Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

BACKGROUND： Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy （AION）. OBJECTIVE ： To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography （FFA）, optical coherence tomography （OCT）, flash visual evoked potential （F-VEP）, and histopathologically confirm its reliability. DESIGN： A randomized control tria SETTINGS ： Department of Ophthalmology, Xi＇an Fourth Hospital; Xi＇an Institute of Ocular Fundus Diseases MATERIALS ： The experiments were carried out in the research room of Xi＇an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK （Military）2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group （n =5）, laser group （n =5）, hematoporphyrin derivative （HPD） group and AION group （n =15）, each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS： In the AION group, the rats were injected with HPD （10 mg/kg） via caudal vein, and then the optic discs were exposed to krypton red （647 nm, 80 mV） for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red （647 rim, 80 mV） for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD （10 mg/kg） via caudal vein; Those in the blank control group were untouched. （1） Visual electrophysiological test： The F-VEP was used to evaluate the function of visual nerve. （2） FFA： After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution （1 mL/kg） was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. （3） After mydriasis and anesthesia as describe above, the rats were examined with OCT. （4） Histological observation： After hematoxylin and eosin （HE） staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES： The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS： Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. （1） Changes in fundus： In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. （2） FFA results： In the AION group, early ＂low fluorescence＂, middle and late ＂high fluorescence＂ were observed in upper optic disc 1 day after model establishment, and there was ＂low fluorescence＂ at 6 days, and the low fluorescence could be observed all the time at 23 days. （3） Visual electrophysiological changes： In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [（71.65±8.81）, （57.58±8.38） ms, t =3.148, P =0.012], and decreased wave amplitude [（4.77±1.90）, （10.06±3.66） μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. （4） OCT results： In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. （5） Histopathological results： At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION ： The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation （647 nm） at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.

A Modified Monte Carlo Model of Speckle Tracking of Shear Wave Induced by Acoustic Radiation Force for Acousto-Optic Elasticity Imaging

A modified Monte Carlo model of speckle tracking of shear wave propagation in scattering media is proposed. The established Monte Carlo model mainly concerns the variations of optical electric field and speckle. The two- dimensional intensity distribution and the time evolution of speckles in different probe locations are obtained. The fluctuation of speckle intensity tracks the acoustic-radiation-force shear wave propagation, and especially the reduction of speckle intensity implies attenuation of shear wave. Then, the shear wave velocity is estimated quantitatively on the basis of the time-to-peak algorithm and linear regression processing. The results reveal that a smaller sampling interval yields higher estimation precision and the shear wave velocity is estimated more efficiently by using speckle intensity difference than by using speckle contrast difference according to the estimation error. Hence, the shear wave velocity is estimated to be 2.25 m/s with relatively high accuracy for the estimation error reaches the minimum （0.071）.

A STUDY ON THE RELIABILITY OF SHORT-TERM AFB_(1)-INDUCED HEPATOCARCINOGENESIS TEST MODEL

In order to test the reliability of γ-GT foci(γ-glutamyltranspeptidase positive hepatocyticfoci) as a preneoplastic marker in AFB-inducedhepatocarcinogenesis, this experiment was car-ried out for a long period after a short-term invivo test model of AFB-induced hepatocarcino-

Modification by Polychlorinated Biphenyls(PCBs)of Cadmium Induced Lesions in the Planarian Model,Dugesia dorotocephala

The appearance of abnormal growths on the planarian, Dugesia dorotocephala, in response to cadmium with and without pre-exposure to L-buthionine-R, S-sulfoximine (BSO) and concurrent exposure to the polychlorinated biphenyls (PCBs) Aroclor 1254, PCB 28, PCB 110 or PCB 126 is described. Pigmented rose thorn (PRT) lesions were non-invasive and appeared in response to PCBs. Post-head (PH) lesions developed in up to 100% of the animals within 6-20 days post-dosing, progressed rather rapidly and were highly invasive. Round tail tip (RTT) lesions appeared in lower frequencies within 10-30 days, but progressed extremely rapidly resulting in tail loss within 48 h. We have referred to these types of lesions as 'tumors', but they are not necessarily characteristic of vertebrate neoplasms.PCBs interacted with cadmium in a complex way, in some cases increasing total lesions and decreasing time-to-lesion and in other cases having the opposite effects. A three-factor (PCB, PCB dose, Cd dose) nested analysis of variance model was used to determine lesion rates in order to compare PCB potencies as potentiators or antagonists. The Aroclor mixture was always the least potent co-toxicant but appeared to be the most potent antagonist; the coplanar PCB 126 was the most potent co-toxicant. The complex response surfaces and the lack of stoichiometry in dose-response relationships indicate that multiple mechanisms are responsible for PH and RTT lesions in planarians. These results emphasize the complexity of PCB toxicities and suggest further studies to validate the planarian model as a screen for combinations or environmental mixtures which may have altered biological potency in other species.

Statistical Modeling of Gate Capacitance Variations Induced by Random Dopants in Nanometer MOSFETs Reserving Correlations

We consider intrinsic gate capacitance variations due to random dopants in the nanometer metal oxide semi- conductor field effect transistor （MOSFET） channel. The variations of total gate capacitance and gate transcapacitances are investigated and the strong correlations between the trans-capacitance variations are discovered. A simple statistical model is proposed for accurately capturing total gate capacitance variability based on the correlations. The model fits very well with the Monte Carlo simulations and the average errors are -0.033% for n-type metal-oxide semiconductor and -0.012% for p-type metal-oxide semiconductor, respectively. Our simulation studies also indicate that, owing to these correlations, the total gate capacitance variability will not dominate in gate capacitance variations.

Human induced pluripotent stem cell based in vitro models of the blood-brain barrier： the future standard？

There is an urgent and tremendous need for human dis- ease models in drug development in order to improve pre- clinical predictability. In the case of brain disorders drugs have to cross the blood-brain barrier （BBB） to enter the central nervous system （CNS）. It was estimated that more than 95% of the drugs cannot cross the BBB.

Study on the hepatocellular carcinoma model with metastasis

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated death around the world due to advanced clinical stage at diagnosis,high incidence of recurrence and metastasis after surgical treatment.It is in urgent need to create appropriate animal models to explore the mechanism,patterns,risk factors,and therapeutic strategies of HCC metastasis and recurrence.However,most of the established models lack the phenotype of invasion and metastasis in patient,or have unstable phenotype.To establish HCC models with stable metastasis phenotype requires profound understanding in cancer metastasis biology and scientific methodology.Over the past 3 decades,HCC models with stable metastasis have been extensively studied.This paper reviewed the history and development of HCC animal models and cell models,focusing on the screening and maintaining of metastatic potential and phenotype.In-depth studies using these models vastly promote the understanding of cellular and molecular mechanisms and development of therapeutic strategies on HCC metastasis.

Theoretical and numerical analysis of coherent Smith-Purcell radiation

Coherent enhancement of Smith-Purcell radiation has attracted people＇s attention not only in adopting a better source but also in beam diagnostics aspect. In this paper, we study the intrinsic mechanism of coherent Smith-Purcell radiation on the basis of the van den Berg model. The emitted power of Smith-Purcell radiation is determined by the bunch profile in transverse and longitudinal directions. For short bunch whose longitudinal pulse length is comparable with the radiation wavelength, it can be concluded approximately that the power is proportional to the square number of electrons per bunch.