Polymeric photosensitizer-embedded self-expanding metal stent for repeatable endoscopic photodynamic therapy of cholangiocarcinoma

Photodynamic therapy (PDT) is a new therapeutic approach for the palliative treatment of malignant bile duct obstruction. In this study, we designed photosensitizer-embedded self-expanding nonvascular metal stent (PDT-stent) which allows repeatable photodynamic treatment of cholangiocarcinoma without systemic injection of photosensitizer. Polymeric photosensitizer (pullulan acetate-conjugated pheophorbide A; PPA) was incorporated in self-expanding nonvascular metal stent. Residence of PPA in the stent was estimated in buffer solution and subcutaneous implantation on mouse. Photodynamic activity of PDT-stent was evaluated through laserexposure on stent-layered tumor cell lines, HCT-116 tumor-xenograft mouse models and endoscopic intervention of PDT-stent on bile duct of mini pigs. Photo-fluorescence imaging of the PDT-stent demonstrated homogeneous embedding of polymeric Pheo-A (PPA) on stent membrane. PDT-stent sustained its photodynamic activities at least for 2 month. And which implies repeatable endoscopic PDT is possible after stent emplacement. The PDT-stent after light exposure successfully generated cytotoxic singlet oxygen in the surrounding tissues, inducing apoptotic degradation of tumor cells and regression of xenograft tumors on mouse models. Endoscopic biliary in-stent photodynamic treatments on minipigs also suggested the potential efficacy of PDT-stent on cholangiocarcinoma. In vivo and in vitro studies revealed our PDT-stent, allows repeatable endoscopic biliary PDT, has the potential for the combination therapy (stent plus PDT) of cholangiocarcinoma. © 2014 Elsevier Ltd.

Levels of glucose and triglycerides in seminal plasma and spermatic motility in guinea pig fed with 10% more in digestible energy

The objective the study was to determine the levels of glucose and triglycerides in seminal plasma of 10 guinea pigs, which were fed for a period of 2 months with a diet containing 10% more ED. The level of glucose found in seminal plasma was 11.59 ± 0.5 mg/dL and triglyceride value was 55.95 ± 3.2 mg/dL, while the motility was 97% on average. We conclude that in guinea pigs the levels both glucose and triglycerides were increased by major level of ED in feed, but the spermatic motility was not.

Particle Image Velocimetry Investigation of a finite amplitude pressure wave

Particle image velocimetry is used to study the motion of gas within a duct subject to the passage of a finite amplitude pressure wave. The wave is representative of the pressure waves found in the exhaust systems of internal combustion engines. Gas particles are accelerated from stationary to 150 m/s and then back to stationary in 8 ms. It is demonstrated that gas particles at the head of the wave travel at the same velocity across the duct cross section at a given point in time. Towards the tail of the wave viscous effects are plainly evident causing the flow profile to tend towards parabolic. However, the instantaneous mean particle velocity across the section is shown to match well with the velocity calculated from a corresponding measured pressure history using 1D gas dynamic theory. The measured pressure history at a point in the duct was acquired using a high speed pressure transducer of the type typically used for engine research in intake and exhaust systems. It is demonstrated that these are unable to follow the rapid changes in pressure accurately and that they are prone to resonate under certain circumstances.

Wideband measurement of the acoustic impedance of tubular objects

A method is discussed for measuring the acoustic impedance of tubular objects that gives accurate results for a wide range of frequencies. The apparatus that is employed is similar to that used in many previously developed methods; it consists of a cylindrical measurement duct fitted with several microphones, of which two are active in each measurement session, and a driver at one of its ends. The object under study is fitted at the other end. The impedance of the object is determined from the microphone signals obtained during excitation of the air inside the 1 duct by the driver, and from three coefficients that are pre-determined using four calibration measurements with closed cylindrical tubes. The calibration procedure is based on the simple mathematical relationships between the impedances of the calibration tubes, and does not require knowledge of the propagation constant. Measurements with a cylindrical tube yield an estimate of the attenuation constant for plane waves, which is found to differ from the theoretical prediction by less than 1.4% in the frequency range 1 kHz-20 kHz. Impedance measurements of objects with abrupt changes in diameter are found to be in good agreement with multimodal theory.

