxygen-doped SWCNTs coated with phospholipid-polyethylene glycol (o-SWCNT-PEG) show exceptional potential, as they emit fluorescence at ∼1300 nm through excitation with 980 nm light. Here, with the aim of putting o-SWCNTs to practical use as an angiographic agent in animal experiments, the retention time after intravenous administration in the vasculature of mice and the biodistribution were studied. To provide bio affinity, the o-SWCNTs were coated with phospholipid polyethylene glycol. The intravenously injected o-SWCNT-PEG circulated within the vasculature for 3 h and cleared within 1 day. There was prominent fluorescence and Raman signals from the SWCNTs in the liver and spleen early in the experiment; the signals remained for 1 month. No apparent abnormalities in weight or appearance were observed after 2 months, suggesting low toxicity of o-SWCNT-PEG. These characteristics of o-SWCNT-PEG would make it useful as an angiographic imaging probe in the NIR-II wavelength range.

Oxygen-doped carbon nanotubes for near-infrared fluorescent labels and imaging probes.

Chemical modification of carbon nanotube surface can controllably modulate their optical properties. Here we report a simple and effective synthesis method of oxygen-doped single-walled carbon nanotubes (o-SWCNTs), in which a thin film of SWCNTs is just irradiated under the UV light for a few minutes in air. By using this method, the epoxide-type oxygen-adducts (ep-SWCNTs) were produced in addition to the ether-type oxygen-adducts (eth-SWCNTs). The Treated (6, 5) ep-SWCNTs show a red-shifted luminescence at ~1280 nm, which corresponds to the most transparent regions for bio-materials. Immunoassay, fluorescence vascular angiography and observation of the intestinal contractile activity of mice were demonstrated by using the produced o-SWCNTs as infrared fluorescent labels and imaging agents.

High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: a new rat model of diabetic nephropathy.

BACKGROUND AND AIM: We have developed a new rat model that mimics the natural course of diabetic nephropathy seen in type 2 diabetes. METHODS: Nine days after intravenous injection of streptozotocin (STZ) (40 mg/kg) or vehicle to 8-week-old male Sprague-Dawley rats, the animals' right kidneys were surgically removed. Two weeks after surgery, the STZ-injected rats were fed on either a high-fat (ST+HF) or a normal (ST) diet, while the vehicle-injected rats were fed on the high-fat diet (HF). RESULTS: Baseline biochemical markers did not differ between the three groups. Only the ST+HF group showed a significant increase in plasma glucose levels after 15 weeks, and simultaneously plasma insulin levels started to decrease, followed by an increase in plasma total cholesterol and triglyceride levels at 25 weeks and slightly later by an increase in blood pressure. In the ST+HF group, significant microalbuminuria was detected at 15 weeks followed by overt proteinuria, both of which were absent in the other two groups. Also in ST+HF, the creatinine clearance rate increased until week 15, and then gradually decreased. Histologically, ST+HF rats showed mesangial expansion at week 25, and diffuse glomerular sclerosis at the end of the experiments. CONCLUSION: The chronological changes in biochemical, physiological and histological markers in ST+HF rats are reminiscent of human type 2 diabetes and nephropathy. Our new model of type 2 diabetic nephropathy should help us to understand the pathophysiology of the disease and serve to explore measures to prevent and treat diabetic nephropathy.

Real-time in vivo virtual histology of colorectal lesions when using the endocytoscopy system.

BACKGROUND: The histological findings of GI lesions are based on light-microscopic examination of H&E-stained thin-slice specimens. Recently, a concept of optical biopsy has been advocated. A study of the observation of colorectal lesions using endocytoscopy to obtain real-time histological images in vivo during endoscopy was performed. DESIGN: Prospective study. AIM: To evaluate the usefulness of optical biopsy of colorectal lesions with the endocytoscopy (E-C) system. PATIENTS: The subjects were 113 consecutive patients who underwent a complete colonic examination, from April 2003 to March 2004, performed by a single colonoscopist. SETTING: Digestive Disease Center of Showa University Northern Yokohama Hospital. RESULTS: With E-C, it was possible to observe lesions at the cellular level and evaluate cellular atypia in addition to structural atypia in vivo. The correlation was statistically significant between the endocytoscopic diagnosis and the histological diagnosis. LIMITATIONS: The endocytoscope had to be touched to the target colonic glands. CONCLUSIONS: It was possible to distinguish neoplastic from non-neoplastic lesions, and also possible to distinguish invasive cancer from adenoma. "Ultra-high" magnifying endoscopy, the E-C system, provides real-time histological images in vivo, which correspond well with those of H&E-stained microscopic images.

Interobserver and intra-observer consistency in the endoscopic assessment of colonic pit patterns.

BACKGROUND: The colonic pit pattern is recognized as an aid to the differential diagnosis between hyperplastic lesions, adenoma, and carcinoma, and is a focus for observation by magnification chromoendoscopy, especially in Japan. This study evaluated intra- and interobserver agreement of experienced endoscopists in the assessment of colonic pit patterns when using the Kudo classification. METHODS: A total of 220 magnification chromoendoscopic pictures of colonic lesions were selected, of which 215 were collected from a consecutive series of patients. The pictures were randomly displayed twice to 6 experienced endoscopists at an interval of 1 week. Each picture was assessed for predominant pit pattern by using the classification of Kudo. Histopathologic diagnosis also was predicted based on the pit pattern diagnosis. Kappa statistics were used to estimate intra- and interobserver variation. RESULTS: The mean (standard deviation) inter- and intra-observer kappa values for experienced endoscopists were 0.716 (0.031) and 0.810 (0.084), respectively. For prediction of histopathology according to the pit pattern diagnosis, the mean (standard deviation) inter- and intra-observer kappa values were 0.776 (0.032) (p = 0.001) and 0.862 (0.069) (p = 0.028), respectively. CONCLUSIONS: For experienced endoscopists, the inter- and intra-observer reproducibility of the classification of colonic pit pattern is good.