Time domain wave separation using multiple microphones

Methods of measuring the acoustic behavior of tubular systems can be broadly characterized as steady state measurements, where the measured signals are analyzed in terms of infinite duration sinusoids, and reflectometry measurements which exploit causality to separate the forward and backward going waves in a duct. This paper sets out a multiple microphone reflectometry technique which performs wave separation by using time domain convolution to track the forward and backward going waves in a cylindrical source tube. The current work uses two calibration runs (one for forward going waves and one for backward going waves) to measure the time domain transfer functions for each pair of microphones. These time domain transfer functions encode the time delay, frequency dependent losses and microphone gain ratios for travel between microphones. This approach is applied to the measurement of wave separation, bore profile and input impedance. The work differs from existing frequency domain methods in that it combines the information of multiple microphones within a time domain algorithm, and differs from existing time domain methods in its inclusion of the effect of losses and gain ratios in intermicrophone transfer functions.

Collagenolytic Activities of the Major Secreted Cathepsin L Peptidases Involved in the Virulence of the Helminth Pathogen, Fasciola hepatica

The temporal expression and secretion of distinct members of a family of virulence-associated cathepsin L cysteine peptidases (FhCL) correlates with the entry and migration of the helminth pathogen Fasciola hepatica in the host. Thus, infective larvae traversing the gut wall secrete cathepsin L3 (FhCL3), liver migrating juvenile parasites secrete both FhCL1 and FhCL2 while the mature bile duct parasites, which are obligate blood feeders, secrete predominantly FhCL1 but also FhCL2.

Gross anatomy of the muscle systems of Fasciola hepatica as visualized by phalloidin-fluorescence and confocal microscopy

Neuropeptides, biogenic amines and acetylcholine are expressed abundantly within the nervous systems of parasitic flatworms, and are particularly evident in the innervation of the musculature. Such associations have implicated the nervous system in locomotion, host attachment and reproductive co-ordination. Information on the muscle systems of parasitic flatworms is generally sparse, in particular those muscles associated with the reproductive system, intestinal tract and attachment apparatus. Also, the use of sectioned material has left description of the 3-dimensional organization of the musculature largely unrecorded. Using fluorescein isothiocyanate (FITC)-labelled phalloidin as a site-specific probe for filamentous actin, applied to whole-mount preparations of adult Fasciola hepatica and examined by confocal scanning laser microscopy, the present work reports on the organization of the major muscle systems in this trematode parasite. A highly regular array of outer circular, intermediate longitudinal and inner diagonal fibres distinguishes the body wall musculature, which is also involved in the development of both ventral and oral suckers. Circular fibres dominate the duct walls of the male and female reproductive systems, whereas the muscles of the intestinal tract have a somewhat diffuse arrangement of fibres. An understanding of the structural complexity of the muscle systems of parasitic flatworms is considered as fundamental to the interpretation of results from physiological experiments.

Does prophylactic endoscopic sphincterotomy prevent recurrent biliary problems in patients with gallstones and a normal cholangiogram?

Endoscopic sphincterotomy (ES) is indicated in patients with confirmed bile duct stones at endoscopic retrograde cholangiopancreatography (ERCP). The role of ES in patients with suspected bile duct stones but a normal cholangiogram, in the prevention of recurrent biliary symptoms, when cholecystectomy is not planned, is unclear.

Cathepsin F cysteine protease of the human liver fluke, Opisthorchis viverrini

The liver fluke Opisthorchis viverrini is classified as a class I carcinogen due to the association between cholangiocarcinoma and chronic O. viverrini infection. During its feeding activity within the bile duct, the parasite secretes several cathepsin F cysteine proteases that may induce or contribute to the pathologies associated with hepatobiliary abnormalities.

Development of the vitellaria of the liver fluke, Fasciola hepatica in the rat host

The development of the vitellaria of Fasciola hepatica within the liver of its rat host was studied by means of whole-mount stained preparations and transmission electron microscopy, together with light and electron immunocytochemistry using an antibody to vitelline protein B, an eggshell precursor protein synthesized by F. hepatica. No vitelline cells could be identified in flukes recovered from the liver parenchyma, by any of the methods used. In contrast, follicles were present in flukes at the earliest time of recovery from the bile duct, namely, 5 weeks 3 days post-infection. The vitellaria in these flukes formed a row of small follicles on either side of the body. Development of the follicles was rapid: by 6 weeks 3 days, the vitellaria resembled those in the adult fluke and eggs were present in the uterus. Immunolabelling was confined to the shell protein globules in the vitelline cells, confirming the packaging of the eggshell protein within the shell globule clusters.

Blown Jet Vortex Generator Control of a Separated Diffuser Flow

The application of blown jet vortex generators to control flow separation in a diffuser with an opening angle of 10° has been studied using the computational fluid dynamics (CFD) code Fluent 6™. Experimental data is available for the uncontrolled flow in the diffuser. The section of the duct upstream of the diffuser has a height H equal to 15 mm; its length and breadth are 101H and 41H respectively; the diffuser has an expansion ratio of 4.7:1. Fully developed flow is achieved upstream of the diffuser. Pipes of diameters equal to 1.5%, 2.5% and 5% of H were considered; pitch angle was constant at 45° and yaw angle was fixed at 60°; velocity ratio was varied from 1.7 to 8.0; both co-rotating and counter-rotating arrays were studied. The best results were obtained with a counter-rotating array of generators with a hole diameter of 5% of H and a velocity ratio of 3.7.

Multi-access communication system in a highly reverberant environment

We investigate by numerical EM simulation the potential communication channel capacity of a reverberant environment using the time reversal approach, excited at 2.4 GHz by ON-OFF keyed RF pulse excitation. It is shown that approximately 725 1.25MHz propagation channels can be allocated with the cavity contains a 4×4 ? or 1×1 ? LOS obstruction positioned between the transceiver antenna and the time reversal unit. Furthermore the results show that two co-located transceiver dipoles separated by a spacing of 3?/4 can successfully resolve a 10ns pulse. Our findings suggest that different independent channels with identical operating frequency can be realized in an enclosed environment such as ventilation duct or underground tunnel. This suggests that there is a possibility of implementing a parallel channel radio link with the minimum inter-antenna spacing of 3?/4 between the transceivers in a rich multipath environment. © 2012 IEEE.

Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium

The basic helix-loop-helix protein achaete-scute homolog-1 (ASH1) is involved in lung neuroendocrine (NE) differentiation and tumor promotion in SV40 transgenic mice. Constitutive expression of human ASH-1 (hASH1) in mouse lung results in hyperplasia and remodeling that mimics bronchiolization of alveoli (BOA), a potentially premalignant lesion of human lung carcinomas. We now show that this is due to sustained cellular proliferation in terminal bronchioles and resistance to apoptosis. Throughout the airway epithelium the expression of anti-apoptotic Bcl-2 and c-Myb was increased and Akt/mTOR pathway activated. Moreover, the expression of matrix metalloproteases (MMPs) including MMP7 was specifically enhanced at the bronchiolo-alveolar duct junction and BOA suggesting that MMPs play a key role in this microenvironment during remodeling. We also detected MMP7 in 70% of human BOA lesions. Knockdown of hASH1 gene in human lung cancer cells in vitro suppressed growth by increasing apoptosis. We also show that forced expression of hASH1 in immortalized human bronchial epithelial cells decreases apoptosis. We conclude that the impact of hASH1 is not limited to cells with NE phenotype. Rather, constitutive expression of hASH1 in lung epithelium promotes remodeling through multiple pathways that are commonly activated during lung carcinogenesis. The collective results suggest a novel model of BOA formation via hASH1-induced suppression of the apoptotic pathway. Our study yields a promising new preclinical tool for chemoprevention of peripheral lung carcinomas. © 2007 USCAP, Inc All rights reserved.

Adaptive calibration of a three-microphone system for acoustic waveguide characterization under time-varying conditions

The pressure and velocity field in a one-dimensional acoustic waveguide can be sensed in a non-intrusive manner using spatially distributed microphones. Experimental characterization with sensor arrangements of this type has many applications in measurement and control. This paper presents a method for measuring the acoustic variables in a duct under fluctuating propagation conditions with specific focus on in-system calibration and tracking of the system parameters of a three-microphone measurement configuration. The tractability of the non-linear optimization problem that results from taking a parametric approach is investigated alongside the influence of extraneous measurement noise on the parameter estimates. The validity and accuracy of the method are experimentally assessed in terms of the ability of the calibrated system to separate the propagating waves under controlled conditions. The tracking performance is tested through measurements with a time-varying mean flow, including an experiment conducted under propagation conditions similar to those in a wind instrument during playing.

Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway

Müllerian inhibiting substance (MIS), a member of the transforming growth factor-beta superfamily, induces regression of the Müllerian duct in male embryos. In this report, we demonstrate MIS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G(1) phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFkappaB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IkappaBalpha expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFkappaB signaling pathway was required for these processes. These results identify the NFkappaB-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers.