Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.

Science.gov (United States)

Martel, Marc O; Wasan, Ajay D; Edwards, Robert R

2013-11-01

To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function. Wiley Periodicals, Inc.

Using Apex To Construct CPM-GOMS Models

Science.gov (United States)

John, Bonnie; Vera, Alonso; Matessa, Michael; Freed, Michael; Remington, Roger

2006-01-01

process for automatically generating computational models of human/computer interactions as well as graphical and textual representations of the models has been built on the conceptual foundation of a method known in the art as CPM-GOMS. This method is so named because it combines (1) the task decomposition of analysis according to an underlying method known in the art as the goals, operators, methods, and selection (GOMS) method with (2) a model of human resource usage at the level of cognitive, perceptual, and motor (CPM) operations. CPM-GOMS models have made accurate predictions about behaviors of skilled computer users in routine tasks, but heretofore, such models have been generated in a tedious, error-prone manual process. In the present process, CPM-GOMS models are generated automatically from a hierarchical task decomposition expressed by use of a computer program, known as Apex, designed previously to be used to model human behavior in complex, dynamic tasks. An inherent capability of Apex for scheduling of resources automates the difficult task of interleaving the cognitive, perceptual, and motor resources that underlie common task operators (e.g., move and click mouse). The user interface of Apex automatically generates Program Evaluation Review Technique (PERT) charts, which enable modelers to visualize the complex parallel behavior represented by a model. Because interleaving and the generation of displays to aid visualization are automated, it is now feasible to construct arbitrarily long sequences of behaviors. The process was tested by using Apex to create a CPM-GOMS model of a relatively simple human/computer-interaction task and comparing the time predictions of the model and measurements of the times taken by human users in performing the various steps of the task. The task was to withdraw $80 in cash from an automated teller machine (ATM). For the test, a Visual Basic mockup of an ATM was created, with a provision for input from (and measurement

Integral transport computation of gamma detector response with the CPM2 code

International Nuclear Information System (INIS)

Jones, D.B.

1989-12-01

CPM-2 Version 3 is an enhanced version of the CPM-2 lattice physics computer code which supports the capabilities to (1) perform a two-dimensional gamma flux calculation and (2) perform Restart/Data file maintenance operations. The Gamma Calculation Module implemented in CPM-2 was first developed for EPRI in the CASMO-1 computer code by Studsvik Energiteknik under EPRI Agreement RP2352-01. The gamma transport calculation uses the CPM-HET code module to calculate the transport of gamma rays in two dimensions in a mixed cylindrical-rectangular geometry, where the basic fuel assembly and component regions are maintained in a rectangular geometry, but the fuel pins are represented as cylinders within a square pin cell mesh. Such a capability is needed to represent gamma transport in an essentially transparent medium containing spatially distributed ''black'' cylindrical pins. Under a subcontract to RP2352-01, RPI developed the gamma production and gamma interaction library used for gamma calculation. The CPM-2 gamma calculation was verified against reference results generated by Studsvik using the CASMO-1 program. The CPM-2 Restart/Data file maintenance capabilities provide the user with options to copy files between Restart/Data tapes and to purge files from the Restart/Data tapes

Coded Aperture Nuclear Scintigraphy: A Novel Small Animal Imaging Technique

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Dawid Schellingerhout

2002-10-01

Full Text Available We introduce and demonstrate the utility of coded aperture (CA nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 × 103 cps/Bq (9400 cpm/μCi, compared to 4.4 × 104 cps/Bq (990 cpm/μCi for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4–6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator. Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.

ROLAIDS-CPM, 1-D Slowing-Down by Collision Problems Method

International Nuclear Information System (INIS)

De Kruijf, W.J.M.

2002-01-01

1 - Description of program or function: ROLAIDS-CPM is based on the AMPX-module ROLAIDS (PSR-315). CPM stands for Collision Probability Method. ROLAIDS is a one-dimensional slowing-down code which uses the interface currents method. ROLAIDS-CPM does not need the assumption of cosine currents at the interface of the zones. Extensions: collision probability method for slab and cylinder geometry; different temperatures for a nuclide can be used; flat lethargy source can be modelled. 2 - Method of solution: Collision probabilities in cylindrical geometry are calculated according to the Carlvik Method. This means that a Gauss integration is used. 3 - Restrictions on the complexity of the problem: The maximum number of zones is 30 for the collision probability method

Trellis coding with Continuous Phase Modulation (CPM) for satellite-based land-mobile communications

Science.gov (United States)

1989-01-01

This volume of the final report summarizes the results of our studies on the satellite-based mobile communications project. It includes: a detailed analysis, design, and simulations of trellis coded, full/partial response CPM signals with/without interleaving over various Rician fading channels; analysis and simulation of computational cutoff rates for coherent, noncoherent, and differential detection of CPM signals; optimization of the complete transmission system; analysis and simulation of power spectrum of the CPM signals; design and development of a class of Doppler frequency shift estimators; design and development of a symbol timing recovery circuit; and breadboard implementation of the transmission system. Studies prove the suitability of the CPM system for mobile communications.

Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

Science.gov (United States)

Horn-Hofmann, Claudia; Priebe, Janosch A; Schaller, Jörg; Görlitz, Rüdiger; Lautenbacher, Stefan

2016-12-01

In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

In vivo binding of a radioiodinated derivative of SCH 23390 (SCH)

International Nuclear Information System (INIS)

McQuade, R.D.; Iorio, L.C.; Chipkin, R.E.; Barnett, A.

1986-01-01

The in vitro binding properties of SCH have been extensively characterized, however, little research has been conducted on its in vivo binding profile. This report is on the characterization of the in vivo binding of 7- 125 I-SCH (71 SCH), which possesses a specific radioactivity of 2200 Ci/mmole and exhibits in vitro binding properties similar to those of 3 H-SCH. Sprague-Dawley rats were injected with 0.02 nmoles of 7ISH, in the absence and presence of 30 nmoles of unlabeled SCH, and were sacrificed at 1,2 and 4 hours post-treatment. The striatum and cerebellum were removed, weighed and the radioactivity was counted. Specific binding was defined as cpm in the absence of SCH less cpm in the presence of SCH. One hour after injection, the striatum of the rats treated with 7ISCH contained 170,000 cpm/g tissue, of which 105,000 cpm/g tissue were specific. The cerebellum of the rats contained 75% fewer cpm/g tissue and did not exhibit specifically bound in the striatum, but not in the cerebellum. Sacrifice after longer periods of time resulted in a 35% decrease in specific binding between 1 and 2 h, and a 70% decrease between 1 and 4 h. The pharmacological profile of the in vivo binding of 7ISCH was determined by the ability of dopaminergic antagonists to inhibit specific binding in the rat striatum 1 h after treatment. Thirty nmoles of SCH caused a 55% inhibition of the specific binding to striatum, while an equal amount of SCH 23388, the inactive S isomer of SCH, resulted in no inhibition. Haloperidol, a D-2 antagonist, did not inhibit the specific binding of 7ISCH to the striatum at doses up to 3000 nmoles. These data indicate that 7ISCH is specifically bound, in vivo, to D-1 receptors in the rat striatum

RETRACTED ARTICLE: Clinical effectiveness of continuous passive motion (CPM) following femoroacetabular impingement surgery in adolescents.

Science.gov (United States)

Hosalkar, Harish; Bomar, James D

2012-08-01

This study hypothesizes that the use of continuous passive motion (CPM) following open femoroacetabular impingement (FAI) surgery in the adolescent population improves clinical outcomes in terms of the modified Harris hip score (mHHS). Twenty-nine symptomatic adolescent FAI patients were postoperatively divided into one of three groups; no CPM, two days of inpatient CPM, and two weeks of CPM. mHHS was used preoperatively and postoperatively at six weeks, three months, six months, and nine months in all cases. Kruskal-Wallis (KW) analysis was performed to determine statistical differences in mHHS. mHHS was then re-evaluated using the Mann-Whitney test. There were no statistically significant differences in hip scores between the three groups preoperatively (p = 0.158). There were statistically significant differences (p CPM had the best outcome scores. The results of this study suggest that postoperative CPM use following open hip preservation surgery for symptomatic FAI in adolescents improves clinical outcomes. These benefits seem to be related to the duration of CPM. Retrospective comparative study, Level III. Patients treated one way compared with patients treated another way at the same institution.

Purification and characterization of a serine protease (CPM-2) with fibrinolytic activity from the dung beetles.

Science.gov (United States)

Ahn, Mi Young; Hahn, Bum-Soo; Ryu, Kang Sun; Hwang, Jae Sam; Kim, Yeong Shik

2005-07-01

Catharsius protease-2 (CPM-2) was isolated from the body of dung beetles, Catharsius molossus, using a three step purification process (ammonium sulfate fractionation, gel filtration on Bio-Gel P-60, and affinity chromatography on DEAE Affi-Gel blue). The purified CPM-2, having a molecular weight of 24 kDa, was assessed homogeneously by SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of CPM-2 was composed of X Val Gln Asp Phe Val Glu Glu Ile Leu. CPM-2 was inactivated by Cu2+ and Zn2+ and strongly inhibited by typical serine proteinase inhibitors such as TLCK, soybean trypsin inhibitor, aprotinin, benzamidine, and alpha1-antitrypsin. However, EDTA, EGTA, cysteine, beta-mercaptoethanol, E64, and elastatinal had little effect on enzyme activity. In addition, antiplasmin and antithrombin III were not sensitive to CPM-2. Based on the results of a fibrinolytic activity test, CPM-2 readily cleaved Aalpha- and Bbeta-chains of fibrinogen and fibrin, and gamma-chain of fibrinogen more slowly. The nonspecific action of the enzyme resulted in extensive hydrolysis, releasing a variety of fibrinopeptides of fibrinogen and fibrin. Polyclonal antibodies of CPM-2 were reactive to the native form of antigen. The ELISA was applied to detect quantities, in nanograms, of the antigen in CPM-2 protein.

Information System Design Methodology Based on PERT/CPM Networking and Optimization Techniques.

Science.gov (United States)

Bose, Anindya

The dissertation attempts to demonstrate that the program evaluation and review technique (PERT)/Critical Path Method (CPM) or some modified version thereof can be developed into an information system design methodology. The methodology utilizes PERT/CPM which isolates the basic functional units of a system and sets them in a dynamic time/cost…

NODAL interpreter for CP/M

International Nuclear Information System (INIS)

Oide, Katsunobu.

1982-11-01

A NODAL interpreter which works under CP/M operating system is made for microcomputers. This interpreter language named NODAL-80 has a similar structure to the NODAL of SPS, but its commands, variables, and expressions are modified to increase the flexibility of programming. NODAL-80 also uses a simple intermediate code to make the execution speed fast without imposing any restriction on the dynamic feature of NODAL language. (author)

Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells

International Nuclear Information System (INIS)

Ettinghausen, S.E.; Lipford, E.H. III; Mule, J.J.; Rosenberg, S.A.

1985-01-01

The authors previously reported that the adoptive transfer of lymphokine-activated killer (LAK) cells plus repetitive injections of recombinant interleukin 2 (IL 2) produced a marked reduction in established pulmonary metastases from a variety of murine sarcomas. The requirement for the exogenous administration of IL 2 prompted a subsequent examination of the role of IL 2 in the in vivo function of transferred LAK cells. The in vivo proliferation and migration patterns of lymphoid cells in C57BL/6 mice were examined after i.v. transfer of LAK cells alone, i.p. injection of IL 2 alone, or the combination of LAK cells and IL 2. A model for in vivo labeling of the DNA of dividing cells was used in which mice were injected with 5-[ 125 I]-iodo-2'-deoxyuridine ( 125 IUdR) and, 20 hr later, their tissues were removed and were counted in a gamma analyzer. A proliferation index (PI) was calculated by dividing the mean cpm of organs of experimentally treated mice by the mean cpm of organs of control mice. In animals given LAK cells alone, the lungs and liver demonstrated little if any uptake of 125 IUdR above saline-treated controls, whereas the same organs of mice receiving 6000 U of IL 2 alone displayed higher radiolabel incorporation. When mice were given LAK cells plus 6000 U of IL 2, their tissues showed an additional increase in 125 IUdR uptake

Contralateral prophylactic mastectomy (CPM): A systematic review of patient reported factors and psychological predictors influencing choice and satisfaction.

Science.gov (United States)

Ager, Brittany; Butow, Phyllis; Jansen, Jesse; Phillips, Kelly-Anne; Porter, David

2016-08-01

Conduct a systematic review of quantitative and qualitative studies exploring patient reported factors and psychological variables influencing the decision to have contralateral prophylactic mastectomy (CPM), and satisfaction with CPM, in women with early stage breast cancer. Studies were identified via databases: Medline, CINAHL, Embase and PsycINFO. Data were extracted by one author and crosschecked by two additional authors for accuracy. The quality of included articles was assessed using standardised criteria by three authors. Of the 1346 unique citations identified, 17 were studies that met the inclusion criteria. Studies included were primarily cross-sectional and retrospective. No study utilised a theoretical framework to guide research and few studies considered psychological predictors of CPM. Fear of breast cancer was the most commonly cited reason for CPM, followed by cosmetic reasons such as desire for symmetry. Overall, women appeared satisfied with CPM, however, adverse/diminished body image, poor cosmetic result, complications, diminished sense of sexuality, emotional issues and perceived lack of education regarding alternative surveillance/CPM efficacy were cited as reasons for dissatisfaction. Current literature has begun to identify patient-reported reasons for CPM; however, the relative importance of different factors and how these factors relate to the process underlying the decision to have CPM are unknown. Of women who considered CPM, limited information is available regarding differences between those who proceed with or ultimately decline CPM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theoretical study on the gas adsorption capacity and selectivity of CPM-200-In/Mg and CPM-200-In/Mg-X (-X = -NH2, -OH, -N, -F).

Science.gov (United States)

Liu, Xiao-le; Chen, Guang-Hui; Wang, Xiu-Jun; Li, Peng; Song, Yi-Bing; Li, Rui-Yan

2017-11-15

The adsorption capacities of a heterometallic metal-organic framework (CPM-200-In/Mg) to VOCs (HCHO, C 2 H 4 , CH 4 , C 2 H 2 , C 3 H 8 , C 2 H 6 , C 2 H 3 Cl, C 2 H 2 Cl 2 , CH 2 Cl 2 and CHCl 3 ) and some inorganic gas molecules (HCN, SO 2 , NO, CO 2 , CO, H 2 S and NH 3 ), as well as its selectivity in ternary mixture systems of natural gas and post-combustion flue gas are theoretically explored at the grand canonical Monte Carlo (GCMC) and density functional theory (DFT) levels. It is shown that CPM-200-In/Mg is suitable for the adsorption of VOCs, particularly for HCHO (up to 0.39 g g -1 at 298 K and 1 bar), and the adsorption capacities of some inorganic gas molecules such as SO 2 , H 2 S and CO 2 match well with the sequence of their polarizability (SO 2 > H 2 S > CO 2 ). The large adsorption capacities of HCN and HCHO in the framework result from the strong interaction between adsorbates and metal centers, based on analyzing the radial distribution functions (RDF). Comparing C 2 H 4 and CH 4 molecules interacting with CPM-200-In/Mg by VDW interaction, we speculate that the high adsorption capacities of their chlorine derivatives in the framework could be due to the existence of halogen bonding or strong electrostatic and VDW interactions. It is found that the basic groups, including -NH 2 , -N and -OH, can effectively improve both the adsorption capacities and selectivity of CPM-200-In/Mg for harmful gases. Note that the adsorption capacity of CPM-200-In/Mg-NH 2 (site 2) (245 cm 3 g -1 ) for CO 2 exceeded that of MOF-74-Mg (228 cm 3 g -1 ) at 273 K and 1 bar and that for HCHO can reach 0.41 g g -1 , which is almost twice that of 438-MOF and nearly 45 times of that in active carbon. Moreover, for natural gas mixtures, the decarburization and desulfurization abilities of CPM-200-In/Mg-NH 2 (site 2) have exceeded those of the MOF-74 series, while for post-combustion flue gas mixtures, the desulfurization ability of CPM-200-In/Mg-NH 2 (site 2) is still

CPM s prepojením na aplikácie BI

OpenAIRE

Klimko, Jozef

2008-01-01

The bachelor thesis is devoted to the issue of Corporate Performance Management (CPM) as a comprehensive approach to managing performance of the company including processes, metrics, methodologies and technologies. The main aim of the bachelor thesis is to bring out a comprehensive view to the questions of Corporate Performance Management, analyse the market and neccessery parts of CPM. The thesis is based on available literature and internet sources dealing with this topic. The thesis is com...

[Efficiency of a postoperative treatment after rotator cuff repair with a continuous passive motion device (CPM)].

Science.gov (United States)

Michael, J W-P; König, D P; Imhoff, A B; Martinek, V; Braun, S; Hübscher, M; Koch, C; Dreithaler, B; Bernholt, J; Preis, S; Loew, M; Rickert, M; Speck, M; Bös, L; Bidner, A; Eysel, P

2005-01-01

The main objective of this study was to prove that a postoperative combined continuous passive motion (CPM) and physiotherapy treatment protocol (CPM group) can achieve 90 degrees active abduction in the shoulder joint earlier than physiotherapy alone (PT group). The indication was a complete tear of the rotator cuff. The study was conducted under in-patient and out-patient conditions. 55 patients were included in this study. The prospective, randomized multicenter study design complies with DIN EN 540. The primary endpoint was the time span until 90 degrees active abduction was achieved by the patients. Patients in the CPM group reached the primary endpoint on average 12 days earlier than the control group. This difference was statistically significant (p = 0.0292). Analyzing the secondary endpoints, e. g., pain and disablement, the results in the CPM group showed again advantages of the combined treatment protocol (CPM + physiotherapy). The postoperative treatment of a total tear of the rotator cuff with a combined continuous passive motion and physiotherapy protocol provided a significantly earlier range of motion in the shoulder joint than physiotherapy alone. There was no report of CPM-related adverse effects.

Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM); Bildgebung bei zentraler pontiner Myelinolyse (CPM) und extrapontiner Myelinolyse (EPM)

Energy Technology Data Exchange (ETDEWEB)

Oergel, Anja; Hauser, Till-Karsten; Naegele, T.; Horger, Marius [Univ. Hospital Tuebingen (Germany). Dept. of Radiology

2017-02-15

CT and NMR Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis were compared with histological results. The clinical appearance and diagnosis using CT and NMR imaging are related to therapy decisions and outcome.

Use of inpatient continuous passive motion versus no CPM in computer-assisted total knee arthroplasty.

Science.gov (United States)

Alkire, Martha R; Swank, Michael L

2010-01-01

Continuous passive motion (CPM) has shown positive effects on tissue healing, edema, hemarthrosis, and joint function (L. Brosseau et al., 2004). CPM has also been shown to increase short-term early flexion and decrease length of stay (LOS) ( L. Brosseau et al., 2004; C. M. Chiarello, C. M. S. Gundersen, & T. O'Halloran, 2004). The benefits of CPM for the population of patients undergoing computer-assisted total knee arthroplasty (TKA) have not been examined. The primary objective of this study was to determine whether the use of CPM following computer-assisted TKA resulted in differences in range of motion, edema/drainage, functional ability, and pain. This was an experimental, prospective, randomized study of patients undergoing unilateral, computer-assisted TKA. The experimental group received CPM thrice daily and physical therapy (PT) twice daily during their hospitalization. The control group received PT twice daily and no CPM during the hospital stay. Both groups received PT after discharge. Measurement included Knee Society scores, Western Ontario McMaster Osteoarthritis Index values, range of motion, knee circumference, and HemoVac drainage. Data were collected at various intervals from preoperatively through 3 months. Although the control group was found to be higher functioning preoperatively, there was no statistically significant difference in flexion, edema or drainage, function, or pain between groups through the 3-month study period.

Global restructuring of the CPM-2 transport algorithm for vector and parallel processing

International Nuclear Information System (INIS)

Vujic, J.L.; Martin, W.R.

1989-01-01

The CPM-2 code is an assembly transport code based on the collision probability (CP) method. It can in principle be applied to global reactor problems, but its excessive computational demands prevent this application. Therefore, a new transport algorithm for CPM-2 has been developed for vector-parallel architectures, which has resulted in an overall factor of 20 speedup (wall clock) on the IBM 3090-600E. This paper presents the detailed results of this effort as well as a brief description of ongoing effort to remove some of the modeling limitations in CPM-2 that inhibit its use for global applications, such as the use of the pure CP treatment and the assumption of isotropic scattering

CPM Pairs from LSPM so far not WDS Listed – Part II

Science.gov (United States)

Knapp, Wilfried; Nanson, John

2017-10-01

The LSPM catalog (Lepine and Shara 2005) is a rich source for CPM pairs we thought already exhausted – but as we found during research for our report “A new concept for counter-checking of assumed CPM pairs” (Knapp and Nanson 2017) there are still many poten-tial CPM pairs indicated in LSPM which as of the end of 2016 are not listed in the WDS cata-log. After our first part on about 40 such objects (Knapp and Nanson 2017) the next report with about 30 additional common proper motion pairs is presented here.

CPM Pairs from LSPM so far not WDS Listed – Part III

Science.gov (United States)

Knapp, Wilfried; Nanson, John

2017-10-01

The LSPM catalog (Lepine and Shara 2005) is a rich source for CPM pairs we thought already exhausted – but as we found during research for our report “A new concept for counter-checking of assumed CPM pairs” (Knapp and Nanson 2017) there are still many poten-tial CPM pairs indicated in LSPM which as of the end of 2016 are not listed in the WDS cata-log. After our first two reports on in total about 70 such objects (Knapp and Nanson 2017) the next paper with about 25 additional potential common proper motion pairs is presented here.

Sealing ability of MTA, CPM, and MBPc as root-end filling materials: a bacterial leakage study.

Science.gov (United States)

Medeiros, Paulo Leal; Bernardineli, Norberti; Cavenago, Bruno Cavalini; Torres, Sérgio Aparecido; Duarte, Marco Antonio Hungaro; Bramante, Clovis Monteiro; Marciano, Marina Angélica

2016-04-01

Objectives To evaluate the sealing ability of three root-end filling materials (white MTA, CPM, and MBPc) using an Enterococcus faecalis leakage model. Material and Methods Seventy single-root extracted human teeth were instrumented and root-ends were resected to prepare 3 mm depth cavities. Root-end preparations were filled with white MTA, CPM, and MBPc cements. Enterococcus faecalis was coronally introduced and the apical portion was immersed in BHI culture medium with phenol red indicator. The bacterial leakage was monitored every 24 h for 4 weeks. The statistical analysis was performed using the Wilcoxon-Gehan test (pCPM and the other groups. Conclusions The epoxy resin-based cement MBPc had lower bacterial leakage compared with the calcium silicate-based cements MTA and CPM.

In Vivo Respiratory-Gated Micro-CT Imaging in Small-Animal Oncology Models

Directory of Open Access Journals (Sweden)

Dawn Cavanaugh

2004-01-01

Full Text Available Micro-computed tomography (micro-CT is becoming an accepted research tool for the noninvasive examination of laboratory animals such as mice and rats, but to date, in vivo scanning has largely been limited to the evaluation of skeletal tissues. We use a commercially available micro-CT device to perform respiratory gated in vivo acquisitions suitable for thoracic imaging. The instrument is described, along with the scan protocol and animal preparation techniques. Preliminary results confirm that lung tumors as small as 1 mm in diameter are visible in vivo with these methods. Radiation dose was evaluated using several approaches, and was found to be approximately 0.15 Gy for this respiratory-gated micro-CT imaging protocol. The combination of high-resolution CT imaging and respiratory-gated acquisitions appears well-suited to serial in vivo scanning.

Evaluation of the constant pressure panel method (CPM) for unsteady air loads prediction

Science.gov (United States)

Appa, Kari; Smith, Michael J. C.

1988-01-01

This paper evaluates the capability of the constant pressure panel method (CPM) code to predict unsteady aerodynamic pressures, lift and moment distributions, and generalized forces for general wing-body configurations in supersonic flow. Stability derivatives are computed and correlated for the X-29 and an Oblique Wing Research Aircraft, and a flutter analysis is carried out for a wing wind tunnel test example. Most results are shown to correlate well with test or published data. Although the emphasis of this paper is on evaluation, an improvement in the CPM code's handling of intersecting lifting surfaces is briefly discussed. An attractive feature of the CPM code is that it shares the basic data requirements and computational arrangements of the doublet lattice method. A unified code to predict unsteady subsonic or supersonic airloads is therefore possible.

Design of Multiple Trellis-Coded Multi-h CPM Based on Super Trellis

Directory of Open Access Journals (Sweden)

X. Liu. A. Liu

2012-12-01

Full Text Available It has been shown that the multiple trellis code can perform better than the conventional trellis code over AWGN channels, at the cost of additional computations per trellis branch. Multiple trellis coded multi-h CPM schemes have been shown in the literature to have attractive power-bandwidth performance at the expense of increased receiver complexity. In this method, the multi-h format is made to be associated with the specific pattern and repeated rather than cyclically changed in time for successive symbol intervals, resulting in a longer effective length of the error event with better performance. It is well known that the rate (n-1/n multiple trellis codes combined with 2^n-level CPM have good power-bandwidth performance. In this paper, a scheme combining rate 1/2 and 2/3 multiple trellis codes with 4- and 8-level multi-h CPM is shown to have better power-bandwidth performance over the upper bound than the scheme with single-h.

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

Science.gov (United States)

Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David

2011-07-01

For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Histological and histomorphometrical evaluation of furcation perforations filled with MTA, CPM and ZOE.

Science.gov (United States)

da Silva, G F; Guerreiro-Tanomaru, J M; Sasso-Cerri, E; Tanomaru-Filho, M; Cerri, P S

2011-02-01

To evaluate the biological response of the periodontium adjacent to furcation perforations in rat molars filled with Endo-CPM-Sealer (CPM), MTA-Angelus (MTA) or zinc oxide-eugenol cement (ZOE). The pulp chamber floors of maxillary right first molar teeth were perforated and sealed with CPM, mineral trioxide aggregate (MTA) or ZOE; the left first molars, without any treatment, were used as controls (CG). After 7, 15, 30 and 60 days, fragments of maxilla were fixed, decalcified and embedded in paraffin. Sections were stained with H&E, Masson's trichrome and submitted to tartrate-resistant acid phosphatase (TRAP) reaction, used as an osteoclast marker. The width of the periodontal space, the numerical density of inflammatory cells and the number of TRAP-positive osteoclasts in the bone surface were measured, and statistical analyses were performed using analysis of variance and Tukey test (P ≤ 0.05). In all experimental groups, the greatest number of inflammatory cells was observed at 7 days, especially in the ZOE group. In this group, the intense inflammatory process was related to a significant increase (P ≤ 0.05) in the number of osteoclasts and, thereby, in an increase in the width of the periodontal space. At 60 days, no significant differences in osteoclast numbers amongst CPM, MTA and CG groups occurred; the periodontal space was also significantly reduced in the experimental groups in comparison with the initial periods. However, in the ZOE group, the periodontal space was significantly larger (P ≤ 0.05) in comparison with MTA-based materials. The periodontium adjacent to perforations filled with MTA and CPM exhibited clear evidence of re-establishment and thus better biocompatibility than ZOE. © 2010 International Endodontic Journal.

Effectiveness of Music Listening in Patients With Total Knee Replacement During CPM Rehabilitation.

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Hsu, Chih-Chung; Chen, Wei-Ming; Chen, Su-Ru; Tseng, Yen-Ting; Lin, Pi-Chu

2016-01-01

This study investigated the effects of music listening on the anxiety, heart rate variability (HRV), and joint range of motion (ROM) of patients undergoing continuous passive motion (CPM) after total knee replacement surgery. An experimental design was used. Participants in the experimental group (n = 49) listened to music from 10 min before receiving CPM until the end of the session (25 min in total) on the first and second day following surgery, whereas participants in the control group (n = 42) did not listen to music but rested quietly in bed starting 10 min before and throughout CPM. Compared with the control group, the experimental group exhibited significantly lower anxiety levels (p CPM angles (p < .05) during treatment and increased active flexion ROM (p < .05) upon discharge. The low-frequency (LF)/high-frequency (HF) power ratio, normalized LF HRV, and normalized HF HRV of the two groups differed significantly, indicating that the patients in the experimental group had greater parasympathetic activity compared with those in the control group. Music listening can effectively reduce patient anxiety and enhance the ROM of their joints during postoperative rehabilitation. Health-care practitioners should consider including music listening as a routine practice for postoperative rehabilitation following orthopedic surgery. © The Author(s) 2015.

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

Science.gov (United States)

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

Maximum-Likelihood Detection Of Noncoherent CPM

Science.gov (United States)

Divsalar, Dariush; Simon, Marvin K.

1993-01-01

Simplified detectors proposed for use in maximum-likelihood-sequence detection of symbols in alphabet of size M transmitted by uncoded, full-response continuous phase modulation over radio channel with additive white Gaussian noise. Structures of receivers derived from particular interpretation of maximum-likelihood metrics. Receivers include front ends, structures of which depends only on M, analogous to those in receivers of coherent CPM. Parts of receivers following front ends have structures, complexity of which would depend on N.

CPM Signals for Satellite Navigation in the S and C Bands.

Science.gov (United States)

Xue, Rui; Sun, Yanbo; Zhao, Danfeng

2015-06-05

Frequency allocations in the L band suitable for global navigation satellite system (GNSS) services are getting crowded and system providers face an ever tougher job when they try to bring in new signals and services while maintaining radio frequency compatibility. With the successive opening of the S and C bands to GNSS service, the multi-band combined navigation is predicted to become a key technology for future high-precision positioning navigation systems, and a single modulation scheme satisfying the requirements in each band is a promising solution for reducing user terminal complexity. A universal modulation scheme based on the continuous phase modulation (CPM) family suitable for the above bands' demands is proposed. Moreover, this paper has put forward two specific CPM signals for the S and C bands, respectively. Then the proposed modulation schemes, together with existing candidates, are comprehensively evaluated. Simulation results show that the proposed CPM signals can not only satisfy the constraint condition of compatibility in different bands well and reduce user terminal complexity, but also provide superior performance in terms of tracking accuracy, multi-path mitigation and anti-jamming compared to other candidate modulation schemes.

Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM).

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Tsukamoto, M; Petersen, K K; Mørch, C D; Arendt-Nielsen, L

2017-12-29

Aims Traditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM. Methods 20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, "0" represented "no pain", and "10" represented "maximal pain"). The pain detection threshold (PDT) was defined as "1" on the VAS scale. Results There was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.

Hyaluron Filler Containing Lidocaine on a CPM Basis for Lip Augmentation: Reports from Practical Experience.

Science.gov (United States)

Fischer, Tanja C; Sattler, Gerhard; Gauglitz, Gerd G

2016-06-01

Lip augmentation with hyaluronic acid fillers is established. As monophasic polydensified hyaluronic acid products with variable density, CPM-HAL1 (Belotero Balance Lidocaine, Merz Aesthetics, Raleigh, NC) and CPM-HAL2 (Belotero Intense Lidocaine, Merz Aesthetics, Raleigh, NC) are qualified for beautification and particularly natural-looking rejuvenation, respectively. The aim of this article was to assess the handling and outcome of lip augmentation using the lidocaine-containing hyaluronic acid fillers, CPM-HAL1 and CPM-HAL2. Data were documented from patients who received lip augmentation by means of beautification and/or rejuvenation using CPM-HAL1 and/or CPM-HAL2. Observation period was 4 months, with assessment of natural outcome, evenness, distribution, fluidity, handling, malleability, tolerability, as well as patient satisfaction and pain. A total of 146 patients from 21 German centers participated. Physicians rated natural outcome and evenness as good or very good for more than 95% of patients. Distribution, fluidity, handling, and malleability were assessed for both fillers as good or very good in more than 91% of patients. At every evaluation point, more than 93% of patients were very or very much satisfied with the product. A total of 125 patients (85.6%) experienced transient injection-related side effects. Pain intensity during the procedure was mild (2.72 ± 1.72 on the 0-10 pain assessment scale) and abated markedly within 30 minutes (0.42 ± 0.57). Lip augmentation with hyaluronic acid fillers produced a long-term cosmetic result. Due to the lidocaine content, procedural pain was low and transient. Accordingly, a high degree of patient satisfaction was achieved that was maintained throughout the observation period. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effectiveness of prolonged use of continuous passive motion (CPM, as an adjunct to physiotherapy, after total knee arthroplasty

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Geesink Ruud JT

2008-04-01

Full Text Available Abstract Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days, followed by PT alone (usual care in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty

Science.gov (United States)

Lenssen, Ton AF; van Steyn, Mike JA; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; Geesink, Ruud JT; Brandt, Piet A van den; De Bie, Rob A

2008-01-01

Background Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Results Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Conclusion Although results indicate that prolonged CPM use

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy, after total knee arthroplasty.

Science.gov (United States)

Lenssen, Ton A F; van Steyn, Mike J A; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; Geesink, Ruud J T; van den Brandt, Piet A; De Bie, Rob A

2008-04-29

Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty. Although research suggests that Continuous Passive Motion (CPM) should be implemented in the first rehabilitation phase after surgery, there is substantial debate about the duration of each session and the total period of CPM application. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we investigated the effectiveness of prolonged CPM use in the home situation as an adjunct to standardised PT. Efficacy was assessed in terms of faster improvements in range of motion (RoM) and functional recovery, measured at the end of the active treatment period, 17 days after surgery. Sixty patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment were randomised over two treatment groups. The experimental group received CPM + PT for 17 consecutive days after surgery, whereas the usual care group received the same treatment during the in-hospital phase (i.e. about four days), followed by PT alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after surgery, both groups received standardised PT. The primary focus of rehabilitation was functional recovery (e.g. ambulation) and regaining RoM in the knee. Prolonged use of CPM slightly improved short-term RoM in patients with limited RoM at the time of discharge after total knee arthroplasty when added to a semi-standard PT programme. Assessment at 6 weeks and three months after surgery found no long-term effects of this intervention Neither did we detect functional benefits of the improved RoM at any of the outcome assessments. Although results indicate that prolonged CPM use might have a small short-term effect

Synthesis of star-branched PLA-b-PMPC copolymer micelles as long blood circulation vectors to enhance tumor-targeted delivery of hydrophobic drugs in vivo

Energy Technology Data Exchange (ETDEWEB)

Long, Li-xia [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Zhao, Jin, E-mail: zhaojin@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Li, Ke; He, Li-gang; Qian, Xiao-ming; Liu, Chao-yong; Wang, Li-mei; Yang, Xin-qi [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China); Sun, Jinjin [Department of General Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211 (China); Ren, Yu [Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070 (China); Kang, Chun-sheng, E-mail: kang97061@yahoo.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Yuan, Xu-bo, E-mail: xbyuan@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072 (China)

2016-09-01

Star-branched amphiphilic copolymer nanocarriers with high-density zwitterionic shell show great promise in drug delivery due to their controllable small size and excellent anti-biofouling properties. This gives the hydrophobic cargo with high stability and long blood circulation in vivo. In the present study, star-branched polylactic acid and poly(2-methacryloyloxyethyl phosphorylcholine) copolymers with (AB{sub 3}){sub 3}–type architecture (PLA-b-PMPC{sub 3}){sub 3} were conceived as drug vectors, and the copolymers were synthesized by an “arm-first” approach via the combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and the click reaction. The self-assembled star-branched copolymer micelles (sCPM) had an average diameter of about 64.5 nm and exhibited an ultra-hydrophilic surface with an ultralow water contact angle of about 12.7°, which efficiently suppressed the adhesion of serum proteins. In vivo experiments showed that the sCPM loading strongly enhanced the blood circulation time of DiI and the plasma half-life of DiI in sCPM was 19.3 h. The relative accumulation concentration in tumor of DiI delivered by sCPM was 2.37-fold higher than that of PLA-PEG, at 4 h after intravenous injection. These results demonstrated that the star-branched copolymer (PLA-b-PMPC{sub 3}){sub 3} is a promising alternative carrier material for intravenous delivery versus classic PEG-modified strategies. - Highlights: • Star-branched amphiphilic copolymer micelles (sCPM) with zwitterionic shells were prepared. • sCPM possess an ultra-hydrophilic surface and thus inhibited the protein absorption. • sCPM can effectively prolong the cargo’s plasma circulation time. • sCPM can enhance the cargo’s passive tumor-targeted delivery.

Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).

Science.gov (United States)

Minor, Agata; Harmer, Karynn; Peters, Nicole; Yuen, Basil Ho; Ma, Sai

2006-01-01

Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study. (c) 2005 Wiley-Liss, Inc.

Differential in vivo gene expression of major Leptospira proteins in resistant or susceptible animal models.

Science.gov (United States)

Matsui, Mariko; Soupé, Marie-Estelle; Becam, Jérôme; Goarant, Cyrille

2012-09-01

Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals.

Central pontine myelinolysis (CPM and extrapontine myelinolysis (EPM following concurrent chemoradiotherapy for nasopharyngeal carcinoma

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Chen-Hui Chong

2016-06-01

Full Text Available Central pontine myelinolysis (CPM is a disease that may present with coma, quadriplegia, or no symptoms at all. It is an iatrogenic demyelinating disease caused most frequently by overzealous correction of chronic hyponatremia and excessive swings in serum osmolality. Lesions can also occur outside the pons as extrapontine myelinolysis (EPM. Herein we have reported a case of CPM and EPM in a patient after chemoradiotherapy for recurrent nasopharyngeal carcinoma.

Effects of structural modifications of N-CPM-normorphine derivatives on agonist and antagonist activities in isolated organs.

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Riba, P; Tóth, Z; Hosztafi, S; Friedmann, T; Fürst, S

2003-01-01

The agonistic and antagonistic properties of N-cyclopropylmethyl (N-CPM) morphine derivatives were observed in mouse vas deferens (MVD), longitudinal muscle of guinea pig ileum (GPI) and rabbit vas deferens (LVD). In MVD the K(e) values of the titled compounds (N-CPM-morphine, N-CPM-isomorphine, N-CPM-dihydromorphine, N-CPM-dihydroisomorpPhine, N-CPM-dihydromorphone and naltrexone) were measured for mu-, kappa- and delta-receptors using normorphine, ethylketocyclazocine (EKC) and D-Pen2-D-Pen5-enkephaline (DPDPE) as selective agonists on the receptors, respectively. For mu-receptors of MVD the tested compounds showed similar affinity. For kappa-receptors the non-iso-6-OH derivatives possessed much less affinity than the iso-derivatives. Similar difference could be observed for delta-receptors. The agonistic activities of these compounds in MVD were observed to be between 0-20% of the inhibition of muscle contractions. In GPI the compounds except naltrexone possessed strong agonistic activities effectively antagonized by nor-binaltorphimine (nor-BNI) (K(e) of nor-BNI was 0.23 nM) suggesting that they were strong kappa-receptor agonists. We investigated these agents in LVD too, which contains kappa-receptors, but they did not produce any agonist potencies. It raises the possibility that the kappa-receptor subtypes of LVD and MVD are different from the kappa-receptor subtype of GPI or the vasa deferentia contain much fewer kappa-receptors than GPI and the intrinsic activities of these compounds are too small to reach the 50% inhibition of the contractions.

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.

Science.gov (United States)

Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y; Tanaka, Minoru; Miyajima, Atsushi

2015-10-13

To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Gerenciamento de Projeto Otimista (GPO): Um Método que Integra PERT/CPM à CCPM

OpenAIRE

Novais, Igor Fontes; Jorge, Eduardo Manoel de Freitas; Junior, Carlos Pereira Costa; Souza, Daniele Tavares

2011-01-01

The time factor for project managers is one of the most worrisome because of difficulties in keeping projects on time, making interesting use of traditional techniques such as PERT/CPM. Another interesting technique that supports the management of time is the Critical Chain (CCPM) based on the Theory of Constraints (TOC). This article presents the method Optimistic Project Management (GPO) that is based on PERT/CPM and CCPM. The method GPO brings as differential a new way of assembling a sche...

Development of in-vivo micro CT system for small animals

Energy Technology Data Exchange (ETDEWEB)

Nam, Ki Yong; Lim, Jong Hyeok; Jeong, Young Jo; Park, Jeong Gwon [Institute for Radiological Imaging Science, Iksan (Korea, Republic of); Park, Jung Bung [DRGEM Corp., Seoul (Korea, Republic of); Yoon, Kwon Ha [Institute for Radiological Imaging Science and Medical School of Radiology, Iksan (Korea, Republic of)

2005-07-01

Computed tomography system with the spatial resolution of {approx}25 {mu}m has been developed for the application to small animals. This system is designed by gantry-rotation type for minimizing animal movement. To get image with micro-spatial resolution, system characteristic such as geometry between main components of source, specimen and detector, field of view, etc., is described in this paper. The requirements of x-ray spot size and CCD pixel size to approach the resolution are discussed. In-vivo imaging test for mouse is also presented as a result.

Development of in-vivo micro CT system for small animals

International Nuclear Information System (INIS)

Nam, Ki Yong; Lim, Jong Hyeok; Jeong, Young Jo; Park, Jeong Gwon; Park, Jung Bung; Yoon, Kwon Ha

2005-01-01

Computed tomography system with the spatial resolution of ∼25 μm has been developed for the application to small animals. This system is designed by gantry-rotation type for minimizing animal movement. To get image with micro-spatial resolution, system characteristic such as geometry between main components of source, specimen and detector, field of view, etc., is described in this paper. The requirements of x-ray spot size and CCD pixel size to approach the resolution are discussed. In-vivo imaging test for mouse is also presented as a result

Alteration and Implementation of the CP/M-86 Operating System for a Multi-User Environment.

Science.gov (United States)

1982-12-01

THE CP/M-86 OPERATING SYSTEM FOR A MULTI-USER ENVIRONMENT by Thomas V. Almquist and David S. Stevens C-, December 1982 ,LU Thesis Advisor : U. R. Kodres...tool$ 044, robo O0eA 6^900091 Approved for public release; distribution unlimited Alteration and Implementation of the CP/M-86 Operating System for a...SCIENCE IN COMPUTER SCIENCE from the NAVAL POSTGRADUATE SCHOOL December 1982 Authors: Approved by: ..... .. . . . . . . . . Thesis Advisor Second

PERT and CPM: A Comparison with Implications for Education.

Science.gov (United States)

Ragan, Stephen W.

Two systematic ways of analyzing and planning the components of a program or project, both used extensively by industry and government, are discussed in this paper. The methods are Program Evaluation and Review Technique (PERT) Networks and Critical Path Method (CPM) Arrow Diagrams. The purposes of this paper are (1) to explore the need for…

Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM)

International Nuclear Information System (INIS)

Oergel, Anja; Hauser, Till-Karsten; Naegele, T.; Horger, Marius

2017-01-01

CT and NMR Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis were compared with histological results. The clinical appearance and diagnosis using CT and NMR imaging are related to therapy decisions and outcome.

Motorized CPM/CAM physiotherapy device with sliding-mode Fuzzy Neural Network control loop.

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Ho, Hung-Jung; Chen, Tien-Chi

2009-11-01

Continuous passive motion (CPM) and controllable active motion (CAM) physiotherapy devices promote rehabilitation of damaged joints. This paper presents a computerized CPM/CAM system that obviates the need for mechanical resistance devices such as springs. The system is controlled by a computer which performs sliding-mode Fuzzy Neural Network (FNN) calculations online. CAM-type resistance force is generated by the active performance of an electric motor which is controlled so as to oppose the motion of the patient's leg. A force sensor under the patient's foot on the device pedal provides data for feedback in a sliding-mode FNN control loop built around the motor. Via an active impedance control feedback system, the controller drives the motor to behave similarly to a damped spring by generating and controlling the amplitude and direction of the pedal force in relation to the patient's leg. Experiments demonstrate the high sensitivity and speed of the device. The PC-based feedback nature of the control loop means that sophisticated auto-adaptable CPM/CAM custom-designed physiotherapy becomes possible. The computer base also allows extensive data recording, data analysis and network-connected remote patient monitoring.

Large-Animal Biventricular Working Heart Perfusion System with Low Priming Volume-Comparison between in vivo and ex vivo Cardiac Function.

Science.gov (United States)

Abicht, Jan-Michael; Mayr, Tanja Axinja Jelena; Jauch, Judith; Guethoff, Sonja; Buchholz, Stefan; Reichart, Bruno; Bauer, Andreas

2018-01-01

Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume. Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL). After 15 minutes of Langendorff perfusion (LM), the system was switched into a biventricular working mode (WM) and studied for 3 hours. During reperfusion, complete unloading of both ventricles and constant-pressure coronary perfusion was achieved. During working mode perfusion, the preload and afterload pressure of both ventricles was controlled within the targeted physiologic range. Functional parameters such as left ventricular work index were reduced in ex vivo working mode (in vivo: 787 ± 186 vs. 1 h WM 498 ± 66 mm Hg·mL/g·min; p  hours while functional and blood parameters are easily accessible. Moreover, because of the minimal priming volume, the novel ex vivo cardiac perfusion circuit allows for autologous perfusion, using the limited amount of blood available from the organ donating animal. Georg Thieme Verlag KG Stuttgart · New York.

Study of CPM Device used for Rehabilitation and Effective Pain Management Following Knee Alloplasty

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Trochimczuk, R.; Kuźmierowski, T.; Anchimiuk, P.

2017-02-01

This paper defines the design assumptions for the construction of an original demonstration of a CPM device, based on which a solid virtual model will be created in a CAD software environment. The overall dimensions and other input parameters for the design were determined for the entire patient population according to an anatomical atlas of human measures. The medical and physiotherapeutic community were also consulted with respect to the proposed engineering solutions. The virtual model of the CPM device that will be created will be used for computer simulations of changes in motion parameters as a function of time, accounting for loads and static states. The results obtained from computer simulation will be used to confirm the correctness of the design adopted assumptions and of the accepted structure of the CPM mechanism, and potentially to introduce necessary corrections. They will also provide a basis for the development of a control strategy for the laboratory prototype and for the selection of the strategy of the patient's rehabilitation in the future. This paper will be supplemented with identification of directions of further research.

Measurements of 42 Wide CPM Pairs with a CCD

Science.gov (United States)

Harshaw, Richard

2015-11-01

This paper addresses the use of a Skyris 618C color CCD camera as a means of obtaining data for analysis in the measurement of wide common proper motion stars. The equipment setup is described and data collection procedure outlined. Results of the measures of 42 CPM stars are presented, showing the Skyris is a reliable device for the measurement of double stars.

NLCQ-1, a novel hypoxic cytotoxin: potentiation of melphalan, cisDDP and cyclophosphamide in vivo

International Nuclear Information System (INIS)

Papadopoulou, Maria V.; Ji Ming; Bloomer, William D.

1998-01-01

Purpose: To investigate in vivo interactions between the recently developed bioreductive agent 4-[3-(2-nitroimidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1) and the chemotherapeutic agents melphalan (L-PAM), cis-platin (cisDDP) and cyclophosphamide (CPM). Methods and Materials: EMT6 and FSaIIC tumor cells were inoculated (subcutaneously) into the leg(s) of female Balb/c and male C3H mice, respectively. Treatment was initiated at 10 mm (EMT6) and 5 mm (FSaIIC) mean tumor diameter. The in vivo-in vitro and tumor regrowth assays were used, respectively, as endpoints. Bone marrow toxicity studies were also performed when the in vivo-in vitro assay was used. Drugs were given by i.p. injection. Tumors were excised 18-h after chemotherapeutic drug administration (Balb/c mice) or measured daily until three times their original size (C3H mice). The optimum administration schedule for potentiation between NLCQ-1 and each chemotherapeutic drug, as well as dose modification factors (DMF) at the optimum time, were determined with the in vivo-in vitro assay. When the tumor regrowth assay was used, each chemotherapeutic agent was given either as a single dose or as a split dose over two consecutive days at the optimum administration time after a 10 mg/kg NLCQ-1 i.p. injection. Results: NLCQ-1 (at 0.33 times MTD), strongly potentiated the antitumor effect of L-PAM, cisDDP and CPM without concurrent enhancement in bone marrow toxicity. Potentiation was strictly schedule dependent and the optimum effect (1.5 to 2 logs killing beyond additivity) was observed when NLCQ-1 was given 60-, 45-, and 110-min before L-PAM, cisDDP, and CPM, respectively. The DMF values at 30% survival were 2.5, 1.9, and 3.8 for L-PAM, cisDDP, and CPM, respectively. DMF values for bone marrow toxicity at 50% survival were ca. 1 for all chemotherapeutic drugs. Pretreatment with NLCQ-1 resulted in 4-12 days extra delay in the regrowth of FSaIIC tumors. Conclusions: These results support the

Non-Invasive in vivo Imaging in Small Animal Research

Directory of Open Access Journals (Sweden)

V. Koo

2006-01-01

Full Text Available Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI, Computed Tomography (CT, Positron Emission Tomography (PET, bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS' ESRD CPM Project.

Science.gov (United States)

Neu, Alicia M; Frankenfield, Diane L

2009-07-01

Although prospective randomized trials have provided important information and allowed the development of evidence-based guidelines in adult hemodialysis (HD) patients, with approximately 800 prevalent pediatric HD patients in the United States, such studies are difficult to perform in this population. Observational data obtained through the Center for Medicare & Medicaid Services' (CMS') End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project have allowed description of the clinical care provided to pediatric HD patients as well as identification of risk factors for failure to reach adult targets for clinical parameters such as hemoglobin, single-pool Kt/V (spKt/V) and serum albumin. In addition, studies linking data from the ESRD CPM Project and the United States Renal Data System have allowed evaluation of associations between achievement of those targets and the outcomes of hospitalization and death. The results of those studies, while unable to prove cause and effect, suggest that the adult ESRD CPM targets may assist in identifying pediatric HD patients at risk for poor outcomes.

Laser-assisted cartilage reshaping: in vitro and in vivo animal studies

Science.gov (United States)

Wang, Zhi; Pankratov, Michail M.; Perrault, Donald F., Jr.; Shapshay, Stanley M.

1995-05-01

Correction of cartilaginous defects in the head and neck area remains a challenge for the surgeon. This study investigated a new technique for laser-assisted cartilage reshaping. The pulsed 1.44 micrometers Nd:YAG laser was used in vitro and in vivo experiments to irradiate cartilage to change it's shape without carbonization or vaporization of tissue. Two watts of average power in non contact manner was used to irradiate and reshape the cartilage. The extracted reshaped cartilage specimens underwent testing of elastic force with a computer assisted measurement system that recorded the changes in elastic force in the specimens from 1 hr to 11 days post-irradiation. An animal model of defective tracheal cartilage (collapsed tracheal wall) was created, allowed to heal for 6 weeks and then corrected endoscopically with the laser-assisted technique. The results of the in vitro and in vivo investigations demonstrated that it was possible to alter the cartilage and that cartilage would retain its new shape. The clinical significance of the technique is evident and warrants further animal studies and clinical trials.

OPTIMIZATION OF TIMES AND COSTS OF PROJECT OF HORIZONTAL LAMINATOR PRODUCTION USING PERT/CPM TECHNICAL

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Fernando Henrique Lermen

2016-09-01

Full Text Available The PERT/CPM is a technique widely used in both the scheduling and in the project feasibility in terms of cost control and time.  In order to optimize time and costs involved in production, the work presented here aims to apply the PERT/CPM technique in the production project of the Horizontal Laminator, a machine used to cut polyurethane foam blocks in the mattresses industries. For the application of PERT/CPM technique in the project of Horizontal Laminator production were identified the activities that compose the project, the dependence between them, the normal and accelerated durations and the normal and accelerated costs. In this study, deterministic estimates for the duration of the activities were considered. The results show that the project can be completed in 520 hours at a total cost of R$7,042.50, when all activities are performed in their normal durations.  When all the activities that compose the critical path are accelerated, the project can be completed in 333.3 hours at a total cost of R$9,263.01. If the activities slacks have been exploited, it can obtain a final total cost of R$6,157.8, without changing the new duration of the project. It is noteworthy that the final total cost of the project if the slacks are used, will be lower than the initial cost. Regarding the initial cost of the project, after the application of the PERT/CPM technique, it presents a decrease of 12.56% of the total project cost.

In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice

International Nuclear Information System (INIS)

Puri, R.K.; Travis, W.D.; Rosenberg, S.A.

1990-01-01

We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-[125I]iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-[125I]iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice

Comparative assessment of fluorescent proteins for in vivo imaging in an animal model system.

Science.gov (United States)

Heppert, Jennifer K; Dickinson, Daniel J; Pani, Ariel M; Higgins, Christopher D; Steward, Annette; Ahringer, Julie; Kuhn, Jeffrey R; Goldstein, Bob

2016-11-07

Fluorescent protein tags are fundamental tools used to visualize gene products and analyze their dynamics in vivo. Recent advances in genome editing have expedited the precise insertion of fluorescent protein tags into the genomes of diverse organisms. These advances expand the potential of in vivo imaging experiments and facilitate experimentation with new, bright, photostable fluorescent proteins. Most quantitative comparisons of the brightness and photostability of different fluorescent proteins have been made in vitro, removed from biological variables that govern their performance in cells or organisms. To address the gap, we quantitatively assessed fluorescent protein properties in vivo in an animal model system. We generated transgenic Caenorhabditis elegans strains expressing green, yellow, or red fluorescent proteins in embryos and imaged embryos expressing different fluorescent proteins under the same conditions for direct comparison. We found that mNeonGreen was not as bright in vivo as predicted based on in vitro data but is a better tag than GFP for specific kinds of experiments, and we report on optimal red fluorescent proteins. These results identify ideal fluorescent proteins for imaging in vivo in C. elegans embryos and suggest good candidate fluorescent proteins to test in other animal model systems for in vivo imaging experiments. © 2016 Heppert et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

External validation of the Cairns Prediction Model (CPM) to predict conversion from laparoscopic to open cholecystectomy.

Science.gov (United States)

Hu, Alan Shiun Yew; Donohue, Peter O'; Gunnarsson, Ronny K; de Costa, Alan

2018-03-14

Valid and user-friendly prediction models for conversion to open cholecystectomy allow for proper planning prior to surgery. The Cairns Prediction Model (CPM) has been in use clinically in the original study site for the past three years, but has not been tested at other sites. A retrospective, single-centred study collected ultrasonic measurements and clinical variables alongside with conversion status from consecutive patients who underwent laparoscopic cholecystectomy from 2013 to 2016 in The Townsville Hospital, North Queensland, Australia. An area under the curve (AUC) was calculated to externally validate of the CPM. Conversion was necessary in 43 (4.2%) out of 1035 patients. External validation showed an area under the curve of 0.87 (95% CI 0.82-0.93, p = 1.1 × 10 -14 ). In comparison with most previously published models, which have an AUC of approximately 0.80 or less, the CPM has the highest AUC of all published prediction models both for internal and external validation. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Perencanaan dan Pengendalian Proyek dengan Metode Pert - CPM Studi Kasus : Fly Over Ahmad Yani – Karawang

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Anggara Hayun A

2005-09-01

Full Text Available The efficiency and effectivity is not a new guide in this global era. As a professional and innovative company, like consultant construction company that always makes customer satisfy, has a good achievement and reputation. There fore, efficiency and affectivity are necessary needed in a company. Article gives some inputs how to manage time become more effective and efficient in finishing project with CPM method. With using CPM method in “fly over project Ahmad Yani-Karawang”, is figured out the optimal time to finish this project which is 184 days.Keywords: 

A unique in vivo approach for investigating antimicrobial materials utilizing fistulated animals

Science.gov (United States)

Berean, Kyle J.; Adetutu, Eric M.; Zhen Ou, Jian; Nour, Majid; Nguyen, Emily P.; Paull, David; McLeod, Jess; Ramanathan, Rajesh; Bansal, Vipul; Latham, Kay; Bishop-Hurley, Greg J.; McSweeney, Chris; Ball, Andrew S.; Kalantar-Zadeh, Kourosh

2015-06-01

Unique in vivo tests were conducted through the use of a fistulated ruminant, providing an ideal environment with a diverse and vibrant microbial community. Utilizing such a procedure can be especially invaluable for investigating the performance of antimicrobial materials related to human and animal related infections. In this pilot study, it is shown that the rumen of a fistulated animal provides an excellent live laboratory for assessing the properties of antimicrobial materials. We investigate microbial colonization onto model nanocomposites based on silver (Ag) nanoparticles at different concentrations into polydimethylsiloxane (PDMS). With implantable devices posing a major risk for hospital-acquired infections, the present study provides a viable solution to understand microbial colonization with the potential to reduce the incidence of infection through the introduction of Ag nanoparticles at the optimum concentrations. In vitro measurements were also conducted to show the validity of the approach. An optimal loading of 0.25 wt% Ag is found to show the greatest antimicrobial activity and observed through the in vivo tests to reduce the microbial diversity colonizing the surface.

Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

DEFF Research Database (Denmark)

Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

2013-01-01

Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

Physiological and Proteomic Analysis of the Rice Mutant cpm2 Suggests a Negative Regulatory Role of Jasmonic Acid in Drought Tolerance

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Rohit Dhakarey

2017-11-01

Full Text Available It is widely known that numerous adaptive responses of drought-stressed plants are stimulated by chemical messengers known as phytohormones. Jasmonic acid (JA is one such phytohormone. But there are very few reports revealing its direct implication in drought related responses or its cross-talk with other phytohormones. In this study, we compared the morpho-physiological traits and the root proteome of a wild type (WT rice plant with its JA biosynthesis mutant coleoptile photomorphogenesis 2 (cpm2, disrupted in the allene oxide cyclase (AOC gene, for insights into the role of JA under drought. The mutant had higher stomatal conductance, higher water use efficiency and higher shoot ABA levels under severe drought as compared to the WT. Notably, roots of cpm2 were better developed compared to the WT under both, control and drought stress conditions. Root proteome was analyzed using the Tandem Mass Tag strategy to better understand this difference at the molecular level. Expectedly, AOC was unique but notably highly abundant under drought in the WT. Identification of other differentially abundant proteins (DAPs suggested increased energy metabolism (i.e., increased mobilization of resources and reactive oxygen species scavenging in cpm2 under drought. Additionally, various proteins involved in secondary metabolism, cell growth and cell wall synthesis were also more abundant in cpm2 roots. Proteome-guided transcript, metabolite, and histological analyses provided further insights into the favorable adaptations and responses, most likely orchestrated by the lack of JA, in the cpm2 roots. Our results in cpm2 are discussed in the light of JA crosstalk to other phytohormones. These results together pave the path for understanding the precise role of JA during drought stress in rice.

[CPM--Continuous Passive Motion: treatment of injured or operated knee-joints using passive movement. A meta-analysis of current literature].

Science.gov (United States)

Kirschner, P

2004-04-01

There is still a controversial discussion in literature about the use of motor driven splints in knee surgery--as the principle of continuous passive motion, CPM. For this reason it seemed useful for an evaluation to look through the papers which were published since 1990. It was obvious, that negative results were published often before this year, but this papers are still quoted standard works. In medical data bases subito-doc.de, medscape.com, medica.de and zbmed.de 230 papers were found by search CPM, continuous passive motion and arthromot. Coincidentally there was a search for authors who were already quoted in other papers. 36 papers concerning CPM after knee surgery were utilized. The role of CPM regarding the range of motion, swelling, duration of hospital stay, use of analgesics, costs, postoperative manipulations, wound healing and thrombo embolic complications was evaluated. Although the results of this partial retrospective, partial prospective, sometimes randomized or double blinded studies are in contradiction, there can only be found a trend to better results. New clinical studies for evidence based guidelines in the handling of continuous passive motion after knee surgery are necessary.

Gerenciamento de Projeto Otimista (GPO: Um Método que Integra PERT/CPM à CCPM

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Igor Fontes Novais

2011-12-01

Full Text Available O fator tempo para os gerentes de projetos é um dos pontos mais preocupantes em razão das dificuldades em manter os projetos no prazo previsto, tornando interessante o uso de técnicas tradicionais como PERT/CPM. Outra técnica interessante que apóia a gestão de tempo é a Corrente Crítica (CCPM baseada na Teoria das Restrições (TOC. Este artigo apresenta o método Gerenciamento de Projeto Otimista (GPO que é baseado na PERT/CPM e na CCPM. O método GPO traz como diferencial uma nova forma de montagem de um cronograma, visando obter durações de atividades e buffers mais precisas.DOI:10.5585/gep.v2i2.25

In Vivo Bioluminescence Imaging for Longitudinal Monitoring of Inflammation in Animal Models of Uveitis.

Science.gov (United States)

Gutowski, Michal B; Wilson, Leslie; Van Gelder, Russell N; Pepple, Kathryn L

2017-03-01

We develop a quantitative bioluminescence assay for in vivo longitudinal monitoring of inflammation in animal models of uveitis. Three models of experimental uveitis were induced in C57BL/6 albino mice: primed mycobacterial uveitis (PMU), endotoxin-induced uveitis (EIU), and experimental autoimmune uveitis (EAU). Intraperitoneal injection of luminol sodium salt, which emits light when oxidized, provided the bioluminescence substrate. Bioluminescence images were captured by a PerkinElmer In Vivo Imaging System (IVIS) Spectrum and total bioluminescence was analyzed using Living Image software. Bioluminescence on day zero was compared to bioluminescence on the day of peak inflammation for each model. Longitudinal bioluminescence imaging was performed in EIU and EAU. In the presence of luminol, intraocular inflammation generates detectable bioluminescence in three mouse models of uveitis. Peak bioluminescence in inflamed PMU eyes (1.46 × 105 photons/second [p/s]) was significantly increased over baseline (1.47 × 104 p/s, P = 0.01). Peak bioluminescence in inflamed EIU eyes (3.18 × 104 p/s) also was significantly increased over baseline (1.09 × 104 p/s, P = 0.04), and returned to near baseline levels by 48 hours. In EAU, there was a nonsignificant increase in bioluminescence at peak inflammation. In vivo bioluminescence may be used as a noninvasive, quantitative measure of intraocular inflammation in animal models of uveitis. Primed mycobacterial uveitis and EIU are both acute models with robust anterior inflammation and demonstrated significant changes in bioluminescence corresponding with peak inflammation. Experimental autoimmune uveitis is a more indolent posterior uveitis and generated a more modest bioluminescent signal. In vivo imaging system bioluminescence is a nonlethal, quantifiable assay that can be used for monitoring inflammation in animal models of uveitis.

The 4-parameter Compressible Packing Model (CPM) including a critical cavity size ratio

Science.gov (United States)

Roquier, Gerard

2017-06-01

The 4-parameter Compressible Packing Model (CPM) has been developed to predict the packing density of mixtures constituted by bidisperse spherical particles. The four parameters are: the wall effect and the loosening effect coefficients, the compaction index and a critical cavity size ratio. The two geometrical interactions have been studied theoretically on the basis of a spherical cell centered on a secondary class bead. For the loosening effect, a critical cavity size ratio, below which a fine particle can be inserted into a small cavity created by touching coarser particles, is introduced. This is the only parameter which requires adaptation to extend the model to other types of particles. The 4-parameter CPM demonstrates its efficiency on frictionless glass beads (300 values), spherical particles numerically simulated (20 values), round natural particles (125 values) and crushed particles (335 values) with correlation coefficients equal to respectively 99.0%, 98.7%, 97.8%, 96.4% and mean deviations equal to respectively 0.007, 0.006, 0.007, 0.010.

Mathematical modeling and experimental breakthrough curves of carbon dioxide adsorption on metal organic framework CPM-5.

Science.gov (United States)

Sabouni, Rana; Kazemian, Hossein; Rohani, Sohrab

2013-08-20

It is essential to capture carbon dioxide from flue gas because it is considered one of the main causes of global warming. Several materials and different methods have been reported for CO2 capturing including adsorption onto zeolites and porous membranes, as well as absorption in amine solutions. All such methods require high energy input and high cost. A new class of porous materials called Metal Organic Frameworks (MOFs) exhibited excellent performance in extracting carbon dioxide from a gas mixture. In this study, the breakthrough curves for the adsorption of carbon dioxide on CPM-5 (crystalline porous materials) were obtained experimentally and theoretically using a laboratory-scale fixed-bed column at different experimental conditions such as feed flow rate, adsorption temperature, and feed concentration. It was found that the CPM-5 has a dynamic CO2 adsorption capacity of 11.9 wt % (2.7 mmol/g) (corresponding to 8 mL/min, 298 K, and 25% v/v CO2). The tested CPM-5 showed an outstanding adsorption equilibrium capacity (e.g., 2.3 mmol/g (10.2 wt %) at 298 K) compared to other adsorbents, which can be considered as an attractive adsorbent for separation of CO2 from flue gas.

Remote in vivo stress assessment of aquatic animals with microencapsulated biomarkers for environmental monitoring

Science.gov (United States)

Gurkov, Anton; Shchapova, Ekaterina; Bedulina, Daria; Baduev, Boris; Borvinskaya, Ekaterina; Meglinski, Igor; Timofeyev, Maxim

2016-11-01

Remote in vivo scanning of physiological parameters is a major trend in the development of new tools for the fields of medicine and animal physiology. For this purpose, a variety of implantable optical micro- and nanosensors have been designed for potential medical applications. At the same time, the important area of environmental sciences has been neglected in the development of techniques for remote physiological measurements. In the field of environmental monitoring and related research, there is a constant demand for new effective and quick techniques for the stress assessment of aquatic animals, and the development of proper methods for remote physiological measurements in vivo may significantly increase the precision and throughput of analyses in this field. In the present study, we apply pH-sensitive microencapsulated biomarkers to remotely monitor the pH of haemolymph in vivo in endemic amphipods from Lake Baikal, and we compare the suitability of this technique for stress assessment with that of common biochemical methods. For the first time, we demonstrate the possibility of remotely detecting a change in a physiological parameter in an aquatic organism under ecologically relevant stressful conditions and show the applicability of techniques using microencapsulated biomarkers for remote physiological measurements in environmental monitoring.

High resolution propagation-based imaging system for in vivo dynamic computed tomography of lungs in small animals

Science.gov (United States)

Preissner, M.; Murrie, R. P.; Pinar, I.; Werdiger, F.; Carnibella, R. P.; Zosky, G. R.; Fouras, A.; Dubsky, S.

2018-04-01

We have developed an x-ray imaging system for in vivo four-dimensional computed tomography (4DCT) of small animals for pre-clinical lung investigations. Our customized laboratory facility is capable of high resolution in vivo imaging at high frame rates. Characterization using phantoms demonstrate a spatial resolution of slightly below 50 μm at imaging rates of 30 Hz, and the ability to quantify material density differences of at least 3%. We benchmark our system against existing small animal pre-clinical CT scanners using a quality factor that combines spatial resolution, image noise, dose and scan time. In vivo 4DCT images obtained on our system demonstrate resolution of important features such as blood vessels and small airways, of which the smallest discernible were measured as 55–60 μm in cross section. Quantitative analysis of the images demonstrate regional differences in ventilation between injured and healthy lungs.

USO DEL MÓDULO DE PREDICCIÓN DE ACCIDENTES (CPM DEL IHSDM PARA EVALUACIÓN DE SEGURIDAD EN SEGMENTOS DE CARRETERAS DE DOS CARRILES

Directory of Open Access Journals (Sweden)

Yasmín Andrea Pérez-Rojas

2013-07-01

Full Text Available The document presents an alternative for the safety evaluation in the segments of highways in Colombia, given the absence of this type of practical in the engineering of Colombian highways. Therefore, it is approached CPM (Crash Prediction Module of the program IHSDM (Interactive Highway Safety Design Model of FHWA (Federal Highway Administration, adopted thoroughly in other countries to assess safety in highways. This way, the description of the main characteristics of the module CPM is presented for the prediction of accidents in segments of highways without considering those happened or related to the intersections. This way, the description of the main characteristics of the module CPM is presented for the prediction of accidents in segments of highways without considering those happened or related to the intersections. Finally, the results obtained by analyzing the CPM module, the algorithms of the prediction pattern, and the methodological proposal will permit obtain an enough database for the use and application of the module in Colombia.

Renaissance of morphological studies: the examination of functional structures in living animal organs using the in vivo cryotechnique.

Science.gov (United States)

Ohno, Shinichi; Saitoh, Yurika; Ohno, Nobuhiko; Terada, Nobuo

2017-01-01

Medical and biological scientists wish to understand the in vivo structures of the cells and tissues that make up living animal organs, as well as the locations of their molecular components. Recently, the live imaging of animal cells and tissues with fluorescence-labeled proteins produced via gene manipulation has become increasingly common. Therefore, it is important to ensure that findings derived from histological or immunohistochemical tissue sections of living animal organs are compatible with those obtained from live images of the same organs, which can be assessed using recently developed digital imaging techniques. Over the past two decades, we have performed immunohistochemical and morphological studies of the cells and tissues in living animal organs using a novel in vivo cryotechnique. The use of a specially designed liquid cryogen system with or without a cryoknife during this cryotechnique solved the technical problems that inevitably arise during the conventional preparation methods employed prior to light or electron microscopic examinations. Our in vivo cryotechnique has been found to be extremely useful for arresting transient physiological processes in cells and tissues and for maintaining their functional components-such as rapidly changing signaling molecules, membrane channels, or receptors-in situ. The purpose of the present review is to describe the basic mechanism underlying cryotechniques and the significance of our in vivo cryotechnique. In addition, it describes various morphological or immunohistochemical findings, observations made using quantum dots, and a Raman cryomicroscopy-based method for assessing oxygen saturation in the erythrocytes flowing through intestinal tissues.

In vivo small animal imaging: Current status and future prospects

International Nuclear Information System (INIS)

Kagadis, George C.; Loudos, George; Katsanos, Konstantinos; Langer, Steve G.; Nikiforidis, George C.

2010-01-01

The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle-photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.

Analysis of the Raven CPM Subtest Scores for a Sample of Gifted Children.

Science.gov (United States)

Kluever, Raymond C.; Green, Kathy E.

The inter-subject/intra-subject subtest patterns (profiles) of the same sample of gifted children were examined based on factors found in a previous study of the Raven Coloured Progressive Matrices Test (CPM) that investigated structural properties with specific application to a sample of gifted children. The sample consisted of 166 children (78…

HYC-24L Demonstrates Greater Effectiveness With Less Pain Than CPM-22.5 for Treatment of Perioral Lines in a Randomized Controlled Trial.

Science.gov (United States)

Butterwick, Kimberly; Marmur, Ellen; Narurkar, Vic; Cox, Sue Ellen; Joseph, John H; Sadick, Neil S; Tedaldi, Ruth; Wheeler, Sarah; Kolodziejczyk, Julia K; Gallagher, Conor J

2015-12-01

This trial compares the effectiveness and safety of HYC-24L (Juvéderm Ultra XC; Allergan plc, Dublin, Ireland) (24 mg/mL of hyaluronic acid, 0.3% lidocaine) and CPM-22.5 (Belotero Balance; Merz Aesthetics, Raleigh, NC) (22.5 mg/mL of hyaluronic acid) for the treatment of perioral lines. Men and women aged 35 years or older with moderate-to-severe perioral lines were recruited for this randomized controlled, rater-blinded, 2-arm trial. The primary endpoint was a comparison of rater-assessed responder rates by the validated 4-point Perioral Lines Severity Scale at Month 6; responders were those who showed a ≥1 point improvement. A secondary endpoint was subject-assessed change in perioral lines measured by the Global Assessment of Change Scale. A total of 136 subjects received treatment and 132 completed the trial (mean age: 58 ± 8 years). Total volume injected was 1.18 mL (HYC-24L) and 1.32 mL (CPM-22.5). At Month 6, a significantly greater proportion of HYC-24L subjects responded to treatment (87%) than CPM-22.5 subjects (72%) (p CPM-22.5 subjects, with the greatest difference at Month 6. No unexpected adverse events occurred. HYC-24L subjects showed a higher response rate and a greater improvement in their perioral lines than CPM-22.5 subjects for up to 6 months.

Specific absorption in vivo of the [{sup 125} I] insulin by the Chrysemys dorbigni turtle thyroid; Captacao especifica in vivo da [{sup 125} I] insulina pela tireoide de tartarugas Chrysemys dorbigni

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Coutinho, Ligia Maria Barbosa

1982-12-31

Based on researches that demonstrate the presence of insulin receptor sites in hypophysis and supra renal, we investigate this hormone specific absorption by the thyroid gland. We used adult males and females Chrysemys dorbigni turtles. It was used a in vivo method consisting of [{sup 125} I] (2 x 10{sup 6} cpm/Kg) insulin intra-aorta administration, and counting of the radioactivity in the gland and blood. 101 refs., 10 figs., 2 tabs.

FMT-XCT: in vivo animal studies with hybrid fluorescence molecular tomography-X-ray computed tomography.

Science.gov (United States)

Ale, Angelique; Ermolayev, Vladimir; Herzog, Eva; Cohrs, Christian; de Angelis, Martin Hrabé; Ntziachristos, Vasilis

2012-06-01

The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360° imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.

Administración de proyectos con Excel usando PERT/CPM

Directory of Open Access Journals (Sweden)

Carlos Azofeifa Zamora

2016-03-01

Full Text Available Se presenta la técnica PERT/CPM de la ciencia administrativa, que ayuda a comprobar y controlar aquellos proyectos que involucran muchas tareas interrelacionadas, mediante la resolución de un problema de la administración de proyectos con la ayuda de la hoja electrónica Excel, además, se realiza un análisis de sus beneficios. También se aplica la técnica PERT/Costos en el control de los costos del proyecto, Nassir Sapag Chain (2001 es una guía especial en este tema.

Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

International Nuclear Information System (INIS)

Shahbazian, F.M.

1985-01-01

Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of [ 14 C]valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements

Specific absorption in vivo of the [125 I] insulin by the Chrysemys dorbigni turtle thyroid

International Nuclear Information System (INIS)

Coutinho, Ligia Maria Barbosa.

1982-01-01

Based on researches that demonstrate the presence of insulin receptor sites in hypophysis and supra renal, we investigate this hormone specific absorption by the thyroid gland. We used adult males and females Chrysemys dorbigni turtles. It was used a in vivo method consisting of [ 125 I] (2 x 10 6 cpm/Kg) insulin intra-aorta administration, and counting of the radioactivity in the gland and blood. 101 refs., 10 figs., 2 tabs

Assessment of hybrid rotation-translation scan schemes for in vivo animal SPECT imaging

International Nuclear Information System (INIS)

Xia Yan; Liu Yaqiang; Wang Shi; Ma Tianyu; Yao Rutao; Deng Xiao

2013-01-01

To perform in vivo animal single photon emission computed tomography imaging on a stationary detector gantry, we introduced a hybrid rotation-translation (HRT) tomographic scan, a combination of translational and limited angle rotational movements of the image object, to minimize gravity-induced animal motion. To quantitatively assess the performance of ten HRT scan schemes and the conventional rotation-only scan scheme, two simulated phantoms were first scanned with each scheme to derive the corresponding image resolution (IR) in the image field of view. The IR results of all the scan schemes were visually assessed and compared with corresponding outputs of four scan scheme evaluation indices, i.e. sampling completeness (SC), sensitivity (S), conventional system resolution (SR), and a newly devised directional spatial resolution (DR) that measures the resolution in any specified orientation. A representative HRT scheme was tested with an experimental phantom study. Eight of the ten HRT scan schemes evaluated achieved a superior performance compared to two other HRT schemes and the rotation-only scheme in terms of phantom image resolution. The same eight HRT scan schemes also achieved equivalent or better performance in terms of the four quantitative indices than the conventional rotation-only scheme. As compared to the conventional index SR, the new index DR appears to be a more relevant indicator of system resolution performance. The experimental phantom image obtained from the selected HRT scheme was satisfactory. We conclude that it is feasible to perform in vivo animal imaging with a HRT scan scheme and SC and DR are useful predictors for quantitatively assessing the performance of a scan scheme. (paper)

Photoluminescent BaMoO4 nanopowders prepared by complex polymerization method (CPM)

International Nuclear Information System (INIS)

Azevedo Marques, Ana Paula de; Melo, Dulce M.A. de; Paskocimas, Carlos A.; Pizani, Paulo S.; Joya, Miryam R.; Leite, Edson R.; Longo, Elson

2006-01-01

The BaMoO 4 nanopowders were prepared by the Complex Polymerization Method (CPM). The structure properties of the BaMoO 4 powders were characterized by FTIR transmittance spectra, X-ray diffraction (XRD), Raman spectra, photoluminescence spectra (PL) and high-resolution scanning electron microscopy (HR-SEM). The XRD, FTIR and Raman data showed that BaMoO 4 at 300 deg. C was disordered. At 400 deg. C and higher temperature, BaMoO 4 crystalline scheelite-type phases could be identified, without the presence of additional phases, according to the XRD, FTIR and Raman data. The calculated average crystallite sizes, calculated by XRD, around 40 nm, showed the tendency to increase with the temperature. The crystallite sizes, obtained by HR-SEM, were around of 40-50 nm. The sample that presented the highest intensity of the red emission band was the one heat treated at 400 deg. C for 2 h, and the sample that displayed the highest intensity of the green emission band was the one heat treated at 700 deg. C for 2 h. The CPM was shown to be a low cost route for the production of BaMoO 4 nanopowders, with the advantages of lower temperature, smaller time and reduced cost. The optical properties observed for BaMoO 4 nanopowders suggested that this material is a highly promising candidate for photoluminescent applications

In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

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Lau, Cia-Hin; Suh, Yousin

2017-01-01

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics. PMID:29333255

Cellulose/soy protein isolate composite membranes: evaluations of in vitro cytocompatibility with Schwann cells and in vivo toxicity to animals.

Science.gov (United States)

Luo, Lihua; Gong, Wenrong; Zhou, Yi; Yang, Lin; Li, Daokun; Huselstein, Celine; Wang, Xiong; He, Xiaohua; Li, Yinping; Chen, Yun

2015-01-01

To evaluate the in vitro cytocompatibility of cellulose/soy protein isolate composite membranes (CSM) with Schwann cells and in vivo toxicity to animals. A series of cellulose/soy protein isolate composite membranes (CSM) were prepared by blending, solution casting and coagulation process. The cytocompatibility of the CSM to Schwann cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by direct cells culture of Schwann cells on the surfaces of the CSM, respectively. The in vivo toxicity of the CSM to animals were also evaluated by acute toxicity testing, skin sensitization testing, pyrogen testing and intracutaneous stimulation testing, respectively, according to the ISO 10993 standard. The MTT assay showed that the cell viability of Schwann cells cultured in extracts from the CSM was higher than that from the neat cellulose membrane without containing SPI component. The direct cells culture indicated that the Schwann cells could attach and grow well on the surface of the CSM and the incorporation of SPI into cellulose contributed to improvement of cell adhesion and proliferation. The evaluations of in vivo biological safety suggested that the CSM showed no acute toxicity, no skin sensitization and no intracutaneous stimulation to the experimental animals. The CSM had in vitro cytocompatibility with Schwann cells and biological safety to animals, suggesting potential for the applications as nerve conduit for the repair of nerve defect.

ADMINISTRACIÓN DEL PROYECTO “DESARROLLO DE CAPACIDADES HUMANAS”, MEDIANTE LAS TÉCNICAS ADMINISTRATIVAS CPM Y PERT, URACCAN – SIUNA, 2012

OpenAIRE

Yader Antonio Ordoñez Aguilar; Eddy Alberto Zamora Díaz; Javier Osmar Artola García

2014-01-01

Esta investigación ha aplicado el Método de la Ruta Crítica (CPM) y las Técnicas de Evaluación y Revisión de Programas (PERT) en la administración del proyecto: “Desarrollo de capacidades técnicas y humanas para la implementación del plan de desarrollo regional con identidad en el sector de Las Minas”, ejecutado en Siuna, 2012, por la URACCAN. Es un estudio aplicativo retrospectivo con un enfoque cuantitativo enmarcado en las técnicas administrativas de proyecto CPM y PERT mediante el program...

Clinical Prediction Models for Cardiovascular Disease: The Tufts PACE CPM Database

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Wessler, Benjamin S.; Lana Lai, YH; Kramer, Whitney; Cangelosi, Michael; Raman, Gowri; Lutz, Jennifer S.; Kent, David M.

2015-01-01

Background Clinical prediction models (CPMs) estimate the probability of clinical outcomes and hold the potential to improve decision making and individualize care. For patients with cardiovascular disease (CVD) there are numerous CPMs available though the extent of this literature is not well described. Methods and Results We conducted a systematic review for articles containing CPMs for CVD published between January 1990 through May 2012. CVD includes coronary heart disease (CHD), heart failure (HF), arrhythmias, stroke, venous thromboembolism (VTE) and peripheral vascular disease (PVD). We created a novel database and characterized CPMs based on the stage of development, population under study, performance, covariates, and predicted outcomes. There are 796 models included in this database. The number of CPMs published each year is increasing steadily over time. 717 (90%) are de novo CPMs, 21 (3%) are CPM recalibrations, and 58 (7%) are CPM adaptations. This database contains CPMs for 31 index conditions including 215 CPMs for patients with CAD, 168 CPMs for population samples, and 79 models for patients with HF. There are 77 distinct index/ outcome (I/O) pairings. Of the de novo models in this database 450 (63%) report a c-statistic and 259 (36%) report some information on calibration. Conclusions There is an abundance of CPMs available for a wide assortment of CVD conditions, with substantial redundancy in the literature. The comparative performance of these models, the consistency of effects and risk estimates across models and the actual and potential clinical impact of this body of literature is poorly understood. PMID:26152680

Discrete tomography in an in vivo small animal bone study.

Science.gov (United States)

Van de Casteele, Elke; Perilli, Egon; Van Aarle, Wim; Reynolds, Karen J; Sijbers, Jan

2018-01-01

This study aimed at assessing the feasibility of a discrete algebraic reconstruction technique (DART) to be used in in vivo small animal bone studies. The advantage of discrete tomography is the possibility to reduce the amount of X-ray projection images, which makes scans faster and implies also a significant reduction of radiation dose, without compromising the reconstruction results. Bone studies are ideal for being performed with discrete tomography, due to the relatively small number of attenuation coefficients contained in the image [namely three: background (air), soft tissue and bone]. In this paper, a validation is made by comparing trabecular bone morphometric parameters calculated from images obtained by using DART and the commonly used standard filtered back-projection (FBP). Female rats were divided into an ovariectomized (OVX) and a sham-operated group. In vivo micro-CT scanning of the tibia was done at baseline and at 2, 4, 8 and 12 weeks after surgery. The cross-section images were reconstructed using first the full set of projection images and afterwards reducing them in number to a quarter and one-sixth (248, 62, 42 projection images, respectively). For both reconstruction methods, similar changes in morphometric parameters were observed over time: bone loss for OVX and bone growth for sham-operated rats, although for DART the actual values were systematically higher (bone volume fraction) or lower (structure model index) compared to FBP, depending on the morphometric parameter. The DART algorithm was, however, more robust when using fewer projection images, where the standard FBP reconstruction was more prone to noise, showing a significantly bigger deviation from the morphometric parameters obtained using all projection images. This study supports the use of DART as a potential alternative method to FBP in X-ray micro-CT animal studies, in particular, when the number of projections has to be drastically minimized, which directly reduces

Micro-computed tomography newly developed for in vivo small animal imaging

International Nuclear Information System (INIS)

Arai, Yoshinori; Ninomiya, Tadashi; Kato, Takafumi; Masuda, Yuji

2005-01-01

The aim of this paper is to report a newly developed micro-computed tomography system for in vivo use. The system was composed of a micro-focus X-ray tube and an image intensifier (I.I.), both of which rotated around the object stage. A guinea pig and a rat were examined. The anesthetized animal was set on the secure object stage. Images of the head of the guinea pig and the tibia knee joint of the rat were taken. In addition, an image of the rat's tail was taken. The reconstruction and the image viewing were carried out using I-View software. The voxel matrix was 512 x 512 x 384. The voxel sizes ranged from 10 x 10 x 10 μm to 100 x 100 x 100 μm. The exposure time was 17 s, and the reconstruction time was 150 s. The head of the guinea pig and the tibia/knee joint of the rat were observed clearly under 100-μm and 30μm voxels, respectively. The trabecular bone of the tail was also observed clearly under a 10 μm voxel. The newly developed micro-computed tomography system makes it possible to obtain images of anesthetized animals set on a secure object stage. Clear bone images of the small animals could be obtained within a short time. (author)

Endoscopic Cerenkov luminescence imaging: in vivo small animal tumor model validation

Science.gov (United States)

Song, Tianming; Bao, Chengpeng; Hu, Zhenhua; Wang, Kun; Liu, Xia; Tian, Jie

2015-03-01

Background: Cerenkov luminescence imaging (CLI) provides a great potential for clinical translation of optical molecular imaging techniques through using clinical approved radiotracers. However, it is difficult to obtain the Cerenkov luminescence signal of deeper biological tissues due to the small magnitude of the signal. To efficiently acquire the weak Cerenkov luminescence, we developed an endoscopic Cerenkov luminescence imaging (ECLI) system to reduce the in vivo imaging depth with minimum invasion, and validated the system on small animal tumor models. Methods: For the ECLI system, the laparoscope was connected to a high sensitive charge-couple device (CCD) camera (DU888+, Andor, UK) by a custom made adapter. We conducted a series of in vitro and in vivo experiments by use of the system. In the in vitro experiment, the endoscopic luminescence images of the 18F-FDG with various activities in EP tubes were acquired using ECLI system, and the sensitivity was compared with conventional CLI system. In the in vivo tumor experiment, 18F-FDG with the activity of 200μCi were intravenously injected into 3 tumor mice. Then the ECLI system was used to acquire the optical images for both non-invasive and invasive conditions. Conclusion: Experimental data showed the ECLI system could detect the 18F-FDG with the activity as low as 1μCi. Furthermore, our preliminary results indicated the possibility of ECLI technique for detecting Cerenkov signals inside the tumor tissue with deeper depth and guiding the surgical operation of tumor excision. We believe that this technique can help to accelerate the clinical translation of CLI.

In Vivo Evaluation of a New Embolic Spherical Particle (HepaSphere) in a Kidney Animal Model

International Nuclear Information System (INIS)

Luis, Esther de; Bilbao, Jose I.; Ciercoles, Jose A. Garcia Jalon de; Martinez-Cuesta, Antonio; Martino Rodriguez, Alba de; Lozano, Maria D.

2008-01-01

HepaSphere is a new spherical embolic material developed in a dry state that absorbs fluids and adapts to the vessel wall, leaving no space between the particle and the arterial wall. The aim of this study was to elucidate the final in vivo size, deformation, final location, and main properties of the particles when reconstituted with two different contrast media (Iodixanol and Ioxaglate) in an animal model. Two sizes of 'dry-state' particles (50-100 and 150-200 μm) were reconstituted using both ionic and nonionic contrast media. The mixture was used to partly embolize both kidneys in an animal model (14 pigs). The animals were sacrificed 4 weeks after the procedure and the samples processed. The final size of the particles was 230.2 ± 62.5 μm for the 50- to 100-μm dry-state particles and 314.4 ± 71 μm for the 150- to 200-μm dry-state particles. When the contrast medium (ionic versus nonionic) used for the reconstitution was studied to compare (Student's t-test) the final size of the particles, no differences were found (p > 0.05). The mean in vivo deformation for HepaSphere was 17.1% ± 12.3%. No differences (p > 0.05) were found in the deformation of the particle regarding the dry-state size or the contrast medium (Mann-Whitney test). We conclude that HepaSphere is stable, occludes perfectly, and morphologically adapts to the vessel lumen of the arteries embolized. There is no recanalization of the arteries 4 weeks after embolization. Its final in vivo size is predictable and the particle has the same properties in terms of size and deformation with the two different contrast media (Iodixanol and Ioxaglate)

Análise de risco em projetos de engenharia: uso do PERT/CPM com simulação

Directory of Open Access Journals (Sweden)

Walter Roberto Hernández Vergara

2017-01-01

Full Text Available PERT/CPM is a tool used in project management that allows the planning, scheduling, and coordination of activities for controlling time and cost. Monte Carlo simulation is a process based on samples of random numbers that assists in decision-making under conditions of risk and uncertainty. This study aims to analyze the restrictions in the construction sector, such as financial budgets and time. Through this analysis, the critical path is determined by the PERT/CPM tool, allowing the acceleration of project activities without exceeding the initial investment. The Monte Carlo simulation allowed carrying out a probabilistic analysis to quantify the inherent sensitivity in project completion and to have a more realistic view of future scenarios. The study was carried out at a construction company that furnished the data for its analysis and application.

State of the art in both in vitro and in vivo aspects of small animal imaging

International Nuclear Information System (INIS)

Maziere, B.; Lebars, D.

2002-01-01

Full text: In vivo imaging for small animals is dramatically expanding due to the coincidence of mainly three technical factors: 1. the explosion in computer power 2. the enhancement in image processing 3. the accessibility and affordability of digital autoradiography systems and small-animal scanners. Among these imaging techniques let us mention the anatomical imaging techniques such as ultrasonography, X-rays and IRM and the functional imaging radioisotopic techniques SPECT and TEP. The main advantage of the first group of imaging techniques is essentially linked to the high resolution of the anatomical images (with the drawback of the necessity of putting the animal at rest using anaesthesia). The main advantages of SPECT and PET are their high sensitivity and the vast number of functions or metabolism they allow to image. The applications for isotopic functional imaging in small animals are increasing rapidly. Factors contributing to this dramatic expansion include the three previous technical factors plus, at least, three methodological factors: 1. the drug discovery process based on receptor / mechanism of action 2. the increasing number of rodent models of human diseases (SCID mice implanted with human tumors, gene knock-out mice, transgene mice) 3. the advances in isotope and validated tracer availability performances Small animal radioisotopic functional imaging for drug development. In vivo quantification of biological processes to measure the mechanism of action of a potential drug and its concentration at the site of action has become mandatory for developing a drug. Rational and efficient means of confirming mechanisms of action are required. For this purpose, PET and/or SPECT functional - biochemical - molecular imaging in small animals are tools of choice for economical reasons (in the domain of drug development, industry is suffering huge opportunity costs by failing to weed out non-performing new active substances until late phases II and III) and

Optimising the Design Process of the Injection Camshaft by Critical Path Method (CPM

Directory of Open Access Journals (Sweden)

Olga-Ioana Amariei

2016-10-01

Full Text Available In the present paper a series of advantages of the CPM method are presented, focusing on the optimization of design duration of an injection camshaft, by cost criteria. The minimum duration of finalizing the design of the injection camshaft will be determined, as well as the total cost associated to this project, normally, and then under crash regime. At the end, two types of sensitivity analysis will be performed: Meeting the desire completation time and Meeting the desired budget cost

Effectiveness of prolonged use of continuous passive motion (CPM) as an adjunct to physiotherapy following total knee arthroplasty: Design of a randomised controlled trial [ISRCTN85759656

Science.gov (United States)

Lenssen, Anton F; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; van Steyn, Mike JA; Geesink, Ruud JT; van den Brandt, Piet A; de Bie, Rob A

2006-01-01

Background Adequate and intensive rehabilitation is an important requirement for successful Total Knee Arthroplasty. The primary focus of early rehabilitation is ambulation of patients and regaining range of motion in the knee. Although research suggests that Continuous Passive Motion should be implemented in the first rehabilitation phase following surgery, there is substantial debate about the duration of each session and the total period of CPM application and. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we intend to investigate the efficacy of prolonged use of a continuous passive motion (CPM) device in the home situation as an adjunct to standardised physical therapy. The experimental treatment is compared to standardised physical therapy, in patients with osteoarthritis of the knee undergoing Total Knee Arthroplasty (TKA). Efficacy will be assessed in terms of faster improvements in range of motion and functional recovery. Seventy patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment (less than 80° of knee flexion at the time of discharge) will be randomised over two treatment groups, a usual care group and an experimental group The experimental group will receive CPM + physiotherapy for 17 consecutive days after surgery, whereas the usual care group will receive the same treatment during the in-hospital phase (i.e. about four days), followed by physical therapy alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after discharge, both groups will receive standardised PT. The primary focus of rehabilitation will be functional recovery (e.g. ambulation) and regaining range of motion (ROM) in the knee. Discussion Because

Effectiveness of prolonged use of continuous passive motion (CPM) as an adjunct to physiotherapy following total knee arthroplasty: design of a randomised controlled trial [ISRCTN85759656].

Science.gov (United States)

Lenssen, Anton F; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; van Steyn, Mike J A; Geesink, Ruud J T; van den Brandt, Piet A; de Bie, Rob A

2006-02-23

Adequate and intensive rehabilitation is an important requirement for successful Total Knee Arthroplasty. The primary focus of early rehabilitation is ambulation of patients and regaining range of motion in the knee. Although research suggests that Continuous Passive Motion should be implemented in the first rehabilitation phase following surgery, there is substantial debate about the duration of each session and the total period of CPM application and. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we intend to investigate the efficacy of prolonged use of a continuous passive motion (CPM) device in the home situation as an adjunct to standardised physical therapy. The experimental treatment is compared to standardised physical therapy, in patients with osteoarthritis of the knee undergoing Total Knee Arthroplasty (TKA). Efficacy will be assessed in terms of faster improvements in range of motion and functional recovery. Seventy patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment (less than 80 degrees of knee flexion at the time of discharge) will be randomised over two treatment groups, a usual care group and an experimental group. The experimental group will receive CPM + physiotherapy for 17 consecutive days after surgery, whereas the usual care group will receive the same treatment during the in-hospital phase (i.e. about four days), followed by physical therapy alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after discharge, both groups will receive standardised PT. The primary focus of rehabilitation will be functional recovery (e.g. ambulation) and regaining range of motion (ROM) in the knee. Because restricted knee ROM affects

A novel animal model for in vivo study of liver cancer metastasis

Institute of Scientific and Technical Information of China (English)

Shinsuke Fujiwara; Katsutoshi Yoshizato; Hikaru Fujioka; Chise Tateno; Ken Taniguchi; Masahiro Ito; Hiroshi Ohishi; Rie Utoh; Hiromi Ishibashi; Takashi Kanematsu

2012-01-01

AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator (uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse line (uPA/SCID mice).Host mice were divided into two groups (A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index (RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A (RI =22.0％ ± 2.6％).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL (range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies (RI =12.0％ ± 6.8％ and 66.0％ ± 12.3％,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of

CPm gene diversity in field isolates of Citrus tristeza virus from Colombia.

Science.gov (United States)

Oliveros-Garay, Oscar Arturo; Martinez-Salazar, Natalhie; Torres-Ruiz, Yanneth; Acosta, Orlando

2009-01-01

The nucleotide sequence diversity of the CPm gene from 28 field isolates of Citrus tristeza virus (CTV) was assessed by SSCP and sequence analyses. These isolates showed two major shared haplotypes, which differed in distribution: A1 was the major haplotype in 23 isolates from different geographic regions, whereas R1 was found in isolates from a discrete region. Phylogenetic reconstruction clustered A1 within an independent group, while R1 was grouped with mild isolates T30 from Florida and T385 from Spain. Some isolates contained several minor haplotypes, which were very similar to, and associated with, the major haplotype.

A Comparison of Red Fluorescent Proteins to Model DNA Vaccine Expression by Whole Animal In Vivo Imaging.

Science.gov (United States)

Kinnear, Ekaterina; Caproni, Lisa J; Tregoning, John S

2015-01-01

DNA vaccines can be manufactured cheaply, easily and rapidly and have performed well in pre-clinical animal studies. However, clinical trials have so far been disappointing, failing to evoke a strong immune response, possibly due to poor antigen expression. To improve antigen expression, improved technology to monitor DNA vaccine transfection efficiency is required. In the current study, we compared plasmid encoded tdTomato, mCherry, Katushka, tdKatushka2 and luciferase as reporter proteins for whole animal in vivo imaging. The intramuscular, subcutaneous and tattooing routes were compared and electroporation was used to enhance expression. We observed that overall, fluorescent proteins were not a good tool to assess expression from DNA plasmids, with a highly heterogeneous response between animals. Of the proteins used, intramuscular delivery of DNA encoding either tdTomato or luciferase gave the clearest signal, with some Katushka and tdKatushka2 signal observed. Subcutaneous delivery was weakly visible and nothing was observed following DNA tattooing. DNA encoding haemagglutinin was used to determine whether immune responses mirrored visible expression levels. A protective immune response against H1N1 influenza was induced by all routes, even after a single dose of DNA, though qualitative differences were observed, with tattooing leading to high antibody responses and subcutaneous DNA leading to high CD8 responses. We conclude that of the reporter proteins used, expression from DNA plasmids can best be assessed using tdTomato or luciferase. But, the disconnect between visible expression level and immunogenicity suggests that in vivo whole animal imaging of fluorescent proteins has limited utility for predicting DNA vaccine efficacy.

Theoretical Prediction on [5]Radialene Sandwich Complexes (CpM)2(C10H10) (Cp = η5-C5H5; M = Fe, Co, Ni): Geometry, Spin States, and Bonding.

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Liu, Nan-Nan; Xue, Ying-Ying; Ding, Yi-Hong

2017-02-09

[5]Radialene, the missing link for synthesis of radialene family, has been finally obtained via the preparation and decomplexation of the [5]radialene-bis-Fe(CO) 3 complex. The stability of [5]radialene complex benefits from the coordination with Fe(CO) 3 by losing free 1,3-butadiene structures to avoid polymerization. In light of the similar coordination ability of half-sandwiches CpM(Cp = η 5 -C 5 H 5 ; M = Fe, Co, Ni), there is a great possibility that the sandwiched complexes of [5]radialene with CpM are available. Herein, we present the first theoretical prediction on the geometry, spin states and bonding of (CpM)(C 10 H 10 ) and (CpM) 2 (C 10 H 10 ). For M = Fe, Co, Ni, the ground states of (CpM)(C 10 H 10 ) and (CpM) 2 (C 10 H 10 ) are doublet and triplet, singlet and singlet, and doublet and triplet states, where each Fe, Co, and Ni adopts 17, 18, and 19 electron-configuration, respectively. In particular, (CpFe) 2 (C 10 H 10 ) and (CpNi) 2 (C 10 H 10 ) have considerable open-shell singlet features. Generally the trans isomers of (CpM) 2 (C 10 H 10 ) with two CpM fragments on the opposite sides of the [5]radialene plane are apparently more stable than the cis ones with CpM fragments on the same side. However, for the singlet and triplet isomers of (CpNi) 2 (C 10 H 10 ) (both cis and trans isomers), the energy differences are relatively small, indicating that these isomers all have the opportunity to exist. Besides, the easy Diels-Alder (DA) dimerization between the [3]dendralene-like fragments of (CpM)(C 10 H 10 ) suggests the great difficulty in isolating the (CpM)(C 10 H 10 ) monomer.

Microscopy of bacterial translocation during small bowel obstruction and ischemia in vivo – a new animal model

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Hafner Mathias

2002-08-01

Full Text Available Abstract Background Existing animal models provide only indirect information about the pathogenesis of infections caused by indigenous gastrointestinal microflora and the kinetics of bacterial translocation. The aim of this study was to develop a novel animal model to assess bacterial translocation and intestinal barrier function in vivo. Methods In anaesthetized male Wistar rats, 0.5 ml of a suspension of green fluorescent protein-transfected E. coli was administered by intraluminal injection in a model of small bowel obstruction. Animals were randomly subjected to non-ischemic or ischemic bowel obstruction. Ischemia was induced by selective clamping of the terminal mesenteric vessels feeding the obstructed bowel loop. Time intervals necessary for translocation of E. coli into the submucosal stroma and the muscularis propria was assessed using intravital microscopy. Results Bacterial translocation into the submucosa and muscularis propria took a mean of 36 ± 8 min and 80 ± 10 min, respectively, in small bowel obstruction. Intestinal ischemia significantly accelerated bacterial translocation into the submucosa (11 ± 5 min, p E. coli were visible in frozen sections of small bowel, mesentery, liver and spleen taken two hours after E. coli administration. Conclusions Intravital microscopy of fluorescent bacteria is a novel approach to study bacterial translocation in vivo. We have applied this technique to define minimal bacterial transit time as a functional parameter of intestinal barrier function.

[Cross-cultural adaptation to the European Portuguese of the questionnaire "Patient Knowledge about their Medications" (CPM-ES-ES)].

Science.gov (United States)

Salmerón Rubio, Joaquín; Iglésias-Ferreira, Paula; García Delgado, Pilar; Mateus-Santos, Henrique; Martínez-Martínez, Fernando

2013-12-01

The scope of this work is to conduct the cross-cultural adaptation from Spanish to European Portuguese of a questionnaire to measure the degree of "Patient Knowledge about their Medications" (CPM-ES-ES). A method based on six steps was applied: 1. Translation into Portuguese, 2. Elaboration of the first consensus version in Portuguese; 3.Back-translation into Spanish; 4. Elaboration of the second consensus version (cultural equivalency); 5. Conducting the pre-test; 6. Evaluation of the overall results. A cross-culturally adapted questionnaire in European Portuguese that measures the degree of "Patient Knowledge about their Medications" is proposed. The pre-test confirmation obtained 100% agreement with the corrected version of the second consensus version after pre-testing. The methodology selected made it possible to cross-culturally adapt the Spanish version of the CPM-ES-ES questionnaire to the Portuguese version. Further studies should demonstrate the equivalence of the psychometric properties of the cross-cultural translation into Portuguese with the original version.

SIC, an intracerebral radiosensitive probe for in vivo neuropharmacology investigations in small laboratory animals: theoretical considerations and practical characteristics

Science.gov (United States)

Pain, F.; Laniece, P.; Mastrippolito, R.; Charon, Y.; Comar, D.; Leviel, V.; Pujol, J. F.; Valentin, L.

2000-02-01

Although high-resolution tomographs provide a new approach that strongly simplifies the measurement of in vivo tracer biodistribution and kinetics in small animals, they suffer from an important drawback: the need for animal anesthesia or immobilization, which restricts the neurophysiological investigations. Furthermore, quantitative in vivo experiments realized on the brain sometimes only require a simple measurement of the radioactivity achieved on a few local points and do not necessarily imply the use of a tomograph, which is a detector of high cost. These constraints led the authors to develop an interacerebral /spl beta/ sensitive probe, sonde intracerebrate (SIC) (French acronym of intracerebral probe) that will allow chronic measurements of the neurophysiological activity in awake and unrestrained small animals. The volume to which the probe is sensitive and the noise contributions to the relevant signal have been evaluated through Monte Carlo simulations. Characterizations of a first prototype based on a small piece of scintillating fiber (500-/spl mu/m diameter and 1-mm length) fused to a same diameter optical fiber coupled in turn to a photomultiplier are also presented. A first configuration of the detector is finally proposed.

De hand van Romme. C.P.M. Romme als staatkundig hoofdredacteur van De Volkskrant (1945-1952

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M. Broersma

2000-01-01

Full Text Available Romme's hand: The politician C.P.M. Romme as editor-in-chief of the 'De Volkskrant' (1945-1952Between 1945 and 1953, C.P.M. Romme held two posts simultaneously; he was both the political leader of the Katholieke Volkspartij (KVP and editor-in-chief of the newspaper 'De Volkskrant'. Many assumptions have been made about this joint position, mostly by theorists and researchers into the subject of 'pillarization'. However, Romme's actual influence on the content of the 'Volkskrant' has not yet been properly researched. This article explores the role that Romme the politician played during his editorship of the 'Volkskrant'. It aims to show how Romme used the newspaper to attain his political goals; especially with regard to maintaining Catholic political unity and social solidarity. He wrote leading articles to influence public opinion, acted in a censorial capacity and invited journalists and political supporters to contribute articles that supported his own views. In 1952, the owner of the newspaper, the 'Katholieke Arbeidersbeweging' (The Trade Union for Catholics, forced Romme to resign. Ironically, it was a conflict about maintaining Catholic political unity - Romme's main political goal – that ultimately led to his resignation.

Improving Overall Equipment Effectiveness Using CPM and MOST: A Case Study of an Indonesian Pharmaceutical Company

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Omega, Dousmaris; Andika, Aditya

2017-12-01

This paper discusses the results of a research conducted on the production process of an Indonesian pharmaceutical company. The company is experiencing low performance in the Overall Equipment Effectiveness (OEE) metric. The OEE of the company machines are below world class standard. The machine that has the lowest OEE is the filler machine. Through observation and analysis, it is found that the cleaning process of the filler machine consumes significant amount of time. The long duration of the cleaning process happens because there is no structured division of jobs between cleaning operators, differences in operators’ ability, and operators’ inability in utilizing available cleaning equipment. The company needs to improve the cleaning process. Therefore, Critical Path Method (CPM) analysis is conducted to find out what activities are critical in order to shorten and simplify the cleaning process in the division of tasks. Afterwards, The Maynard Operation and Sequence Technique (MOST) method is used to reduce ineffective movement and specify the cleaning process standard time. From CPM and MOST, it is obtained the shortest time of the cleaning process is 1 hour 28 minutes and the standard time is 1 hour 38.826 minutes.

Effectiveness of prolonged use of continuous passive motion (CPM as an adjunct to physiotherapy following total knee arthroplasty: Design of a randomised controlled trial [ISRCTN85759656

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Geesink Ruud JT

2006-02-01

Full Text Available Abstract Background Adequate and intensive rehabilitation is an important requirement for successful Total Knee Arthroplasty. The primary focus of early rehabilitation is ambulation of patients and regaining range of motion in the knee. Although research suggests that Continuous Passive Motion should be implemented in the first rehabilitation phase following surgery, there is substantial debate about the duration of each session and the total period of CPM application and. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. Methods In a randomised controlled trial we intend to investigate the efficacy of prolonged use of a continuous passive motion (CPM device in the home situation as an adjunct to standardised physical therapy. The experimental treatment is compared to standardised physical therapy, in patients with osteoarthritis of the knee undergoing Total Knee Arthroplasty (TKA. Efficacy will be assessed in terms of faster improvements in range of motion and functional recovery. Seventy patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment (less than 80° of knee flexion at the time of discharge will be randomised over two treatment groups, a usual care group and an experimental group The experimental group will receive CPM + physiotherapy for 17 consecutive days after surgery, whereas the usual care group will receive the same treatment during the in-hospital phase (i.e. about four days, followed by physical therapy alone (usual care in the first two weeks after hospital discharge. From 18 days to three months after discharge, both groups will receive standardised PT. The primary focus of rehabilitation will be functional recovery (e.g. ambulation and regaining range of motion (ROM in the knee

Laser-enhanced high-intensity focused ultrasound heating in an in vivo small animal model

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Jo, Janggun; Yang, Xinmai

2016-11-01

The enhanced heating effect during the combination of high-intensity focused ultrasound (HIFU) and low-optical-fluence laser illumination was investigated by using an in vivo murine animal model. The thighs of murine animals were synergistically irradiated by HIFU and pulsed nano-second laser light. The temperature increases in the target region were measured by a thermocouple under different HIFU pressures, which were 6.2, 7.9, and 9.8 MPa, in combination with 20 mJ/cm2 laser exposures at 532 nm wavelength. In comparison with conventional laser therapies, the laser fluence used here is at least one order of magnitude lower. The results showed that laser illumination could enhance temperature during HIFU applications. Additionally, cavitation activity was enhanced when laser and HIFU irradiation were concurrently used. Further, a theoretical simulation showed that the inertial cavitation threshold was indeed decreased when laser and HIFU irradiation were utilized concurrently.

Kinematic Analysis of Cpm Machine Supporting to Rehabilitation Process after Surgical Knee Arthroscopy and Arthroplasty

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Trochimczuk, R.; Kuźmierowski, T.

2014-11-01

Existing commercial solutions of the CPM (Continuous Passive Motion) machines are described in the paper. Based on the analysis of existing solutions we present our conceptual solution to support the process of rehabilitation of the knee joint which is necessary after arthroscopic surgery. For a given novel structure we analyze and present proprietary algorithms and the computer application to simulate the operation of our PCM device. In addition, we suggest directions for further research.

Assessing the inter- and intra-animal variability of in vivo OsteoProbe skeletal measures in untreated dogs

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Erin M.B. McNerny

2016-12-01

Full Text Available The OsteoProbe is a second-generation reference point indentation (RPI device without a reference probe that is designed to simplify RPI testing for clinical use. Successful clinical implementation of the OsteoProbe would benefit from a better understanding of how its output, bone material strength index (BMSi, relates to the material properties of bone and under what conditions it reliably correlates with fracture risk. Large animal models have the potential to help fill this knowledge gap, as cadaveric studies are retrospective and limited by incomplete patient histories (including the potential use of bone matrix altering drugs such as bisphosphonates. The goal of this study was to assess the intra and inter-animal variability of OsteoProbe measures in untreated beagle dogs (n = 12, and to evaluate this variability in comparison to traditional mechanical testing. OsteoProbe measurements were performed in vivo on the left tibia of each dog and repeated 6 months later on the day of sacrifice. Within-animal variation of BMSi (CV of 5–10 indents averaged 8.9 and 9.0% at the first and second timepoints, respectively. In contrast, inter-animal variation of BMSi increased from 5.3% to 9.1%. The group variation of BMSi was on par with that of traditional 3-point mechanical testing; inter-animal variation was 10% for ultimate force, 13% for stiffness, and 12% for total work as measured on the femur. There was no significant change in mean BMSi after 6 months, but the individual change with time across the 12 dogs was highly variable, ranging from −12.4% to +21.7% (mean 1.6%, SD 10.6%. No significant correlations were found between in vivo tibia BMSi and femur mechanical properties measured by ex vivo 3-pt bending, but this may be a limitation of sample size or the tests being performed on different bones. No relationship was found between BMSi and tissue mineral density, but a strong positive correlation was found between BMSi and tibia

Preparation and characterizations of Ba0.8Ca0.2TiO3 by complex polymerization method (CPM)

International Nuclear Information System (INIS)

Motta, F.V.; Marques, A.P.A.; Escote, M.T.; Melo, D.M.A.; Ferreira, A.G.; Longo, E.; Leite, E.R.; Varela, J.A.

2008-01-01

Ba 0.8 Ca 0.2 TiO 3 (BCT) was prepared by the complex polymerization method (CPM) using Ba 0.8 Ca 0.2 CO 3 and [Ti[OCH(CH 3 ) 2 ] 4 as starting materials. The powders were crystallized at several temperatures from 400 to 1200 deg. C using different times (from 1 to 8 h). The phase evolution and the physical properties were characterized by X-ray diffraction, Raman and IR spectroscopy. Such results indicate that the precursor Ba 0.8 Ca 0.2 CO 3 used in the synthesis of Ba 0.8 Ca 0.2 TiO 3 promotes an effective complexation of the ions Ca 2+ in the matrix of BaTiO 3 . After heat treatment for 2 h at 600 deg. C the phase BCT was obtained with absence of the CaTiO 3 or BaCO 3 phases. The CPM is an efficient method in the synthesis of the BCT, using small reaction time and low temperature and cost for the preparation of these powders

Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

International Nuclear Information System (INIS)

Yang Yongfeng; Tai Yuanchuan; Siegel, Stefan; Newport, Danny F; Bai, Bing; Li, Quanzheng; Leahy, Richard M; Cherry, Simon R

2004-01-01

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17 640 LSO crystals each measuring 0.975 x 0.975 x 12.5 mm 3 , which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 μl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150-750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235 000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24 600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250-750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

International Nuclear Information System (INIS)

Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf; Schramm, Nils

2005-01-01

The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [ 123 I]FP-CIT. [ 123 I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [ 123 I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99m Tc-DPD and 99m Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [ 123 I]FP-CIT scans with images of brain perfusion obtained with 99m Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V '' 3 ) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (ttest, two-tailed, p '' 3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [ 123 I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [ 123 I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems. (orig.)

Ex vivo effects of lysine clonixinate on cyclooxygenases in rat lung and stomach preparations.

Science.gov (United States)

Franchi, A M; Di Girolamo, G; De los Santos, A R; Marti, M L; Gimeno, M A

1999-01-01

Lysine clonixinate (LC) is an anti-inflammatory, anti-pyretic and analgesic drug with minor digestive side effects, which might suggest a weak COX-1 inhibitor. The aim of this study focused on ex vivo effects of LC 40 mg/kg ip and indomethacin (INDO) 10 mg/kg ip in lung and stomach preparations of control rats and LPS-treated rats (5 mg/kg ip). The non-steroidal antiinflammatory drugs were administered concomitantly, following three hours and before one, two or three hours of LPS treatment. Tissues were weighed and incubated in 2 ml of Kress Ringer Bicarbonate buffer containing glucose (11 mM) under an atmosphere of 95% oxygen and 5% CO(2). Approximately 200 mg of tissue were used for each determination; 0.25 microCi of (14)C-arachidonic acid was added to each tube and the tissues were incubated for 60 min. Prostanoids were extracted from the incubation medium and separated by TLC. Results were expressed as a percentage of the total radioactivity of the plates (% of cpm on plate/100 mg ww). It was found that LC animals that were not given LPS did not modify the synthesis of PGE(2); in lung and stomach tissues showing that did not inhibit COX-1 activity. However, LC inhibited clearly the synthesis of PGE(2) in both preparations obtained from LPS-treated animals. The inhibition was shown when the rats were treated concomitantly, 3 h after or 1 or 2 h before the injection of LPS.

In vivo fluorescence enhanced optical tomography reconstruction of lung cancer of non immersed small animals

Science.gov (United States)

Hervé, L.; Koenig, A.; Da Silva, A.; Berger, M.; Boutet, J.; Dinten, J. M.; Peltié, P.; Rizo, P.

2007-02-01

Fluorescence enhanced diffuse optical tomography (fDOT) is envisioned to be useful to collect functional information from small animal models. For oncology applications, cancer-targeted fluorescent markers can be used as a surrogate of the cancer activity. We are developing a continuous wave fDOT bench intended to be integrated in systems dedicated to whole body small animal fluorescence analyses. The focus is currently put on the reconstruction of non immersed small animals imaged by a CCD camera. The reconstruction stage already corrects the tissue heterogeneity artifacts through the computation of an optical heterogeneity map. We will show how this formalism coupled with the determination of the animal boundaries performed by a laser scanner, can be used to manage non contact acquisitions. The time of reconstruction for a 10 × 9 laser source positions, 45 × 40 detector elements and 14 × 11 × 14 mesh voxels is typically 10 minutes on a 3GHz PCs corresponding to the acquisition time allowing the two tasks to be performed in parallel. The system is validated on an in vivo experiment performed on three healthy nude mice and a mouse bearing a lung tumor at 10, 12 and 14 days after implantation allowing the follow up of the disease. The 3D fluorescence reconstructions of this mouse are presented and the total fluorescence amounts are compared.

Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

Energy Technology Data Exchange (ETDEWEB)

Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

2005-03-01

The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

Contracting in vivo research: what are the issues?

Science.gov (United States)

Underwood, Wendy J

2007-07-01

As a result of increasing internal and external pressures, research institutions are using contract research organizations for the conduct of in vivo research. Many issues arise when contracting animal research, including concern regarding animal health and welfare. Each sponsor institution should develop a program for outsourced in vivo research that evaluates and ensures appropriate care and use of research animals. Each sponsoring institution should consider establishing a policy and procedure for how outsourced in vivo studies will be approved, conducted, and monitored. An approved list of contract facilities can be established on the basis of accepted standards for animal care and use. Written contracts should include confidentiality agreements, the delineation of animal ownership, and the expectation to comply with all applicable regulations and guidelines for research animal care and use. Finally, a process for communication of adverse study or animal welfare events should be established. Thorough evaluation of contract organizations will help ensure appropriate research animal care and use.

Biocompatibility and setting time of CPM-MTA and white Portland cement clinker with or without calcium sulfate.

Science.gov (United States)

Bramante, Clovis Monteiro; Kato, Marcia Magro; Assis, Gerson Francisco de; Duarte, Marco Antonio Hungaro; Bernardineli, Norberti; Moraes, Ivaldo Gomes de; Garcia, Roberto Brandão; Ordinola-Zapata, Ronald; Bramante, Alexandre Silva

2013-01-01

To evaluate the biocompatibility and the setting time of Portland cement clinker with or without 2% or 5% calcium sulfate and MTA-CPM. Twenty-four mice (Rattus norvegicus) received subcutaneously polyethylene tubes filled with Portland cement clinker with or without 2% or 5% calcium sulfate and MTA. After 15, 30 and 60 days of implantation, the animals were killed and specimens were prepared for microscopic analysis. For evaluation of the setting time, each material was analyzed using Gilmore needles weighing 113.5 g and 456.5 g, according to the ASTM specification Number C266-08 guideline. Data were analyzed by ANOVA and Tukey's test for setting time and Kruskal-Wallis and Dunn test for biocompatibility at 5% significance level. Histologic observation showed no statistically significant difference of biocompatibility (p>0.05) among the materials in the subcutaneous tissues. For the setting time, clinker without calcium sulfate showed the shortest initial and final setting times (6.18 s/21.48 s), followed by clinker with 2% calcium sulfate (9.22 s/25.33 s), clinker with 5% calcium sulfate (10.06 s/42.46 s) and MTA (15.01 s/42.46 s). All the tested materials showed biocompatibility and the calcium sulfate absence shortened the initial and final setting times of the white Portland cement clinker.

Sealing ability of grar MTA AngelusTM, CPM TM and MBPc used as apical plugs.

Science.gov (United States)

Orosco, Fernando Accorsi; Bramante, Clovis Monteiro; Garcia, Roberto Brandão; Bernadineli, Norberti; Moraes, Ivaldo Gomes de

2008-01-01

This study evaluated the sealing ability of apical plugs fabricated with gray MTA Angelus sealer, CPM TM sealer and MBPc sealer. The root canals of 98 extracted single-rooted human teeth were instrumented with #5 to #1 Gates Glidden drills according to the crown-down technique until the #1 drill could pass through the apical foramen. The specimens were then prepared with K-files, starting with an ISO 50 until an ISO 90 could be visualized 1 mm beyond the apex. After root canal preparation, the external surface of each root was rendered impermeable and roots were assigned to 3 experimental groups (n = 30), which received a 5-mm thick apical plug of gray MTA Angelus, CPM and MBPc, and two control groups (n=4). The remaining portion of the canal in the experimental groups was filled by the lateral condensation technique. The teeth of each group, properly identified, were fixed on utility wax by their crowns and were placed in plastic flasks, leaving the apex free and facing upward. The flasks were filled with 0.2% Rhodamine B solution, pH 7.0, so as to completely cover the root apex of all teeth. The sealing ability was analyzed by measuring 0.2% Rhodamine B leakage after all groups had been maintained in this solution for 48 hours. Data were analyzed statistically by Kruskal-Wallis test and Dunn test with a=5%. The results showed that, among the tested materials used for fabrication of apical plugs, MBPc sealer had the least amount of leakage with statistically significant difference (p<0.05).

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

Science.gov (United States)

Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

2018-03-01

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Measurements of WDS Objects Found in Images Taken for Detecting CPM Pairs in the LSPM Catalog

Science.gov (United States)

Knapp, Wilfried; Nanson, John

2017-10-01

During our research for CPM objects in the LSPM catalog so far not included in the WDS catalog part II (Knapp and Nanson 2017) we found by chance a surprisingly large number of WDS objects in the field of view of several images taken for this project. To use the existing image material in the best possible way we decided to take measurements of these objects and to look at other existing catalog data allowing a check for potential common proper motion. This report presents the findings of this research.

Transparency in the reporting of in vivo pre-clinical pain research: The relevance and implications of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines.

Science.gov (United States)

Rice, Andrew S C; Morland, Rosemary; Huang, Wenlong; Currie, Gillian L; Sena, Emily S; Macleod, Malcolm R

2017-12-29

Clear reporting of research is crucial to the scientific process. Poorly designed and reported studies are damaging not only to the efforts of individual researchers, but also to science as a whole. Standardised reporting methods, such as those already established for reporting randomised clinical trials, have led to improved study design and facilitated the processes of clinical systematic review and meta-analysis. Such standards were lacking in the pre-clinical field until the development of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines. These were prompted following a survey which highlighted a widespread lack of robust and consistent reporting of pre-clinical in vivo research, with reports frequently omitting basic information required for study replication and quality assessment. The resulting twenty item checklist in ARRIVE covers all aspects of experimental design with particular emphasis on bias reduction and methodological transparency. Influential publishers and research funders have already adopted ARRIVE. Further dissemination and acknowledgement of the importance of these guidelines is vital to their widespread implementation. Conclusions and implications Wide implementation of the ARRIVE guidelines for reporting of in vivo preclinical research, especially pain research, are essential for a much needed increased transparency and quality in publishing such research. ARRIVE will also positively influence improvements in experimental design and quality, assist the conduct of accurate replication studies of important new findings and facilitate meta-analyses of preclinical research.

CT with a CMOS flat panel detector integrated on the YAP-(S)PET scanner for in vivo small animal imaging

International Nuclear Information System (INIS)

Di Domenico, Giovanni; Cesca, Nicola; Zavattini, Guido; Auricchio, Natalia; Gambaccini, Mauro

2007-01-01

Several research groups are pursuing multimodality simultaneous functional and morphological imaging. In this line of research the high resolution YAP-(S)PET small animal integrated PET-SPECT imaging system, constructed by our group of medical physics at the University of Ferrara, is being upgraded with a computed tomography (CT). In this way it will be possible to perform in vivo molecular and genomic imaging studies on small animals (such as mice and rats) and at the same time obtain morphological information necessary for both attenuation correction and accurate localization of the region under investigation. We have take simultaneous PET-CT and SPECT-CT images of phantoms obtained with a single scanner

Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies.

Science.gov (United States)

Pietzsch, J; Bergmann, R; Wuest, F; Pawelke, B; Hultsch, C; van den Hoff, J

2005-12-01

The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer's disease and atherosclerosis. As a representative example, oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Radiolabelling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [(18)F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [(18)F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution of 2 mm). From this study we conclude that the use of [(18)F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.

Sealing ability of grar MTA AngelusTM, CPM TM and MBPc used as apical plugs

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Fernando Accorsi Orosco

2008-02-01

Full Text Available This study evaluated the sealing ability of apical plugs fabricated with gray MTA AngelusTM sealer, CPM TM sealer and MBPc sealer. The root canals of 98 extracted single-rooted human teeth were instrumented with #5 to #1 Gates Glidden drills according to the crown-down technique until the #1 drill could pass through the apical foramen. The specimens were then prepared with K-files, starting with an ISO 50 until an ISO 90 could be visualized 1 mm beyond the apex. After root canal preparation, the external surface of each root was rendered impermeable and roots were assigned to 3 experimental groups (n = 30, which received a 5-mm thick apical plug of gray MTA AngelusTM, CPM TM and MBPc, and two control groups (n=4. The remaining portion of the canal in the experimental groups was filled by the lateral condensation technique. The teeth of each group, properly identified, were fixed on utility wax by their crowns and were placed in plastic flasks, leaving the apex free and facing upward. The flasks were filled with 0.2% Rhodamine B solution, pH 7.0, so as to completely cover the root apex of all teeth. The sealing ability was analyzed by measuring 0.2% Rhodamine B leakage after all groups had been maintained in this solution for 48 hours. Data were analyzed statistically by Kruskal-Wallis test and Dunn test with a=5%. The results showed that, among the tested materials used for fabrication of apical plugs, MBPc sealer had the least amount of leakage with statistically significant difference (p<0.05.

In vivo animal studies with sugammadex.

NARCIS (Netherlands)

Booij, L.H.D.J.; Egmond, J. van; Driessen, J.J.; Boer, H.D. de

2009-01-01

A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of

Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

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Heidi Mulcahy

2011-10-01

Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

Senescent changes in the ribosomes of animal cells in vivo and in vitro

Science.gov (United States)

Miquel, J.; Johnson, J. E., Jr.

1979-01-01

The paper examines RNA-ribosomal changes observed in protozoa and fixed postmitotic cells, as well as the characteristics of intermitotic cells. Attention is given to a discussion of the implications of the reported ribosomal changes as to the senescent deterioration of protein synthesis and physiological functions. A survey of the literature suggests that, while the data on ribosomal change in dividing cells both in vivo and in vitro are inconclusive, there is strong histological and biochemical evidence in favor of some degree of quantitative ribosomal loss in fixed postmitotic cells. Since these decreases in ribosomes are demonstrated in differential cells from nematodes, insects and mammals, they may represent a universal manifestation of cytoplasmic senescence in certain types of fixed postmitotic animal cells. The observed variability in ribosomal loss for cells belonging to the same type suggests that this involution phenomenon is rather related to the wear and tear suffered by a particular cell.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

Science.gov (United States)

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

2015-01-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

METHOD FOR SIMULTANEOUS 90SR AND 137CS IN-VIVO MEASUREMENTS OF SMALL ANIMALS AND OTHER ENVIRONMENTAL MEDIA DEVELOPED FOR THE CONDITIONS OF THE CHERNOBYL EXCLUSION ZONE

Energy Technology Data Exchange (ETDEWEB)

Farfan, E.; Jannik, T.

2011-10-01

To perform in vivo simultaneous measurements of the {sup 90}Sr and {sup 137}Cs content in the bodies of animals living in the Chernobyl Exclusion Zone (ChEZ), an appropriate method and equipment were developed and installed in a mobile gamma beta spectrometry laboratory. This technique was designed for animals of relatively small sizes (up to 50 g). The {sup 90}Sr content is measured by a beta spectrometer with a 0.1 mm thick scintillation plastic detector. The spectrum processing takes into account the fact that the measured object is 'thick-layered' and contains a comparable quantity of {sup 137}Cs, which is a characteristic condition of the ChEZ. The {sup 137}Cs content is measured by a NaI scintillation detector that is part of the combined gamma beta spectrometry system. For environmental research performed in the ChEZ, the advantages of this method and equipment (rapid measurements, capability to measure live animals directly in their habitat, and the capability of simultaneous {sup 90}Sr and {sup 137}Cs measurements) far outweigh the existing limitations (considerations must be made for background radiation and the animal size, skeletal shape and body mass). The accuracy of these in vivo measurements is shown to be consistent with standard spectrometric and radiochemical methods. Apart from the in vivo measurements, the proposed methodology, after a very simple upgrade that is also described in the article, works even more accurately with samples of other media, such as soil and plants.

Fast Missile Boat Project Planning using CPM and What If Analysis Method

Science.gov (United States)

Silvianita; Firmansyah, R.; Rosyid, D. M.; Suntoyo; Chamelia, D. M.

2018-03-01

This paper discusses analysis of fast ship missile project planning with CPM and What If analysis.The poor performance can cause project delay and cost overruns, these two things often occur in a project management. Scheduling has an important role to control the project. Good scheduling is required because it will affect the product quality. Scheduling is useful to manage the activities so that the project completion time can be as short as possible and it is used to determine the costs of the project are in optimum condition. The alternatives that can be used to overcome the delay project namely increasing labor and equipment.Project planning can be done to determine whether the project is already in an optimum condition. Alternatives that can be used to overcome the delay in the project is to increase labor and equipment, the next is to look for the optimum solution taking into account the duration and gain of each alternative.

The clinical utility of nuclear magnetic resonance spectroscopy: recent in vitro, in vivo animal and clinical observations

International Nuclear Information System (INIS)

Blackstock, A. William; Kwock, Lester; Mukherji, Suresh K.; Schiro, Sharon; Tepper, Joel E.

1995-01-01

Purpose/Objective: Combined radiation and 5-fluorouracil (5-FU) has resulted in improved outcomes in patients treated with gastrointestinal malignancies and squamous cancers of the head and neck. In our first aim, we proposed that the enhanced cell kill and tumor regression observed with the combination of 5-FU and radiation is related to radiation potentiating the anti-tumor effects of 5-FU. Using fluorine-19 ( 19 F) nuclear magnetic resonance (nmr) we non-invasively determined the tumor clearance rates of 5-FU +/- radiation in an animal model and used this research tool to predict tumor response in patients receiving concurrent radiation and 5-FU therapy. Our second aim was to evaluate the use of proton ( 1 H) nmr spectroscopy to non-invasively determine the spectral characteristics of malignant tumors in the head and neck and liver and correlate these clinical observations with in vitro and in vivo data. Materials and Methods: 1 H and 19 F spectroscopic analysis were performed with a 2.0T Otsuka magnetic resonance imaging and spectroscopy system. 1 H nmr patient studies were done on a clinical 1.5T Philips MR system. In vitro magnetic resonance spectroscopy (MRS) studies were performed on a 11 T Bruker nmr system. Animal experiments for the 19 F nmr studies were performed on 3-6 week old female (Nu/Nu) athymic nude mice. Animals were injected s.c. with 10 6 human colon adenocarcinoma (HT-29) cells. At a tumor size of 1.0 cm, animals in the first group received i.v. 5-FU (100 mg/kg) immediately prior to spectroscopic analysis. Animals in the second group were treated with a single radiation dose of either 2 Gy or 10 Gy just prior to the 5-FU injection and subsequent spectroscopy. Spectroscopic analyses were performed at 20-30 minute intervals for 4-6 hr's. Results: 19 F nmr: A decrease in tumor clearance was observed in tumors pre-treated with a single dose of irradiation (2.0 Gy and 10 Gy). The clearance rate of the 5-FU for non-irradiated animals was 0.0178 min

Scheduling of House Development Projects with CPM and PERT Method for Time Efficiency (Case Study: House Type 36)

Science.gov (United States)

Kholil, Muhammad; Nurul Alfa, Bonitasari; Hariadi, Madjumsyah

2018-04-01

Network planning is one of the management techniques used to plan and control the implementation of a project, which shows the relationship between activities. The objective of this research is to arrange network planning on house construction project on CV. XYZ and to know the role of network planning in increasing the efficiency of time so that can be obtained the optimal project completion period. This research uses descriptive method, where the data collected by direct observation to the company, interview, and literature study. The result of this research is optimal time planning in project work. Based on the results of the research, it can be concluded that the use of the both methods in scheduling of house construction project gives very significant effect on the completion time of the project. The company’s CPM (Critical Path Method) method can complete the project with 131 days, PERT (Program Evaluation Review and Technique) Method takes 136 days. Based on PERT calculation obtained Z = -0.66 or 0,2546 (from normal distribution table), and also obtained the value of probability or probability is 74,54%. This means that the possibility of house construction project activities can be completed on time is high enough. While without using both methods the project completion time takes 173 days. So using the CPM method, the company can save time up to 42 days and has time efficiency by using network planning.

Study and development of a high resolution tomograph for the γ radio-imagery in vivo of small animals

International Nuclear Information System (INIS)

Valda Ochoa, A.

1995-01-01

By the use of molecular radio-labelled tracers, molecular biology can reveal some aspects of the functional organisation of the brain. Non invasive in vivo brain research on small laboratory animals, like mice or rats, require analysis of structures of some cubic millimeters present in a brain of the order of a cubic centimeter. Since imaging performances of positron emission tomography (PET) and single photon emission tomography (SPECT) fail in this research field, we present here a high resolution tomograph (TOHR) based on an original principle that allows to overcome the compromise between detection efficiency and spatial resolution. TOHR is a radiation counter device having a large solid angle focusing collimator. By the use of radio-tracers decaying by a cascade of two photons, coincidence detection offers an accurate delimitation of the analysed region and improves spatial resolution. TOHR acts as a scanner, so the image is built voxel by voxel by moving the animal relative to the detector. A numerical feasibility study of such a system shows that a sub millimeter spatial resolution can be achieved. We show that the chemical etching technique is well suited for manufacturing a multi-module focusing collimator by building and testing two such modules. Finally a numerical simulation exhibits TOHR's performance in a neuro-pharmacological experiment on a rat. From these results, other application of TOHR are envisaged, such as oncology (in vivo evolution of tumours) or gene therapy (distribution of viral particles in the brain). (author). 51 refs., 73 figs., 3 tabs

Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

Science.gov (United States)

Sugimine, S; Saito, S; Araki, T; Yamamoto, K; Obata, H

2017-07-01

Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R 2  = 0.51, p CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia. © 2017 European Pain Federation - EFIC®.

Chimeric animal models in human stem cell biology.

Science.gov (United States)

Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

2009-01-01

The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

ASSOCIATION OF COSTUMER VALUE CHAIN ANALYSIS TO QUALITY FUNCTION DEPLOYMENT: DIFFERENT IDENTIFIED COSTUMERS AND REQUIREMENTS ON DEVELOPMENT OF CPM DEVICE

Directory of Open Access Journals (Sweden)

Raffaela Leane Zenni Tanure

2013-06-01

Full Text Available This study aims to present the differences between the use of QFD and its association with CVCA tool in the development of a CPM device for elbow and forearm rehabilitation. To achieve this goal, the study was divided into three steps. The development of a conceptual model that integrates the proposed CVCA + QFD tool for application in the health device development was done in the first step. The second step consisted of applying the proposed model, referring to the QFD method using 8 matrixes: quality matrix, product, characteristics of the parts, process, process parameters, human resources, infrastructure and costs matrix. The proposed conceptual model was employed fully in the third step, allowing the comparison between the methods. The results enabled to identify a discrepancy between the critical costumers in the use of mentioned methods. Customers were limited to the direct and indirect users in the QFD application: the patient, physician and physical therapist. This list got a considerable increase when CVCA was applied: the clinical engineering, product engineering, process and reliability engineering, project and product managers, financial sector, quality system and regulatory issues. These results show the importance of analyzing the supply chain systemically in order to consider all stakeholders to the CPM device development. Thus, needs and relationships delineation of all process customers can be done.

Oncology In Vivo Data Integration for Hypothesis Generation

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Wei Jia

2012-06-01

Full Text Available AstraZeneca’s Oncology in vivo data integration platform brings multidimensional data from animal model efficacy, pharmacokinetic and pharmacodynamic data to animal model profiling data and public in vivo studies. Using this platform, scientists can cluster model efficacy and model profiling data together, quickly identify responder profiles and correlate molecular characteristics to pharmacological response. Through meta-analysis, scientists can compare pharmacology between single and combination treatments, between different drug scheduling and administration routes.

Detecting metastasis of gastric carcinoma using high-resolution micro-CT system: in vivo small animal study

Science.gov (United States)

Liu, Junting; Tian, Jie; Liang, Jimin; Li, Xiangsi; Yang, Xiang; Chen, Xiaofeng; Chen, Yi; Zhou, Yuanfang; Wang, Xiaorui

2011-03-01

Immunocytochemical and immunofluorescence staining are used for identifying the characteristics of metastasis in traditional ways. Micro-computed tomography (micro-CT) is a useful tool for monitoring and longitudinal imaging of tumor in small animal in vivo. In present study, we evaluated the feasibility of the detection for metastasis of gastric carcinoma by high-resolution micro-CT system with omnipaque accumulative enhancement method in the organs. Firstly, a high-resolution micro-CT ZKKS-MCT-sharp micro-CT was developed by our research group and Guangzhou Zhongke Kaisheng Medical Technology Co., Ltd. Secondly, several gastric carcinoma models were established through inoculating 2x106 BGC-823 gastric carcinoma cells subcutaneously. Thirdly, micro-CT scanning was performed after accumulative enhancement method of intraperitoneal injection of omnipaque contrast agent containing 360 mg iodine with a concentration of 350 mg I/ml. Finally, we obtained high-resolution anatomical information of the metastasis in vivo in a BALB/c NuNu nude mouse, the 3D tumor architecture is revealed in exquisite detail at about 35 μm spatial resolution. In addition, the accurate shape and volume of the micrometastasis as small as 0.78 mm3 can be calculated with our software. Overall, our data suggest that this imaging approach and system could be used to enhance the understanding of tumor proliferation, metastasis and could be the basis for evaluating anti-tumor therapies.

The ''in vivo'' distribution of carbon 11 labeled-nicotine in animals. A method suitable for use in man

International Nuclear Information System (INIS)

Maziere, M.; Berger, G.; Plummer, D.; Comar, D.; Masse, R.

1978-01-01

A method is described to label nicotine with carbon 11. A hundred millicuries can be obtained, in 45 minutes, with a high specific activity. This labeling of nicotine has allowed an ''in vivo'' study of the distribution of this very toxic drug in animals. Five minutes after injection in rabbits or monkeys, it was shown with a gamma camera or with a positron camera that the radioactivity was very rapidly distributed throughout the tissues especially in brain, lungs and kidneys. 11 C-nicotine readily penetrates the blood-brain barrier and the brain radioactivity decreases very sharply with time. The eyes however retained activity, possibly in the retina. Unfortunately the monkey is not the ideal subject for 11 C-nicotine brain study because: the brain is small, considering the resolution of the cameras and the cerebral lobes are also quite overlaped in this animal; Japanese authors have shown that compared with dogs the nicotine brain uptake is lower, due to the high affinity of nicotine for skeletal muscle which occupies approximately forty to fifty % of the body weight of the monkey. Also in monkeys, the nicotine destruction is faster than in dogs because there is a higher enzyme nicotine metabolizing activity in the liver of this animal. The differences observed between various animals studies using nicotine indicate that we should not draw any firm conclusions about the behaviour of this drug in humans. In order to do so, examinations must be conducted in man and the method described in spite of its limitations provides a means for such a study

Evaluation of in vivo biocompatibility of different devices for interventional closure of the patent ductus arteriosus in an animal model

OpenAIRE

Sigler, M; Handt, S; Seghaye, M; von Bernuth, G; Grabitz, R

2000-01-01

OBJECTIVE—To evaluate the in vivo biocompatibility of three different devices following interventional closure of a patent ductus arteriosus (PDA) in an animal model.
MATERIALS AND METHODS—A medical grade stainless steel coil (n = 8), a nickel/titanium coil (n = 10), and a polyvinylalcohol foam plug knitted on a titanium wire frame (n = 11) were used for interventional closure of PDA in a neonatal lamb model. The PDA had been maintained by repetitive angioplasty. Between one and 278 days afte...

Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds

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Gauglitz G

2017-12-01

Full Text Available Gerd Gauglitz,1 Stephanie Steckmeier,1 Julian Pötschke,2 Hannah Schwaiger,1 1Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany; 2Department of Plastic and Hand Surgery, Klinikum St Georg gGmbH, Leipzig, Germany Purpose: Cohesive Polydensified Matrix® hyaluronic acid (CPM-HA volumizer has been used successfully for several years to reverse biometric volume loss during facial aging. This observational study explored the additive effect on nasolabial folds when CPM-HA volumizer is injected into the neighboring cheek area.Patients and methods: In this open-label, prospective, postmarketing noninterventional study, 18 adult patients seeking esthetic enhancement of the lateral cheek hollows and cheekbone area were injected with CPM-HA volumizer integrated with lidocaine (CPM-HA-VL in the upper or lower cheek area. Safety and performance of CPM-HA-VL up to 12 months after injection with follow-up visits at week 4 and month 3, 6, and 12 were assessed. The primary endpoint was improvement of cheek fullness on the validated Merz Aesthetics Scales. Additionally, changes in nasolabial folds were quantified using a phaseshift rapid in vivo measurement of skin optical three-dimensional (3D in vivo measurement device. Results: Patients (94.4% female, median age 52 years, age range 39–69 years were injected with a mean volume of 2.5±1.1 mL CPM-HA-VL per side. Immediately after injection, mean severity for upper and lower cheek fullness assessed on the validated MAS improved from 2.5±0.6 and 2.8±0.5, respectively, to 1.0±0.0, and remained unchanged through month 12. Improvement in relation to baseline was attested on the Global Aesthetics Improvement Scale for all assessments. Compared with baseline, the following assessments offered a statistical significance in the reduction of wrinkle depth of nasolabial folds (maximum depth reduction by 30.4% at 3 months according to optical 3D in vivo measurements. Pain during

Cefpiramide(CPM)の前立腺組織内移行に関する検討

OpenAIRE

高田, 耕; 川村, 繁美; 吉田, 郁彦

1988-01-01

12例の前立腺肥大症患者を対象とし,CPM 1.0 gの静脈内投与を行い,血清内濃度および恥骨後式前立腺摘除術にて採取した前立腺組織内への移行を検討した.CPMの組織内濃度は,グラム陰性菌のみならずグラム陽性菌に対しても,その抗菌作用が期待できる値を示した

Cytokines: applications in domestic food animals.

Science.gov (United States)

Blecha, F

1991-01-01

Cytokines such as human, bovine, and porcine interferons and human and bovine interleukin-1 and interleukin-2 have been used in vivo in cattle and pigs. Colony-stimulating factors and tumor necrosis factor alpha have been evaluated in vitro in food animals. Studies to evaluate cytokines in domestic food animals have shown that specific and nonspecific immunomodulation is possible in immunosuppressed or pathogen-exposed animals. Cytokine prophylaxis or therapy in food animals may have the greatest potential for control of respiratory disease and mastitis.

In vivo analysis of tissue by Raman microprobe: examination of human skin lesions and esophagus Barrett's mucosa on an animal model

Science.gov (United States)

Tfayli, Ali; Piot, Olivier; Derancourt, Sylvie; Cadiot, Guillaume; Diebold, Marie D.; Bernard, Philippe; Manfait, Michel

2006-02-01

In the last few years, Raman spectroscopy has been increasingly used for the characterization of normal and pathological tissues. A new Raman system, constituted of optic fibers bundle coupled to an axial Raman spectrometer (Horiba Jobin Yvon SAS), was developed for in vivo investigations. Here, we present in vivo analysis on two tissues: human skin and esophagus mucosa on a rat model. The skin is a directly accessible organ, representing a high diversity of lesions and cancers. Including malignant melanoma, basal cell carcinoma and the squamous cell carcinoma, skin cancer is the cancer with the highest incidence worldwide. Several Raman investigations were performed to discriminate and classify different types of skin lesions, on thin sections of biopsies. Here, we try to characterize in vivo the different types of skin cancers in order to be able to detect them in their early stages of development and to define precisely the exeresis limits. Barrett's mucosa was also studied by in vivo examination of rat's esophagus. Barrett's mucosa, induced by gastro-esophageal reflux, is a pretumoral state that has to be carefully monitored due to its high risk of evolution in adenocarcinoma. A better knowledge of the histological transformation of esophagus epithelium in a Barrett's type will lead to a more efficient detection of the pathology for its early diagnosis. To study these changes, an animal model (rats developing Barrett's mucosa after duodenum - esophagus anastomosis) was used. Potential of vibrational spectroscopy for Barrett's mucosa identification is assessed on this model.

Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

Science.gov (United States)

Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

2016-01-01

Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

Directory of Open Access Journals (Sweden)

Olivia Perwitasari

Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

State-of-the-art of small animal imaging with high-resolution SPECT

International Nuclear Information System (INIS)

Nikolaus, S.; Wirrwar, A.; Antke, C.; Kley, K.; Mueller, H.W.

2005-01-01

During the recent years, in vivo imaging of small animals using SPECT has become of growing relevance. Along with the development of dedicated high-resolution small animal SPECT cameras, an increasing number of conventional clinical scanners has been equipped with single or multipinhole collimators. This paper reviews the small animal tomographs, which are operating at present and compares their performance characteristics. Furthermore, we describe the in vivo imaging studies, which have been performed so far with the individual scanners and survey current approaches to optimize molecular imaging with small animal SPECT. (orig.)

In vivo turnover rates of rat peripheral blood and spleen LGL

International Nuclear Information System (INIS)

Reichardt, D.; Mason, L.H.; Rolstad, B.; Reynolds, C.W.

1986-01-01

Recently much data has accumulated on the morphology and function of LGL. However, there is still little definitive information regarding the lineage and in vivo dynamics of these cells. The present experiments were designed to study one aspect of LGL biology, their in vivo turnover rate. F344 rats were injected 2x daily with 100 μCi 3 HTdR for 1-7 days, their bone marrow (BM) spleens (SPL) and peripheral blood (PB) collected, and LGL and T cells isolated on Percoll gradients. These cell preparations were counted for total radioactivity by scintillation counting and % of labeled cells determined by autoradiography. The results demonstrated the highest 3 HTdR counts were from Percoll fractions 1 and 2 (LGL) with almost no CPM in those fractions containing T cells. The autoradiography data demonstrated that PB and SPL LGL, unlike T cells, were derived from a rapidly dividing precursor population since 30-40% of the LGL were labeled by a 5 day 3 HTdR pulse. In contrast 3 HTdR. Calculations of the approximate steady state turnover rates in these normal rats were BM = 5 days, LGL = 7 days and T cells = >30 days. These results clearly demonstrate that unlike mature T cells, PB and SPL LGL are derived from a rapidly dividing precursor population. More definitive experiments to calculate the half-life of these cells are currently underway

Chlropyrifos-methyl shows anti-androgenic activity without estrogenic activity in rats

International Nuclear Information System (INIS)

Kang, Hwan Goo; Jeong, Sang Hee; Cho, Joon Hyoung; Kim, Dong Gyu; Park, Jong Myung; Cho, Myung Haing

2004-01-01

Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain storage and agriculture, has been suspected as endocrine disrupter by a few in vitro studies. This study was performed to investigate the (anti-) estrogenicity and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay and rat Hershberger assay. CPM with or without 17β-estradiol were administered to 20 days old female rats to investigate its (anti-) estrogenic activity. Uterine and vaginal weight, uterine epithelial cell height were not affected by the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative vagina weight in 17β-estradiol treated immature female rats without any changing of uterine weight. Relative liver weight was increased with decrease of body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with or without testosterone propionate were administered to castrated rat of 51 days old for 10 days to investigate the (anti-)androgenic activity,. The weight of relative and absolute androgen-dependent accessory sex organs; seminal vesicle with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP), levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were unchanged by the treatment of CPM alone. While CPM induced the increase of relative adrenal gland weight, CPM 50 mg/kg decreased the weights of CV/CG, VP, CG and LABC without change of GP without changing of GP when it was treated with TP. In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in immature female rats, but it represents anti-androgenic activity by inhibition of the TP-stimulated increase of the weight of accessory sex organs

In vivo and in vitro testing for selenium and selenium compounds bioavailability assessment in foodstuff.

Science.gov (United States)

Moreda-Piñeiro, Jorge; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar

2017-03-04

The assessment of selenium and selenium species bioavailability in foodstuff is of special concern on the context of human nutrition. In vivo (human and animal), and in vitro tests are important approaches for estimating the bioavailability of toxic and essential compounds to humans. An overview on in vivo and in vitro bioavailability assays for releasing selenium and selenium species in foodstuffs is summarized. Se and Se species content in a foodstuff critically influence Se bioavailability and bioactivity to humans and animals. Se bioavailability is affected by foodstuff-matrix major composition and minor components. Foodstuffs processing and/or treatments could enhancement or decrease Se bioavailability. Experimental conditions such as the selection of healthy status of examined people (in in vivo humans approaches), the selection of animal model (in vivo animals approaches), or the selection of GI conditions (in in vitro tests) could determines the results. Thus, international standardized protocol for in vivo and in vitro approaches assessment is mandatory.

Application of quantitative autoradiography to the measurement of biochemical processes in vivo

International Nuclear Information System (INIS)

Sokoloff, L.

1985-01-01

Quantitative autoradiography makes it possible to measure the concentrations of isotopes in tissues of animals labeled in vivo. In a few cases, the administration of a judiciously selected labeled chemical compound and a properly designed procedure has made it possible to use this capability to measure the rate of a chemical process in animals in vivo. Emission tomography, and particularly positron emission tomography, provides a means to extend this capability to man and to assay the rates of biochemical processes in human tissues in vivo. It does not, however, obviate the need to adhere to established principles of chemical and enzyme kinetics and tracer theory. Generally, all such methods, whether to be used in man with positron emission tomography or in animals with autoradiography, must first be developed by research in animals with autoradiography, because it is only in animals that the measurements needed to validate the basic assumptions of the methods can be tested and evaluated

Technology challenges in small animal PET imaging

International Nuclear Information System (INIS)

Lecomte, Roger

2004-01-01

Positron Emission Tomography (PET) is a non-invasive nuclear imaging modality allowing biochemical processes to be investigated in vivo with sensitivity in the picomolar range. For this reason, PET has the potential to play a major role in the emerging field of molecular imaging by enabling the study of molecular pathways and genetic processes in living animals non-invasively. The challenge is to obtain a spatial resolution that is appropriate for rat and mouse imaging, the preferred animal models for research in biology, while achieving a sensitivity adequate for real-time measurement of rapid dynamic processes in vivo without violating tracer kinetic principles. An overview of the current state of development of dedicated small animal PET scanners is given, and selected applications are reported and discussed with respect to performance and significance to research in biology

Review on Sources and Handling Method of Pesticide Residues in Animal Products

Directory of Open Access Journals (Sweden)

Indraningsih

2006-06-01

Full Text Available Field studies and literature search showed that some pesticide residues either organochlorines (OC or organophosphates (OP were detected in animal products (meat and milk . Pesticide residues in meat collected from West Java were detected at the level of 0 .8 ppb lindane and 62 ppb diazinon . While in meat from Lampung was detected at the level of 7 ppb lindane . 2 .7 heptachlor, 0 .8 endosulfan and 0 .5 ppb aldrin . Furthermore, pesticide residues were also detected in the milk collected from West, Central and East Java . The levels of lindane were 2,3 ; 15,9 ; 0,2 ppb ; heptachlor 8 ; 0 .4 and 0,05 ppb; diazinon 8 ; 0 and 1,8 ppb; CPM 0,4 ; 0,8 and 0 ppb ; endosulfan 0,1 ; 0,04 and 0,05 ppb for West, Central and East Java, respectively . The source of pesticide contamination in animal products is generally originated from feed materials, fodders . contaminated soils and water around the farm areas . Minimalization approach of pesticide residues in animal products could be conducted integratedly, such as through chemical process, biodegradation using microorganisms . Organic farming system is recognised as an alternative that may be applied to minimise contamination on agricultural land, eventually reducing pesticide residues in the agricultural products . Feeding with organic agricultural by-products with low pesticide residues appears to reduce pesticide residues in animal products . In order to eliminate pesticide contamination in soil, it has to be conducted progressively by implementing sustainable organic farming .

In vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice

International Nuclear Information System (INIS)

Grissom, R.E. Jr.; Brownie, C.; Guthrie, F.E.

1987-01-01

Dermal absorption is a major portal of entry for a wide variety of potentially toxic substances. In vivo and in vitro investigations assessing penetration of topically applied xenobiotics using both human and other animals have been conducted. Current ethical considerations have drastically curtailed the testing of xenobiotics in human volunteers; consequently, dermal penetration in humans is usually estimated from in vivo tests in animals and in vitro tests using either human or animal skin. In order for in vitro penetration results to be meaningful, there needs to be close relationship with in vivo data. The objective of the present study was to investigate the relationship between in vivo and in vitro penetration of both hydrophilic and lipophilic 14 C-labelled compounds in mice

Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

Science.gov (United States)

Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

Animal health and production

International Nuclear Information System (INIS)

Kallfelz, F.A.; Lengemann, F.W.

1984-01-01

Some applications of the use of radioisotopes and radiation in animal health and production research are reviewed. These include various techniques associated with both the qualitative localization and quantitative measurements of isotopes in animals; comparator studies in which measurement of the radioactivity in one part of a system will allow computation of the mass or volume in another part; in vivo and in vitro applications of isotope dilution studies; and the use of isotopes in dynamic systems analyses. The use of stable isotopes in mass spectrometry, activation analysis and nuclear magnetic resonance in animal research is also briefly reviewed. Finally some of the successful uses of radiation produced by radioactive sources or various types of generators of electromagnetic radiations in animal production and health studies are described. (U.K.)

[123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine - an in vivo imaging study with a dedicated small animal SPECT

International Nuclear Information System (INIS)

Nikolaus, Susanne; Larisch, Rolf; Wirrwar, Andreas; Jamdjeu-Noune, Marlyse; Antke, Christina; Beu, Markus; Mueller, Hans-Wilhelm; Schramm, Nils

2005-01-01

This study assessed [ 123 I]iodobenzamide binding to the rat dopamine D 2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. Subsequent to baseline quantifications of D 2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D 2 receptors and dopamine transporters, respectively. Striatal baseline equilibrium ratios (V 3 '' ) of [ 123 I]iodobenzamide binding were 1.42±0.31 (mean±SD). After pre-treatment with haloperidol and methylphenidate, V 3 '' values decreased to 0.54±0.46 (p 123 I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D 2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [ 123 I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [ 123 I]iodobenzamide binding to D 2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine. (orig.)

Effect of diabetes on in vivo metabolism of [35S]-labeled glomerular basement membrane

International Nuclear Information System (INIS)

Cohen, M.P.; Surma, M.L.

1984-01-01

Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of [ 35 S]-sulfate into normal and streptozotocin-diabetic rats. The biosynthesis and turnover of sulfated glycosaminoglycans in the GBM was determined from the specific activity of [ 35 S] after pronase digestion of basement membranes purified from glomeruli isolated 1-7 days after injection. Peak radiolabeling of both normal and diabetic GBM occurred 24 h after injection and, when corrected for differences in serum sulfate specific activities, was less in diabetic than in normal samples. The specific activity of GBM sulfate, expressed as cpm/microgram uronic acid, progressively diminished over the ensuing period of study in both normal and diabetic samples. The rate of decrease in specific activity of [ 35 S]-labeled GBM was not significantly different in diabetic preparations compared with that in normal controls. The findings are compatible with diminished sulfation and/or production but normal turnover of glycosaminoglycans in the renal GBM in experimental diabetes

Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

Science.gov (United States)

Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

2015-05-07

The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

Advancing Molecular Therapies through In Vivo Bioluminescent Imaging

Directory of Open Access Journals (Sweden)

Anton McCaffrey

2003-04-01

Full Text Available Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLI is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals.

Science.gov (United States)

Punt, Ans; Peijnenburg, Ad A C M; Hoogenboom, Ron L A P; Bouwmeester, Hans

2017-01-01

The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data.

In vitro GABA transport in the neurohypophysis from rats with hereditary diabetes insipidus and after osmotic stimulation

International Nuclear Information System (INIS)

Hamberger, A.; Norstroem, A.; Sandberg, M.; Svanberg, U.

1979-01-01

The present study reports on a series of experiments in which the osmotic state of the animal correlates with the concentration of GABA in the pituitary as well as with uptake and release of exogenous GABA. Male rats (200-250 g) of the Sprague-Dawley strain and Brattleboro rats with hereditary hypothalamic diabetes insipidus (D.I.) were used and the uptake of [ 3 H]GABA into the posterior pituitary, studied. Radioactivity was determined by liquid scintillation spectrometry. The radioactivity expressed as cpm/mg protein did not differ proportionally from that expressed as cpm/mg wet weight among control and experimental rats. For radiolabelling of neurophysin in vivo, L-[ 35 S]cystein-hydrochloride was injected into the supraoptic nucleus. The total release of [ 35 S] was proportional to the release of labelled neurophysin. The endogenous levels of most amino acids in the neurohypophysis did not differ appreciably from those of whole brain. The GABA level in the D.I. glands was close to the detection limit of the method and was reduced compared to control glands. Otherwise, no marked difference appeared between control and D.I. glands. (Auth.)

Biological response of Sr-containing coating with various surface treatments on titanium substrate for medical applications

Energy Technology Data Exchange (ETDEWEB)

Yang, Shih-Ping [Department of Materials Science and Engineering, National Cheng Kung University, Tainan, Taiwan (China); Lee, Tzer-Min, E-mail: tmlee@mail.ncku.edu.tw [Institute of Oral Medicine, National Cheng Kung University, Tainan, Taiwan (China); School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lui, Truan-Sheng [Department of Materials Science and Engineering, National Cheng Kung University, Tainan, Taiwan (China)

2015-08-15

Graphical abstract: - Highlights: • Sr-containing coating prepared by plasma spraying and micro-arc oxidation process, respectively. • MAO coating stimulated high ECM-like structures of cells on early stage. • Sr-containing specimens had high cell responses on late stage. • Sr-MAO coating is a desirable implant surface treatment for clinical applications. - Abstract: An implant requires a suitable surface to trigger osteointegration. The surface characteristics and chemical composition are important factors in this process. Plasma spraying and micro-arc oxidation can be used to fabricate rough and porous structures for medical applications. Strontium (Sr) has been shown to prevent osteoporosis in vitro and in vivo. However, few scientists have evaluated the biological response of Sr-containing coatings on different surface treatments. In this study, a sand-blasted (SB) surface (as the control), plasma-sprayed hydroxyapatite (HA) and Sr-substituted HA coatings (HAPS and SrHAPS, respectively), calcium phosphate and Sr-containing calcium phosphate micro-arc oxidation surface (CPM and SrCPM, respectively) were analyzed in terms of human osteoblastic cell (MG63) response. Sr was confirmed to be incorporated into the surface. SrHAPS and SrCPM specimens had higher cell responses than those of the HAPS and CPM groups, respectively. The cells cultured on SrCPM and SrHAPS specimens exhibited high proliferation and differentiation. However, CPM and SrCPM specimens stimulated more ECM-like structures than other specimens. The results show that Sr-containing coatings have good characteristics that enhance cell response. The SrCPM coating is a suitable implant surface treatment for clinical applications.

Biological response of Sr-containing coating with various surface treatments on titanium substrate for medical applications

International Nuclear Information System (INIS)

Yang, Shih-Ping; Lee, Tzer-Min; Lui, Truan-Sheng

2015-01-01

Graphical abstract: - Highlights: • Sr-containing coating prepared by plasma spraying and micro-arc oxidation process, respectively. • MAO coating stimulated high ECM-like structures of cells on early stage. • Sr-containing specimens had high cell responses on late stage. • Sr-MAO coating is a desirable implant surface treatment for clinical applications. - Abstract: An implant requires a suitable surface to trigger osteointegration. The surface characteristics and chemical composition are important factors in this process. Plasma spraying and micro-arc oxidation can be used to fabricate rough and porous structures for medical applications. Strontium (Sr) has been shown to prevent osteoporosis in vitro and in vivo. However, few scientists have evaluated the biological response of Sr-containing coatings on different surface treatments. In this study, a sand-blasted (SB) surface (as the control), plasma-sprayed hydroxyapatite (HA) and Sr-substituted HA coatings (HAPS and SrHAPS, respectively), calcium phosphate and Sr-containing calcium phosphate micro-arc oxidation surface (CPM and SrCPM, respectively) were analyzed in terms of human osteoblastic cell (MG63) response. Sr was confirmed to be incorporated into the surface. SrHAPS and SrCPM specimens had higher cell responses than those of the HAPS and CPM groups, respectively. The cells cultured on SrCPM and SrHAPS specimens exhibited high proliferation and differentiation. However, CPM and SrCPM specimens stimulated more ECM-like structures than other specimens. The results show that Sr-containing coatings have good characteristics that enhance cell response. The SrCPM coating is a suitable implant surface treatment for clinical applications

SU-E-T-481: In Vivo and Post Mortem Animal Irradiation: Measured Vs. Calculated Doses

Energy Technology Data Exchange (ETDEWEB)

Heintz, P [Univ New Mexico Radiology Dept., Albuquerque, NM (United States); Heintz, B [Texas Oncology, PA, Southlake, TX (United States); Sandoval, D [University of New Mexico, Albuquerque, NM (United States); Weber, W; Melo, D; Guilmette, R [Lovelace Respiratory Research Institute, Albuquerque, NM (United States)

2015-06-15

Purpose: Computerized radiation therapy treatment planning is performed on almost all patients today. However it is seldom used for laboratory irradiations. The first objective is to assess whether modern radiation therapy treatment planning (RTP) systems accurately predict the subject dose by comparing in vivo and decedent dose measurements to calculated doses. The other objective is determine the importance of using a RTP system for laboratory irradiations. Methods: 5 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the absorbed dose at 5 levels (carina, lung, heart, liver and rectum) during whole body irradiation. The subjects were treated with large opposed lateral fields and extended distances to cover the entire subject using a Varian 600C linac. CT simulation was performed ante-mortem (AM) and post-mortem (PM). To compare AM and PM doses, calculation points were placed at the location of each dosimeter in the treatment plan. The measured results were compared to the results using Varian Eclipse and Prowess Panther RTP systems. Results: The Varian and Prowess treatment planning system agreed to within in +1.5% for both subjects. However there were significant differences between the measured and calculated doses. For both animals the calculated central axis dose was higher than prescribed by 3–5%. This was caused in part by inaccurate measurement of animal thickness at the time of irradiation. For one subject the doses ranged from 4% to 7% high and the other subject the doses ranged 7% to 14% high when compared to the RTP doses. Conclusions: Our results suggest that using proper CT RTP system can more accurately deliver the prescribed dose to laboratory subjects. It also shows that there is significant dose variation in such subjects when inhomogeneities are not considered in the planning process.

Compound list: clomipramine [Open TG-GATEs

Lifescience Database Archive (English)

Full Text Available clomipramine CPM 00121 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/clomipramine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/clomipramine...vo/Liver/Single/clomipramine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc....jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/clomipramine.Rat.in_vivo.Liver.Repeat.zip ...

Radiation-induced bystander effects in vivo are sex specific

International Nuclear Information System (INIS)

Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

2008-01-01

Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes

Radiation-induced bystander effects in vivo are sex specific

Energy Technology Data Exchange (ETDEWEB)

Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada); Kovalchuk, Olga [Department of Biological Sciences, University of Lethbridge, Alberta T1K 3M4 (Canada)], E-mail: olga.kovalchuk@uleth.ca

2008-07-03

Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naive cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

Radiation-induced bystander effects in vivo are sex specific.

Science.gov (United States)

Koturbash, Igor; Kutanzi, Kristy; Hendrickson, Karl; Rodriguez-Juarez, Rocio; Kogosov, Dmitry; Kovalchuk, Olga

2008-07-03

Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.

How animals move: comparative lessons on animal locomotion.

Science.gov (United States)

Schaeffer, Paul J; Lindstedt, Stan L

2013-01-01

Comparative physiology often provides unique insights in animal structure and function. It is specifically through this lens that we discuss the fundamental properties of skeletal muscle and animal locomotion, incorporating variation in body size and evolved difference among species. For example, muscle frequencies in vivo are highly constrained by body size, which apparently tunes muscle use to maximize recovery of elastic recoil potential energy. Secondary to this constraint, there is an expected linking of skeletal muscle structural and functional properties. Muscle is relatively simple structurally, but by changing proportions of the few muscle components, a diverse range of functional outputs is possible. Thus, there is a consistent and predictable relation between muscle function and myocyte composition that illuminates animal locomotion. When animals move, the mechanical properties of muscle diverge from the static textbook force-velocity relations described by A. V. Hill, as recovery of elastic potential energy together with force and power enhancement with activation during stretch combine to modulate performance. These relations are best understood through the tool of work loops. Also, when animals move, locomotion is often conveniently categorized energetically. Burst locomotion is typified by high-power outputs and short durations while sustained, cyclic, locomotion engages a smaller fraction of the muscle tissue, yielding lower force and power. However, closer examination reveals that rather than a dichotomy, energetics of locomotion is a continuum. There is a remarkably predictable relationship between duration of activity and peak sustainable performance.

Cannabidiol Does Not Convert to Δ9-Tetrahydrocannabinol in an In Vivo Animal Model.

Science.gov (United States)

Wray, Louise; Stott, Colin; Jones, Nicholas; Wright, Stephen

2017-01-01

Introduction: Cannabidiol (CBD) can convert to Δ 9 -tetrahydrocannabinol (THC) in vitro with prolonged exposure to simulated gastric fluid; however, in vitro conditions may not be representative of the in vivo gut environment. Using the minipig, we investigated whether enteral CBD converts to THC in vivo . Materials and Methods: Synthetic CBD (100 mg/mL) was administered orally in a sesame oil formulation twice daily to minipigs ( N =3) in 15 mg/kg doses for 5 consecutive days. Blood samples were taken before and 1, 2, 4, and 6 h after morning doses on Days 1 and 5. Six hours after the final dose on Day 5, the animals were euthanized, and samples of gastrointestinal (GI) tract contents were obtained. Liquid chromatography with tandem mass spectrometry analysis determined CBD, THC, and 11-hydroxy-THC (11-OH-THC) concentrations. Lower limits of quantification: plasma CBD=1 ng/mL, plasma THC and 11-OH-THC=0.5 ng/mL, GI tract CBD=2 ng/mL, and GI tract THC and 11-OH-THC=1 ng/mL. Results: THC and 11-OH-THC were undetectable in all plasma samples. Maximum plasma concentrations ( C max ) of CBD were observed between 1 and 4 h on Days 1 and 5. CBD was present in plasma 6 h after administration on Days 1 (mean 33.6 ng/mL) and 5 (mean 98.8 ng/mL). Mean C max CBD values, 328 ng/mL (Day 1) and 259 ng/mL (Day 5), were within range of those achieved in clinical studies. Mean CBD exposure over 6 h was similar on Days 1 (921 h·ng/mL) and 5 (881 h·ng/mL). THC and 11-OH-THC were not detected in all GI tract samples. Mean CBD concentrations reached 84,500 ng/mL in the stomach and 43,900 ng/mL in the small intestine. Conclusions: Findings of the present study show that orally dosed CBD, yielding clinically relevant plasma exposures, does not convert to THC in the minipig, a species predictive of human GI tract function.

Hyperpolarized singlet NMR on a small animal imaging system

DEFF Research Database (Denmark)

Laustsen, Christoffer; Pileio, Giuseppe; Tayler, Michael C. D.

2012-01-01

Nuclear spin hyperpolarization makes a significant advance toward overcoming the sensitivity limitations of in vivo magnetic resonance imaging, particularly in the case of low-gamma nuclei. The sensitivity may be improved further by storing the hyperpolarization in slowly relaxing singlet...... populations of spin- 1/2 pairs. Here, we report hyperpolarized 13C spin order transferred into and retrieved from singlet spin order using a small animal magnetic resonance imaging scanner. For spins in sites with very similar chemical shifts, singlet spin order is sustained in high magnetic field without...... requiring strong radiofrequency irradiation. The demonstration of robust singlet-to-magnetization conversion, and vice versa, on a small animal scanner, is promising for future in vivo and clinical deployments....

Study and development of a high resolution tomograph for the {gamma} radio-imagery in vivo of small animals; Etude et developpement d`un tomographe haute resolution pour la radio-imagerie {gamma} in vivo de petits animaux

Energy Technology Data Exchange (ETDEWEB)

Valda Ochoa, A

1995-06-23

By the use of molecular radio-labelled tracers, molecular biology can reveal some aspects of the functional organisation of the brain. Non invasive in vivo brain research on small laboratory animals, like mice or rats, require analysis of structures of some cubic millimeters present in a brain of the order of a cubic centimeter. Since imaging performances of positron emission tomography (PET) and single photon emission tomography (SPECT) fail in this research field, we present here a high resolution tomograph (TOHR) based on an original principle that allows to overcome the compromise between detection efficiency and spatial resolution. TOHR is a radiation counter device having a large solid angle focusing collimator. By the use of radio-tracers decaying by a cascade of two photons, coincidence detection offers an accurate delimitation of the analysed region and improves spatial resolution. TOHR acts as a scanner, so the image is built voxel by voxel by moving the animal relative to the detector. A numerical feasibility study of such a system shows that a sub millimeter spatial resolution can be achieved. We show that the chemical etching technique is well suited for manufacturing a multi-module focusing collimator by building and testing two such modules. Finally a numerical simulation exhibits TOHR`s performance in a neuro-pharmacological experiment on a rat. From these results, other application of TOHR are envisaged, such as oncology (in vivo evolution of tumours) or gene therapy (distribution of viral particles in the brain). (author). 51 refs., 73 figs., 3 tabs.

Learning Curve in a Western Training Center of the Circumferential En Bloc Esophageal Endoscopic Submucosal Dissection in an In Vivo Animal Model

Directory of Open Access Journals (Sweden)

Miguel A. Tanimoto

2011-01-01

Full Text Available Aim. Evaluate the feasibility to overcome the learning curve in a western training center of the en bloc circumferential esophageal (ECE- ESD in an in vivo animal model. Methods. ECE-ESD was performed on ten canine models under general anesthesia on artificial lesions at the esophagus marked with coagulation points. After the ESD each canine model was euthanized and surgical resection of the esophagus and stomach was carried out according to “the Principles of Humane Experimental Technique, Russel and Burch.” The specimen was fixed with needles on cork submerged in formalin with the esophagus and stomach then delivered to the pathology department to be analyzed. Results. ECE-ESD was completed without complications in the last 3/10 animal models. Mean duration for the procedures was 192±35 minutes (range 140–235 minutes. All the procedures were done at the animal lab surgery room with cardio pulmonary monitoring and artificial ventilation by staff surgery members and a staff member of the Gastroenterology department trained during 1999–2001 at the Fujigaoka hospital of the Showa U. in Yokohama, Japan, length (range 15–18 mm and 51±6.99 width (range 40–60 mm. Conclusion. ECE-ESD training is feasible in canine models for postgraduate endoscopy fellows.

Nanotoxicity: the growing need for in vivo study.

Science.gov (United States)

Fischer, Hans C; Chan, Warren C W

2007-12-01

Nanotoxicology is emerging as an important subdiscipline of nanotechnology. Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on elucidating the relationship between the physical and chemical properties (e.g. size, shape, surface chemistry, composition, and aggregation) of nanostructures with induction of toxic biological responses. In the past five years, a majority of nanotoxicity research has focused on cell culture systems; however, the data from these studies could be misleading and will require verification from animal experiments. In vivo systems are extremely complicated and the interactions of the nanostructures with biological components, such as proteins and cells, could lead to unique biodistribution, clearance, immune response, and metabolism. An understanding of the relationship between the physical and chemical properties of the nanostructure and their in vivo behavior would provide a basis for assessing toxic response and more importantly could lead to predictive models for assessing toxicity. In this review article, we describe the assumptions and challenges in the nanotoxicity field and provide a rationale for in vivo animal studies to assess nanotoxicity.

9 CFR 147.16 - Procedure for the evaluation of mycoplasma reactors by in vivo bio-assay (enrichment).

Science.gov (United States)

2010-01-01

... mycoplasma reactors by in vivo bio-assay (enrichment). 147.16 Section 147.16 Animals and Animal Products... the evaluation of mycoplasma reactors by in vivo bio-assay (enrichment). This procedure has been shown... publications: (a) Bigland, C. H. and A. J. DaMassa, “A Bio-Assay for Mycoplasma Gallisepticum.” In: United...

Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium labeled bile acid analogues to study (altered) hepatic transporter function

International Nuclear Information System (INIS)

Neyt, Sara; Vliegen, Maarten; Verreet, Bjorn; De Lombaerde, Stef; Braeckman, Kim; Vanhove, Christian; Huisman, Maarten Thomas; Dumolyn, Caroline; Kersemans, Ken; Hulpia, Fabian; Van Calenbergh, Serge; Mannens, Geert; De Vos, Filip

2016-01-01

Introduction: Hepatobiliary transport mechanisms are crucial for the excretion of substrate toxic compounds. Drugs can inhibit these transporters, which can lead to drug–drug interactions causing toxicity. Therefore, it is important to assess this early during the development of new drug candidates. The aim of the current study is the (radio)synthesis, in vitro and in vivo evaluation of a technetium labeled chenodeoxycholic and cholic acid analogue: [ 99m Tc]-DTPA-CDCA and [ 99m ]Tc-DTPA-CA, respectively, as biomarker for disturbed transporter functionality. Methods: [99mTc]-DTPA-CDCA([ 99m Tc]-3a) and [99mTc]-DTPA-CA ([ 99m Tc]-3b) were synthesized and evaluated in vitro and in vivo. Uptake of both tracers was investigated in NTCP, OCT1, OATP1B1, OATP1B3 transfected cell lines. K m and V max values were determined and compared to [ 99m Tc]-mebrofenin ([ 99m Tc]-MEB). Efflux was investigated by means of CTRL, MRP2 and BSEP transfected inside-out vesicles. Metabolite analysis was performed using pooled human liver S9. Wild type (n = 3) and rifampicin treated (n = 3) mice were intravenously injected with 37 MBq of tracer. After dynamic small-animal SPECT and short CT acquisitions, time–activity curves of heart, liver, gallbladder and intestines were obtained. Results: We demonstrated that OATP1B1 and OATP1B3 are the involved uptake transporters of both compounds. Both tracers show a higher affinity compared to [ 99m Tc]-MEB, but are in a similar range as endogenous bile acids for OATP1B1 and OATP1B3. [ 99m Tc]-3a shows higher affinities compared to [ 99m Tc]-3b. V max values were lower compared to [ 99m Tc]-MEB, but in the same range as endogenous bile acids. MRP2 was identified as efflux transporter. Less than 7% of both radiotracers was metabolized in the liver. In vitro results were confirmed by in vivo results. Uptake in the liver and efflux to gallbladder + intestines and urinary bladder of both tracers was observed. Transport was inhibited by rifampicin

In vitro and in vivo studies with [18F]fluorocholine on digestive tumoral cell lines and in an animal model of metastasized endocrine tumor

International Nuclear Information System (INIS)

Nejjari, Mimoun; Kryza, David; Poncet, Gilles; Roche, Colette; Perek, Nathalie; Chayvialle, Jean-Alain; Le Bars, Didier; Scoazec, Jean-Yves; Janier, Marc; Borson-Chazot, Francoise

2008-01-01

Purpose: The aim of this study was to investigate (a) in vitro the relationship between [ 18 F]fluorocholine ([ 18 F]FCH) uptake and cell growth in endocrine cell lines and (b) in vivo the uptake of [ 18 F]FCH by tumoral sites in an animal model of metastasized endocrine tumor. Methods: In vitro studies were conducted on three endocrine and two nonendocrine digestive tumoral cell lines. The proliferative ratio was estimated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The uptake of [ 18 F]FCH and that of [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) were measured before and after cytotoxic therapy. [ 18 F]FCH biodistribution was studied in nude mice and in an endocrine xenografted mice model. Results: The [ 18 F]FCH uptake in tumoral cell lines was related to their proliferative capacities as measured by the MTT assay in basal conditions. After cytotoxic therapy, the IC 50 values calculated with the [ 18 F]FCH incorporation test were very close to those determined with the MTT assay. Biodistribution studies showed that [ 18 F]FCH was predominantly concentrated in the liver and kidney of nude mice. In the STC-1 xenografted animal model, the uptake of [ 18 F]FCH in the primary tumor was only 1.1%. On autoradiography and micro-positron emission tomography, there was no uptake of [ 18 F]FCH in liver metastases but there was a significant uptake of [ 18 F]FDG. Conclusions: In vitro studies suggested that the incorporation of [ 18 F]FCH in endocrine tumor cell lines was related to their growth capacities; however, in vivo studies conducted in an endocrine xenografted animal model showed an uptake of [ 18 F]FCH in hepatic metastases lower than that in normal liver cells. An influence of the microenvironment or a competition phenomenon for [ 18 F]FCH uptake between normal liver and endocrine tumor cells cannot be excluded

Potency testing of veterinary vaccines: the way from in vivo to in vitro.

Science.gov (United States)

Romberg, Judith; Lang, Stefan; Balks, Elisabeth; Kamphuis, Elisabeth; Duchow, Karin; Loos, Daniela; Rau, Henriette; Motitschke, Andreas; Jungbäck, Carmen

2012-01-01

Current quality control of inactivated animal vaccines still focuses on the potency of final products in a batch-wise manner. Animal welfare concerns as well as scientific considerations have led to the '3Rs-concept' that comprises the refinement of animal procedures, the reduction of animal numbers, and the replacement of animal models. Although the 3Rs-concept has been widely accepted as a fundamental principle, the number of approved alternatives for in vivo tests is still limited. To promote further progress, the international scientific workshop 'Potency Testing of Veterinary Vaccines: The Way from in vivo to in vitro' was held at the Paul-Ehrlich-Institut in Langen, Germany, on 01-03 December 2010. More than 130 participants from industry, academia and regulatory authorities discussed the current state of the 3Rs-concept, examples of its successful implementation as well as still existing hurdles. Special emphasis was laid on the 'consistency approach' that aims to ensure relevant quality attributes of vaccine batches by in vitro analyses during production rather than by in vivo potency tests on the final product. This report provides an overview of the insights gained, including the recommendations produced at the end of the workshop. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

Mind the gap – towards complete and transparent reporting of animal research

DEFF Research Database (Denmark)

Tillmann, Sandra

2018-01-01

Several initiatives have been taken to standardise the reporting of animal studies in peer-reviewed scientific journals, such as the ARRIVE (Animal Research: Reporting of In Vivo Experiments) and GSPC (Gold Standard Publication Checklist) guidelines. Surprisingly, many publications still lack key...

Development of a computer-assisted system for model-based condylar position analysis (E-CPM).

Science.gov (United States)

Ahlers, M O; Jakstat, H

2009-01-01

Condylar position analysis is a measuring method for the three-dimensional quantitative acquisition of the position of the mandible in different conditions or at different points in time. Originally, the measurement was done based on a model, using special mechanical condylar position measuring instruments, and on a research scale with mechanical-electronic measuring instruments. Today, as an alternative, it is possible to take measurements with electronic measuring instruments applied directly to the patient. The computerization of imaging has also facilitated condylar position measurement by means of three-dimensional data records obtained by imaging examination methods, which has been used in connection with the simulation and quantification of surgical operation results. However, the comparative measurement of the condylar position at different points in time has so far not been possible to the required degree. An electronic measuring instrument, allowing acquisition of the condylar position in clinical routine and facilitating later calibration with measurements from later examinations by data storage and use of precise equalizing systems, was therefore designed by the present authors. This measuring instrument was implemented on the basis of already existing components from the Reference CPM und Cadiax Compact articulator and registration systems (Gamma Dental, Klosterneuburg, Austria) as well as the matching CMD3D evaluation software (dentaConcept, Hamburg).

Novel In Vitro/Ex Vivo Animal Modeling for Filovirus Aerosol Infection

Science.gov (United States)

2014-09-01

Infection PRINCIPAL INVESTIGATOR: Ayesha Mahmood, Ph.D. CONTRACTING ORGANIZATION: Sanofi Pasteur VaxDesign Corporation...ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT Sanofi Pasteur VaxDesign Corporation Orlando, Florida, 32826 9...a collaborative research effort between the USAMRIID Labs and Sanofi Pasteur VaxDesign to develop in vitro and ex vivo viral disease model systems

Comparison of OQPSK and CPM for Communications at 60 GHz with a Nonideal Front End

Directory of Open Access Journals (Sweden)

Jimmy Nsenga

2007-03-01

Full Text Available Short-range digital communications at 60 GHz have recently received a lot of interest because of the huge bandwidth available at those frequencies. The capacity offered to the users could finally reach 2 Gbps, enabling the deployment of new multimedia applications. However, the design of analog components is critical, leading to a possible high nonideality of the front end (FE. The goal of this paper is to compare the suitability of two different air interfaces characterized by a low peak-to-average power ratio (PAPR to support communications at 60 GHz. On one hand, we study the offset-QPSK (OQPSK modulation combined with a channel frequency-domain equalization (FDE. On the other hand, we study the class of continuous phase modulations (CPM combined with a channel time-domain equalizer (TDE. We evaluate their performance in terms of bit error rate (BER considering a typical indoor propagation environment at 60 GHz. For both air interfaces, we analyze the degradation caused by the phase noise (PN coming from the local oscillators; and by the clipping and quantization errors caused by the analog-to-digital converter (ADC; and finally by the nonlinearity in the PA.

Comparison of OQPSK and CPM for Communications at 60 GHz with a Nonideal Front End

Directory of Open Access Journals (Sweden)

Nsenga Jimmy

2007-01-01

Full Text Available Short-range digital communications at 60 GHz have recently received a lot of interest because of the huge bandwidth available at those frequencies. The capacity offered to the users could finally reach 2 Gbps, enabling the deployment of new multimedia applications. However, the design of analog components is critical, leading to a possible high nonideality of the front end (FE. The goal of this paper is to compare the suitability of two different air interfaces characterized by a low peak-to-average power ratio (PAPR to support communications at 60 GHz. On one hand, we study the offset-QPSK (OQPSK modulation combined with a channel frequency-domain equalization (FDE. On the other hand, we study the class of continuous phase modulations (CPM combined with a channel time-domain equalizer (TDE. We evaluate their performance in terms of bit error rate (BER considering a typical indoor propagation environment at 60 GHz. For both air interfaces, we analyze the degradation caused by the phase noise (PN coming from the local oscillators; and by the clipping and quantization errors caused by the analog-to-digital converter (ADC; and finally by the nonlinearity in the PA.

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus

Directory of Open Access Journals (Sweden)

Bernaba M

2014-11-01

Full Text Available Mario Bernaba, Kevin A Johnson, Jiang-Ti Kong, Sean MackeyStanford Systems Neuroscience and Pain Laboratory, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: Conditioned pain modulation (CPM is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus may inhibit the perceived pain of a subsequent stimulus (the test stimulus. Animal studies suggest that CPM is mediated by a spino–bulbo–spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.Methods: We conducted a within-subject, crossover study of healthy adults to determine the extent to which CPM is affected by 1 threatening and reassuring evaluation and 2 imagery alone of a cold conditioning stimulus. We used a heat stimulus individualized to 5/10 on a visual analog scale as the testing stimulus and computed the magnitude of CPM by subtracting the postconditioning rating from the baseline pain rating of the heat stimulus.Results: We found that although evaluation can increase the pain rating of the conditioning stimulus, it did not significantly alter the magnitude of CPM. We also found that imagery of cold pain alone did not result in statistically significant CPM effect.Conclusion: Our results suggest that CPM is primarily dependent on sensory input, and that the cortical processes of evaluation and imagery have little impact on CPM. These findings lend support for CPM as a useful tool for probing endogenous analgesia through subcortical mechanisms.Keywords: conditioned pain modulation, endogenous analgesia, evaluation, imagery, cold presser test, CHEPS, contact heat-evoked potential stimulator

Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries

Science.gov (United States)

2010-07-01

skin treatment and storage Clinical and Histopathologic Data Confirmation of Preliminary Data and Reproducibility of Xenotransplantation Model...the counts per minute ( cpm ) for the responses at each of the time points, which have lower cpms (see red circles around cpm values on pgs. 49-50...although the blade was fresh for each animal. The skin grafts were kept moist and cold in a saline-filled Petri dish on ice while being trimmed to the

In vivo cell tracking with bioluminescence imaging

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)

2015-03-15

Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

In vivo (/sup 3/H)flunitrazepam binding: imaging of receptor regulation

Energy Technology Data Exchange (ETDEWEB)

Ciliax, B.J.; Penney, J.B. Jr.; Young, A.B.

1986-08-01

The use of (/sup 3/H)flunitrazepam as a ligand to measure alterations in benzodiazepine receptors in vivo in rats was investigated. Animals were injected with (/sup 3/H)flunitrazepam i.v., arterial samples of (/sup 3/H)flunitrazepam were obtained and, later, the animals were sacrificed to assay brain binding. (/sup 3/H)flunitrazepam enters the brain rapidly and binds to benzodiazepine receptors. About two-thirds of this binding is blocked by predosing the animals with 5 mg/kg of clonazepam. The amount of remaining (nonspecific) binding correlates very well (r = 0.88) with the amount of radioactivity found in plasma at the time of death. A series of rats were lesioned unilaterally with kainic acid in the caudate-putamen several months before the infusion of (/sup 3/H)flunitrazepam. In vivo autoradiography in lesioned rats showed that benzodiazepine binding in globus pallidus and substantia nigra on the side of the lesion was increased significantly as compared to the intact side. The observed changes in benzodiazepine binding were similar to those observed previously in lesioned rats using in vitro techniques. Thus, benzodiazepine receptor regulation can be imaged quantitatively using in vivo binding techniques.

Cannabidiol Does Not Convert to Δ9-Tetrahydrocannabinol in an In Vivo Animal Model

OpenAIRE

Wray, Louise; Stott, Colin; Jones, Nicholas; Wright, Stephen

2017-01-01

Abstract Introduction: Cannabidiol (CBD) can convert to Δ9-tetrahydrocannabinol (THC) in vitro with prolonged exposure to simulated gastric fluid; however, in vitro conditions may not be representative of the in vivo gut environment. Using the minipig, we investigated whether enteral CBD converts to THC in vivo. Materials and Methods: Synthetic CBD (100 mg/mL) was administered orally in a sesame oil formulation twice daily to minipigs (N=3) in 15 mg/kg doses for 5 consecutive days. Blood samp...

Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

Science.gov (United States)

Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

2017-12-01

Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

ADMINISTRACIÓN DEL PROYECTO “DESARROLLO DE CAPACIDADES HUMANAS”, MEDIANTE LAS TÉCNICAS ADMINISTRATIVAS CPM Y PERT, URACCAN – SIUNA, 2012

Directory of Open Access Journals (Sweden)

Yader Antonio Ordoñez Aguilar

2014-09-01

Full Text Available Esta investigación ha aplicado el Método de la Ruta Crítica (CPM y las Técnicas de Evaluación y Revisión de Programas (PERT en la administración del proyecto: “Desarrollo de capacidades técnicas y humanas para la implementación del plan de desarrollo regional con identidad en el sector de Las Minas”, ejecutado en Siuna, 2012, por la URACCAN. Es un estudio aplicativo retrospectivo con un enfoque cuantitativo enmarcado en las técnicas administrativas de proyecto CPM y PERT mediante el programa WinQSB, en la administración del proyecto en estudio.De acuerdo a los resultados, todo el proyecto puede concluirse en 51.3 meses, equivalente a 4 años y 3 meses, teniendo 12 actividades críticas, las cuales representan que un retraso en cualquiera de estas ocasionaría un retraso en todo el proyecto. El costo total de las actividades de este proyecto es de 617,863.00 euros y el costo total de la ruta crítica es de 231,585.00 euros. El proyecto incurre en otros costos, tales como: mano de obra, transporte, servicios de consulta, evaluación, entre otros, que también forman parte del presupuesto total del proyecto, siendo este de 1,040,251.00 euros. El proyecto necesitó más tiempo para poder concluir cada una de las actividades, ya que en su planificación inicial estaba programado a terminarse en 3 años, lo cual no se cumplió porque tuvieron que solicitar una prórroga de tres meses para la conclusión total del mismo. La ventaja en la aplicación del Método de la Ruta Crítica, es que dio la perspectiva para tener la información del proyecto de manera organizada y lista para cualquier revisión; una de las principales desventajas es que se tuvo que organizar todas las actividades con respecto a sus predecesores inmediatos y tener conocimiento del método, así como el programa WinQSB para evitar resultados adversos.Palabras clave: Técnicas administrativas; Programa WINQSB; actividades críticas; ruta crítica; predecesores

Non-animal Replacements for Acute Toxicity Testing.

Science.gov (United States)

Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

2015-07-01

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

The biological application of small animal PET imaging

International Nuclear Information System (INIS)

Myers, Ralph

2001-01-01

The short history of small animal PET is reviewed in the context of its application in the laboratory. Early work has demonstrated a role for the technique in both drug development and in the in vivo monitoring of neuroreceptor function with time. As spatial resolution approaches 1 mm, challenges in quantification remain. However, the ability to carry out animal PET studies that are analogous to human PET will form an important bridge between laboratory and clinical sciences

Applying the ARRIVE Guidelines to an In Vivo Database.

Directory of Open Access Journals (Sweden)

Natasha A Karp

2015-05-01

Full Text Available The Animal Research: Reporting of In Vivo Experiments (ARRIVE guidelines were developed to address the lack of reproducibility in biomedical animal studies and improve the communication of research findings. While intended to guide the preparation of peer-reviewed manuscripts, the principles of transparent reporting are also fundamental for in vivo databases. Here, we describe the benefits and challenges of applying the guidelines for the International Mouse Phenotyping Consortium (IMPC, whose goal is to produce and phenotype 20,000 knockout mouse strains in a reproducible manner across ten research centres. In addition to ensuring the transparency and reproducibility of the IMPC, the solutions to the challenges of applying the ARRIVE guidelines in the context of IMPC will provide a resource to help guide similar initiatives in the future.

Cystoscopic optical coherence tomography for urinary bladder imaging in vivo

Science.gov (United States)

Wang, Z. G.; Adler, H.; Chan, D.; Jain, A.; Xie, H. K.; Wu, Z. L.; Pan, Y. T.

2006-02-01

This paper summarizes the development of new 2D MEMS mirrors and the pertinent modification to improve OCT endoscopic catheter packaging suitable for in vivo imaging diagnosis of bladder cancers. Comparative study of the newly developed endocopic OCT versus the bench-top OCT is presented. Results of in vivo OCT cystoscopy based on a porcine acute inflammation model are presented to compare time-domain OCT and spectral-domain OCT for in vivo imaging. In addition, results of spectral-domain Doppler OCT are presented to image blood flow in the lamina propria of the bladder. The results of our in vivo animal study using the presented OCT endoscope are discussed for potential problems in the future clinical applications.

Influence of calcination temperature on the zirconia microstructure synthesized by complex polymerization method (CPM): a comparative study

Energy Technology Data Exchange (ETDEWEB)

Santos, R.L.P.; Mota, F.V.; Nascimento, R.M.; Henriques, B.P.; Silva, F.S.; Assis, R. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil)

2016-07-01

Full text: The aim of this study was to accomplish a previous characterization of the zirconia synthesized by Complex Polymerization Method (CPM) using yttria as stabilizing agent and different calcination temperatures. The powders were crystallized at 800, 900 and 1000 °C for 2h. The structural evolution Y-TZP powders were characterized by X-Ray Diffraction (XRD) and Micro-Raman Spectroscopy. The thermal properties of the calcined pre-pyrolyzed (350 °C for 4 h), samples were investigated by simultaneous thermo analysis (TGA/DTA). After heat treatment the phase Y-TZP was obtained of a single-phase, with absence of the deleterious phases. The results show that average crystallite size of the powder synthesized with 3% of Yttria dopant, increased from 11.5 to 27.9 nm when the calcination temperature increased from 800 to 1000 °C. This behavior was observed for all specimens independent of the Yttria content. The micro-Raman indicate the presence of the tetragonal phase for all samples independent of the calcination temperature employed. (author)

Prostate Cell Specific Regulation of Androgen Receptor Phosphorylation in Vivo

Science.gov (United States)

2009-11-01

average counts per minute ( CPM ). Columns, mean (*, P = 0.006); error bars, SE. ART-27 Inhibits AR Target Genes www.aacrjournals.org 3145 Cancer Res 2009; 69...publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with

Helium induces preconditioning in human endothelium in vivo

NARCIS (Netherlands)

Smit, Kirsten F.; Oei, Gezina T. M. L.; Brevoord, Daniel; Stroes, Erik S.; Nieuwland, Rienk; Schlack, Wolfgang S.; Hollmann, Markus W.; Weber, Nina C.; Preckel, Benedikt

2013-01-01

Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min.

Cellular Immune Response Against Firefly Luciferase After Sleeping Beauty–Mediated Gene Transfer In Vivo

Science.gov (United States)

Podetz-Pedersen, Kelly M.; Vezys, Vaiva; Somia, Nikunj V.; Russell, Stephen J.

2014-01-01

Abstract The Sleeping Beauty (SB) transposon system has been shown to mediate new gene sequence integration resulting in long-term expression. Here the effectiveness of hyperactive SB100X transposase was tested, and we found that hydrodynamic co-delivery of a firefly luciferase transposon (pT2/CaL) along with SB100X transposase (pCMV-SB100X) resulted in remarkably sustained, high levels of luciferase expression. However, after 4 weeks there was a rapid, animal-by-animal loss of luciferase expression that was not observed in immunodeficient mice. We hypothesized that this sustained, high-level luciferase expression achieved using the SB100X transposase elicits an immune response in pT2/CaL co-administered mice, which was supported by the rapid loss of luciferase expression upon challenge of previously treated animals and in naive animals adoptively transferred with splenocytes from previously treated animals. Specificity of the immune response to luciferase was demonstrated by increased cytokine expression in splenocytes after exposure to luciferase peptide in parallel with MHC I–luciferase peptide tetramer binding. This anti-luciferase immune response observed following continuous, high-level luciferase expression in vivo clearly impacts its use as an in vivo reporter. As both an immunogen and an extremely sensitive reporter, luciferase is also a useful model system for the study of immune responses following in vivo gene transfer and expression. PMID:25093708

Method and apparatus for animal positioning in imaging systems

Science.gov (United States)

Hadjioannou, Arion-Xenofon; Stout, David B.; Silverman, Robert W.

2013-01-01

An apparatus for imaging an animal includes a first mounting surface, a bed sized to support the animal and releasably secured to or integral with the first mounting surface. The apparatus also includes a plurality of straps, each having a first end in a fixed position relative to the bed and a second end for tightening around a limb of the animal. A method for in-vivo imaging of an animal includes providing an animal that has limbs, providing a first mounting surface, and providing a bed removably secured to or integral with the mounting surface and sized to support the animal as well as being coupled to a plurality of straps. The method also includes placing the animal on the bed between the plurality of straps and tightening at least two of the plurality of straps around at least two of the limbs such that the animal is substantially secured in place relative to the bed.

Understanding in vivo modelling of depression in non-human animals: a systematic review protocol

DEFF Research Database (Denmark)

Bannach-Brown, Alexandra; Liao, Jing; Wegener, Gregers

2016-01-01

experimental model(s) to induce or mimic a depressive-like phenotype. Data that will be extracted include the model or method of induction; species and gender of the animals used; the behavioural, anatomical, electrophysiological, neurochemical or genetic outcome measure(s) used; risk of bias......The aim of this study is to systematically collect all published preclinical non-human animal literature on depression to provide an unbiased overview of existing knowledge. A systematic search will be carried out in PubMed and Embase. Studies will be included if they use non-human animal......-analysis of the preclinical studies modelling depression-like behaviours and phenotypes in animals....

Animal and non-animal experiments in nanotechnology - the results of a critical literature survey.

Science.gov (United States)

Sauer, Ursula G

2009-01-01

A literature survey funded by the Foundation Animalfree Research was performed to obtain an overview on animal experiments in nanotechnology. Scientific articles from Germany, France, the United Kingdom, Italy, the Netherlands and Switzerland published between 2004 and 2007 were collected. A total of 164 articles was retrieved covering in vivo nanotechnological research. The majority of animal experiments were conducted in "nanomedicine", i.e. nanotechnology in the health care area, to study targeted drug, vaccine or gene delivery. Further areas of research relate to nanotechnology-based imaging technologies, the toxicity of nanomaterials, tissue engineering for regenerative treatments, and magnetic tumour thermotherapy. Many experiments were classified as moderately and even severely distressful to the animals. Due to the significance of the scientific topics pursued, the possible scientific benefit of the research depicted in the articles is also assigned to be moderate to high. Nevertheless, it has to be asked whether such animal experiments are truly the only means to answer the scientific questions addressed in nanotechnology. An overview on non-animal test methods used in nanotechnological research revealed a broad spectrum of methodologies applied in a broad spectrum of scientific areas, including those for which animal experiments are being performed. Explicit incentives to avoid animal experiments in nanotechnology currently can only be found in the area of nanotoxicology, but not in the area of nanomedicine. From the point of view of animal welfare, not least because of the new technologies that arise due to nanotechnology, it is time for a paradigm change both in fundamental and applied biomedical research to found research strategies on non-animal test methods.

Development of realistic chest phantom for calibration of in-vivo plutonium counting facilities

International Nuclear Information System (INIS)

Shirotani, Takashi

1987-06-01

We have developed realistic chest phantom with removable model organs. The phantom is a torso and is terminated just above the femoral region. Tissue equivalent materials used in the phantom have been made of polyurethane with different amounts of ester of phosphoric acid, in order to simulate human soft tissues such as muscle, muscle-adipose mixtures and cartilage. Lung simulant has been made of foamed polyurethane. Capsulized small sources can be inserted into the holes, drilled in each sliced section of the model organ. Counting efficiencies, obtained with a pair of 12 cm diameter phoswich detectors set above the phantom chest, are 0.195 cpm/nCi for Pu-239 and 44.07 cpm/nCi for Am-241, respectively. The results agree well with efficiencies obtained with IAEA-Phantom. We conclude that the phantom can be used as a standard phantom for the calibration of Pu chest counting equipment. (author)

Outcomes of laryngohyoid suspension techniques in an ovine model of profound oropharyngeal dysphagia.

Science.gov (United States)

Johnson, Christopher M; Venkatesan, Naren N; Siddiqui, M Tausif; Cates, Daniel J; Kuhn, Maggie A; Postma, Gregory M; Belafsky, Peter C

2017-12-01

To evaluate the efficacy of various techniques of laryngohyoid suspension in the elimination of aspiration utilizing a cadaveric ovine model of profound oropharyngeal dysphagia. Animal study. The head and neck of a Dorper cross ewe was placed in the lateral fluoroscopic view. Five conditions were tested: baseline, thyroid cartilage to hyoid approximation (THA), thyroid cartilage to hyoid to mandible (laryngohyoid) suspension (LHS), LHS with cricopharyngeus muscle myotomy (LHS-CPM), and cricopharyngeus muscle myotomy (CPM) alone. Five 20-mL trials of barium sulfate were delivered into the oropharynx under fluoroscopy for each condition. Outcome measures included the penetration aspiration scale (PAS) and the National Institutes of Health (NIH) Swallow Safety Scale (NIH-SSS). Median baseline PAS and NIH-SSS scores were 8 and 6, respectively, indicating severe impairment. THA scores were not improved from baseline. LHS alone reduced the PAS to 1 (P = .025) and NIH-SSS to 2 (P = .025) from baseline. LHS-CPM reduced the PAS to 1 (P = .025) and NIH-SSS to 0 (P = .025) from baseline. CPM alone did not improve scores. LHS-CPM displayed improved NIH-SSS over LHS alone (P = .003). This cadaveric model represents end-stage profound oropharyngeal dysphagia such as what could result from severe neurological insult. CPM alone failed to improve fluoroscopic outcomes in this model. Thyrohyoid approximation also failed to improve outcomes. LHS significantly improved both PAS and NIH-SSS. The addition of CPM to LHS resulted in improvement over suspension alone. NA. Laryngoscope, 127:E422-E427, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Interrogation of inhibitor of nuclear factor κB α/nuclear factor κB (IκBα/NF-κB) negative feedback loop dynamics: from single cells to live animals in vivo.

Science.gov (United States)

Moss, Britney L; Elhammali, Adnan; Fowlkes, Tiffanie; Gross, Shimon; Vinjamoori, Anant; Contag, Christopher H; Piwnica-Worms, David

2012-09-07

Full understanding of the biological significance of negative feedback processes requires interrogation at multiple scales as follows: in single cells, cell populations, and live animals in vivo. The transcriptionally coupled IκBα/NF-κB negative feedback loop, a pivotal regulatory node of innate immunity and inflammation, represents a model system for multiscalar reporters. Using a κB(5)→IκBα-FLuc bioluminescent reporter, we rigorously evaluated the dynamics of ΙκBα degradation and subsequent NF-κB transcriptional activity in response to diverse modes of TNFα stimulation. Modulating TNFα concentration or pulse duration yielded complex, reproducible, and differential ΙκBα dynamics in both cell populations and live single cells. Tremendous heterogeneity in the transcriptional amplitudes of individual responding cells was observed, which was greater than the heterogeneity in the transcriptional kinetics of responsive cells. Furthermore, administration of various TNFα doses in vivo generated ΙκBα dynamic profiles in the liver resembling those observed in single cells and populations of cells stimulated with TNFα pulses. This suggested that dose modulation of circulating TNFα was perceived by hepatocytes in vivo as pulses of increasing duration. Thus, a robust bioluminescent reporter strategy enabled rigorous quantitation of NF-κB/ΙκBα dynamics in both live single cells and cell populations and furthermore, revealed reproducible behaviors that informed interpretation of in vivo studies.

How can in vitro models best reflect in vivo Staphylococcus biofilms?

DEFF Research Database (Denmark)

Meyer, Rikke Louise

In vitro biofilm models are the basis for most studies of biofilm biology because they enable high-throughput analyses without the expenditure of animals. But how do we ensure that what we learn from in vitro studies is relevant in vivo? Biofilms grown in standard laboratory media do not interact...... with host factors and are thus profoundly different from in vivo biofilms. We therefore need in vitro models that are as in vivo-like as possible. We investigated how the addition of divalent cations and human plasma to brain heart infusion broth affected biofilm formation by Staphylococcus aureus...

Aortic lipid and 125I-albumin accumulation in streptozotocin-diabetic guinea pigs: prevention by insulin treatment

International Nuclear Information System (INIS)

Schlosser, M.J.; Bannon, A.W.; Verlangieri, A.J.

1986-01-01

Diabetes mellitus, a major risk factor of atherosclerosis, is associated with the aortic accumulation of macromolecules. The authors have examined this relationship in the streptozotocin (STZ)-diabetic guinea pig, a species (like man) unable to synthesize ascorbic acid and susceptible to atherosclerosis. Male Dunkin-Hartley guinea pigs received STZ (150 mg/kg, i.c.) or vehicle (control). After 5 days, insulin (10 U/kg/day) was given to half the STZ animals (STZ-INS0 while the remaining half (STZ-SAL) and controls received saline. 25 days later, animals were given 125 I-albumin (100 μCi/kg, i.a.). Activity was determined in plasma at 5 (C/sub p5), 15 and 30 minutes, and in the upper thoracic aorta after 30 minutes. Histopathological changes were evaluated in the lower aorta. Aortic albumin permeability defined as cpm/cm 2 /sec, cpm/cm 2 /sec/C/sub p5/, or cpm/C/sub p5//g tissue was significantly elevated in the STZ-SAL group compared to both STZ-INS and control groups; these latter two groups were not significantly different from each other. Oil-Red-O positive material (lipid) occurred at multifocal areas within the intima of the STZ-SAL animals only. This study demonstrates (1) an abnormal increase in aortic permeability to albumin, (2) histological evidence of early atherosclerotic lesions, and (3) that insulin treatment can prevent these angiopathies in this STZ-diabetic animal model

Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments.

Directory of Open Access Journals (Sweden)

Valerie C Henderson

Full Text Available The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external or programmatic research activity they primarily address.We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.

Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments.

Science.gov (United States)

Henderson, Valerie C; Kimmelman, Jonathan; Fergusson, Dean; Grimshaw, Jeremy M; Hackam, Dan G

2013-01-01

The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address. We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria--most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation. By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice. Please see later in the article for the Editors' Summary.

The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

Science.gov (United States)

Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

2014-04-01

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

Near-infrared optical imaging of nucleic acid nanocarriers in vivo.

Science.gov (United States)

Rome, Claire; Gravier, Julien; Morille, Marie; Divita, Gilles; Bolcato-Bellemin, Anne-Laure; Josserand, Véronique; Coll, Jean-Luc

2013-01-01

Noninvasive, real-time optical imaging methods are well suited to follow the in vivo distribution of nucleic acid nanocarriers, their dissociation, and the resulting gene expression or inhibition. Indeed, most small animal imaging devices perform bioluminescence and fluorescence measurements without moving the animal, allowing a simple, rapid, and cost-effective method of investigation of several parameters at a time, in longitudinal experiments that can last for days or weeks.Here we help the reader in choosing adapted near-infrared (NIR) fluorophores or pairs of fluorophores for Förster resonance energy transfer assays, imaging of reporter genes, as well as nanocarriers for in vivo gene and siRNA delivery. In addition, we present the labeling methods of these macromolecules and of their payload and the protocols to detect them using bioluminescence and NIR fluorescence imaging in mice.

Advances in Small Animal Imaging Systems

International Nuclear Information System (INIS)

Loudos, George K.

2007-01-01

The rapid growth in genetics and molecular biology combined with the development of techniques for genetically engineering small animals has led to an increased interest in in vivo laboratory animal imaging during the past few years. For this purpose, new instrumentation, data acquisition strategies, and image processing and reconstruction techniques are being developed, researched and evaluated. The aim of this article is to give a short overview of the state of the art technologies for high resolution and high sensitivity molecular imaging techniques, primarily positron emission tomography (PET) and single photon emission computed tomography (SPECT). The basic needs of small animal imaging will be described. The evolution in instrumentation in the past two decades, as well as the commercially available systems will be overviewed. Finally, the new trends in detector technology and preliminary results from challenging applications will be presented. For more details a number of references are provided

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives.

Science.gov (United States)

Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

2016-01-01

Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

Directory of Open Access Journals (Sweden)

Mohan Kumar Pasupuleti

2016-01-01

Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

In Vivo Self-Powered Wireless Cardiac Monitoring via Implantable Triboelectric Nanogenerator.

Science.gov (United States)

Zheng, Qiang; Zhang, Hao; Shi, Bojing; Xue, Xiang; Liu, Zhuo; Jin, Yiming; Ma, Ye; Zou, Yang; Wang, Xinxin; An, Zhao; Tang, Wei; Zhang, Wei; Yang, Fan; Liu, Yang; Lang, Xilong; Xu, Zhiyun; Li, Zhou; Wang, Zhong Lin

2016-07-26

Harvesting biomechanical energy in vivo is an important route in obtaining sustainable electric energy for powering implantable medical devices. Here, we demonstrate an innovative implantable triboelectric nanogenerator (iTENG) for in vivo biomechanical energy harvesting. Driven by the heartbeat of adult swine, the output voltage and the corresponding current were improved by factors of 3.5 and 25, respectively, compared with the reported in vivo output performance of biomechanical energy conversion devices. In addition, the in vivo evaluation of the iTENG was demonstrated for over 72 h of implantation, during which the iTENG generated electricity continuously in the active animal. Due to its excellent in vivo performance, a self-powered wireless transmission system was fabricated for real-time wireless cardiac monitoring. Given its outstanding in vivo output and stability, iTENG can be applied not only to power implantable medical devices but also possibly to fabricate a self-powered, wireless healthcare monitoring system.

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

Directory of Open Access Journals (Sweden)

Michael D. Burkitt

2017-02-01

Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

Laser-enhanced cavitation during high intensity focused ultrasound: An in vivo study

OpenAIRE

Cui, Huizhong; Zhang, Ti; Yang, Xinmai

2013-01-01

Laser-enhanced cavitation during high intensity focused ultrasound (HIFU) was studied in vivo using a small animal model. Laser light was employed to illuminate the sample concurrently with HIFU radiation. The resulting cavitation was detected with a passive cavitation detector. The in vivo measurements were made under different combinations of HIFU treatment depths, laser wavelengths, and HIFU durations. The results demonstrated that concurrent light illumination during HIFU has the potentia...

Cerenkov Luminescence Tomography for In Vivo Radiopharmaceutical Imaging

Directory of Open Access Journals (Sweden)

Jianghong Zhong

2011-01-01

Full Text Available Cerenkov luminescence imaging (CLI is a cost-effective molecular imaging tool for biomedical applications of radiotracers. The introduction of Cerenkov luminescence tomography (CLT relative to planar CLI can be compared to the development of X-ray CT based on radiography. With CLT, quantitative and localized analysis of a radiopharmaceutical distribution becomes feasible. In this contribution, a feasibility study of in vivo radiopharmaceutical imaging in heterogeneous medium is presented. Coupled with a multimodal in vivo imaging system, this CLT reconstruction method allows precise anatomical registration of the positron probe in heterogeneous tissues and facilitates the more widespread application of radiotracers. Source distribution inside the small animal is obtained from CLT reconstruction. The experimental results demonstrated that CLT can be employed as an available in vivo tomographic imaging of charged particle emitters in a heterogeneous medium.

In vivo assessment of 111In labelled lymphocyte gut homing in a TNBS colitis mouse model determined by dedicated animal pinhole SPECT

International Nuclear Information System (INIS)

Bennink, R.J.; Bruin, C.M. de; Montfrans, C. van; Jonge, W.J. de; Deventer, S.J. van; Velde, A.A. te

2002-01-01

score 12 ± 0.8 and 7 ± 0.4 respectively), indicating functionality of labelled reinjected cells. Conclusion: Homing of TNBS-sensitised lymphocytes can be assessed in vivo by means of dedicated animal pinhole SPECT. This technique enables serial measurement of specific cell trafficking in TNBS colitis with potential of in vivo evaluation of novel anti-inflammatory strategies in inflammatory bowel disease

Factors influencing preclinical in vivo evaluation of mumps vaccine strain immunogenicity.

Science.gov (United States)

Halassy, B; Kurtović, T; Brgles, M; Lang Balija, M; Forčić, D

2015-01-01

Immunogenicity testing in animals is a necessary preclinical assay for demonstration of vaccine efficacy the results of which are often the basis for the decision whether to proceed or withdraw the further development of the novel vaccine candidate. However, in vivo assays are rarely, if at all, optimized and validated. Here we clearly demonstrate the importance of in vivo assay (mumps virus immunogenicity testing in guinea pigs) optimization for gaining reliable results and the suitability of Fractional factorial design of experiments (DoE) for such a purpose. By the use of DoE with resolution IV (2IV((4-1))) we clearly revealed that the parameters significantly increasing assay sensitivity were interval between animal immunizations followed by the body weight of experimental animals. The quantity (0 versus 2%) of the stabilizer (fetal bovine serum, FBS) in the sample was shown as non-influencing parameter in DoE setup. However, the separate experiment investigating only the FBS influence, and performed under other parameters optimally set, showed that FBS also influences the results of immunogenicity assay. Such finding indicated that (a) factors with strong influence on the measured outcome can hide the effects of parameters with modest/low influence and (b) the matrix of mumps virus samples to be compared for immunogenicity must be identical for reliable virus immunogenicity comparison. Finally the 3 mumps vaccine strains widely used for decades in the licensed vaccines were for the first time compared in an animal model, and results obtained were in line with their reported immunogenicity in human population supporting the predictive power of the optimized in vivo assay.

Are animal models useful for studying human disc disorders / degeneration?

NARCIS (Netherlands)

Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

2008-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

Science.gov (United States)

Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K. M.; Gomez-Cabrera, M. C.; Vina, J.; Borras, C.

2015-01-01

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol. PMID:26221416

2.5D Representations Combining in vivo 3D MRI and ex vivo 2D MSI Approaches to Study the Lipid Distribution in the Whole Sheep Brain

OpenAIRE

Labas , Valérie; Teixeira-Gomes , Ana Paula; Andersson , Frédéric; Ménigot , Sébastien; Batailler , Martine; Adriaensen , Hans; Migaud , Martine; Chaillou , Elodie

2015-01-01

National audience; Mass Spectrometry Imaging (MSI) provides easily high spatially resolved masses allowing characterization of endogenous lipids. These latter constitute about 70% of the composition of the white matter of the brain which can be implicated in developmental and/or cognitive troubles. In order to examine the molecular distribution of lipids in whole sheep brain, and especially in white/grey matter, we combined in vivo and ex vivo images, obtained in the same animals, using Magne...

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

Directory of Open Access Journals (Sweden)

Zapata Ana X

2006-03-01

Full Text Available Abstract Background For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM to induce neutropenia. Although high doses (350–450 mg/kg are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. Methods Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus, meningoencephalitis (S. pneumoniae, and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis. Results The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm3. Profound neutropenia (≤10 neutrophils/mm3 was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. Conclusion A CPM total dose of 250 mg/kg is sufficient to induce

In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs

Science.gov (United States)

Kay, Mark A.; Rothenberg, Steven; Landen, Charles N.; Bellinger, Dwight A.; Leland, Frances; Toman, Carol; Finegold, Milton; Thompson, Arthur R.; Read, M. S.; Brinkhous, Kenneth M.; Woo, Savio L. C.

1993-10-01

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting. factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.

In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

Directory of Open Access Journals (Sweden)

Cristina Botella

Full Text Available Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31 versus an Augmented Reality system (N = 32 in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

Science.gov (United States)

Botella, Cristina; Pérez-Ara, M Ángeles; Bretón-López, Juana; Quero, Soledad; García-Palacios, Azucena; Baños, Rosa María

2016-01-01

Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

Animal models and therapeutic molecular targets of cancer: utility and limitations

Directory of Open Access Journals (Sweden)

Cekanova M

2014-10-01

Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

In vitro and in vivo evaluation of a new large animal spirometry device using mainstream CO2 flow sensors.

Science.gov (United States)

Ambrisko, T D; Lammer, V; Schramel, J P; Moens, Y P S

2014-07-01

A spirometry device equipped with mainstream CO2 flow sensor is not available for large animal anaesthesia. To measure the resistance of a new large animal spirometry device and assess its agreement with reference methods for volume measurements. In vitro experiment and crossover study using anaesthetised horses. A flow partitioning device (FPD) equipped with 4 human CO2 flow sensors was tested. Pressure differences were measured across the whole FPD and across each sensor separately using air flows (range: 90-720 l/min). One sensor was connected to a spirometry monitor for in vitro volume (3, 5 and 7 l) measurements. These measurements were compared with a reference method. Five anaesthetised horses were used for tidal volume (VT) measurements using the FPD and a horse-lite sensor (reference method). Bland-Altman analysis, ANOVA and linear regression analysis were used for data analysis. Pressure differences across each sensor were similar suggesting equal flow partitioning. The resistance of the device increased with flow (range: 0.3-1.5 cmH2 O s/l) and was higher than that of the horse-lite. The limits of agreement for volume measurements were within -1 and 2% in vitro and -12 and 0% in vivo. Nine of 147 VT measurements in horses were outside of the ± 10% limits of acceptance but most of these erroneous measurements occurred with VTs lower than 4 l. The determined correction factor for volume measurements was 3.97 ± 0.03. The limits of agreement for volume measurements by the new device were within ± 10% using clinically relevant range of volumes. The new spirometry device can be recommended for measurement of VT in adult Warmblood horses. © 2013 EVJ Ltd.

Near-infrared quantum-dot-based non-invasive in vivo imaging of squamous cell carcinoma U14

International Nuclear Information System (INIS)

Cao Yu'an; Yang Kai; Li Zhigang; Zhao Cheng; Yang Jia; Shi Chunmeng

2010-01-01

Near-infrared (near-ir) quantum dots (QDs) are well known for their excellent optical characteristics. They hold great potential for applications in non-invasive long term observation and tracing of cells in vivo. Here, near-ir QDs with an emission wavelength of 800 nm (QD800) were used to label squamous cell carcinoma cell line U14 (U14/QD800). The effect of tissue depth and animal fur on the imaging sensitivity and stability was evaluated following subcutaneous and intramuscular injection into Kunming mice, employing an in vivo imaging system. We have demonstrated that QD800-based visual in vivo imaging increased the sensitivity of cancer early detection by a factor of 100 compared with traditional detection methods. More importantly, this study proved for the first time that animal fur has a serious impact on the detection sensitivity and duration of QD-based in vivo imaging. In general, the duration and sensitivity of QD800 for in vivo imaging were not greatly affected by a depth less than 1.8 ± 0.21 mm (subcutaneous or intramuscular). This study provides critical reference data for further research on near-ir QD-based early detection and in vivo visual observation of cancer.

Application of Voxel Phantoms to Study the Influence of Heterogeneous Distribution of Actinides in Lungs on In Vivo Counting Calibration Factors Using Animal Experimentations

Energy Technology Data Exchange (ETDEWEB)

Lamart, S.; Pierrat, N.; De Carlan, L.; Franck, D. [IRSN/DRPH/SDI/LEDI, BP 17, F-92 262 Fontenay-aux-Roses (France); Dudoignon, N. [IRSN/DRPH/SRBE/LRPAT, BP 17, F-92 262 Fontenay-aux-Roses (France); Rateau, S.; Van der Meeren, A.; Rouit, E. [CEA/DSV/DRR/SRCA/LRT BP no 12, F-91680 Bruyeres-le-Chatel (France); Bottlaender, M. [CEA/SHFJ, 4, place du General Leclerc F-91400 Orsay (France)

2006-07-01

Calibration of lung counting system dedicated to retention assessment of actinides in the lungs remains critical due to large uncertainties in calibration factors. Among them, the detector positioning, the chest wall thickness and composition (muscle/fat) assessment, and the distribution of the contamination are the main parameters influencing the detector response. In order to reduce these uncertainties, a numerical approach based on the application of voxel phantoms (numerical phantoms based on tomographic images, CT or MRI) associated to a Monte-Carlo code (namely M.C.N.P.) was developed. It led to the development of a dedicated tool, called O.E.D.I.P.E., that allows to easily handle realistic voxel phantoms for the simulation of in vivo measurement (or dose calculation, application that will not be presented in this paper). The goal of this paper is to present our study of the influence of the lung distribution on calibration factors using both animal experimentations and our numerical method. Indeed, physical anthropomorphic phantoms used for calibration always consider a uniform distribution of the source in the lungs, which is not true in many contamination conditions. The purpose of the study is to compare the response of the measurement detectors using a real distribution of actinide particles in the lungs, obtained from animal experimentations, with the homogeneous one considered as the reference. This comparison was performed using O.E.D.I.P.E. that can almost simulate any source distribution. A non human primate was contaminated heterogeneously by intra-tracheal administration of actinide oxide. After euthanasia, gamma spectrometry measurements were performed on the pulmonary lobes to obtain the distribution of the contamination in the lungs. This realistic distribution was used to simulate an heterogeneous contamination in the numerical phantom of the non human primate, which was compared with a simulation of an homogeneous contamination presenting the

Application of Voxel Phantoms to Study the Influence of Heterogeneous Distribution of Actinides in Lungs on In Vivo Counting Calibration Factors Using Animal Experimentations

International Nuclear Information System (INIS)

Lamart, S.; Pierrat, N.; De Carlan, L.; Franck, D.; Dudoignon, N.; Rateau, S.; Van der Meeren, A.; Rouit, E.; Bottlaender, M.

2006-01-01

Calibration of lung counting system dedicated to retention assessment of actinides in the lungs remains critical due to large uncertainties in calibration factors. Among them, the detector positioning, the chest wall thickness and composition (muscle/fat) assessment, and the distribution of the contamination are the main parameters influencing the detector response. In order to reduce these uncertainties, a numerical approach based on the application of voxel phantoms (numerical phantoms based on tomographic images, CT or MRI) associated to a Monte-Carlo code (namely M.C.N.P.) was developed. It led to the development of a dedicated tool, called O.E.D.I.P.E., that allows to easily handle realistic voxel phantoms for the simulation of in vivo measurement (or dose calculation, application that will not be presented in this paper). The goal of this paper is to present our study of the influence of the lung distribution on calibration factors using both animal experimentations and our numerical method. Indeed, physical anthropomorphic phantoms used for calibration always consider a uniform distribution of the source in the lungs, which is not true in many contamination conditions. The purpose of the study is to compare the response of the measurement detectors using a real distribution of actinide particles in the lungs, obtained from animal experimentations, with the homogeneous one considered as the reference. This comparison was performed using O.E.D.I.P.E. that can almost simulate any source distribution. A non human primate was contaminated heterogeneously by intra-tracheal administration of actinide oxide. After euthanasia, gamma spectrometry measurements were performed on the pulmonary lobes to obtain the distribution of the contamination in the lungs. This realistic distribution was used to simulate an heterogeneous contamination in the numerical phantom of the non human primate, which was compared with a simulation of an homogeneous contamination presenting the

Animal Models of Tick-Borne Hemorrhagic Fever Viruses

Directory of Open Access Journals (Sweden)

Heinz Feldmann

2013-05-01

Full Text Available Tick-borne hemorrhagic fever viruses (TBHFV are detected throughout the African and Eurasian continents and are an emerging or re-emerging threat to many nations. Due to the largely sporadic incidences of these severe diseases, information on human cases and research activities in general have been limited. In the past decade, however, novel TBHFVs have emerged and areas of endemicity have expanded. Therefore, the development of countermeasures is of utmost importance in combating TBHFV as elimination of vectors and interrupting enzootic cycles is all but impossible and ecologically questionable. As in vivo models are the only way to test efficacy and safety of countermeasures, understanding of the available animal models and the development and refinement of animal models is critical in negating the detrimental impact of TBHFVs on public and animal health.

Animal models of contraception: utility and limitations

Directory of Open Access Journals (Sweden)

Liechty ER

2015-04-01

Full Text Available Emma R Liechty,1 Ingrid L Bergin,1 Jason D Bell2 1Unit for Laboratory Animal Medicine, 2Program on Women's Health Care Effectiveness Research, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA Abstract: Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development. Keywords: nonhuman primate, preclinical, in vivo, contraceptive devices

Platelet lysate as a substitute for animal serum for the ex-vivo expansion of mesenchymal stem/stromal cells: present and future.

Science.gov (United States)

Astori, Giuseppe; Amati, Eliana; Bambi, Franco; Bernardi, Martina; Chieregato, Katia; Schäfer, Richard; Sella, Sabrina; Rodeghiero, Francesco

2016-07-13

The use of fetal bovine serum (FBS) as a cell culture supplement is discouraged by regulatory authorities to limit the risk of zoonoses and xenogeneic immune reactions in the transplanted host. Additionally, FBS production came under scrutiny due to animal welfare concerns. Platelet derivatives have been proposed as FBS substitutes for the ex-vivo expansion of mesenchymal stem/stromal cells (MSCs) since platelet-derived growth factors can promote MSC ex-vivo expansion. Platelet-derived growth factors are present in platelet lysate (PL) obtained after repeated freezing-thawing cycles of the platelet-rich plasma or by applying physiological stimuli such as thrombin or CaCl2.PL-expanded MSCs have been used already in the clinic, taking advantage of their faster proliferation compared with FBS-expanded preparations. Should PL be applied to other biopharmaceutical products, its demand is likely to increase dramatically. The use of fresh platelet units for the production of PL raises concerns due to limited availability of platelet donors. Expired units might represent an alternative, but further data are needed to define safety, including pathogen reduction, and functionality of the obtained PL. In addition, relevant questions concerning the definition of PL release criteria, including concentration ranges of specific growth factors in PL batches for various clinical indications, also need to be addressed. We are still far from a common definition of PL and standardized PL manufacture due to our limited knowledge of the mechanisms that mediate PL-promoting cell growth. Here, we concisely discuss aspects of PL as MSC culture supplement as a preliminary step towards an agreed definition of the required characteristics of PL for the requirements of manufacturers and users.

In vivo electrophysiological measurement of the rat ulnar nerve with axonal excitability testing

DEFF Research Database (Denmark)

Wild, Brandon M.; Morris, Renée; Moldovan, Mihai

2018-01-01

Electrophysiology enables the objective assessment of peripheral nerve function in vivo. Traditional nerve conduction measures such as amplitude and latency detect chronic axon loss and demyelination, respectively. Axonal excitability techniques "by threshold tracking" expand upon these measures...... by providing information regarding the activity of ion channels, pumps and exchangers that relate to acute function and may precede degenerative events. As such, the use of axonal excitability in animal models of neurological disorders may provide a useful in vivo measure to assess novel therapeutic...... interventions. Here we describe an experimental setup for multiple measures of motor axonal excitability techniques in the rat ulnar nerve. The animals are anesthetized with isoflurane and carefully monitored to ensure constant and adequate depth of anesthesia. Body temperature, respiration rate, heart rate...

In vivo bioluminescence imaging of cell differentiation in biomaterials: a platform for scaffold development.

Science.gov (United States)

Bagó, Juli R; Aguilar, Elisabeth; Alieva, Maria; Soler-Botija, Carolina; Vila, Olaia F; Claros, Silvia; Andrades, José A; Becerra, José; Rubio, Nuria; Blanco, Jerónimo

2013-03-01

In vivo testing is a mandatory last step in scaffold development. Agile longitudinal noninvasive real-time monitoring of stem cell behavior in biomaterials implanted in live animals should facilitate the development of scaffolds for tissue engineering. We report on a noninvasive bioluminescence imaging (BLI) procedure for simultaneous monitoring of changes in the expression of multiple genes to evaluate scaffold performance in vivo. Adipose tissue-derived stromal mensenchymal cells were dually labeled with Renilla red fluorescent protein and firefly green fluorescent protein chimeric reporters regulated by cytomegalovirus and tissue-specific promoters, respectively. Labeled cells were induced to differentiate in vitro and in vivo, by seeding in demineralized bone matrices (DBMs) and monitored by BLI. Imaging results were validated by RT-polymerase chain reaction and histological procedures. The proposed approach improves molecular imaging and measurement of changes in gene expression of cells implanted in live animals. This procedure, applicable to the simultaneous analysis of multiple genes from cells seeded in DBMs, should facilitate engineering of scaffolds for tissue repair.

A radiopaque electrospun scaffold for engineering fibrous musculoskeletal tissues: Scaffold characterization and in vivo applications.

Science.gov (United States)

Martin, John T; Milby, Andrew H; Ikuta, Kensuke; Poudel, Subash; Pfeifer, Christian G; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2015-10-01

Tissue engineering strategies have emerged in response to the growing prevalence of chronic musculoskeletal conditions, with many of these regenerative methods currently being evaluated in translational animal models. Engineered replacements for fibrous tissues such as the meniscus, annulus fibrosus, tendons, and ligaments are subjected to challenging physiologic loads, and are difficult to track in vivo using standard techniques. The diagnosis and treatment of musculoskeletal conditions depends heavily on radiographic assessment, and a number of currently available implants utilize radiopaque markers to facilitate in vivo imaging. In this study, we developed a nanofibrous scaffold in which individual fibers included radiopaque nanoparticles. Inclusion of radiopaque particles increased the tensile modulus of the scaffold and imparted radiation attenuation within the range of cortical bone. When scaffolds were seeded with bovine mesenchymal stem cells in vitro, there was no change in cell proliferation and no evidence of promiscuous conversion to an osteogenic phenotype. Scaffolds were implanted ex vivo in a model of a meniscal tear in a bovine joint and in vivo in a model of total disc replacement in the rat coccygeal spine (tail), and were visualized via fluoroscopy and microcomputed tomography. In the disc replacement model, histological analysis at 4 weeks showed that the scaffold was biocompatible and supported the deposition of fibrous tissue in vivo. Nanofibrous scaffolds that include radiopaque nanoparticles provide a biocompatible template with sufficient radiopacity for in vivo visualization in both small and large animal models. This radiopacity may facilitate image-guided implantation and non-invasive long-term evaluation of scaffold location and performance. The healing capacity of fibrous musculoskeletal tissues is limited, and injury or degeneration of these tissues compromises the standard of living of millions in the US. Tissue engineering repair

Animal lectins: potential receptors for ginseng polysaccharides

Directory of Open Access Journals (Sweden)

So Hee Loh

2017-01-01

Full Text Available Panax ginseng Meyer, belonging to the genus Panax of the family Araliaceae, is known for its human immune system-related effects, such as immune-boosting effects. Ginseng polysaccharides (GPs are the responsible ingredient of ginseng in immunomodulation, and are classified as acidic and neutral GPs. Although GPs participate in various immune reactions including the stimulation of immune cells and production of cytokines, the precise function of GPs together with its potential receptor(s and their signal transduction pathways have remained largely unknown. Animal lectins are carbohydrate-binding proteins that are highly specific for sugar moieties. Among many different biological functions in vivo, animal lectins especially play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens or that are inaccessible on host cells. This review summarizes the immunological activities of GPs and the diverse roles of animal lectins in the immune system, suggesting the possibility of animal lectins as the potential receptor candidates of GPs and giving insights into the development of GPs as therapeutic biomaterials for many immunological diseases.

Biological distribution of reactor produced 18F-FDG. Local experience

International Nuclear Information System (INIS)

Sierralta, M.P.; Massardo, T.; Gil, M.C.; Chandia, M.; Godoy, N.; Troncoso, F.; Jofre, M.J.

2002-01-01

Introduction: Quality control through an animal model that relates bio distribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after recent myocardial infarction, the use of reactor produced 18F-FDG (a radiotracer usually obtained in cyclotron) is proposed, production of wish had never been attempted in our country. The aim of the study was to compare the specific activities found in the different tissues after the injection of this reactor produced radiopharmaceutical with those obtained by others authors with cyclotron 18F-FDG. Material WISTAR female white mice, men weight 25,28 +/- 1,09 g (23,8-26,9 range) in standard support conditions was used. 1,22 MBq (33 mCi) of 18F-FDG were injected in a lateral tail vein. Previously anaesthetised with Chloroform, the animals were sacrificed by jugular section at 5, 30 and 60 minutes intervals post injection. Blood and organs were removed (liver, lungs, heart, brain, urine plus bladder, kidneys, femur, muscle and quivers), placed in vials, then weighed, and finally taken to a Gamma Packard Minaxi γ Auto-gamma 5000 serie counter to obtain the counts per minute (cpm) (previously the empty vials were weighed too). At same time, STANDARDS (STD) (3 dilutions) cpm and BACKGROUND (BKG) cpm were collected. We calculate 1) mean BKG cpm, 2) mean STD cpm, who then were corrected by decay factor and dilution, and 3) each one of the tissues cpm, that then were corrected by decay factor, divided by the corresponding dilution cpm and multiplied by 100 to obtain the Injected Activity % (IA%). Finally, the IA% was divided by the tissue weight and get the Specific Activity (SA). Mean and standard deviation for each tissue at the 3 intervals were calculated. Results: The uptake distribution at 30 and 60 minutes were similar between reactor and cyclotron produced 18F-FDG, with significant bigger SA in heart and brain respect of the rest organs. There were significant

Biological distribution of reactor produced 18F-FDG. Local experience

Energy Technology Data Exchange (ETDEWEB)

Sierralta, M P [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Military Hospital Nuclear Medicine Department, Santiago (Chile); Massardo, T [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Gil, M C [CGM Nuclear, Santiago (Chile); Chandia, M; Godoy, N; Troncoso, F [CCHEN, CEN La Reina, Santiago (Chile); Jofre, M J [Military Hospital Nuclear Medicine Department, Santiago (Chile)

2002-09-01

Introduction: Quality control through an animal model that relates bio distribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after recent myocardial infarction, the use of reactor produced 18F-FDG (a radiotracer usually obtained in cyclotron) is proposed, production of wish had never been attempted in our country. The aim of the study was to compare the specific activities found in the different tissues after the injection of this reactor produced radiopharmaceutical with those obtained by others authors with cyclotron 18F-FDG. Material WISTAR female white mice, men weight 25,28 +/- 1,09 g (23,8-26,9 range) in standard support conditions was used. 1,22 MBq (33 mCi) of 18F-FDG were injected in a lateral tail vein. Previously anaesthetised with Chloroform, the animals were sacrificed by jugular section at 5, 30 and 60 minutes intervals post injection. Blood and organs were removed (liver, lungs, heart, brain, urine plus bladder, kidneys, femur, muscle and quivers), placed in vials, then weighed, and finally taken to a Gamma Packard Minaxi {gamma} Auto-gamma 5000 serie counter to obtain the counts per minute (cpm) (previously the empty vials were weighed too). At same time, STANDARDS (STD) (3 dilutions) cpm and BACKGROUND (BKG) cpm were collected. We calculate 1) mean BKG cpm, 2) mean STD cpm, who then were corrected by decay factor and dilution, and 3) each one of the tissues cpm, that then were corrected by decay factor, divided by the corresponding dilution cpm and multiplied by 100 to obtain the Injected Activity % (IA%). Finally, the IA% was divided by the tissue weight and get the Specific Activity (SA). Mean and standard deviation for each tissue at the 3 intervals were calculated. Results: The uptake distribution at 30 and 60 minutes were similar between reactor and cyclotron produced 18F-FDG, with significant bigger SA in heart and brain respect of the rest organs. There were significant

Educación ambiental no formal y actitud hacia la conservación del medio ambiente de la población del C.P.M. Francisco Bolognesi de Tacna

OpenAIRE

Santana Soto, Humberto Jacinto

2017-01-01

El objetivo fue determinar el efecto de la educación ambiental no formal en la actitud hacia la conservación medioambiental de la población del C.P.M. Bolognesi de Tacna en el 2016. El diseño fue cuasiexperimental intrasujetos, con una muestra de 33 pobladores. Principales resultados, la puntuación promedio de la escala de actitud en la dimensión cognitiva, afectiva, conativa y puntuación total, después de la aplicación del estímulo fue superior en el grupo experimental respecto del control. ...

Nanodiamond for biolabelling and toxicity evaluation in the zebrafish embryo in vivo.

Science.gov (United States)

Lin, Y-C; Wu, K-T; Lin, Z-R; Perevedentseva, E; Karmenyan, A; Lin, M-D; Cheng, C-L

2016-08-01

Nanodiamond (ND) has been proposed for various biomedical applications, including bioimaging, biosensing and drug delivery, owing to its physical-chemical properties and biocompatibility. Particularly, ND has been demonstrated as fluorescence- and Raman-detectable labels in many cellular models. Different surface functionalization methods have been developed, varying the ND's surface properties and rendering the possibility to attach biomolecules to provide interaction with biological targets. For this, toxicity is of major concern in animal models. Aside from cellular models, a cost-effective animal test will greatly facilitate the development of applications. In this study, we use the rapid, sensitive and reproducible zebrafish embryo model for in vivo nanotoxicity test. We optimize the conditions for using this animal model and analyze the zebrafish embryonic development in the presence of ND. ND is observed in the embryo in vivo using laser confocal fluorescence microscopy and fluorescence lifetime imaging. Using the zebrafish model for a safety evaluation of ND-based nanolabel is discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo NMR spectroscopy of the liver. Spectroscopie RMN du foie in vivo

Energy Technology Data Exchange (ETDEWEB)

Jehenson, P.; Cuenod, C.A.; Syrota, A. (CEA, 91 - Orsay (FR). Service Hospitalier Frederic Joliot)

1989-01-01

The application of in vivo MR spectroscopy to the study of the liver is currently an expanding field of research. Owing to technical difficulties, the results obtained thus far were mainly those of animal observations. Several nuclei have been considered: hydrogen, phosphorus, carbon or fluorine. This non-traumatic method allows following and quantifying the various metabolic pathways, especially during hepatic diseases. The major metabolic pathways, i.e. neoglycogenesis, glycogenolysis, Krebs' cycle, etc., are studied, as well as their alterations during diseases such as ischemia, diabetes or alcoholism. The development of this promising technique requires the cooperation of various clinical and fundamental disciplines.

Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study.

Science.gov (United States)

Aide, Nicolas; Louis, Marie-Hélène; Dutoit, Soizic; Labiche, Alexandre; Lemoisson, Edwige; Briand, Mélanie; Nataf, Valérie; Poulain, Laurent; Gauduchon, Pascal; Talbot, Jean-Noël; Montravers, Françoise

2007-10-01

To evaluate the accuracy of semi-quantitative small-animal PET data, uncorrected for attenuation, and then of the same semi-quantitative data corrected by means of recovery coefficients (RCs) based on phantom studies. A phantom containing six fillable spheres (diameter range: 4.4-14 mm) was filled with an 18F-FDG solution (spheres/background activity=10.1, 5.1 and 2.5). RCs, defined as measured activity/expected activity, were calculated. Nude rats harbouring tumours (n=50) were imaged after injection of 18F-FDG and sacrificed. The standardized uptake value (SUV) in tumours was determined with small-animal PET and compared to ex-vivo counting (ex-vivo SUV). Small-animal PET SUVs were corrected with RCs based on the greatest tumour diameter. Tumour proliferation was assessed with cyclin A immunostaining and correlated to the SUV. RCs ranged from 0.33 for the smallest sphere to 0.72 for the largest. A sigmoidal correlation was found between RCs and sphere diameters (r(2)=0.99). Small-animal PET SUVs were well correlated with ex-vivo SUVs (y=0.48x-0.2; r(2)=0.71) and the use of RCs based on the greatest tumour diameter significantly improved regression (y=0.84x-0.81; r(2)=0.77), except for tumours with important necrosis. Similar results were obtained without sacrificing animals, by using PET images to estimate tumour dimensions. RC-based corrections improved correlation between small-animal PET SUVs and tumour proliferation (uncorrected data: Rho=0.79; corrected data: Rho=0.83). Recovery correction significantly improves both accuracy of small-animal PET semi-quantitative data in rat studies and their correlation with tumour proliferation, except for largely necrotic tumours.

Modulating Hippocampal Plasticity with In Vivo Brain Stimulation

Science.gov (United States)

2016-11-17

wires were left unhooked from stimulation device. Following stimulation , the animals were returned to their homecage until time of euthanasia and...current stimulation (tDCS) to enhance cognitive training: effect of timing of stimulation . Exp Brain Res 232:3345-3351. 15 DISTRIBUTION...AFRL-RH-WP-TR-2016-0082 MODULATING HIPPOCAMPAL PLASTICITY WITH IN-VIVO BRAIN STIMULATION Joyce G. Rohan Oakridge Institute

On the relation of vitamin A to the protein biosynthesis in the organism of intact animals and during the action of ionizing radiation

International Nuclear Information System (INIS)

Leutskij, K.M.; Baran, M.M.; Batsura, A.F.

1975-01-01

Rats were investigated to determine the separate and joint effects of A-avitaminosis and ionizing radiation on protein biosynthesis in the tunica mucosa of the small intestine (cpm/10 mg ribosomal protein; M+-m). X-raying of control and A-avitaminotic animals was shown to result in decline of protein synthesis by 20 and 47 per cent, respectively. The joint action of A-avitaminosis in and irradiation of the organism enhanced the resultant variations in protein biosynthesis, which subsequently decreased by 60 per cent. Vitamin A-alcohol, introduced in the form of an aqueous emulsion into the incubation medium in vitro, was found to affect protein biosynthesis. Retinol (3 μg/ml) introduced in vitro increased inclusion of 14 C-leucine in the proteins of the acellular protein-synthesizing system in control and A-avitaminotic animals by 15 and 38 per cent, respectively. Addition of retinol (6μg/ml) increased inclusion of 14 C-leucine in control and A-avitaminotic rats by 11 and 18 per cent, respectively. Protein synthesis was found to have reliably increased by 17 per cent following introduction of retinol (3 μg) into the incubation medium of irradiated control animals. Protein biosynthesis was assumed to be the principal irradiation-affected stage in the system of biochemical processes in the intestine [ru

Animal Cancer Models of Skeletal Metastasis

Directory of Open Access Journals (Sweden)

Catherine Hibberd

2013-01-01

Full Text Available The bony skeleton is one of the most common sites of metastatic spread of cancer and is a significant source of morbidity in cancer patients, causing pain and pathologic fracture, impaired ambulatory ability, and poorer quality of life. Animal cancer models of skeletal metastases are essential for better understanding of the molecular pathways behind metastatic spread and local growth and invasion of bone, to enable analysis of host-tumor cell interactions, identify barriers to the metastatic process, and to provide platforms to develop and test novel therapies prior to clinical application in human patients. Thus, the ideal model should be clinically relevant, reproducible and representative of the human condition. This review summarizes the current in vivo animal models used in the study of cancer metastases of the skeleton.

In vivo growth-restricted and reversible malignancy induced by Human Herpesvirus-8/ KSHV: a cell and animal model of virally induced Kaposi's sarcoma

Science.gov (United States)

Mutlu, Agata D'Agostino; Cavallin, Lucas E.; Vincent, Loïc; Chiozzini, Chiara; Eroles, Pilar; Duran, Elda M.; Asgari, Zahra; Hooper, Andrea T.; La Perle, Krista M. D.; Hilsher, Chelsey; Gao, Shou-Jiang; Dittmer, Dirk P.; Rafii, Shahin; Mesri, Enrique A.

2007-01-01

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth-restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS. PMID:17349582

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

Science.gov (United States)

Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

2010-01-06

It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Imaging the glutamatergic system in vivo - relevance to schizophrenia

Energy Technology Data Exchange (ETDEWEB)

Bressan, R.A.; Pilowsky, L.S. [Inst. of Psychiatry, London (United Kingdom); Inst. of Nuclear Medicine, University College of London Medical School (United Kingdom)

2000-11-01

Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system. (orig.)

Imaging the glutamatergic system in vivo - relevance to schizophrenia

International Nuclear Information System (INIS)

Bressan, R.A.; Pilowsky, L.S.

2000-01-01

Schizophrenia is a devastating psychiatric illness. Its pathophysiology is not fully clarified. Animal data, in vitro and indirect in vivo imaging support glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction in the disorder. A lack of suitable ligands has obstructed direct evaluation of the NMDA receptor hypofunction hypothesis of schizophrenia. Many research groups are working towards developing appropriate single-photon emission tomography and positron emission tomography ligands for the NMDA receptor. This paper briefly presents evidence for links between glutamatergic system dysfunction and schizophrenia. It reviews the radioligands to evaluate glutamatergic receptors in vivo and discusses issues in developing novel ligands for the glutamatergic system. (orig.)

Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research

Science.gov (United States)

Dörendahl, Antje; Leich, Nora; Vietze, Julia; Steinfath, Matthias; Chmielewska, Justyna; Hensel, Andreas; Grune, Barbara; Schönfelder, Gilbert

2017-01-01

In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models. PMID:29240762

Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

Science.gov (United States)

Bert, Bettina; Dörendahl, Antje; Leich, Nora; Vietze, Julia; Steinfath, Matthias; Chmielewska, Justyna; Hensel, Andreas; Grune, Barbara; Schönfelder, Gilbert

2017-12-01

In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

Directory of Open Access Journals (Sweden)

Bettina Bert

2017-12-01

Full Text Available In the European Union (EU, animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

In Vivo Differentiation of Complementary Contrast Media at Dual-Energy CT

Science.gov (United States)

Mongan, John; Rathnayake, Samira; Fu, Yanjun; Wang, Runtang; Jones, Ella F.; Gao, Dong-Wei

2012-01-01

Purpose: To evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios. Materials and Methods: Approval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium. Results: Clear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase–enhanced CT scan simultaneously in a single examination. Conclusion: Commercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo. © RSNA, 2012 PMID:22778447

Resveratrol and cancer: focus on in vivo evidence

Science.gov (United States)

Carter, Lindsay G; D'Orazio, John A; Pearson, Kevin J

2014-01-01

Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, however, comparatively fewer studies that have investigated resveratrol treatment and cancer outcomes in vivo, perhaps limited by its poor bioavailability when taken orally. Although research in cell culture has shown promising and positive effects of resveratrol, evidence from rodents and humans is inconsistent. This review highlights the in vivo effects of resveratrol treatment on breast, colorectal, liver, pancreatic, and prostate cancers. Resveratrol supplementation in animal models of cancer has shown positive, neutral as well as negative outcomes depending on resveratrol route of administration, dose, tumor model, species, and other factors. Within a specific cancer type, there is variability between studies with respect to strain, age, and sex of animal used, timing and method of resveratrol supplementation, and dose of resveratrol used to study cancer endpoints. Together, the data suggest that many factors need to be considered before resveratrol can be used for human cancer prevention or therapy. PMID:24500760

Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

International Nuclear Information System (INIS)

Loudos, George; Kagadis, George C.; Psimadas, Dimitris

2011-01-01

Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.

Difluoromethylornithine enhanced uptake of tritiated putrescine in 9L rat brain tumors

International Nuclear Information System (INIS)

Redgate, E.S.; Grudziak, A.G.; Deutsch, M.; Boggs, S.S.

1997-01-01

Difluoromethylornithine (DFMO) depletes endogenous putrescine and enhances the uptake of and retention of [ 3 H] putrescine in vitro. To determine if DFMO also enhances uptake of [ 3 H] putrescine in vivo, DFMO and trace doses of [ 3 H] putrescine, dissolved in artificial CSF, were infused into growing (6-9 day) 9L brain tumors by means of osmotic pumps. When 7-day osmotic pumps were loaded with 1 μCi [ 3 H] putrescine, with or without 10 or 100 mM DFMO, pumped at 1 μl/h, the mean uptake after 3 days was 168 ± 62 cpm/mg tumor (17 rats) without DFMO, 300 ± 197 cpm/mg tumor (11 rats) with 10 mM DFMO and 1088 ± 421 cpm/mg tumor (11 rats) with 100 mM DFMO (p ≤ 0.05 vs. control). Significantly less radioactivity was detected in the contralateral brain and in nonbrain tissues (0.5 ± 0.1 to 14 ± 5 cpm/mg). To measure the extent of [ 3 H] putrescine distribution in the tumor, the same dose of drugs was delivered for a longer period of time, using 14-day pumps to allow tumors to become large enough to be divided into 1.4 mm thick transections. The mean radioactivity in the sections from eight control rats receiving [ 3 H] putrescine without DFMO were not significantly different between the sections (174 ± 61 cpm/mg tumor for sections containing the cannulas, 273 ± 61 and 259 ± 91 cpm/mg for adjacent sections). In the six rats given 100 mM DFMO there was a significant increase in mean radioactivity in the cannula containing section (2251 ± 919 cpm/mg tumor). Mean counts from adjacent sections in these rats were 97 ± 44 and 33 ± 13 cpm/mg. Values for contralateral corpus striatum and nonbrain tissues ranged from 0.7 ± 0.3 to 4.3 ± 1.5 cpm/mg tissue. When DFMO was delivered directly to the tumors while [ 3 H] putrescine was infused intraperitoneally, the uptake in the tumor slices was low (5-10 cpm/mg in different slices). These results demonstrate that infusion of DFMO directly into growing 9L brain tumors can selectively enhance the uptake of exogenous [ 3 H

Anatomy of large animal spines and its comparison to the human spine: a systematic review.

Science.gov (United States)

Sheng, Sun-Ren; Wang, Xiang-Yang; Xu, Hua-Zi; Zhu, Guo-Qing; Zhou, Yi-Fei

2010-01-01

Animal models have been commonly used for in vivo and in vitro spinal research. However, the extent to which animal models resemble the human spine has not been well known. We conducted a systematic review to compare the morphometric features of vertebrae between human and animal species, so as to give some suggestions on how to choose an appropriate animal model in spine research. A literature search of all English language peer-reviewed publications was conducted using PubMed, OVID, Springer and Elsevier (Science Direct) for the years 1980-2008. Two reviewers extracted data on the anatomy of large animal spines from the identified articles. Each anatomical study of animals had to include at least three vertebral levels. The anatomical data from all animal studies were compared with the existing data of the human spine in the literature. Of the papers retrieved, seven were included in the review. The animals in the studies involved baboon, sheep, porcine, calf and deer. Distinct anatomical differences of vertebrae were found between the human and each large animal spine. In cervical region, spines of the baboon and human are more similar as compared to other animals. In thoracic and lumbar regions, the mean pedicle height of all animals was greater than the human pedicles. There was similar mean pedicle width between animal and the human specimens, except in thoracic segments of sheep. The human spinal canal was wider and deeper in the anteroposterior plane than any of the animals. The mean human vertebral body width and depth were greater than that of the animals except in upper thoracic segments of the deer. However, the mean vertebral body height was lower than that of all animals. This paper provides a comprehensive review to compare vertebrae geometries of experimental animal models to the human vertebrae, and will help for choosing animal model in vivo and in vitro spine research. When the animal selected for spine research, the structural similarities and

- In vivo monitoring of 5-FU

OpenAIRE

Lucas, Susanne

2010-01-01

The aim of the present study was to establish the in vivo-monitoring of the enrichment of 5-FU liposomes in liver and liver metastases by MRI methods. Relative signal intensities of liver and tumor tissue were determined. After sacrifying animals concentrations of 5-FU and it´s active intracellular metabolite M3 were measured by HPLC techniques. We used CC531 adenocarcinoma in the liver of WAG/Rij rats as a standardized liver tumor model in our investigatio...

In vitro and in vivo antitrypanosomal activity of Xanthium strumarium leaves.

Science.gov (United States)

Talakal, T S; Dwivedi, S K; Sharma, S R

1995-12-15

Antitrypanosomal activity of crude 50% ethanolic extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity at all four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml, in vitro. In vivo trial revealed that the extract exerted antitrypanosomal effect at dosage of 100, 300 and 1000 mg/kg, intraperitoneally. At 100 and 300 mg/kg doses the survival period of the Trypanosoma evansi infected mice was significantly prolonged. However, the extract was found to be toxic to the animals at 1000 mg/kg dose.

Validity of bioluminescence measurements for noninvasive in vivo imaging of tumor load in small animals

NARCIS (Netherlands)

Klerk, Clara P. W.; Overmeer, Renée M.; Niers, Tatjana M. H.; Versteeg, Henri H.; Richel, Dick J.; Buckle, Tessa; van Noorden, Cornelis J. F.; van Tellingen, Olaf

2007-01-01

A relatively new strategy to longitudinally monitor tumor load in intact animals and the effects of therapy is noninvasive bioluminescence imaging (BLI). The validity of BLI for quantitative assessment of tumor load in small animals is critically evaluated in the present review. Cancer cells are

Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity.

Directory of Open Access Journals (Sweden)

Dmitry Akhmedov

Full Text Available The cAMP response element binding protein (CREB is induced during fasting in the liver, where it stimulates transcription of rate-limiting gluconeogenic genes to maintain metabolic homeostasis. Adenoviral and transgenic CREB reporters have been used to monitor hepatic CREB activity non-invasively using bioluminescence reporter imaging. However, adenoviral vectors and randomly inserted transgenes have several limitations. To overcome disadvantages of the currently used strategies, we created a ROSA26 knock-in CREB reporter mouse line (ROSA26-CRE-luc. cAMP-inducing ligands stimulate the reporter in primary hepatocytes and myocytes from ROSA26-CRE-luc animals. In vivo, these animals exhibit little hepatic CREB activity in the ad libitum fed state but robust induction after fasting. Strikingly, CREB was markedly stimulated in liver, but not in skeletal muscle, after overnight voluntary wheel-running exercise, uncovering differential regulation of CREB in these tissues under catabolic states. The ROSA26-CRE-luc mouse line is a useful resource to study dynamics of CREB activity longitudinally in vivo and can be used as a source of primary cells for analysis of CREB regulatory pathways ex vivo.

The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

Science.gov (United States)

Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

2017-08-02

The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

Free Radical Imaging Using In Vivo Dynamic Nuclear Polarization-MRI.

Science.gov (United States)

Utsumi, Hideo; Hyodo, Fuminori

2015-01-01

Redox reactions that generate free radical intermediates are essential to metabolic processes, and their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. The development of an in vivo electron spin resonance (ESR) spectrometer and its imaging enables us noninvasive and direct measurement of in vivo free radical reactions in living organisms. The dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), also called PEDRI or OMRI, is also a new imaging method for observing free radical species in vivo. The spatiotemporal resolution of free radical imaging with DNP-MRI is comparable with that in MRI, and each of the radical species can be distinguished in the spectroscopic images by changing the frequency or magnetic field of ESR irradiation. Several kinds of stable nitroxyl radicals were used as spin probes to detect in vivo redox reactions. The signal decay of nitroxyl probes, which is determined with in vivo DNP-MRI, reflects the redox status under oxidative stress, and the signal decay is suppressed by prior administration of antioxidants. In addition, DNP-MRI can also visualize various intermediate free radicals from the intrinsic redox molecules. This noninvasive method, in vivo DNP-MRI, could become a useful tool for investigating the mechanism of oxidative injuries in animal disease models and the in vivo effects of antioxidant drugs. © 2015 Elsevier Inc. All rights reserved.

In vivo effects of Sainfoin (Onobrychis viciifolia) on parasitic nematodes in calves

DEFF Research Database (Denmark)

Desrues, Oliver; Pena-Espinoza, Miguel Angel; Hansen, T.V.A.

Sainfoin (Onobrychis viciifolia) is a fodder legume containing condensed tannins known to improve protein self-sufficiency, animal health and environment. In addition, anthelmintic effects have been demonstrated in vitro against cattle nematodes, and in vivo against nematodes of small ruminants...

Ultrasonic brain therapy: First trans-skull in vivo experiments on sheep using adaptive focusing

Science.gov (United States)

Pernot, Mathieu; Aubry, Jean-Francois; Tanter, Michael; Fink, Mathias; Boch, Anne-Laure; Kujas, Michèle

2004-05-01

A high-power prototype dedicated to trans-skull therapy has been tested in vivo on 20 sheep. The array is made of 200 high-power transducers working at 1-MHz central and is able to reach 260 bars at focus in water. An echographic array connected to a Philips HDI 1000 system has been inserted in the therapeutic array in order to perform real-time monitoring of the treatment. A complete craniotomy has been performed on half of the treated animal models in order to get a reference model. On the other animals, a minimally invasive surgery has been performed thanks to a time-reversal experiment: a hydrophone was inserted at the target inside the brain thanks to a 1-mm2 craniotomy. A time-reversal experiment was then conducted through the skull bone with the therapeutic array to treat the targeted point. For all the animals a specified region around the target was treated thanks to electronic beam steering. Animals were finally divided into three groups and sacrificed, respectively, 0, 1, and 2 weeks after treatment. Finally, histological examination confirmed tissue damage. These in vivo experiments highlight the strong potential of high-power time-reversal technology.

A hyperspectral fluorescence system for 3D in vivo optical imaging

International Nuclear Information System (INIS)

Zavattini, Guido; Vecchi, Stefania; Mitchell, Gregory; Weisser, Ulli; Leahy, Richard M; Pichler, Bernd J; Smith, Desmond J; Cherry, Simon R

2006-01-01

In vivo optical instruments designed for small animal imaging generally measure the integrated light intensity across a broad band of wavelengths, or make measurements at a small number of selected wavelengths, and primarily use any spectral information to characterize and remove autofluorescence. We have developed a flexible hyperspectral imaging instrument to explore the use of spectral information to determine the 3D source location for in vivo fluorescence imaging applications. We hypothesize that the spectral distribution of the emitted fluorescence signal can be used to provide additional information to 3D reconstruction algorithms being developed for optical tomography. To test this hypothesis, we have designed and built an in vivo hyperspectral imaging system, which can acquire data from 400 to 1000 nm with 3 nm spectral resolution and which is flexible enough to allow the testing of a wide range of illumination and detection geometries. It also has the capability to generate a surface contour map of the animal for input into the reconstruction process. In this paper, we present the design of the system, demonstrate the depth dependence of the spectral signal in phantoms and show the ability to reconstruct 3D source locations using the spectral data in a simple phantom. We also characterize the basic performance of the imaging system

The radiosensitizing effects of ornidazole in hypoxic mammalian tissue: an in vivo study

International Nuclear Information System (INIS)

Okkan, S.; Uzel, R.

1982-01-01

In this study the sensitizing effects of ornidazole is investigated in vivo. The selected test system is the acute killing effect of radiation within 4-6 days after abdominal irradiation ranging from 9 to 24 Gy, in groups of C 57 black mice. Ornidazole is given intraperitoneally in 500 mg/kg, 100 mg/kg, 20 mg/kg doses prior to irradiation of animals breathing air, oxygen or nitrogen. A decreae of LD 50 dose is observed from 24.39 +/- 5.66 to 16.38 +/- 1.86 and 18.04 +/- 2.48 Gy, respectively, in nitrogen breathing animals. No sensitizing effect was observed in doses of 20 mg/kg. Enhancement Ratio (ER) was found to be 1.48 +/- 0.25 and 1.35 +/- 0.27; relative sensitizing efficiency (RSE) was 40% and 29% respectively. No sensitizing effect was observed in animals irradiated in oxic conditions. These results showed that ornidazole (Ro-7-0207) has a sensitizing effect on hypoxic cells in vivo. It is worthwhile to try this drug in a clinical study

In vivo metabolism of clebopride in three animal species and in man.

Science.gov (United States)

Segura, J; Bakke, O M; Huizing, G; Beckett, A H

1980-01-01

Clebopride is extensively metabolized in the rat, rabbit, dog, and man. By use of chromatographic methods, up to 25 metabolites in hydrolyzed and nonhydrolyzed urine have been detected. All four species produced the same main metabolites, as indicated by thin-layer chromatography. These, isolated from urine of the three animal species, were identified as N-(4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide, N-(4'-piperidyl-2'-one)-2-methoxy-4-amino-5-chlorobenzamide, and N-(1'-alpha-hydroxybenzyl-4'-piperidyl)-2-methoxy-4-amino-5-chlorobenzamide (tentative structure of a carbinolamine more stable than expected). In the dog, 2-methoxy-4-amino-5-chlorobenzoic acid was also detected. N4-glucuronidation of clebopride and some of its metabolites has been shown to occur in the three animal species. The rabbit produced large amounts of these conjugates. Clebopride N4-sulfonate was not present in the urine of any of the species investigated.

Defining human mesenchymal stem cell efficacy in vivo

Directory of Open Access Journals (Sweden)

Lennon Donald P

2010-10-01

Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

Elementary of animal model for percutaneous and ocular penetration

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Kalpesh Chhotalal Ashara

2016-12-01

Full Text Available Models of animal are the most appropriate method for assessments of human in-vivo percutaneous and ocular penetrations. Monkey and rodents are used for the same. There are several nuts and bolts of each one, so it is necessary to study each one separately. Monkey, porcine and guinea pig penetration are correlated with that of human skin. The skin of rodents, lupus, pigs, etc. has more penetration properties than human skin. Rabbit, goat and sheep eye are mostly used for ocular penetration. The researcher also used hen’s egg chorioallantoic membrane test for ocular irritation study. The other animals’ cornea, cul-de-sac, eyeballs and prepared corneal epithelial models are very less in practice. Web-based alternative non-animal models are also available instead of animal models too. This article describes characteristics of monkeys, pigs, rats, rabbits, guinea pigs and hairless rodents, HuSki model, Cellophane® membrane, egg membrane, gelatin membrane, animal models for ophthalmic delivery, hen’s egg chorioallantoic membrane test, prepared corneal epithelial models and web-based alternative non-animal database.

Vivo-morpholinos induced transient knockdown of physical activity related proteins.

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David P Ferguson

Full Text Available Physical activity is associated with disease prevention and overall wellbeing. Additionally there has been evidence that physical activity level is a result of genetic influence. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. Vivo-morpholinos are a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo-morpholinos in a mouse model for voluntary physical activity with several sub-objectives. We observed that Vivo-morpholinos achieved between 60-97% knockdown of Drd1-, Vmat2-, and Glut4-protein in skeletal muscle, the delivery moiety of Vivo-morpholinos (scramble did not influence physical activity and that a cocktail of multiple Vivo-morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo-morpholinos injected intravenously alone did not significantly knockdown Vmat2-protein expression in the brain (p = 0.28. However, the use of a bradykinin analog to increase blood-brain-barrier permeability in conjunction with the Vivo-morpholinos significantly (p = 0.0001 decreased Vmat2-protein in the brain with a corresponding later over-expression of Vmat2 coincident with a significant (p = 0.0016 increase in physical activity. We conclude that Vivo-morpholinos can be a valuable tool in determining causal gene-phenotype relationships in whole animal models.

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

International Nuclear Information System (INIS)

Umeda, Izumi O.; Tani, Kotaro; Tsuda, Keisuke

2012-01-01

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of 111 In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice. Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30 min, better image quality was obtained with pinhole apertures diameter of 1.4 mm than of 1.0 mm. The obtained best spatial resolution was 1.3 mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0 mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2-0.5 MBq/mL. Liposomes containing 111 In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous 111 In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2 MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes. Intratumoral heterogeneity was successfully visualized under the optimized

Status Survey of Bunkers 738A and 825A at Spangdahlem AB, Germany

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2015-10-02

cpm ), to activity in units of dpm...lnl’lt R~dvul. 1.500 V - 2% AANGE REFERENCE ".~S FOUND" CORRECT E) MUI.TI?t. ER CAl POINT READING READING :< 1000 400 CPM 400,000 CPM 400,0 0Q CPM ...1000 100 CPM 100.000 CPM 100,0 00 CPM X 100 400 CPM 40,0(•0 CPM 40,000 CPM )( 100 100 CPM 10 .0GO CPM 10 .000 CPM X 10 400 CPM 4 ,000

Humane Society International's global campaign to end animal testing.

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Seidle, Troy

2013-12-01

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 European sales ban for newly animal-tested cosmetics, in achieving the June 2013 cosmetics animal testing ban in India as well as major cosmetics regulatory policy shifts in China and South Korea, and in securing precedent-setting reductions in in vivo data requirements for pesticides in the EU through the revision of biocides and plant protection product regulations, among others. HSI is currently working to export these life-saving measures to more than a dozen industrial and emerging economies. 2013 FRAME.

The measurement of oxygen in vivo using EPR techniques

International Nuclear Information System (INIS)

Swartz, Harold M.; Clarkson, Robert B.

1998-01-01

The measurement of pO 2 in vivo using EPR has some features which have already led to very useful applications and this approach is likely to have increasingly wide and effective use. It is based on the effect of oxygen on EPR spectra which provides a sensitive and accurate means to measure pO 2 quantitatively. The development of oxygen-sensitive paramagnetic materials which are very stable, combined with instrumental developments, has been crucial to the in vivo applications of this technique. The physical basis and biological applications of in vivo EPR oximetry are reviewed, with particular emphasis on the use of EPR spectroscopy at 1 GHz using particulate paramagnetic materials for the repetitive and non-invasive measurement of pO 2 in tissues. In vivo EPR has already produced some very useful results which have contributed significantly to solving important biological problems. The characteristics of EPR oximetry which appear to be especially useful are often complementary to existing techniques for measuring oxygen in tissues. These characteristics include the capability of making repeated measurements from the same site, high sensitivity to low levels of oxygen, and non-invasive options. The existing techniques are especially useful for studies in small animals, where the depth of measurements is not an overriding issue. In larger animals and potentially in human subjects, non-invasive techniques seem to be immediately applicable to study phenomena very near the surface (within 10 mm) while invasive techniques have some very promising uses. The clinical uses of EPR oximetry which seem especially promising and likely to be undertaken in the near future are long-term monitoring of the status and response to treatment of peripheral vascular disease and optimizing cancer therapy by enabling it to be modified on the basis of the pO 2 measured in the tumour. (author)

Dissemination bias in systematic reviews of animal research: a systematic review.

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Katharina F Mueller

Full Text Available Systematic reviews of preclinical studies, in vivo animal experiments in particular, can influence clinical research and thus even clinical care. Dissemination bias, selective dissemination of positive or significant results, is one of the major threats to validity in systematic reviews also in the realm of animal studies. We conducted a systematic review to determine the number of published systematic reviews of animal studies until present, to investigate their methodological features especially with respect to assessment of dissemination bias, and to investigate the citation of preclinical systematic reviews on clinical research.Eligible studies for this systematic review constitute systematic reviews that summarize in vivo animal experiments whose results could be interpreted as applicable to clinical care. We systematically searched Ovid Medline, Embase, ToxNet, and ScienceDirect from 1st January 2009 to 9th January 2013 for eligible systematic reviews without language restrictions. Furthermore we included articles from two previous systematic reviews by Peters et al. and Korevaar et al.The literature search and screening process resulted in 512 included full text articles. We found an increasing number of published preclinical systematic reviews over time. The methodological quality of preclinical systematic reviews was low. The majority of preclinical systematic reviews did not assess methodological quality of the included studies (71%, nor did they assess heterogeneity (81% or dissemination bias (87%. Statistics quantifying the importance of clinical research citing systematic reviews of animal studies showed that clinical studies referred to the preclinical research mainly to justify their study or a future study (76%.Preclinical systematic reviews may have an influence on clinical research but their methodological quality frequently remains low. Therefore, systematic reviews of animal research should be critically appraised before

In silico modeling for tumor growth visualization.

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Jeanquartier, Fleur; Jean-Quartier, Claire; Cemernek, David; Holzinger, Andreas

2016-08-08

Cancer is a complex disease. Fundamental cellular based studies as well as modeling provides insight into cancer biology and strategies to treatment of the disease. In silico models complement in vivo models. Research on tumor growth involves a plethora of models each emphasizing isolated aspects of benign and malignant neoplasms. Biologists and clinical scientists are often overwhelmed by the mathematical background knowledge necessary to grasp and to apply a model to their own research. We aim to provide a comprehensive and expandable simulation tool to visualizing tumor growth. This novel Web-based application offers the advantage of a user-friendly graphical interface with several manipulable input variables to correlate different aspects of tumor growth. By refining model parameters we highlight the significance of heterogeneous intercellular interactions on tumor progression. Within this paper we present the implementation of the Cellular Potts Model graphically presented through Cytoscape.js within a Web application. The tool is available under the MIT license at https://github.com/davcem/cpm-cytoscape and http://styx.cgv.tugraz.at:8080/cpm-cytoscape/ . In-silico methods overcome the lack of wet experimental possibilities and as dry method succeed in terms of reduction, refinement and replacement of animal experimentation, also known as the 3R principles. Our visualization approach to simulation allows for more flexible usage and easy extension to facilitate understanding and gain novel insight. We believe that biomedical research in general and research on tumor growth in particular will benefit from the systems biology perspective.

Effect of gradual weight-bearing on regenerated articular cartilage after joint distraction and motion in a rabbit model.

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Nishino, Tomofumi; Ishii, Tomoo; Chang, Fei; Yanai, Takaji; Watanabe, Arata; Ogawa, Takeshi; Mishima, Hajime; Nakai, Kenjiro; Ochiai, Naoyuki

2010-05-01

The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight-bearing system and continuous passive motion (CPM). A full-thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group (n=6), GWB was started 6 weeks after surgery. In the CPM group (n=6), CPM with EFD was applied in the same manner without GWB. The control group (n=5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one-third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin-O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen-positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. Copyright (c) 2009 Orthopaedic Research Society.

In vivo cellular imaging using fluorescent proteins - Methods and Protocols

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M. Monti

2012-12-01

Full Text Available The discovery and genetic engineering of fluorescent proteins has revolutionized cell biology. What was previously invisible to the cell often can be made visible with the use of fluorescent proteins. With this words, Robert M. Hoffman introduces In vivo Cellular Imaging Using Fluorescent proteins, the eighteen chapters book dedicated to the description of how fluorescence proteins have changed the way to analyze cellular processes in vivo. Modern researches aim to study new and less invasive methods able to follow the behavior of different cell types in different biological contexts: for example, how cancer cells migrate or how they respond to different therapies. Also, in vivo systems can help researchers to better understand animal embryonic development so as how fluorescence proteins may be used to monitor different processes in living organisms at the molecular and cellular level.

Real-time dynamic imaging of virus distribution in vivo.

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Sean E Hofherr

2011-02-01

Full Text Available The distribution of viruses and gene therapy vectors is difficult to assess in a living organism. For instance, trafficking in murine models can usually only be assessed after sacrificing the animal for tissue sectioning or extraction. These assays are laborious requiring whole animal sectioning to ascertain tissue localization. They also obviate the ability to perform longitudinal or kinetic studies in one animal. To track viruses after systemic infection, we have labeled adenoviruses with a near-infrared (NIR fluorophore and imaged these after intravenous injection in mice. Imaging was able to track and quantitate virus particles entering the jugular vein simultaneous with injection, appearing in the heart within 500 milliseconds, distributing in the bloodstream and throughout the animal within 7 seconds, and that the bulk of virus distribution was essentially complete within 3 minutes. These data provide the first in vivo real-time tracking of the rapid initial events of systemic virus infection.

Fetal microglial in vitro phenotype depends on prior in vivo inflammation

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Mingju eCao

2015-08-01

Full Text Available Objective. Neuroinflammation in utero may result in life-long neurological disabilities. The molecular mechanisms whereby microglia contribute to this response remain incompletely understood. Methods. Lipopolysaccharide (LPS or saline were administered intravenously to non-anesthetized chronically instrumented near-term fetal sheep to model fetal inflammation in vivo. Microglia were then isolated from in vivo LPS and saline (naïve exposed animals. To mimic the second hit of neuroinflammation, these microglia were then re-exposed to LPS in vitro. Cytokine responses were measured in vivo and subsequently in vitro in the primary microglia cultures derived from these animals. We sequenced the whole transcriptome of naïve and second hit microglia and profiled their genetic expression to define molecular pathways disrupted during neuroinflammation.Results. In vivo LPS exposure resulted in IL-6 increase in fetal plasma 3 h post LPS exposure. Even though not histologically apparent, microglia acquired a pro-inflammatory phenotype in vivo that was sustained and amplified in vitro upon second hit LPS exposure as measured by IL-1β response in vitro and RNAseq analyses. While NFKB and Jak-Stat inflammatory pathways were up regulated in naïve microglia, heme oxygenase 1 (HMOX1 and Fructose-1,6-bisphosphatase (FBP genes were uniquely differentially expressed in the second hit microglia. Microglial calreticulin/LRP genes implicated in microglia-neuronal communication relevant for the neuronal development were up regulated in second hit microglia.Discussion. We identified a unique HMOX1down and FBPup phenotype of microglia exposed to the double-hit suggesting interplay of inflammatory and metabolic pathways as a memory of prior inflammatory insult. These findings suggest new therapeutic targets for early postnatal intervention to prevent brain injury.

Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it

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Niehues SM

2010-08-01

Full Text Available Abstract Purpose Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model. Material and Methods Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined. Results Median liver density was 1.07 g/ml. Regression analysis showed a high correlation of r2 = 0.985 between CT-volumetry and water displacement. CTvolumetry was found to be 13% higher than water displacement volumetry (p Conclusion In this study the only relevant factor leading to the difference between in vivo CT-volumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.

Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

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Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

2011-07-26

The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ex-vivo assessment and non-invasive in vivo imaging of internal hemorrhages in Aga2/+ mutant mice

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Ermolayev, Vladimir [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Cohrs, Christian M. [Institute for Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Mohajerani, Pouyan; Ale, Angelique [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Hrabé de Angelis, Martin [Institute for Experimental Genetics, Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany); Ntziachristos, Vasilis, E-mail: v.ntziachristos@tum.de [Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Building 56, Ingolstädter Landstraße 1, D-85764 Neuherberg (Germany)

2013-03-08

Highlights: ► Aga2/+ mice, model for Osteogenesis imperfecta, have type I collagen mutation. ► Aga2/+ mice display both moderate and severe phenotypes lethal 6–11th postnatal. ► Internal hemorrhages studied in Aga2/+ vs. control mice at 6 and 9 days postnatal. ► Anatomical and functional findings in-vivo contrasted to the ex-vivo appearance. -- Abstract: Mutations in type I collagen genes (COL1A1/2) typically lead to Osteogenesis imperfecta, the most common heritable cause of skeletal fractures and bone deformation in humans. Heterozygous Col1a1{sup Aga2/+}, animals with a dominant mutation in the terminal C-propeptide domain of type I collagen develop typical skeletal hallmarks and internal hemorrhages starting from 6 day after birth. The disease progression for Aga2/+ mice, however, is not uniform differing between severe phenotype lethal at the 6–11th day of life, and moderate-to-severe one with survival to adulthood. Herein we investigated whether a new modality that combines X-ray computer tomography with fluorescence tomography in one hybrid system can be employed to study internal bleedings in relation to bone fractures and obtain insights into disease progression. The disease phenotype was characterized on Aga2/+ vs. wild type mice between 6 and 9 days postnatal. Anatomical and functional findings obtained in-vivo were contrasted to the ex-vivo appearance of the same tissues under cryo-slicing.

Ex-vivo assessment and non-invasive in vivo imaging of internal hemorrhages in Aga2/+ mutant mice

International Nuclear Information System (INIS)

Ermolayev, Vladimir; Cohrs, Christian M.; Mohajerani, Pouyan; Ale, Angelique; Hrabé de Angelis, Martin; Ntziachristos, Vasilis

2013-01-01

Highlights: ► Aga2/+ mice, model for Osteogenesis imperfecta, have type I collagen mutation. ► Aga2/+ mice display both moderate and severe phenotypes lethal 6–11th postnatal. ► Internal hemorrhages studied in Aga2/+ vs. control mice at 6 and 9 days postnatal. ► Anatomical and functional findings in-vivo contrasted to the ex-vivo appearance. -- Abstract: Mutations in type I collagen genes (COL1A1/2) typically lead to Osteogenesis imperfecta, the most common heritable cause of skeletal fractures and bone deformation in humans. Heterozygous Col1a1 Aga2/+ , animals with a dominant mutation in the terminal C-propeptide domain of type I collagen develop typical skeletal hallmarks and internal hemorrhages starting from 6 day after birth. The disease progression for Aga2/+ mice, however, is not uniform differing between severe phenotype lethal at the 6–11th day of life, and moderate-to-severe one with survival to adulthood. Herein we investigated whether a new modality that combines X-ray computer tomography with fluorescence tomography in one hybrid system can be employed to study internal bleedings in relation to bone fractures and obtain insights into disease progression. The disease phenotype was characterized on Aga2/+ vs. wild type mice between 6 and 9 days postnatal. Anatomical and functional findings obtained in-vivo were contrasted to the ex-vivo appearance of the same tissues under cryo-slicing

In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal biomechanics assessed in-vitro. An animal pilot study.

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Rogala, Maja M; Danielewska, Monika E; Antończyk, Agnieszka; Kiełbowicz, Zdzisław; Rogowska, Marta E; Kozuń, Marta; Detyna, Jerzy; Iskander, D Robert

2017-09-01

The aim was to ascertain whether the characteristics of the corneal pulse (CP) measured in-vivo in a rabbit eye change after short-term artificial increase of intraocular pressure (IOP) and whether they correlate with corneal biomechanics assessed in-vitro. Eight New Zealand white rabbits were included in this study and were anesthetized. In-vivo experiments included simultaneous measurements of the CP signal, registered with a non-contact method, IOP, intra-arterial blood pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP. Afterwards, thickness of post-mortem corneas was determined and then uniaxial tensile tests were conducted leading to estimates of their Young's modulus (E). At the baseline IOP, backward stepwise regression analyses were performed in which successively the ocular biomechanical, biometric and cardiovascular predictors were separately taken into account. Results of the analysis revealed that the 3rd CP harmonic can be statistically significantly predicted by E and central corneal thickness (Models: R 2  = 0.662, p biomechanics in-vitro was confirmed. In particular, spectral analysis revealed that higher amplitude and power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP harmonic correlates positively with the corresponding harmonic of the BPL signal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

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Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

1999-07-01

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Fluorescence Imaging of Fast Retrograde Axonal Transport in Living Animals

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Dawid Schellingerhout

2009-11-01

Full Text Available Our purpose was to enable an in vivo imaging technology that can assess the anatomy and function of peripheral nerve tissue (neurography. To do this, we designed and tested a fluorescently labeled molecular probe based on the nontoxic C fragment of tetanus toxin (TTc. TTc was purified, labeled, and subjected to immunoassays and cell uptake assays. The compound was then injected into C57BL/6 mice (N = 60 for in vivo imaging and histologic studies. Image analysis and immunohistochemistry were performed. We found that TTc could be labeled with fluorescent moieties without loss of immunoreactivity or biologic potency in cell uptake assays. In vivo fluorescent imaging experiments demonstrated uptake and retrograde transport of the compound along the course of the sciatic nerve and in the spinal cord. Ex vivo imaging and immunohistochemical studies confirmed the presence of TTc in the sciatic nerve and spinal cord, whereas control animals injected with human serum albumin did not exhibit these features. We have demonstrated neurography with a fluorescently labeled molecular imaging contrast agent based on the TTc.

Bacteria-mediated in vivo delivery of quantum dots into solid tumor

International Nuclear Information System (INIS)

Liu, Ying; Zhou, Mei; Luo, Dan; Wang, Lijun; Hong, Yuankai; Yang, Yepeng; Sha, Yinlin

2012-01-01

Highlights: ► New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. ► Bifidobacterium bifidum delivery system has intrinsic biocompatibility. ► The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis.

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Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-06-01

Animal models published within the past 18 months on asthma, food allergy and anaphylaxis, all conditions of rising public health concern, were reviewed. While domestic animals spontaneously develop asthma, food allergy and anaphylaxis, in animal models, divergent sensitization and challenge routes, dosages, intervals and antigens are used to induce asthmatic, food allergic or anaphylactic phenotypes. This must be considered in the interpretation of results. Instead of model antigens, gradually relevant allergens such as house dust mite in asthma, and food allergens like peanut, apple and peach in food allergy research were used. Novel engineered mouse models such as a mouse with a T-cell receptor for house dust mite allergen Der p 1, or with transgenic human hFcγR genes, facilitated the investigation of single molecules of interest. Whole-body plethysmography has become a state-of-the-art in-vivo readout in asthma research. In food allergy and anaphylaxis research, novel techniques were developed allowing real-time monitoring of in-vivo effects following allergen challenge. Networks to share tissues were established as an effort to reduce animal experiments in allergy which cannot be replaced by in-vitro measures. Natural and artificial animal models were used to explore the pathophysiology of asthma, food allergy and anaphylaxis and to improve prophylactic and therapeutic measures. Especially the novel mouse models mimicking molecular aspects of the complex immune network in asthma, food allergy and anaphylaxis will facilitate proof-of-concept studies under controlled conditions.

Favipiravir elicits antiviral mutagenesis during virus replication in vivo.

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Arias, Armando; Thorne, Lucy; Goodfellow, Ian

2014-10-21

Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

Alternative developmental toxicity models for assessing the in vivo embryotoxicity of azoles

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Dimopoulou, Myrto

2018-01-01

The implementation of regulations for protecting both humans and the environment from potential chemical health hazards, as well as the increase of global pressure for reducing, refining and replacing animal experiments promote the development and application of alternatives to in vivo

White blood cell-based detection of asymptomatic scrapie infection by ex vivo assays.

Directory of Open Access Journals (Sweden)

Sophie Halliez

Full Text Available Prion transmission can occur by blood transfusion in human variant Creutzfeldt-Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods--in vitro, ex vivo and in vivo assays--to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages. However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease.

Improving planning, design, reporting and scientific quality of animal experiments by using the Gold Standard Publication Checklist, in addition to the ARRIVE guidelines

NARCIS (Netherlands)

Hooijmans, C.R.; Vries, R.B.M. de; Leenaars, M.; Curfs, J.H.A.J.; Ritskes-Hoitinga, M.

2011-01-01

Several studies have demonstrated serious omissions in the way research that use animals is reported. In order to improve the quality of reporting of animal experiments, the Animals in research: reporting in vivo experiments (ARRIVE) Guidelines were published in the British Journal of Pharmacology

In vivo measurement of hemodynamic information in stenosed rat blood vessels using X-ray PIV.

Science.gov (United States)

Park, Hanwook; Park, Jun Hong; Lee, Sang Joon

2016-11-28

Measurements of the hemodynamic information of blood flows, especially wall shear stress (WSS), in animal models with circulatory vascular diseases (CVDs) are important to understand the pathological mechanism of CVDs. In this study, X-ray particle image velocimetry (PIV) with high spatial resolution was applied to obtain velocity field information in stenosed blood vessels with high WSS. 3D clips fabricated with a 3D printer were applied to the abdominal aorta of a rat cadaver to induce artificial stenosis in the real blood vessel of an animal model. The velocity and WSS information of blood flows in the stenosed vessel were obtained and compared at various stenosis severities. In vivo measurement was also conducted by fastening a stenotic clip on a live rat model through surgical intervention to reduce the flow rate to match the limited temporal resolution of the present X-ray PIV system. Further improvement of the temporal resolution of the system might be able to provide in vivo measurements of hemodynamic information from animal disease models under physiological conditions. The present results would be helpful for understanding the relation between hemodynamic characteristics and the pathological mechanism in animal CVD models.

125I-Fibrin deposition in contact sensitivity reactions in the mouse. Sensitivity of the assay for quantitating reactions after active or passive sensitization

International Nuclear Information System (INIS)

Mekori, Y.A.; Dvorak, H.F.; Galli, S.J.

1986-01-01

The clotting associated with delayed hypersensitivity (DH) responses in the mouse by sensitizing the animals to the contactant oxazolone (Ox), and then administering 125 I-guinea pig fibrinogen i.v. 10 to 30 min before antigen challenge 5 days later. Early (4 to 8 hr) contact sensitivity (CS) responses in immunized mice were barely detectable by three conventional measures of CS, but the total 125 I-cpm in ears challenged with hapten was 3.6 to 4.5 x that in control ears challenged with vehicle alone; moreover, the amount of urea-insoluble cpm (cross-linked 125 I-fibrin-associated cpm) in the reactions to Ox was 6.5-fold to 8.2-fold that present in the control reactions. In 24 hr reactions that were near peak intensity by measurements of ear swelling, ear weight ratios, and ratios of 125 I-5-iodo-2-deoxyuridine-labeled leukocyte infiltration, the cpm in antigen-challenged ears exceeded that in control ears by 13-fold to 53-fold. In addition, antigen-challenged ears contained 27 to 300 x the urea-insoluble cpm present in control ears. 125 I-Fibrin deposition was not a specific characteristic of CS reactions, because a small amount of urea-insoluble reactivity was also detected in some reactions to Ox in native mice. Nevertheless, the assay was exquisitely sensitive and readily detected quantitative differences between the immunologically specific and nonspecific reactions at very early intervals after challenge or with suboptimal doses of antigen

Endotoxin tolerance does not limit mild ischemia-reperfusion injury in humans in vivo.

NARCIS (Netherlands)

Draisma, A.; Goeij, M. de; Wouters, C.W.; Riksen, N.P.; Oyen, W.J.G.; Rongen, G.A.P.J.M.; Boerman, O.C.; Deuren, M. van; Hoeven, J.G. van der; Pickkers, P.

2009-01-01

Animal studies have shown that previous exposure to lipopolysaccharide (LPS) can limit ischemia-reperfusion injury. We tested whether pretreatment with LPS also protects against ischemia-reperfusion injury in humans in vivo. Fourteen volunteers received bolus injections of incremental dosages of LPS

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

International Nuclear Information System (INIS)

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

2006-01-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

Light Emission Requires Exposure to the Atmosphere in Ex Vivo Bioluminescence Imaging

Directory of Open Access Journals (Sweden)

Yusuke Inoue

2006-04-01

Full Text Available The identification of organs bearing luciferase activity by in vivo bioluminescence imaging (BLI is often difficult, and ex vivo imaging of excised organs plays a complementary role. This study investigated the importance of exposure to the atmosphere in ex vivo BLI. Mice were inoculated with murine pro-B cell line Ba/F3 transduced with firefly luciferase and p190 BCR-ABL. They were killed following in vivo BLI, and whole-body imaging was done after death and then after intraperitoneal air injection. In addition, the right knee was exposed and imaged before and after the adjacent bones were cut. Extensive light signals were seen on in vivo imaging. The luminescence disappeared after the animal was killed, and air injection restored the light emission from the abdomen only, suggesting a critical role of atmospheric oxygen in luminescence after death. Although no substantial light signal at the right knee was seen before bone cutting, light emission was evident after cutting. In conclusion, in ex vivo BLI, light emission requires exposure to the atmosphere. Bone destruction is required to demonstrate luciferase activity in the bone marrow after death.

The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

Science.gov (United States)

van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

2015-07-15

Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

In vivo quantitative imaging of point-like bioluminescent and fluorescent sources: Validation studies in phantoms and small animals post mortem

Science.gov (United States)

Comsa, Daria Craita

2008-10-01

There is a real need for improved small animal imaging techniques to enhance the development of therapies in which animal models of disease are used. Optical methods for imaging have been extensively studied in recent years, due to their high sensitivity and specificity. Methods like bioluminescence and fluorescence tomography report promising results for 3D reconstructions of source distributions in vivo. However, no standard methodology exists for optical tomography, and various groups are pursuing different approaches. In a number of studies on small animals, the bioluminescent or fluorescent sources can be reasonably approximated as point or line sources. Examples include images of bone metastases confined to the bone marrow. Starting with this premise, we propose a simpler, faster, and inexpensive technique to quantify optical images of point-like sources. The technique avoids the computational burden of a tomographic method by using planar images and a mathematical model based on diffusion theory. The model employs in situ optical properties estimated from video reflectometry measurements. Modeled and measured images are compared iteratively using a Levenberg-Marquardt algorithm to improve estimates of the depth and strength of the bioluminescent or fluorescent inclusion. The performance of the technique to quantify bioluminescence images was first evaluated on Monte Carlo simulated data. Simulated data also facilitated a methodical investigation of the effect of errors in tissue optical properties on the retrieved source depth and strength. It was found that, for example, an error of 4 % in the effective attenuation coefficient led to 4 % error in the retrieved depth for source depths of up to 12mm, while the error in the retrieved source strength increased from 5.5 % at 2mm depth, to 18 % at 12mm depth. Experiments conducted on images from homogeneous tissue-simulating phantoms showed that depths up to 10mm could be estimated within 8 %, and the relative

Stored Radioactive Material Landfill Site no. 7 (LF-7), Massachusetts Military Reservation, Cape Cod, MA

Science.gov (United States)

2013-03-07

11 FIQI’i’Ut OOUC!JIC:C W(HIO ,U:I ICC~OIW. co:wtO artS Alii /IAT!OICAL GUI.:O a.u<:. liASSAOIUS:4’"T:’S W’l-iCO.l RE?I.Y TD ATTN OF1 102 FW/srr9...100 CPM j,DDO CPM /, [)C>D CPM X 1 400 CPM ~DD CPM 4bD CPM X 1 100 CPM /C’O CPM IOO CPM Log Scale 200 CPM i?-DD CPM 9-DO CPM DIGITAL SCALER READOUT

Clinical applications of in vivo fluorescence confocal laser scanning microscopy

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Oh, Chilhwan; Park, Sangyong; Kim, Junhyung; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Chun, Byungseon; Gweon, Daegab

2008-02-01

Living skin for basic and clinical research can be evaluated by Confocal Laser Scanning Microscope (CLSM) non-invasively. CLSM imaging system can achieve skin image its native state either "in vivo" or "fresh biopsy (ex vivo)" without fixation, sectioning and staining that is necessary for routine histology. This study examines the potential fluorescent CLSM with a various exogenous fluorescent contrast agent, to provide with more resolution images in skin. In addition, in vivo fluorescent CLSM researchers will be extended a range of potential clinical application. The prototype of our CLSM system has been developed by Prof. Gweon's group. The operating parameters are composed of some units, such as illuminated wavelength 488 nm, argon illumination power up to 20mW on the skin, objective lens, 0.9NA oil immersion, axial resolution 1.0μm, field of view 200μm x 100μm (lateral resolution , 0.3μm). In human volunteer, fluorescein sodium was administrated topically and intradermally. Animal studies were done in GFP transgenic mouse, IRC mouse and pig skin. For imaging of animal skin, fluorescein sodium, acridine orange, and curcumine were used for fluorescein contrast agent. We also used the GFP transgenic mouse for fluorescein CLSM imaging. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. Curcumin is a yellow food dye that has similar fluorescent properties to fluorescein sodium. Acridin Orange can be highlight nuclei in viable keratinocyte. In vivo CLSM of transgenic GFP mouse enable on in vivo, high resolution view of GFP expressing skin tissue. GFP signals are brightest in corneocyte, kertinocyte, hair and eccrine gland. In intact skin, absorption of fluorescein sodium by individual corneocyte and hair. Intradermal administrated the fluorescein sodium, distinct outline of keratinocyte cell border could be seen. In

In vivo study of immunogenicity and kinetic characteristics of a quantum dot-labelled baculovirus.

Science.gov (United States)

Wang, Meng; Zheng, Zhenhua; Meng, Jin; Wang, Han; He, Man; Zhang, Fuxian; Liu, Yan; Hu, Bin; He, Zike; Hu, Qinxue; Wang, Hanzhong

2015-09-01

Nanomaterials conjugated with biomacromolecules, including viruses, have great potential for in vivo applications. Therefore, it is important to evaluate the safety of nanoparticle-conjugated macromolecule biomaterials (Nano-mbio). Although a number of studies have assessed the risks of nanoparticles and macromolecule biomaterials in living bodies, only a few of them investigated Nano-mbios. Here we evaluated the in vivo safety profile of a quantum dot-conjugated baculovirus (Bq), a promising new Nano-mbio, in mice. Each animal was injected twice intraperitoneally with 50 μg virus protein labelled with around 3*10(-5)nmol conjugated qds. Control animals were injected with PBS, quantum dots, baculovirus, or a mixture of quantum dots and baculovirus. Blood, tissues and body weight were analysed at a series of time points following both the first and the second injections. It turned out that the appearance and behaviour of the mice injected with Bq were similar to those injected with baculovirus alone. However, combination of baculovirus and quantum dot (conjugated or simply mixed) significantly induced stronger adaptive immune responses, and lead to a faster accumulation and longer existence of Cd in the kidneys. Thus, despite the fact that both quantum dot and baculovirus have been claimed to be safe in vivo, applications of Bq in vivo should be cautious. To our knowledge, this is the first study examining the interaction between a nanoparticle-conjugated virus and a living body from a safety perspective, providing a basis for in vivo application of other Nano-mbios. Copyright © 2015 Elsevier Ltd. All rights reserved.

EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the risk of transmission of classical scrapie via in vivo derived embryo transfer in ovine animals

DEFF Research Database (Denmark)

Hald, Tine; Baggesen, Dorte Lau

. Under natural exposure conditions, animals that are heterozygous or homozygous A136R154R171 display respectively a low or negligible risk of being infected. The genetic control of the susceptibility to classical scrapie is also likely to impact on the risk of transmitting the disease via embryo transfer......The risk of transmission of classical scrapie via the transfer of in vivo derived embryo in ovines was assessed, taking into account the scientific information made available since the last EFSA opinion on this topic (2010) (see http://www.efsa.europa.eu/en/efsajournal/pub/1429.htm). The potential...... impact of PrP genotype of the embryo and/or of the ram and donor ewe on this risk was also assessed. The new data made available over the last three years further reinforce the view that classical scrapie could be vertically transmitted in sheep. Since the possibility of such vertical transmission...

Combined in vivo and ex vivo analysis of mesh mechanics in a porcine hernia model.

Science.gov (United States)

Kahan, Lindsey G; Lake, Spencer P; McAllister, Jared M; Tan, Wen Hui; Yu, Jennifer; Thompson, Dominic; Brunt, L Michael; Blatnik, Jeffrey A

2018-02-01

Hernia meshes exhibit variability in mechanical properties, and their mechanical match to tissue has not been comprehensively studied. We used an innovative imaging model of in vivo strain tracking and ex vivo mechanical analysis to assess effects of mesh properties on repaired abdominal walls in a porcine model. We hypothesized that meshes with dissimilar mechanical properties compared to native tissue would alter abdominal wall mechanics more than better-matched meshes. Seven mini-pigs underwent ventral hernia creation and subsequent open repair with one of two heavyweight polypropylene meshes. Following mesh implantation with attached radio-opaque beads, fluoroscopic images were taken at insufflation pressures from 5 to 30 mmHg on postoperative days 0, 7, and 28. At 28 days, animals were euthanized and ex vivo mechanical testing performed on full-thickness samples across repaired abdominal walls. Testing was conducted on 13 mini-pig controls, and on meshes separately. Stiffness and anisotropy (the ratio of stiffness in the transverse versus craniocaudal directions) were assessed. 3D reconstructions of repaired abdominal walls showed stretch patterns. As pressure increased, both meshes expanded, with no differences between groups. Over time, meshes contracted 17.65% (Mesh A) and 0.12% (Mesh B; p = 0.06). Mesh mechanics showed that Mesh A deviated from anisotropic native tissue more than Mesh B. Compared to native tissue, Mesh A was stiffer both transversely and craniocaudally. Explanted repaired abdominal walls of both treatment groups were stiffer than native tissue. Repaired tissue became less anisotropic over time, as mesh properties prevailed over native abdominal wall properties. This technique assessed 3D stretch at the mesh level in vivo in a porcine model. While the abdominal wall expanded, mesh-ingrown areas contracted, potentially indicating stresses at mesh edges. Ex vivo mechanics demonstrate that repaired tissue adopts mesh properties, suggesting

The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo

DEFF Research Database (Denmark)

Verhagen, H.; Aruoma, O.I.; van Delft, J.H.M.

2003-01-01

There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near......, provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2......) The nature of the test substance; (3) Valid and invalid test systems; (4) The selection of dose levels and gender; (5) Reversal of the effects induced by oxidants, carcinogens and mutagens; (6) Route of administration; (7) Number and validity of test variables; (8) Repeatability and reproducibility; (9...

Lipidots: competitive organic alternative to quantum dots for in vivo fluorescence imaging

Science.gov (United States)

Gravier, Julien; Navarro, Fabrice P.; Delmas, Thomas; Mittler, Frédérique; Couffin, Anne-Claude; Vinet, Françoise; Texier, Isabelle

2011-09-01

The use of fluorescent nanostructures can bring several benefits on the signal to background ratio for in vitro microscopy, in vivo small animal imaging, and image-guided surgery. Fluorescent quantum dots (QDs) display outstanding optical properties, with high brightness and low photobleaching rate. However, because of their toxic element core composition and their potential long term retention in reticulo-endothelial organs such as liver, their in vivo human applications seem compromised. The development of new dye-loaded (DiO, DiI, DiD, DiR, and Indocyanine Green (ICG)) lipid nanoparticles for fluorescence imaging (lipidots) is described here. Lipidot optical properties quantitatively compete with those of commercial QDs (QTracker®705). Multichannel in vivo imaging of lymph nodes in mice is demonstrated for doses as low as 2 pmols of particles. Along with their optical properties, fluorescent lipidots display very low cytotoxicity (IC50 > 75 nM), which make them suitable tools for in vitro, and especially in vivo, fluorescence imaging applications.

Allergenic potential of novel proteins - What can we learn from animal production?

Science.gov (United States)

Ekmay, Ricardo D; Coon, Craig N; Ladics, Gregory S; Herman, Rod A

2017-10-01

Currently, risk assessment of the allergenic potential of novel proteins relies heavily on evaluating protein digestibility under normal conditions based on the theory that allergens are more resistant to gastrointestinal digestion than non-allergens. There is also proposed guidance for expanded in vitro digestibility assay conditions to include vulnerable sub-populations. One of the underlying rationales for the expanded guidance is that current in vitro assays do not accurately replicate the range of physiological conditions. Animal scientists have long sought to predict protein and amino acid digestibility for precision nutrition. Monogastric production animals, especially swine, have gastrointestinal systems similar to humans, and evaluating potential allergen digestibility in this context may be beneficial. Currently, there is no compelling evidence that the mechanisms sometimes postulated to be associated with allergenic sensitization, e.g. antacid modification of stomach pH, are valid among production animals. Furthermore, examples are provided where non-biologically representative assays are better at predicting protein and amino acid digestibility compared with those designed to mimic in vivo conditions. Greater emphasis should be made to align in vitro assessments with in vivo data. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

In vivo recording of aerodynamic force with an aerodynamic force platform: from drones to birds.

Science.gov (United States)

Lentink, David; Haselsteiner, Andreas F; Ingersoll, Rivers

2015-03-06

Flapping wings enable flying animals and biomimetic robots to generate elevated aerodynamic forces. Measurements that demonstrate this capability are based on experiments with tethered robots and animals, and indirect force calculations based on measured kinematics or airflow during free flight. Remarkably, there exists no method to measure these forces directly during free flight. Such in vivo recordings in freely behaving animals are essential to better understand the precise aerodynamic function of their flapping wings, in particular during the downstroke versus upstroke. Here, we demonstrate a new aerodynamic force platform (AFP) for non-intrusive aerodynamic force measurement in freely flying animals and robots. The platform encloses the animal or object that generates fluid force with a physical control surface, which mechanically integrates the net aerodynamic force that is transferred to the earth. Using a straightforward analytical solution of the Navier-Stokes equation, we verified that the method is accurate. We subsequently validated the method with a quadcopter that is suspended in the AFP and generates unsteady thrust profiles. These independent measurements confirm that the AFP is indeed accurate. We demonstrate the effectiveness of the AFP by studying aerodynamic weight support of a freely flying bird in vivo. These measurements confirm earlier findings based on kinematics and flow measurements, which suggest that the avian downstroke, not the upstroke, is primarily responsible for body weight support during take-off and landing.

Noninvasive control of rhodamine-loaded capsules distribution in vivo

Science.gov (United States)

Stelmashchuk, O.; Tarakanchikova, Y.; Seryogina, E.; Piavchenko, G.; Zherebtsov, E.; Dunaev, A.; Popov, A.; Meglinski, I.

2018-04-01

Using fluorescence spectroscopy system with fibre-optical probe, we investigated the dynamics of propagation and circulation in the microcirculatory system of experimental nanocapsules fluorescent-labelled (rhodamine TRITC) nanocapsules. The studies were carried out in clinically healthy Wistar rats. The model animals were divided into control group and group received injections of the nanocapsules. The fluorescent measurements conducted transcutaneously on the thigh surface. The administration of the preparation with the rhodamine concentration of 5 mg/kg of animal weight resulted in twofold increase of fluorescence intensity by reference to the baseline level. As a result of the study, it was concluded that fluorescence spectroscopy can be used for transdermal measurements of the rhodamine-loaded capsules in vivo.

In vivo biodistribution of CNTs using a BALB/c mouse experimental model.

Science.gov (United States)

Fufă, Mariana Oana Mihaela; Mihaiescu, Dan Eduard; Mogoantă, Laurenţiu; Bălşeanu, Tudor Adrian; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai; Bolocan, Alexandra

2015-01-01

Due to their unique behaviors, carbon nanotubes (CNTs)-based systems meet essential requirements for modern applications, such as electronics, optics, photovoltaics, fuel cells, aerospace engineering, military and biomedical applications. CNTs biocompatibility and toxic effects were assessed both in vitro and in vivo, in terms of hemocompatibility, cytocompatibility, immunoreactions and genetic behavior. The aim of this paper is to evaluate the in vivo biodistribution and biocompatibility of carbon nanopowder synthesized by plasma processing, using a BALB/c mouse experimental model. Three months old BALB/c mice were aseptically injected with 100 μL of 1 mg/mL dispersions. The obtained carbon-based nano-systems were dispersed in saline solution and subsequently sterilized by using a 30 minutes treatment with UV irradiation. The reference mice were injected with 100 μL of saline. The mice were kept under standard conditions of light, temperature, humidity, food and water (ad libitum) before the vital organ harvest. The animal welfare was daily monitored. At two and 10 days after the inoculation, the animals were euthanized under general anesthesia, for the sampling of internal organs (brain, myocardium, pancreas, liver, lung, kidney and spleen). No animal died during the experiment. Brain, myocardium and pancreas were histologically normal, with no tissue damage, inflammatory infiltrate or inorganic deposits. CNTs were evidenced only in hepatic, renal, pulmonary and spleen tissue samples. Increased amounts of inorganic granular structures were reported after 10 days of treatment, when compared to the short-term (two days) inoculation. Our BALB/c mouse experimental model was found to be useful for the in vivo assessment of biodistribution and biocompatibility of CNTs.

Prebiotics from marine macroalgae for human and animal health applications.

LENUS (Irish Health Repository)

O'Sullivan, Laurie

2010-01-01

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and\\/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.

Validating in vivo Raman spectroscopy of bone in human subjects

Science.gov (United States)

Esmonde-White, Francis W. L.; Morris, Michael D.

2013-03-01

Raman spectroscopy can non-destructively measure properties of bone related to mineral density, mineral composition, and collagen composition. Bone properties can be measured through the skin in animal and human subjects, but correlations between the transcutaneous and exposed bone measurements have only been reported for human cadavers. In this study, we examine human subjects to collect measurements transcutaneously, on surgically exposed bone, and on recovered bone fragments. This data will be used to demonstrate in vivo feasibility and to compare transcutaneous and exposed Raman spectroscopy of bone. A commercially available Raman spectrograph and optical probe operating at 785 nm excitation are used for the in vivo measurements. Requirements for applying Raman spectroscopy during a surgery are also discussed.

Real-time temperature monitoring during radiofrequency treatments on ex-vivo animal model by fiber Bragg grating sensors

Science.gov (United States)

Palumbo, Giovanna; Tosi, Daniele; Schena, Emiliano; Massaroni, Carlo; Ippolito, Juliet; Verze, Paolo; Carlomagno, Nicola; Tammaro, Vincenzo; Iadicicco, Agostino; Campopiano, Stefania

2017-05-01

Fiber Bragg Grating (FBG) sensors applied to bio-medical procedures such as surgery and rehabilitation are a valid alternative to traditional sensing techniques due to their unique characteristics. Herein we propose the use of FBG sensor arrays for accurate real-time temperature measurements during multi-step RadioFrequency Ablation (RFA) based thermal tumor treatment. Real-time temperature monitoring in the RF-applied region represents a valid feedback for the success of the thermo-ablation procedure. In order to create a thermal multi-point map around the tumor area to be treated, a proper sensing configuration was developed. In particular, the RF probe of a commercial medical instrumentation, has been equipped with properly packaged FBGs sensors. Moreover, in order to discriminate the treatment areas to be ablated as precisely as possible, a second array 3.5 cm long, made by several FBGs was used. The results of the temperature measurements during the RFA experiments conducted on ex-vivo animal liver and kidney tissues are presented herein. The proposed FBGs based solution has proven to be capable of distinguish different and consecutive discharges and for each of them, to measure the temperature profile with a resolution of 0.1 °C and a minimum spatial resolution of 5mm. Based upon our experiments, it is possible to confirm that the temperature decreases with distance from a RF peak ablation, in accordance with RF theory. The proposed solution promises to be very useful for the surgeon because a real-time temperature feedback allows for the adaptation of RFA parameters during surgery and better delineates the area under treatment.

Mesoporous persistent nanophosphors for in vivo optical bioimaging and drug-delivery

Science.gov (United States)

Maldiney, Thomas; Ballet, Benoit; Bessodes, Michel; Scherman, Daniel; Richard, Cyrille

2014-10-01

Based upon the ambitious idea that one single particle could serve multiple purposes at the same time, the combination and simultaneous use of imaging and therapeutics has lately arisen as one of the most promising prospects among nanotechnologies directed toward biomedical applications. Intended for both therapeutics and diagnostics in vivo, highly complex nanostructures were specifically designed to simultaneously act as optical imaging probes and delivery vehicles. Yet, such multifunctional photonic nanoplatforms usually exploit fluorescence phenomena which require constant excitation light through biological tissues and thus significantly reduce the detection sensitivity due to the autofluorescence from living animals. In order to overcome this critical issue, the present article introduces a novel multifunctional agent based on persistent luminescence mesoporous nanoparticles. Being composed of a hybrid chromium-doped zinc gallate core/mesoporous silica shell architecture, we show that this nanotechnology can be used as an efficient doxorubicin-delivery vehicle presenting a higher cytotoxicity toward U87MG cells than its unloaded counterpart in vitro. In addition, we demonstrate that a persistent luminescence signal from these doxorubicin-loaded mesoporous nanophosphors opens a new way to highly sensitive detection in vivo, giving access to the real-time biodistribution of the carrier without any autofluorescence from the animal tissues. This new persistent luminescence-based hybrid nanotechnology can be easily applied to the delivery of any therapeutic agent, thus constituting a versatile and sensitive optical nanotool dedicated to both therapeutic and diagnostic applications in vivo.Based upon the ambitious idea that one single particle could serve multiple purposes at the same time, the combination and simultaneous use of imaging and therapeutics has lately arisen as one of the most promising prospects among nanotechnologies directed toward biomedical

Advanced Small Animal Conformal Radiation Therapy Device.

Science.gov (United States)

Sharma, Sunil; Narayanasamy, Ganesh; Przybyla, Beata; Webber, Jessica; Boerma, Marjan; Clarkson, Richard; Moros, Eduardo G; Corry, Peter M; Griffin, Robert J

2017-02-01

We have developed a small animal conformal radiation therapy device that provides a degree of geometrical/anatomical targeting comparable to what is achievable in a commercial animal irradiator. small animal conformal radiation therapy device is capable of producing precise and accurate conformal delivery of radiation to target as well as for imaging small animals. The small animal conformal radiation therapy device uses an X-ray tube, a robotic animal position system, and a digital imager. The system is in a steel enclosure with adequate lead shielding following National Council on Radiation Protection and Measurements 49 guidelines and verified with Geiger-Mueller survey meter. The X-ray source is calibrated following AAPM TG-61 specifications and mounted at 101.6 cm from the floor, which is a primary barrier. The X-ray tube is mounted on a custom-made "gantry" and has a special collimating assembly system that allows field size between 0.5 mm and 20 cm at isocenter. Three-dimensional imaging can be performed to aid target localization using the same X-ray source at custom settings and an in-house reconstruction software. The small animal conformal radiation therapy device thus provides an excellent integrated system to promote translational research in radiation oncology in an academic laboratory. The purpose of this article is to review shielding and dosimetric measurement and highlight a few successful studies that have been performed to date with our system. In addition, an example of new data from an in vivo rat model of breast cancer is presented in which spatially fractionated radiation alone and in combination with thermal ablation was applied and the therapeutic benefit examined.

Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it.

Science.gov (United States)

Niehues, Stefan M; Unger, J K; Malinowski, M; Neymeyer, J; Hamm, B; Stockmann, M

2010-08-20

Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model. Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined. Median liver density was 1.07g/ml. Regression analysis showed a high correlation of r(2) = 0.985 between CT-volumetry and water displacement. CT-volumetry was found to be 13% higher than water displacement volumetry (pvolumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.

Preliminary studies with [18F]haloperidol: a radioligand for in vivo studies of the dopamine receptors

International Nuclear Information System (INIS)

Tewson, T.J.; Raichle, M.E.; Welch, M.J.

1980-01-01

The authors report a synthesis of [ 18 F]haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system. (Auth.)

Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

Science.gov (United States)

Mueller, Ralf S; Olivry, Thierry

2017-08-30

The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

In vitro and in vivo models for testing arrhythmogenesis in drugs.

Science.gov (United States)

Carlsson, L

2006-01-01

The steadily increasing list of drugs associated with prolongation of the QT interval and torsades de pointes (TdP) constitute a medical problem of major concern. Hence, there is a need at an early stage to identify drug candidates with an inherent capacity to induce repolarization-related proarrhythmias, avoiding exposure of large populations to potentially harmful drugs. Furthermore, the availability of clinically relevant and predictive animal models should reduce the risk that effective and potentially life-saving drugs never reach the market. This review will discuss the pros and cons of some in vivo and in vitro animal models for assessing proarrhythmia liability.

Bacteria-mediated in vivo delivery of quantum dots into solid tumor

Energy Technology Data Exchange (ETDEWEB)

Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

2012-09-07

Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Energy Technology Data Exchange (ETDEWEB)

Galanzha, Ekaterina I. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Zharov, Vladimir P., E-mail: zharovvladimirp@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

2013-12-10

Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 10{sup 3}–10{sup 4} CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 10{sup 2}–10{sup 3} times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

Directory of Open Access Journals (Sweden)

Xinhua Chen

Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

A Very High Spatial Resolution Detector for Small Animal PET

International Nuclear Information System (INIS)

Kanai Shah, M.S.

2007-01-01

Positron Emission Tomography (PET) is an in vivo analog of autoradiography and has the potential to become a powerful new tool in imaging biological processes in small laboratory animals. PET imaging of small animals can provide unique information that can help in advancement of human disease models as well as drug development. Clinical PET scanners used for human imaging are bulky, expensive and do not have adequate spatial resolution for small animal studies. Hence, dedicated, low cost instruments are required for conducting small animal studies with higher spatial resolution than what is currently achieved with clinical as well as dedicated small animal PET scanners. The goal of the proposed project is to investigate a new all solid-state detector design for small animal PET imaging. Exceptionally high spatial resolution, good timing resolution, and excellent energy resolution are expected from the proposed detector design. The Phase I project was aimed at demonstrating the feasibility of producing high performance solid-state detectors that provide high sensitivity, spatial resolution, and timing characteristics. Energy resolution characteristics of the new detector were also investigated. The goal of the Phase II project is to advance the promising solid-state detector technology for small animal PET and determine its full potential. Detectors modules will be built and characterized and finally, a bench-top small animal PET system will be assembled and evaluated

Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

Science.gov (United States)

Rangarajan, Janaki Raman; Vande Velde, Greetje; van Gent, Friso; de Vloo, Philippe; Dresselaers, Tom; Depypere, Maarten; van Kuyck, Kris; Nuttin, Bart; Himmelreich, Uwe; Maes, Frederik

2016-11-01

Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.

Preclinical Development and In Vivo Efficacy of Ceftiofur-PLGA Microparticles

Science.gov (United States)

Vilos, Cristian; Velasquez, Luis A.; Rodas, Paula I.; Zepeda, Katherine; Bong, Soung-Jae; Herrera, Natalia; Cantin, Mario; Simon, Felipe; Constandil, Luis

2015-01-01

Drug delivery systems based on polymeric microparticles represent an interesting field of development for the treatment of several infectious diseases for humans and animals. In this work, we developed PLGA microparticles loaded with ceftiofur (PLGA-cef), a third- generation cephalosporin that is used exclusively used in animals. PLGA-cef was prepared by the double emulsion w/o/w method, and exhibited a diameter in the range of 1.5–2.2 μm, and a negative ζ potential in the range of -35 to -55 mV. The loading yield of PLGA-cef was ~7% and encapsulation efficiency was approximately 40%. The pharmacokinetic study demonstrated a sustained release profile of ceftiofur for 20 days. PLGA-cef administrated in a single dose was more effective than ceftiofur non-encapsulated in rats challenged with S. Typhimurium. The in vivo toxicological evaluation showed that PLGA-cef did not affect the blood biochemical, hematological and hemostasis parameters. Overall, the PLGA-cef showed slow in vivo release profile, high antibacterial efficacy, and low toxicity. The results obtained supports the safe application of PLGA-cef as sustained release platform in the veterinary industry. PMID:25915043

In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.

Science.gov (United States)

Uddin, Md Imam; Evans, Stephanie M; Craft, Jason R; Capozzi, Megan E; McCollum, Gary W; Yang, Rong; Marnett, Lawrence J; Uddin, Md Jashim; Jayagopal, Ashwath; Penn, John S

2016-08-05

Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs.

DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo.

Science.gov (United States)

Zubradt, Meghan; Gupta, Paromita; Persad, Sitara; Lambowitz, Alan M; Weissman, Jonathan S; Rouskin, Silvi

2017-01-01

Coupling of structure-specific in vivo chemical modification to next-generation sequencing is transforming RNA secondary structure studies in living cells. The dominant strategy for detecting in vivo chemical modifications uses reverse transcriptase truncation products, which introduce biases and necessitate population-average assessments of RNA structure. Here we present dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), which encodes DMS modifications as mismatches using a thermostable group II intron reverse transcriptase. DMS-MaPseq yields a high signal-to-noise ratio, can report multiple structural features per molecule, and allows both genome-wide studies and focused in vivo investigations of even low-abundance RNAs. We apply DMS-MaPseq for the first analysis of RNA structure within an animal tissue and to identify a functional structure involved in noncanonical translation initiation. Additionally, we use DMS-MaPseq to compare the in vivo structure of pre-mRNAs with their mature isoforms. These applications illustrate DMS-MaPseq's capacity to dramatically expand in vivo analysis of RNA structure.

Authentication of Primordial Characteristics of the CLBL-1 Cell Line Prove the Integrity of a Canine B-Cell Lymphoma in a Murine In Vivo Model

OpenAIRE

Rütgen, Barbara C.; Willenbrock, Saskia; Reimann-Berg, Nicola; Walter, Ingrid; Fuchs-Baumgartinger, Andrea; Wagner, Siegfried; Kovacic, Boris; Essler, Sabine E.; Schwendenwein, Ilse; Nolte, Ingo; Saalmüller, Armin; Escobar, Hugo Murua

2012-01-01

Cell lines are key tools in cancer research allowing the generation of neoplasias in animal models resembling the initial tumours able to mimic the original neoplasias closely in vivo. Canine lymphoma is the major hematopoietic malignancy in dogs and considered as a valuable spontaneous large animal model for human Non-Hodgkin's Lymphoma (NHL). Herein we describe the establishment and characterisation of an in vivo model using the canine B-cell lymphoma cell line CLBL-1 analysing the stabilit...

Rates of in vivo (arterial) and in vitro biocorrosion for pure magnesium.

Science.gov (United States)

Bowen, Patrick K; Drelich, Adam; Drelich, Jaroslaw; Goldman, Jeremy

2015-01-01

The development of magnesium-based materials for bioabsorbable stents relies heavily on corrosion testing by immersion in pseudophysiological solutions, where magnesium degrades faster than it does in vivo. The quantitative difference in corrosion kinetics in vitro and in vivo is largely unknown, but, if determined, would help reduce dependence on animal models. In order to create a quantitative in vitro-in vivo correlation based on an accepted measure of corrosion (penetration rate), commercially pure magnesium wires were corroded in vivo in the abdominal aortas of rats for 5-32 days, and in vitro for up to 14 days using Dulbecco's modified eagle medium. Cross-sectioning, scanning electron microscopy, image analysis, a modified penetration rate tailored to degraded wires, and empirical modeling were used to analyze the corroded specimens. In vitro penetration rates were consistently higher than comparable in vivo rates by a factor of 1.2-1.9× (±0.2×). For a sample <20% corroded, an approximate in vitro-in vivo multiplier of 1.3 ± 0.2× was applied, whereas a multiplier of 1.8 ± 0.2× became appropriate when the magnesium specimen was 25-35% degraded. © 2014 Wiley Periodicals, Inc.

Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-fallypride

International Nuclear Information System (INIS)

Kaur, Jasmeet; Khararjian, Armen; Coleman, Robert A.; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

2014-01-01

Objectives: The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-fallypride and 11 C-fallypride. Methods: Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-fallypride scan or a 11 C-fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results: In vitro studies showed 18 F-fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-fallypride and 11 C-fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-fallypride in spinal cord sections. Conclusions: Our studies showed 18 F-fallypride and 11 C-fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord

Two-photon microscopy imaging of thy1GFP-M transgenic mice: a novel animal model to investigate brain dendritic cell subsets in vivo.

Directory of Open Access Journals (Sweden)

Claudia Laperchia

Full Text Available Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype.With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity of dendritic cells (DCs, and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

Algorithm optimization for multitined radiofrequency ablation: comparative study in ex vivo and in vivo bovine liver.

Science.gov (United States)

Appelbaum, Liat; Sosna, Jacob; Pearson, Robert; Perez, Sarah; Nissenbaum, Yizhak; Mertyna, Pawel; Libson, Eugene; Goldberg, S Nahum

2010-02-01

To prospectively optimize multistep algorithms for largest available multitined radiofrequency (RF) electrode system in ex vivo and in vivo tissues, to determine best energy parameters to achieve large predictable target sizes of coagulation, and to compare these algorithms with manufacturer's recommended algorithms. Institutional animal care and use committee approval was obtained for the in vivo portion of this study. Ablation (n = 473) was performed in ex vivo bovine liver; final tine extension was 5-7 cm. Variables in stepped-deployment RF algorithm were interrogated and included initial current ramping to 105 degrees C (1 degrees C/0.5-5.0 sec), the number of sequential tine extensions (2-7 cm), and duration of application (4-12 minutes) for final two to three tine extensions. Optimal parameters to achieve 5-7 cm of coagulation were compared with recommended algorithms. Optimal settings for 5- and 6-cm final tine extensions were confirmed in in vivo perfused bovine liver (n = 14). Multivariate analysis of variance and/or paired t tests were used. Mean RF ablation zones of 5.1 cm +/- 0.2 (standard deviation), 6.3 cm +/- 0.4, and 7 cm +/- 0.3 were achieved with 5-, 6-, and 7-cm final tine extensions in a mean of 19.5 min +/- 0.5, 27.9 min +/- 6, and 37.1 min +/- 2.3, respectively, at optimal settings. With these algorithms, size of ablation at 6- and 7-cm tine extension significantly increased from mean of 5.4 cm +/- 0.4 and 6.1 cm +/- 0.6 (manufacturer's algorithms) (P mean diameter in specified time: 5.5 cm +/- 0.4 in 18.5 min +/- 0.5 (5-cm extensions) and 5.7 cm +/- 0.2 in 21.2 min +/- 0.6 (6-cm extensions). Large zones of coagulation of 5-7 cm can be created with optimized RF algorithms that help reduce number of tine extensions compared with manufacturer's recommendations. Such algorithms are likely to facilitate the utility of these devices for RF ablation of focal tumors in clinical practice. (c) RSNA, 2010.

Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the injury site in vitro and in vivo

DEFF Research Database (Denmark)

Robel, Stefanie; Bardehle, Sophia; Lepier, Alexandra

2011-01-01

signals, the small RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an in vitro scratch assay as a minimal wounding model and found that astrocytes lacking Cdc42 (Cdc42Δ) were still able to form protrusions, although in a nonoriented way. Consequently, they failed to migrate...... in a directed manner toward the scratch. When animals were injured in vivo through a stab wound, Cdc42Δ astrocytes developed protrusions properly oriented toward the lesion, but the number of astrocytes recruited to the lesion site was significantly reduced. Surprisingly, however, lesions in Cdc42Δ animals...

Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs.

Science.gov (United States)

Koh, H L; Woo, S O

2000-11-01

Traditional Chinese medicine (TCM) is gaining popularity as a form of complementary and alternative medicine. Reports of efficacy of TCM are increasing in numbers. TCM includes both crude Chinese medicinal materials (plants, animal parts and minerals) and Chinese proprietary medicine (CPM) [final dosage forms]. Despite the belief that CPM and herbal remedies are of natural origin, unlike Western medicine, and are hence safe and without many adverse effects, there have been numerous reports of adverse effects associated with herbal remedies. Factors affecting the safety of herbal medicines include intrinsic toxicity, adulteration, substitution, contamination, misidentification, lack of standardisation, incorrect preparation and/or dosage and inappropriate labelling and/or advertising. Hence, new regulations on the control of CPM were enforced in Singapore with effect from 1 September 1999. These include licensing and labelling requirements, as well as control of microbial contamination. This article also reviews reports of excessive toxic heavy metals and undeclared drugs in CPM in Singapore between 1990 and 1997. The names, uses, toxic heavy metal or drug detected and the year of detection are tabulated. Information on the brand or manufacturer's name are provided whenever available. The public and healthcare professionals should be better informed of the basic concept of TCM and its usefulness, as well as the potential adverse effects associated with its use. Greater control over the safety and quality of CPM could be achieved through good manufacturing practice, regulatory control, research, education, reporting usage of Chinese medicine (as in drug history) as well as reporting of adverse events.

Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

Energy Technology Data Exchange (ETDEWEB)

Deglon, N. [Atomic Energy Commission (CEA), Dept. of Medical Research and MIRCen Program, 91 - Orsay (France)

2006-07-01

The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral

Gene transfer in rodents and primates as a new tool for modeling diseases in animals and assessing functions by in vivo imaging

International Nuclear Information System (INIS)

Deglon, N.

2006-01-01

The identification of disease-causing genes in familial forms of neuro-degenerative disorders and the development of genetic models closely replicating human CNS pathologies have drastically changed our understanding of the molecular events leading to neuronal cell death. If these achievements open new opportunities of therapeutic interventions efficient delivery systems taking into account the specificity of the central nervous system are required to administer therapeutic candidates. In addition, there is a need to develop 1) genetic models in large animals that replicate late stages of the diseases and 2) imaging techniques suitable for longitudinal, quantitative and non-invasive evaluation of disease progression and the evaluation of new therapeutic strategies. Over the last few years, we have investigated the potential of lentiviral vectors as tool to model and treat CNS disorders. The use of lentiviral vectors to create animal model of these pathologies holds various advantages compared to classical transgenic approaches. Viral vectors are versatile, highly flexible tools to perform in vivo studies. Multiple genetic models can be created in a short period of time. High transduction efficiencies as well as robust and sustained trans-gene expression lead to the rapid appearance of functional and behavioral abnormalities and severe neuro-degeneration. Targeted injections in different brain areas can be used to investigate the regional specificity of the neuro-pathology and eliminate potential side effects associated with a widespread over-expression of the trans-gene. Finally, models can be established in different mammalian species including non-human primates, thereby providing an opportunity to assess complex behavioral changes and perform longitudinal follow-up of neuro-pathological alterations by imaging. We have demonstrated the proof of principle of this approach for Huntington's disease. We have shown that the intratriatal injection of lentiviral vector

Pre-clinical research in small animals using radiotherapy technology. A bidirectional translational approach

International Nuclear Information System (INIS)

Tillner, Falk; Buetof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang; Helmholtz-Zentrum Dresden-Rossendorf, Dresden; Technische Univ. Dresden; Helmholtz-Zentrum Dresden-Rossendorf, Dresden

2014-01-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained.

Pre-clinical research in small animals using radiotherapy technology. A bidirectional translational approach

Energy Technology Data Exchange (ETDEWEB)

Tillner, Falk; Buetof, Rebecca [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; Thute, Prasad [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Krause, Mechthild [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Enghardt, Wolfgang [Technische Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Technische Univ. Dresden (Germany). Dept. of Radiation Oncology; Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). Inst. of Radiooncology

2014-07-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained.

A novel ex-vivo porcine renal xenotransplantation model using a pulsatile machine preservation system.

Science.gov (United States)

Guarrera, James V; Stone, Jonathan; Tulipan, Jacob; Jhang, Jeffrey; Arrington, Ben; Boykin, Jason; Markowitz, Glen; Ratner, Lloyd E

2011-01-01

Animal models to investigate pathophysiology and xenotransplantation require complex techniques and significant animal utilization. The aim of the study was to develop a reliable ex-vivo technique to test xenotransplant interventions. Miniature Swine being utilized for a nonsurvival study acted as donor animals. Kidneys were flushed and rapidly explanted and chilled to 4°C. Kidneys were assigned to be the control (CK) (n=3) and the mate were used as a Xenograft Kidneys (XK) (n=3). Kidneys were perfused on separate Waters RM 3 perfusion devices. Perfusion temperature was 35-37°C and pressure was 100-110/60-70 mmHg at 60 pulses per minute. CKs were reperfused with autologous blood collected at the time of organ procurement. XKs were reperfused using freshly donated whole human blood. Physical characteristics, urine output were recorded. Core needle biopsies were obtained and examined by a blinded pathologist for evidence of antibody mediated rejection. XK kidneys demonstrated homogenous reperfusion which rapidly became patchy at 5-7 minutes. XK kidneys had become complete black and thrombosed by 60-70 minutes. XK biopsies demonstrated peritubular capillaritis. CK kidneys demonstrated homogenous reperfusion and urine production. H&E stain of CKs only demonstrated nonspecific inflammation. Our ex-vivo porcine xenotransplant model shows early promise as a tool for studying Xeno- associated hyperacute rejection. This technique saves resources and animal utilization.

An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

Science.gov (United States)

Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

2009-09-01

Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

Fluorescence based molecular in vivo imaging

International Nuclear Information System (INIS)

Ebert, Bernd

2008-01-01

Molecular imaging represents a modern research area that allows the in vivo study of molecular biological process kinetics using appropriate probes and visualization methods. This methodology may be defined- apart from the contrast media injection - as non-abrasive. In order to reach an in vivo molecular process imaging as accurate as possible the effects of the used probes on the biological should not be too large. The contrast media as important part of the molecular imaging can significantly contribute to the understanding of molecular processes and to the development of tailored diagnostics and therapy. Since more than 15 years PTB is developing optic imaging systems that may be used for fluorescence based visualization of tissue phantoms, small animal models and the localization of tumors and their predecessors, and for the early recognition of inflammatory processes in clinical trials. Cellular changes occur during many diseases, thus the molecular imaging might be of importance for the early diagnosis of chronic inflammatory diseases. Fluorescent dyes can be used as unspecific or also as specific contrast media, which allow enhanced detection sensitivity

Persistent luminescence of Eu, Mn, Dy doped calcium phosphates for in-vivo optical imaging

Energy Technology Data Exchange (ETDEWEB)

Rosticher, Céline [UPMC Univ Paris 06, CNRS, UMR 7574, Chimie de la Matière Condensée de Paris, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05 (France); Viana, Bruno, E-mail: bruno.viana@chimie-paristech.fr [PSL Research University, Chimie ParisTech-CNRS, Institut de Recherche de Chimie Paris, 11 rue Pierre et Marie Curie, 75005 Paris (France); Maldiney, Thomas; Richard, Cyrille [Unité de Technologies Chimiques et Biologiques pour la Santé, CNRS, UMR 8258, Paris Cedex F-75270 (France); Inserm U1022, Paris Cedex F-75270 (France); Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, Sorbonne Paris Cité, Paris Cedex F-75270 (France); Chanéac, Corinne, E-mail: corinne.chaneac@upmc.fr [UPMC Univ Paris 06, CNRS, UMR 7574, Chimie de la Matière Condensée de Paris, Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05 (France)

2016-02-15

Biocompatible nanoparticles possessing persistent luminescence properties offer attractive possibilities for in vivo imaging applications as it allows an excitation of the sensors outside the animal before injection and a long-lasting emission of light. Here we report the development of highly biocompatible calcium phosphate nanoparticles doped with europium, Mn{sup 2+} and Ln{sup 3+} (Ln{sup 3+}=Dy{sup 3+}, Pr{sup 3+}) ions synthesized by hydrothermal route and tailored to present red-near infrared persistent luminescence after UV excitation. Nanosize biphasic HAp/β-TCP compounds with sphere and rod-shaped were obtained. Two emission bands in the red-near infrared range were observed and attributed to {sup 4}T{sub 1}→{sup 6}A{sub 1} transitions of Mn{sup 2+} ions in HAp/β-TCP. An annealing treatment in reductive atmosphere post-synthesis was essential to reveal persistent luminescence properties. Indeed, such thermal treatment allows reducing Eu{sup 3+} ions in Eu{sup 2+} ions and generating required defaults as oxygen vacancies in the crystal necessary for red emission in accordance with persistent luminescence mechanism. These nanoparticles have been tested for the first time for in vivo imaging on small animal as proof of concept of prospective highly biocompatible nanoprobes. - Highlights: • Biocompatible HAp/b-TCP nanoparticles with persistent luminescence are investigated. • Reducing step induced persistent luminescence. • Nanoparticles have been tested for the first time for in vivo imaging. • Persistent luminescence is observed after 10 min in vivo.

Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo.

Science.gov (United States)

Fröhlich, Eleonore

2015-01-01

Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.

Molecular imaging of small animals with dedicated PET tomographs

International Nuclear Information System (INIS)

Chatziioannou, A.F.

2002-01-01

Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology. (orig.)

In-vivo laser induced urethral stricture animal model for investigating the potential of LDR-brachytherapy

Science.gov (United States)

Sroka, Ronald; Lellig, Katja; Bader, Markus; Stief, Christian; Weidlich, Patrick; Wechsel, G.; Assmann, Walter; Becker, R.; Fedorova, O.; Khoder, Wael

2015-02-01

Purpose: Treatment of urethral strictures is a major challenge in urology. For investigation of different treatment methods an animal model was developed by reproducible induction of urethral strictures in rabbits to mimic the human clinical situation. By means of this model the potential of endoluminal LDR brachytherapy using β-irradiation as prophylaxis of recurrent urethral strictures investigated. Material and Methods: A circumferential urethral stricture was induced by energy deposition using laser light application (wavelength λ=1470 nm, 10 W, 10 s, applied energy 100 J) in the posterior urethra of anaesthetized New Zealand White male rabbits. The radial light emitting fiber was introduced by means of a children resectoscope (14F). The grade of urethral stricture was evaluated in 18 rabbits using videourethroscopy and urethrography at day 28 after stricture induction. An innovative catheter was developed based on a β-irradiation emitting foil containing 32P, which was wrapped around the application system. Two main groups (each n=18) were separated. The "internal urethrotomy group" received after 28days of stricture induction immediately after surgical urethrotomy of the stricture the radioactive catheter for one week in a randomized, controlled and blinded manner. There were 3 subgroups with 6 animals each receiving 0 Gy, 15 Gy and 30 Gy. In contrast animals from the "De Nuovo group" received directly after the stricture induction (day 0) the radioactive catheter also for the duration of one week divided into the same dose subgroups. In order to determine the radiation tolerance of the urethral mucosa, additional animals without any stricture induction received a radioactive catheter applying a total dose of 30 Gy (n=2) and 15 Gy (n=1). Cystourethrography and endoscopic examination of urethra were performed on all operation days for monitoring treatment progress. Based on these investigation a classification of the stricture size was performed and

An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles

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Prakash Gangadaran

2018-02-01

Full Text Available Extracellular vesicles (EVs are currently being considered as promising drug delivery vehicles. EVs are naturally occurring vesicles that exhibit many characteristics favorable to serve as drug delivery vehicles. In addition, EVs have inherent properties for treatment of cancers and other diseases. For research and clinical translation of use of EVs as drug delivery vehicles, in vivo tracking of EVs is essential. The latest molecular imaging techniques enable the tracking of EVs in living animals. However, each molecular imaging technique has its certain advantages and limitations for the in vivo imaging of EVs; therefore, understanding the molecular imaging techniques is essential to select the most appropriate imaging technology to achieve the desired imaging goal. In this review, we summarize the characteristics of EVs as drug delivery vehicles and the molecular imaging techniques used in visualizing and monitoring EVs in in vivo environments. Furthermore, we provide a perceptual vision of EVs as drug delivery vehicles and in vivo monitoring of EVs using molecular imaging technologies.

Preliminary studies with (/sup 18/F)haloperidol: a radioligand for in vivo studies of the dopamine receptors

Energy Technology Data Exchange (ETDEWEB)

Tewson, T J; Raichle, M E; Welch, M J [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

1980-06-16

The authors report a synthesis of (/sup 18/F)haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system.

Engineering Cell Fate for Tissue Regeneration by In Vivo Transdifferentiation.

Science.gov (United States)

de Lázaro, I; Kostarelos, K

2016-02-01

Changes in cell identity occur in adult mammalian organisms but are rare and often linked to disease. Research in the last few decades has thrown light on how to manipulate cell fate, but the conversion of a particular cell type into another within a living organism (also termed in vivo transdifferentiation) has only been recently achieved in a limited number of tissues. Although the therapeutic promise of this strategy for tissue regeneration and repair is exciting, important efficacy and safety concerns will need to be addressed before it becomes a reality in the clinical practice. Here, we review the most relevant in vivo transdifferentiation studies in adult mammalian animal models, offering a critical assessment of this potentially powerful strategy for regenerative medicine.

In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study

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Tiing Yee Siow

2013-01-01

Full Text Available 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP is a neurotoxin commonly used to produce an animal model of Parkinson’s disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO synthase- (nNOS- derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess in vivo due to its extremely short biological half-life, and so in vivo evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, in vivo localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI, intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first in vivo evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.

Prebiotics from Marine Macroalgae for Human and Animal Health Applications

Science.gov (United States)

O’Sullivan, Laurie; Murphy, Brian; McLoughlin, Peter; Duggan, Patrick; Lawlor, Peadar G.; Hughes, Helen; Gardiner, Gillian E.

2010-01-01

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date. PMID:20714423

Evaluation of photon-absorptiometry for determination of bone mineral content in experimental animals

International Nuclear Information System (INIS)

Krasznai, I.; Szathmary, M.; Horvath, Cs.; Hollo, G.; Fabu, G.

1994-01-01

Instruments commonly used for determination of bone mineral content in human were evaluated for their use in small laboratory animals. By measuring bone phantoms and rat femurs in vitro, authors found 0.015 and 0.034 g/cm sensitivity for (SPA) and (DEXA) methods, respectively. High reproducibility was obtained, with values of relative standard deviations being <2 and approximately 4% for SPA and DEXA, respectively. Both techniques were found suitable for determination of bone mineral content of laboratory animals, but DEXA is suggested as the preferred method for evaluations under in vivo circumstances. (N.T.)

Continuous passive motion and physical therapy (CPM) versus physical therapy (PT) versus delayed physical therapy (DPT) after surgical release for elbow contractures; a study protocol for a prospective randomized controlled trial.

Science.gov (United States)

Viveen, Jetske; Doornberg, Job N; Kodde, Izaak F; Goossens, Pjotr; Koenraadt, Koen L M; The, Bertram; Eygendaal, Denise

2017-11-22

The elbow is prone to stiffness after trauma. To regain functional elbow motion several conservative- and surgical treatment options are available. Conservative treatment includes physical therapy, intra-articular injections with corticosteroids and a static progressive or dynamic splinting program. If conservative treatment fails, an operative release of the posttraumatic stiff elbow is often performed. The best Evidence-Based rehabilitation protocol for patients after an operative release is unknown to date and differs per surgeon, hospital and country. Options include early- or delayed motion supervised by a physical therapist, immediate continuous passive motion (CPM), (night) splinting and a static progressive or dynamic splinting program. The SET-Study (Stiff Elbow Trial) is a single-centre, prospective, randomized controlled trial. The primary objective of this study is to compare the active Range of Motion (ROM) (flexion arc and rotational arc) twelve months after surgery between three groups. The first group will receive in-hospital CPM in combination with early motion Physical Therapy (PT) supervised by a physical therapist, the second group will receive only in-hospital early motion PT supervised by a physical therapist and the third group will receive outpatient supervised PT from postoperative day seven till ten. Secondary outcome measures will be Patient Reported Outcome Measures (PROMs) including the Mayo Elbow Performance Score (MEPS), the Oxford Elbow Score (OES), the quick Disabilities of Arm, Shoulder and Hand (qDASH) score, Visual Analogue pain Scale in rest and activity (VAS), Pain Catastrophizing Scale (PCS), the Short Form (SF)-36, the Centre for Epidemiological Studies Depression Scale Revised (CESD-R) and the Work Rehabilitation Questionnaire (WORQ) for the upper limb. A successful completion of this trial will provide evidence on the best rehabilitation protocol in order to (re)gain optimal motion after surgical release of the stiff elbow

Calorie Restriction Effect of Heat-Processed Onion Extract (ONI Using In Vitro and In Vivo Animal Models

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Yu-Ri Kang

2018-03-01

Full Text Available Onion (Allium cepa L. is widely consumed as food or medicinal plant due to its well-defined health benefits. The antioxidant and antihyperlipidemic effects of onion and its extracts have been reported well. However, very limited information on anti-hyperglycemic effect is available in processed onion extracts. In our previous study, we reported that Amadori rearrangement compounds (ARCs produced by heat-processing in Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. To prove the enhancement of anti-hyperglycemic effect and ARCs content by heat-processing in onion extract, a correlation between the anti-hyperglycemic activity and the total content of ARCs of heat-processed onion extract (ONI was investigated. ONI has a high content of ARCs and had high rat small intestinal sucrase inhibitory activity (0.34 ± 0.03 mg/mL, IC50 relevant for the potential management of postprandial hyperglycemia. The effect of ONI on the postprandial blood glucose increase was investigated in Sprague Dawley (SD rats fed on sucrose or starch meals. The maximum blood glucose levels (Cmax of heat-processed onion extract were significantly decreased by about 8.7% (from 188.60 ± 5.37 to 172.27 ± 3.96, p < 0.001 and 14.2% (from 204.04 ± 8.73 to 175.13 ± 14.09, p < 0.01 in sucrose and starch loading tests, respectively. These results indicate that ARCs in onion extract produced by heat-processing have anti-diabetic effect by suppressing carbohydrate absorption via inhibition of intestinal sucrase, thereby reducing the postprandial increase of blood glucose. Therefore, enhancement of ARCs in onion by heat-processing might be a good strategy for the development of the new product on the management of hyperglycemia.

Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

Science.gov (United States)

Siebelt, Michiel; Korthagen, Nicoline; Wei, Wu; Groen, Harald; Bastiaansen-Jenniskens, Yvonne; Müller, Christina; Waarsing, Jan Hendrik; de Jong, Marion; Weinans, Harrie

2015-12-05

Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRβ(+) macrophages. Furthermore

RECOVERY IN VIVO OF NONCULTURABLE SUBPOPULATION OF SALMONELLA ENTERICA

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Yudin I.P.

2015-12-01

Full Text Available Introduction. As one of mesophilic, easily cultivated species of pathogenic bacteria, Salmonella enterica transformed into viable but nonculturable (VNC state in response to environmental stresses, including action of biocides. The cells in this state, preserve the integrity of membranes and metabolism of some, but not detected by conventional methods of cultivation. Some researchers suggest that the evolutionary significance of this phenomenon is part of an adaptive response aimed at long-term survival of bacteria in adverse conditions; others argue that it is the result of stochastic cellular damage, in which nonculturable cells are in a state of gradual death. In any case, the phenomenon of existence VNC pathogens if they retain the ability to restore its growth in vivo is a significant problem in medicine, pharmaceutical, veterinary, food industry. VNC subpopulation of S. enterica was obtained under action of ethanol. In this paper was investigated in vivo resuscitation VNC S. enterica using intraperitoneal injection of mice. Materials and methods. Obtaining of stressful S. enterica populations. Bacteria were grown to exponential phase in broth Luria–Bertani (LB. To 1.0 ml sample suspension diluted to 1.5 × 106 cells/ml was added 1.0 ml of ethanol at a concentration of 40 % (v/v. After exposure of 10 to 600 minutes in the suspension were added 8.0 ml of phosphate buffered saline (FBS, washed by centrifugation (4500 g for 5 minutes and serially diluted at a ratio of 1:10 (v/v samples were stained with LIVE/DEAD BacLight (produced by "Invitrogen", USA, filtrated on membrane filters for fluorescence microscopy and parallel plated on LB agar cup to determine colony-forming units (CFU per ml. In vivo resuscitation VNC S. enterica was made following way. Three groups of animals were inoculated by intraperitoneal injection: 1 103 culturable cells (0.1 ml suspension containing 104 CFU / ml; 2 103 VNC cells (0.1 ml suspension containing 104 cells

Growth Performance, Haematological Indices and Cost Benefits of ...

African Journals Online (AJOL)

Lenovo pc

2College of Animal Science and Livestock Production ... composition of CPM and diets used were determined using standard procedures. ... It was concluded that cassava peel meal can totally replace maize with or without enzyme ... In Nigeria, the livestock sector has not ... livestock for promoting health and economy of.

Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

International Nuclear Information System (INIS)

Delzescaux, T.

2006-01-01

Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals (μ-CT, μ-MRI and μ-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, μ-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([ 14 C]Deoxyglucose for cerebral glucose metabolism, [ 14 C]leucine for cerebral protein synthesis [ 14 C]iodoantipyrine for cerebral blood flow), as well as the microscopic range of

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

Science.gov (United States)

Gandhi, Gopalsamy Rajiv; Santos, Victor Santana; Denadai, Marina; da Silva Calisto, Valdete Kaliane; de Souza Siqueira Quintans, Jullyana; de Oliveira E Silva, Ana Mara; de Souza Araújo, Adriano Antunes; Narain, Narendra; Cuevas, Luis Eduardo; Júnior, Lucindo José Quintans; Gurgel, Ricardo Queiroz

2017-08-01

Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study

International Nuclear Information System (INIS)

Mahmoud, Ahmed M; Ding, Xuan; Dutta, Debaditya; Kim, Kang; Singh, Vijay P

2014-01-01

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5–14 MHz) for both imaging and heating and a high-frequency (13–24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ∼3 s and ∼9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (−0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (−0.124�

Discussion on the establishment of blood glucose fluctuation animal models

OpenAIRE

Chun-Liu Gai; Jing-Ru Zhao; Xiao-Long Chen

2014-01-01

AIM: To provide the experimental basis for the in vivo study of blood glucose fluctuation injury mechanism, through intraperitoneal injection of glucose to establish blood glucose fluctuation animal models and to simulate blood glucose fluctuation of patients with diabetes.METHODS: Rats were randomly divided into four groups: normal control group(NC), normal fluctuation group(NF), diabetes mellitus group(DM)and diabetes fluctuation group(DF). Diabetic models were induced through intraperitone...

In Vivo Pattern Classification of Ingestive Behavior in Ruminants Using FBG Sensors and Machine Learning

OpenAIRE

Pegorini, Vinicius; Karam, Leandro Zen; Pitta, Christiano Santos Rocha; Cardoso, Rafael; da Silva, Jean Carlos Cardozo; Kalinowski, Hypolito Jos?; Ribeiro, Richardson; Bertotti, F?bio Luiz; Assmann, Tangriani Simioni

2015-01-01

Pattern classification of ingestive behavior in grazing animals has extreme importance in studies related to animal nutrition, growth and health. In this paper, a system to classify chewing patterns of ruminants in in vivo experiments is developed. The proposal is based on data collected by optical fiber Bragg grating sensors (FBG) that are processed by machine learning techniques. The FBG sensors measure the biomechanical strain during jaw movements, and a decision tree is responsible for th...

Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

Science.gov (United States)

2013-01-01

Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

Analysis of Endothelial Adherence of Bartonella henselae and Acinetobacter baumannii Using a Dynamic Human Ex Vivo Infection Model

OpenAIRE

Weidensdorfer, Marko; Chae, Ju Ik; Makobe, Celestine; Stahl, Julia; Averhoff, Beate; Müller, Volker; Schürmann, Christoph; Brandes, Ralf P.; Wilharm, Gottfried; Ballhorn, Wibke; Christ, Sara; Linke, Dirk; Fischer, Doris; Göttig, Stephan; Kempf, Volkhard A. J.

2016-01-01

Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome...

Pre-clinical research in small animals using radiotherapy technology--a bidirectional translational approach.

Science.gov (United States)

Tillner, Falk; Thute, Prasad; Bütof, Rebecca; Krause, Mechthild; Enghardt, Wolfgang

2014-12-01

For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained. Copyright © 2014. Published by Elsevier GmbH.

A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

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Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

2011-01-01

Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

Varenicline increases in vivo striatal dopamine D2/3 receptor binding: an ultra-high-resolution pinhole [123I]IBZM SPECT study in rats

International Nuclear Information System (INIS)

Crunelle, Cleo L.; Wit, Tim C. de; Bruin, Kora de; Ramakers, Ruud M.; Have, Frans van der; Beekman, Freek J.; Brink, Wim van den; Booij, Jan

2012-01-01

Introduction: Ex vivo storage phosphor imaging rat studies reported increased brain dopamine D 2/3 receptor (DRD 2/3 ) availability following treatment with varenicline, a nicotinergic drug. However, ex vivo studies can only be performed using cross-sectional designs. Small-animal imaging offers the opportunity to perform serial assessments. We evaluated whether high-resolution pinhole single photon emission computed tomography (SPECT) imaging in rats was able to reproduce previous ex vivo findings. Methods: Rats were imaged for baseline striatal DRD 2/3 availability using ultra-high-resolution pinhole SPECT (U-SPECT-II) and [ 123 I]IBZM as a radiotracer, and randomized to varenicline (n=7; 2 mg/kg) or saline (n=7). Following 2 weeks of treatment, a second scan was acquired. Results: Significantly increased striatal DRD 2/3 availability was found following varenicline treatment compared to saline (time⁎treatment effect): posttreatment difference in binding potential between groups corrected for initial baseline differences was 2.039 (P=.022), indicating a large effect size (d=1.48). Conclusions: Ultra-high-resolution pinhole SPECT can be used to assess varenicline-induced changes in DRD 2/3 availability in small laboratory animals over time. Future small-animal studies should include imaging techniques to enable repeated within-subjects measurements and reduce the amount of animals.

In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model

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Umoh, Joseph U.; Sampaio, Arthur V.; Welch, Ian; Pitelka, Vasek; Goldberg, Harvey A.; Underhill, T. Michael; Holdsworth, David W.

2009-04-01

The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 µm. At 6 weeks, the BMC in control animals (4.37 ± 0.66 mg) was significantly lower (p small BMC changes in animals.

The weanling Yorkshire pig as an animal model for measuring percutaneous penetration

International Nuclear Information System (INIS)

Reifenrath, W.G.; Hawkins, G.S.

1986-01-01

Percutaneous penetration of compounds of varying lipid solubility was studied in three systems, in vivo with the data from weanling Yorkshire pigs compared to data reported for nine compounds in man, in vivo with the same nine compounds on either weanling Yorkshire pig skin or human skin grafted to athymic nude mice and in vitro with twelve compounds on weanling Yorkshire pig skin and human skin mounted on a skin penetration/evaporation apparatus. Correlations (P<0.05) were found between in vivo pig values and those reported for man (r=0.83), between values for human and pig skin grafted to nude mice (r=0.69) and between in vitro human and in vitro pig skin values (r=0.76). The in vitro skin penetration system provides a valid approximation of a chemical's penetration through human skin; therefore, the number of animals required to obtain such information is reduced

Contemporary Animal Models For Human Gene Therapy Applications.

Science.gov (United States)

Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Nelson, Everette Jacob Remington

2015-01-01

Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus

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Aysen eGargili

2013-08-01

Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and transmission of CCHFV in nature, comparatively little is known of CCHFV-tick interactions. This is mostly due to the fact that establishing tick colonies is laborious, and working with CCHFV requires a biosafety level 4 laboratory (BSL4 in many countries. Nonetheless, an in vivo transmission model is essential to understand the epidemiology of the transmission cycle of CCHFV. In addition, important parameters such as vectorial capacity of tick species, levels of infection in the host necessary to infect the tick, and aspects of virus transmission by tick bite including the influence of tick saliva, cannot be investigated any other way. Here, we evaluate the influence of different laboratory animal species as hosts supporting the life cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host of choice for the maintenance of the uninfected colonies due to high larval attachment rates, shorter larval-nymphal feeding times, higher nymphal molting rates, high egg hatching rates and higher conversion efficiency index. Furthermore, we describe the successful establishment of an in vivo transmission model CCHFV in a BSL4 biocontainment setting using interferon knockout mice. This will give us a new tool to study the transmission and interaction of CCHFV with its tick vector.

Prospective Study of Surgical Decision-making Processes for Contralateral Prophylactic Mastectomy in Women With Breast Cancer.

Science.gov (United States)

Parker, Patricia A; Peterson, Susan K; Bedrosian, Isabelle; Crosby, Melissa A; Shen, Yu; Black, Dalliah M; Babiera, Gildy; Kuerer, Henry M; Ying, Jun; Dong, Wenli; Cantor, Scott B; Brewster, Abenaa M

2016-01-01

We prospectively examined the psychosocial predictors and the decision-making process regarding contralateral prophylactic mastectomy (CPM) among women with sporadic breast cancer. Increasing numbers of women with breast cancer are seeking CPM. Data are limited about the surgical decision-making process and the psychosocial factors that influence interest in CPM. Women with early-stage unilateral breast cancer (n = 117) were recruited before their first surgical visit at MD Anderson and completed questionnaires assessing knowledge of and interest in CPM and associated psychosocial factors. After the appointment, women and their surgeons completed questions about the extent that various surgical options (including CPM) were discussed; also, the women rated their perceived likelihood of having CPM and the surgeons rated the appropriateness of CPM. Before their first visit, 50% of women were moderately to extremely interested in CPM and 12 (10%) of women had CPM at the time of their primary breast cancer surgery. Less knowledge about breast cancer (P = 0.02) and greater cancer worry (P = 0.03) predicted interest in CPM. Greater cancer worry predicted who had CPM (P = 0.02). Interest in CPM before surgical visit and the likelihood of having CPM after the visit differed (P ≤ 0.001). Surgeons' rating of the appropriateness of CPM and the patient's reported likelihood of having CPM were not significantly different (P = 0.49). Interest in CPM is common among women with sporadic breast cancer. The informational and emotional aspects of CPM may affect the decision to have CPM and should be addressed when discussing surgical options.

High-throughput screen for novel antimicrobials using a whole animal infection model.

Science.gov (United States)

Moy, Terence I; Conery, Annie L; Larkins-Ford, Jonah; Wu, Gang; Mazitschek, Ralph; Casadei, Gabriele; Lewis, Kim; Carpenter, Anne E; Ausubel, Frederick M

2009-07-17

The nematode Caenorhabditis elegans is a unique whole animal model system for identifying small molecules with in vivo anti-infective properties. C. elegans can be infected with a broad range of human pathogens, including Enterococcus faecalis, an important human nosocomial pathogen. Here, we describe an automated, high-throughput screen of 37,200 compounds and natural product extracts for those that enhance survival of C. elegans infected with E. faecalis. Using a robot to dispense live, infected animals into 384-well plates and automated microscopy and image analysis, we identified 28 compounds and extracts not previously reported to have antimicrobial properties, including six structural classes that cure infected C. elegans animals but do not affect the growth of the pathogen in vitro, thus acting by a mechanism of action distinct from antibiotics currently in clinical use.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

Science.gov (United States)

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

Science.gov (United States)

Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

Acute In Vivo Response to an Alternative Implant for Urogynecology

Directory of Open Access Journals (Sweden)

Sabiniano Roman Regueros

2014-01-01

Full Text Available Purpose. To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI and pelvic organ prolapse (POP. Methods. A biodegradable scaffold was produced from poly-L-lactic acid (PLA using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. Results. Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. Conclusions. The acute in vivo response to an alternative implant (both with and without cells for the treatment of SUI and POP showed good acute integration into the host tissues.

In vivo radiation sensitivity of glioblastoma multiforme

International Nuclear Information System (INIS)

Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

1995-01-01

Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF 2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD 50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD 50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD 50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD 50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 ± 13.1 Gy. The TCD 50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 ± 6.4. The difference between the average TCD 50 of GBM and SCC was not significant. The STS and CC xenografts had TCD 50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD 50 in vivo and the SF 2 or D 0 in vitro. Conclusions: Our data on GBM xenografts showed a wide range of sensitivities to single dose

In vivo radiation sensitivity of glioblastoma multiforme

Energy Technology Data Exchange (ETDEWEB)

Taghian, Alphonse; Freeman, Jill; Suit, Herman; DuBois, Willem; Budach, Wilfried; Baumann, Michael

1995-04-30

Purpose: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF{sub 2} values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD{sub 50} (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD{sub 50} of the xenografts and the sensitivity of the corresponding cell lines in vitro. Methods and Materials: The TCD{sub 50} assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. Results: The TCD{sub 50} values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 {+-} 13.1 Gy. The TCD{sub 50} values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 {+-} 6.4. The difference between the average TCD{sub 50} of GBM and SCC was not significant. The STS and CC xenografts had TCD{sub 50} values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD{sub 50} in vivo and the SF{sub 2} or D{sub 0} in vitro. Conclusions: Our data on GBM

An automated robot arm system for small animal tissue biopsy under dual-image modality

International Nuclear Information System (INIS)

Huang, Y.H.; Wu, T.H.; Lin, M.H.; Yang, C.C.; Guo, W.Y.; Wang, Z.J.; Chen, C.L.; Lee, J.S.

2006-01-01

The ability to non-invasively monitor cell biology in vivo is one of the most important goals of molecular imaging. Imaging procedures could be inter-subject performed repeatedly at different investigating stages; thereby need not sacrifice small animals during the entire study period. Thus, the ultimate goal of this study was to design a stereotactic image-guided system for small animals and integrated it with an automatic robot arm for in vivo tissue biopsy analysis. The system was composed of three main parts, including one small animal stereotactic frame, one imaging-fusion software and an automatic robot arm system. The system has been thoroughly evaluated with three components; the robot position accuracy was 0.05±0.02 mm, the image registration accuracy was 0.37±0.18 mm and the system integration was satisfactorily within 1.20±0.39 mm of error. From these results, the system demonstrated sufficient accuracy to guide the micro-injector from the planned delivery routes into practice. The entire system accuracy was limited by the image fusion and orientation procedures, due to its nature of the blurred PET imaging obtained from the small objects. The primary improvement is to acquire as higher resolution as possible the fused imaging for localizing the targets in the future

Animal welfare: an animal science approach.

Science.gov (United States)

Koknaroglu, H; Akunal, T

2013-12-01

Increasing world population and demand for animal-derived protein puts pressure on animal production to meet this demand. For this purpose animal breeding efforts were conducted to obtain the maximum yield that the genetic makeup of the animals permits. Under the influence of economics which is the driving force behind animal production, animal farming became more concentrated and controlled which resulted in rearing animals under confinement. Since more attention was given on economics and yield per animal, animal welfare and behavior were neglected. Animal welfare which can be defined as providing environmental conditions in which animals can display all their natural behaviors in nature started gaining importance in recent years. This does not necessarily mean that animals provided with good management practices would have better welfare conditions as some animals may be distressed even though they are in good environmental conditions. Consumers are willing to pay more for welfare-friendly products (e.g.: free range vs caged egg) and this will change the animal production practices in the future. Thus animal scientists will have to adapt themselves for the changing animal welfare rules and regulations that differ for farm animal species and countries. In this review paper, animal welfare is discussed from an animal science standpoint. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

In vivo serial sampling of epididymal sperm in mice.

Science.gov (United States)

Del Val, Gonzalo Moreno; Robledano, Patricia Muñoz

2013-07-01

This study was undertaken to refine the techniques of in vivo collection of sperm in the mouse. The principal objective was to offer a viable, safe and reliable method for serial collection of in vivo epididimary sperm through the direct puncture of the epididymis. Six C57Bl/6J males were subjected to the whole experiment. First we obtain a sperm sample of the right epididymis, and perform a vasectomy on the left side. This sample was used in an in vitro fertilization (IVF) experiment while the males were individually housed for 10 days to let them recover from the surgery, and then their fertility was tested with natural matings until we obtained a litter of each one. After that, the animals were subjected another time to the same process (sampling, recover and natural mating). The results of these experiments were a fertilization average value of 56.7%, and that all the males had a litter in the first month after the natural matings. This study documented the feasibility of the epididimary puncture technique to in vivo serial sampling of sperm in the mouse.

Evaluation of an ex vivo murine local lymph node assay: multiple endpoint comparison.

Science.gov (United States)

Piccotti, Joseph R; Knight, Stephanie A; Gillhouse, Kimberly; Lagattuta, Mark S; Bleavins, Michael R

2006-01-01

The local lymph node assay (LLNA) is used to assess the skin sensitization potential of chemicals. In the standard assay, mice are treated topically on the dorsum of both ears with test substance for 3 days. Following 2 days of rest, the initiation of the hypersensitivity response is evaluated by injecting (3)H-thymidine into a tail vein, and then measuring the levels of radioisotope incorporated into the DNA of lymph node cells draining the ears. In the current study, BALB/c mice were treated with the contact sensitizers hexylcinnamic aldehyde (HCA) and oxazolone, and the nonsensitizer methyl salicylate. The proliferative response of lymph node cells was evaluated in an ex vivo assay, in which isolated cells were cultured in vitro with (3)H-thymidine. Treatment of mice with HCA at 5-50% resulted in concentration-related increases in (3)H-thymidine incorporation, with stimulation indices ranging from 3 to 14. Low animal-to-animal variability was seen in three replicate assays testing HCA at 25%. As anticipated, the proliferative response induced by the potent sensitizer oxazolone at 0.25% was greater than HCA at all concentrations tested. Stimulation indices of 1.5 and 3 were seen in two independent experiments with methyl salicylate. These equivocal findings were likely due to the irritancy properties of the compound. Importantly, measuring ex vivo (3)H-thymidine incorporation was more sensitive than evaluating lymph node weight and cellularity, and in vitro bromodeoxyuridine incorporation. Furthermore, the results of the ex vivo LLNA were comparable to the standard assay. This study provided evidence that supports the use of an ex vivo LLNA for hazard assessment of contact hypersensitivity. Copyright 2006 John Wiley & Sons, Ltd.

Gas transport during in vitro and in vivo preclinical testing of inert gas therapies

Directory of Open Access Journals (Sweden)

Ira Katz

2016-01-01

Full Text Available New gas therapies using inert gases such as xenon and argon are being studied, which require in vitro and in vivo preclinical experiments. Examples of the kinetics of gas transport during such experiments are analyzed in this paper. Using analytical and numerical models, we analyze an in vitro experiment for gas transport to a 96 cell well plate and an in vivo delivery to a small animal chamber, where the key processes considered are the wash-in of test gas into an apparatus dead volume, the diffusion of test gas through the liquid media in a well of a cell test plate, and the pharmacokinetics in a rat. In the case of small animals in a chamber, the key variable controlling the kinetics is the chamber wash-in time constant that is a function of the chamber volume and the gas flow rate. For cells covered by a liquid media the diffusion of gas through the liquid media is the dominant mechanism, such that liquid depth and the gas diffusion constant are the key parameters. The key message from these analyses is that the transport of gas during preclinical experiments can be important in determining the true dose as experienced at the site of action in an animal or to a cell.

Establishment study of the in vivo imaging analysis with small animal imaging modalities for bio-durg development

International Nuclear Information System (INIS)

Jang, Beomsu; Park, Sanghyeon; Choi, Dae Seong; Park, Jeonghoon; Jung, Uhee; Lee, Yun Jong

2012-01-01

In this study, we established the image modalities (micro-PET, SPECT/CT) using the experimental animal (mouse) for the development of imaging assessment method for the bio-durg and extramural collaboration proposal. We examined the micro-SPECT/CT, PET imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and imaging study using the Siemens Inveon micro-multimodality system (SPECT/CT) and micro-PET with 99m Tc tricarbonyl bifunctional chelators and 18 F-clotrimazole derivative. SPECT imaging studies were performed with 99m Tc tricarbonyl BFCs. PET imaging study was performed with 18 F-clotrimazole derivatives. We performed the PET image study of 18 F-clotrimazole derivatives using U87MG tumor bearing mice. Also we tested the intramural and extramural collaboration using small animal imaging modalities and prepared the draft of extramural R and D operation manual for small animal imaging modalities and the experimental animal imaging facility. These research results can be utilized as a basic image study protocols and data for the image assessment of drugs including biological drug

New quantitative and multi-modal approach for in-vivo studies of small animals: coupling of the {beta}-microprobe with magnetic techniques and development of voxelized rat and mouse phantoms; Nouvelle approche multimodale et quantitative pour les etudes in vivo chez le petit animal: couplage de la {beta}-MicroProbe aux techniques magnetiques et developpement de fantomes de rat et de souris voxelises

Energy Technology Data Exchange (ETDEWEB)

Desbree, A

2005-09-15

For the last 15 years, animal models that mimic human disorders have become ubiquitous participants to understand biological mechanisms and human disorders and to evaluate new therapeutic approaches. The necessity to study these models in the course of time has stimulated the development of instruments dedicated to in vivo small animal studies. To further understand physiopathological processes, the current challenge is to couple simultaneously several of these methods. Given this context, the combination of the magnetic and radioactive techniques remains an exciting challenge since it is still limited by strict technical constraints. Therefore we propose to couple the magnetic techniques with the radiosensitive Beta-Microprobe, developed in the IPB group and which shown to be an elegant alternative to PET measurements. In this context, the thesis was dedicated to the study of the coupling feasibility from a physical point of view, by simulation and experimental characterizations. Then, the determination of a biological protocol was carried out on the basis of pharmacokinetic studies. The experiments have shown the possibility to use the probe for radioactive measurements under intense magnetic field simultaneously to anatomical images acquisitions. Simultaneously, we have sought to improve the quantification of the radioactive signal using a voxelized phantom of a rat brain. Finally, the emergence of transgenic models led us to reproduce pharmacokinetic studies for the mouse and to develop voxelized mouse phantoms. (author)

Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Directory of Open Access Journals (Sweden)

Ashkan Maccabi

Full Text Available Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E, long term shear modulus (η, and time constant (τ in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Science.gov (United States)

Maccabi, Ashkan; Shin, Andrew; Namiri, Nikan K; Bajwa, Neha; St John, Maie; Taylor, Zachary D; Grundfest, Warren; Saddik, George N

2018-01-01

Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research.

The role of the pharmaceutical animal health industry in post-marketing surveillance of resistance.

Science.gov (United States)

Lens, S

1993-06-01

The pharmaceutical animal health industry must be committed to the total life cycle of products, i.e. during both the pre- and post-marketing period. Support of antibacterial agents during the postmarketing period is not restricted to maintaining a well-established distribution and promotion system. Care has to be taken continuously to maintain and/or improve the quality, safety (for user, target animal and environment) and clinical efficacy. The pharmaceutical industry contributes to this by: 1. Introducing antibacterials in different animal species for the most effective disease condition only and by ensuring the veterinary profession is informed about relevant findings on: a. the mechanism of action; b. pharmacodynamic properties; c. pharmacokinetic properties (plasma, target tissue); d. clinical efficacy data and in vitro sensitivity data; e. valid species-specific MIC breakpoints; f. precise dose and treatment regime. 2. Updating on a regular basis on: a. new findings on the mechanism of action (in vitro and in vivo); b. the optimal use program in the light of changes in animal husbandry, farm management and epidemiology on national and international level; c. adjustment of species-specific MIC breakpoints when necessary. 3. Providing continuous information in collaboration with animal health laboratories about: a. clinical field surveillance for efficacy (national, international); b. in vitro sensitivity/resistance surveillance (national, international); c. use of in vitro data to support prediction of in vivo efficacy. Surveillance of resistance, in vitro, is therefore part of a package of information needed on a routine basis by the pharmaceutical industry to allow the best possible use of antibacterials and to minimize induction of resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

AAV2-mediated in vivo immune gene therapy of solid tumours

LENUS (Irish Health Repository)

Collins, Sara A

2010-12-20

Abstract Background Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy. Methods Immune-competent Balb\\/C or C57 mice bearing subcutaneous JBS fibrosarcoma or Lewis Lung Carcinoma (LLC) tumour xenografts respectively were treated by intra-tumoural administration of AAV2 vector encoding the immune up-regulating cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) and the co-stimulatory molecule B7-1 to subcutaneous tumours, either alone or in combination with intra-muscular (IM) delivery of AAV2 vector encoding Nk4 14 days prior to tumour induction. Tumour growth and survival was monitored for all animals. Cured animals were re-challenged with tumourigenic doses of the original tumour type. In vivo cytotoxicity assays were used to investigate establishment of cell-mediated responses in treated animals. Results AAV2-mediated GM-CSF, B7-1 treatment resulted in a significant reduction in tumour growth and an increase in survival in both tumour models. Cured animals were resistant to re-challenge, and induction of T cell mediated anti-tumour responses were demonstrated. Adoptive transfer of splenocytes to naïve animals prevented tumour establishment. Systemic production of Nk4 induced by intra-muscular (IM) delivery of Nk4 significantly reduced subcutaneous tumour growth. However, combination of Nk4 treatment with GM-CSF, B7-1 therapy reduced the efficacy of the immune therapy. Conclusions Overall, this study demonstrates the potential for in vivo AAV2 mediated immune gene therapy, and provides data on the inter-relationship between tumour

Animal health and production

International Nuclear Information System (INIS)

Kallfelz, F.A.; Lengemann, F.W.

1984-01-01

An outline review is presented of the use of radioisotopes and radiation in animal health and production research. Techniques covered are the qualitative localization of a radioisotope (static and dynamic measurements, detection procedures involving locating concentration sites of labelled toxins, parasites, abnormal blood cells, etc.), quantitative measurement of isotopes (absorption and excretion, transfer across membranes) comparator studies (determination of mass, volume or flow), isotope dilution and related studies (in vivo and in vitro applications, determination of total body red cell or plasma volume), dynamic systems (single compartmental systems such as rumen studies and the suckling lamb or calf, multiple exits from a compartment and multiple doses), stable isotopes and mass spectrometry, activation analysis and nuclear magnetic resonance, and the use of internal irradiation (sterile male technique, control of insects and parasites, production of attenuated vaccines etc.). (U.K.)

A dynamic real time in vivo and static ex vivo analysis of granulomonocytic cell migration in the collagen-induced arthritis model.

Directory of Open Access Journals (Sweden)

Ruth Byrne

Full Text Available Neutrophilic granulocytes and monocytes (granulomonocytic cells; GMC drive the inflammatory process at the earliest stages of rheumatoid arthritis (RA. The migratory behavior and functional properties of GMC within the synovial tissue are, however, only incompletely characterized. Here we have analyzed GMC in the murine collagen-induced arthritis (CIA model of RA using multi-photon real time in vivo microscopy together with ex vivo analysis of GMC in tissue sections.GMC were abundant as soon as clinical arthritis was apparent. GMC were motile and migrated randomly through the synovial tissue. In addition, we observed the frequent formation of cell clusters consisting of both neutrophilic granulocytes and monocytes that actively contributed to the inflammatory process of arthritis. Treatment of animals with a single dose of prednisolone reduced the mean velocity of cell migration and diminished the overall immigration of GMC.In summary, our study shows that the combined application of real time in vivo microscopy together with elaborate static post-mortem analysis of GMC enables the description of dynamic migratory characteristics of GMC together with their precise location in a complex anatomical environment. Moreover, this approach is sensitive enough to detect subtle therapeutic effects within a very short period of time.

Effects of chlorphentermine and phentermine on the pulmonary disposition of 5-hydroxytryptamine in the rat in vivo

International Nuclear Information System (INIS)

Morita, T.; Mehendale, H.M.

1983-01-01

This study was designed to examine whether chlorphentermine (CP) affects pulmonary disposition of 5-hydroxytryptamine (5-HT) in rat in vivo. Further, the effects of CP were compared with those of phentermine (P), the nonchlorinated congener. The right jugular vein and left carotid artery of male Sprague-Dawley rats were cannulated and fresh saline solution containing 150 micrograms indocyanine green and a mixture of labeled and unlabeled 5-HT was injected into the jugular vein, and arterial blood samples were collected for 20 s. In order to compare the effect of CP and P on pulmonary disposition of 5-HT, 2.6 nmol [ 14 C]-5-HT was employed for in vivo single-pass experiments. Each animal was used for 2 in vivo single-pass experiments. After the first experiment, which served as a control, animals received an indicated dose of CP or P, to commence the second ''drug-treated'' in vivo experiment. Pulmonary clearance of 5-HT was inhibited by prior administration of CP (1 mg/kg) by 42%, whereas at the highest dose (20 mg/kg) P inhibited 5-HT clearance by only 25%. Pulmonary accumulation of CP was greater than P at higher doses, and the inhibition of 5-HT clearance correlated with the pulmonary accumulation of these drugs. In addition to the in vivo demonstration of the CP inhibition of pulmonary clearance of 5-HT in the rat, these studies also demonstrate a higher affinity of the lung tissue for CP than for P and a greater propensity for the impairment of pulmonary 5-HT clearance

ANKARA İLİ DELİCE İLÇESİ KÖPRÜSÜNÜN CPM METODU İLE MÜHENDİSLİK KRİTERLERİNİN BELİRLENMESİ

Directory of Open Access Journals (Sweden)

M. Haluk ÇELİK

1995-02-01

Full Text Available Bu çalışmada malzeme olarak seçilmiş olan Ankara ili sınırları içinde yer alan, Delice İlçe Merkezi'nden geçmekte olan Koru deresinde ulaşımı sağlamak amacı ile 13.70 m mesnet açıklığında 8 m platform genişliğinde kirişli betonarme köprü inşaatının CPM-PERT metodu ile iyi bir planlama ve yapımında kullanılan minimum süre ve maliyeti hesaplanmaktır. Projede yapılan her hesapta en erken ve en geç tamamlanma süreleri göz önüne alınmıştır.

Optical coherence tomography imaging of cranial meninges post brain injury in vivo

Institute of Scientific and Technical Information of China (English)

Woo June Choi; Ruikang K.Wang

2017-01-01

We report a new application of optical coherence tomography (OCT) to investigate the cranial meninges in an animal model of brain injury in vivo.The injury is induced in a mouse due to skull thinning,in which the repeated and excessive drilling exerts mechanical stress on the mouse brain through the skull,resulting in acute and mild brain injury.Transcranial OCT imaging reveals an interesting virtual space between the cranial meningeal layers post skull thinning,which is gradually closed within hours.The finding suggests a promise of OCT as an effective tool to monitor the mechanical trauma in the small animal model of brain injury.

A Rugged Ultra-Wideband (UWB) Circular Planar Monopole for Multichannel Radar

Science.gov (United States)

2016-03-01

Introduction 1 2 Fundamental Design and Performance of a UWB- CPM 2 3 Introduction to the Vivaldi Antenna and Contrast to the UWB- CPM 3 4 Baseline UWB- CPM 7...5. First Revision of the UWB- CPM 12 6. Second Revision of the UWB- CPM 21 7. Second Revision UWB- CPM versus the Vivaldi 28 8. Summary and...return loss for the baseline UWB- CPM with and without a reflector ...........................................................................8 Fig. 6

Use of Transgenic and Mutant Animal Models in the Study of Heterocyclic Amine-induced Mutagenesis and Carcinogenesis

Science.gov (United States)

Dashwood, Roderick H.

2008-01-01

Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. During the past 5 years or so, HCAs have been tested in a number of novel in vivo murine models, including the following: lacZ, lacI, cII, c-myc/lacZ, rpsL, and gptΔ transgenics, XPA−/−, XPC−/−, Msh2+/−, Msh2−/− and p53+/− knock-outs, Apc mutant mice (ApcΔ716, Apc1638N, Apcmin), and A33ΔNβ-cat knock-in mice. Several of these models have provided insights into the mutation spectra induced in vivo by HCAs in target and non-target organs for tumorigenesis, as well as demonstrating enhanced susceptibility to HCA-induced tumors and preneoplastic lesions. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac. PMID:12542973

Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

Science.gov (United States)

Bazyar, Soha; Inscoe, Christina R.; O'Brian, E. Timothy; Zhou, Otto; Lee, Yueh Z.

2017-12-01

Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200-1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size  ≈  4  ×  10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM  =  246  ±  32 µm center-to-center  =  926  ±  23 µm peak-to-valley dose ratio  =  24.35  ±  2.10 collimator relative output factor  =  0.84  ±  0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP  =  glioblastoma B16-F10  =  melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p  film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.

Construction of In Vivo Fluorescent Imaging of Echinococcus granulosus in a Mouse Model.

Science.gov (United States)

Wang, Sibo; Yang, Tao; Zhang, Xuyong; Xia, Jie; Guo, Jun; Wang, Xiaoyi; Hou, Jixue; Zhang, Hongwei; Chen, Xueling; Wu, Xiangwei

2016-06-01

Human hydatid disease (cystic echinococcosis, CE) is a chronic parasitic infection caused by the larval stage of the cestode Echinococcus granulosus. As the disease mainly affects the liver, approximately 70% of all identified CE cases are detected in this organ. Optical molecular imaging (OMI), a noninvasive imaging technique, has never been used in vivo with the specific molecular markers of CE. Thus, we aimed to construct an in vivo fluorescent imaging mouse model of CE to locate and quantify the presence of the parasites within the liver noninvasively. Drug-treated protoscolices were monitored after marking by JC-1 dye in in vitro and in vivo studies. This work describes for the first time the successful construction of an in vivo model of E. granulosus in a small living experimental animal to achieve dynamic monitoring and observation of multiple time points of the infection course. Using this model, we quantified and analyzed labeled protoscolices based on the intensities of their red and green fluorescence. Interestingly, the ratio of red to green fluorescence intensity not only revealed the location of protoscolices but also determined the viability of the parasites in vivo and in vivo tests. The noninvasive imaging model proposed in this work will be further studied for long-term detection and observation and may potentially be widely utilized in susceptibility testing and therapeutic effect evaluation.

Direct evaluation of radiation damage in human hematopoietic progenitor cells in vivo

International Nuclear Information System (INIS)

Kyoizumi, Seishi; McCune, J.M.; Namikawa, Reiko

1994-01-01

We have developed techniques by which normal functional elements of human bone marrow can be implanted into immunodeficient C.B-17 scid/scid (SCID) mice. Afterward, long-term multilineage human hematopoiesis is sustained in vivo. We evaluated the effect of irradiation on the function of human bone marrow with this in vivo model. After whole-body X irradiation of the engrafted animals, it was determined that the D 0 value of human committed progenitor cells within the human marrow was 1.00 ± 0.09 (SEM) Gy for granulocyte-macrophage colony-forming units (CFU-GM) and 0.74 ± 0.12 Gy for erythroidburst-forming units (BFU-E). The effects of irradiation on the hematopoietic elements were reduced when the radioprotective agent WR-2721 was administered prior to irradiation. After low-dose irradiation, recovery of human granulocyte colony-stimulating factor (G-CSF). This small animal model may prove amenable for the analysis of the risk of the exposure of humans to irradiation as well as for the development of new modalities for the prevention and treatment of radiation-induced hematopoietic damage. 41 refs., 5 figs., 1 tab

Spermatogonial stem cells from domestic animals: progress and prospects.

Science.gov (United States)

Zheng, Yi; Zhang, Yaqing; Qu, Rongfeng; He, Ying; Tian, Xiue; Zeng, Wenxian

2014-03-01

Spermatogenesis, an elaborate and male-specific process in adult testes by which a number of spermatozoa are produced constantly for male fertility, relies on spermatogonial stem cells (SSCs). As a sub-population of undifferentiated spermatogonia, SSCs are capable of both self-renewal (to maintain sufficient quantities) and differentiation into mature spermatozoa. SSCs are able to convert to pluripotent stem cells during in vitro culture, thus they could function as substitutes for human embryonic stem cells without ethical issues. In addition, this process does not require exogenous transcription factors necessary to produce induced-pluripotent stem cells from somatic cells. Moreover, combining genetic engineering with germ cell transplantation would greatly facilitate the generation of transgenic animals. Since germ cell transplantation into infertile recipient testes was first established in 1994, in vivo and in vitro study and manipulation of SSCs in rodent testes have been progressing at a staggering rate. By contrast, their counterparts in domestic animals, despite the failure to reach a comparable level, still burgeoned and showed striking advances. This review outlines the recent progressions of characterization, isolation, in vitro propagation, and transplantation of spermatogonia/SSCs from domestic animals, thereby shedding light on future exploration of these cells with high value, as well as contributing to the development of reproductive technology for large animals.

Pluripotent stem cells and reprogrammed cells in farm animals.

Science.gov (United States)

Nowak-Imialek, Monika; Kues, Wilfried; Carnwath, Joseph W; Niemann, Heiner

2011-08-01

Pluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.

An in vivo technique for the measurement of bone blood flow in animals

International Nuclear Information System (INIS)

Rosenthal, M.S.; DeLuca, P.M. Jr.; Pearson, D.W.; Nickles, R.J.; Lehner, C.E.; Lanphier, E.H.

1987-01-01

A new technique to measure the in vivo clearance of 41 Ar from the bone mineral matrix is demonstrated following fast neutron production of 41 Ar in bone via the 44 Ca(n,α) reaction at 14.1 MeV. At the end of irradiation, the 41 Ar activity is assayed with a Ge(Li) detector where sequential gamma-ray spectra are taken. Following full-energy peak integration, background and dead time correction, the activity of 41 Ar as a function of time is determined. Results indicated that the Ar washout from bone in rats using this technique was approximately 16 ml (100 ml min) -1 and in agreement with other measurement techniques. For sheep the bone perfusion in the tibia was approximately 1.9+-0.2 ml (100 ml min) -1 . (author)

COMPANION ANIMALS SYMPOSIUM: Future aspects and perceptions of companion animal nutrition and sustainability.

Science.gov (United States)

Deng, P; Swanson, K S

2015-03-01

Companion animals play an important role in our lives and are now considered to be and treated as family members in a majority of households in the United States. Because of the high number of pets that now exist, an increasingly stronger pet-human bond, and the importance placed on health and longevity, the pet food industry has realized steady growth over the last few decades. Despite past successes and opportunities that exist in the future, there are also challenges that must be considered. This review will present a brief overview of the current pet food industry and address some of the key issues moving forward. In regards to companion animal research, recent advances and future needs in the areas of canine and feline metabolism, aging, clinical disease, and the gut microbiome using molecular and high-throughput assays; chemical, in vitro, and in vivo testing of feed ingredients; and innovative pet food processing methods is discussed. Training the future workforce for the pet food industry is also of great importance. Recent trends on student demographics and their species and careers of interest, changing animal science department curricula, and technology's impact on instruction are provided. Finally, the sustainability of the pet food industry is discussed. Focus was primarily placed on the disconnect that exists between opinions and trends of consumers and the nutrient recommendations for dogs and cats, the desire for increasing use of animal-based and human-grade products, the overfeeding of pets and the pet obesity crisis, and the issues that involve the evaluation of primary vs. secondary products in terms of sustainability. Moving forward, the pet food industry will need to anticipate and address challenges that arise, especially those pertaining to consumer expectations, the regulatory environment, and sustainability. Given the already strong and increasingly dynamic market for pet foods and supplies, an academic environment primed to supply a

Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

Energy Technology Data Exchange (ETDEWEB)

Delzescaux, T. [Service Hospitalier Frederic Joliot, Isotopic Imaging, 91 - Orsay (France)

2006-07-01

Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals ({mu}-CT, {mu}-MRI and {mu}-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, {mu}-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([{sup 14}C]Deoxyglucose for cerebral glucose metabolism, [{sup 14}C]leucine for cerebral protein synthesis [{sup 14}C]iodoantipyrine for cerebral blood flow), as well as

Microstructural imaging of human neocortex in vivo.

Science.gov (United States)

Edwards, Luke J; Kirilina, Evgeniya; Mohammadi, Siawoosh; Weiskopf, Nikolaus

2018-03-24

The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using R 1 maps as proxies for myelin content) and investigation of cortical iron deposition with age (using R 2 * maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and

A spinal cord window chamber model for in vivo longitudinal multimodal optical and acoustic imaging in a murine model.

Directory of Open Access Journals (Sweden)

Sarah A Figley

Full Text Available In vivo and direct imaging of the murine spinal cord and its vasculature using multimodal (optical and acoustic imaging techniques could significantly advance preclinical studies of the spinal cord. Such intrinsically high resolution and complementary imaging technologies could provide a powerful means of quantitatively monitoring changes in anatomy, structure, physiology and function of the living cord over time after traumatic injury, onset of disease, or therapeutic intervention. However, longitudinal in vivo imaging of the intact spinal cord in rodent models has been challenging, requiring repeated surgeries to expose the cord for imaging or sacrifice of animals at various time points for ex vivo tissue analysis. To address these limitations, we have developed an implantable spinal cord window chamber (SCWC device and procedures in mice for repeated multimodal intravital microscopic imaging of the cord and its vasculature in situ. We present methodology for using our SCWC to achieve spatially co-registered optical-acoustic imaging performed serially for up to four weeks, without damaging the cord or induction of locomotor deficits in implanted animals. To demonstrate the feasibility, we used the SCWC model to study the response of the normal spinal cord vasculature to ionizing radiation over time using white light and fluorescence microscopy combined with optical coherence tomography (OCT in vivo. In vivo power Doppler ultrasound and photoacoustics were used to directly visualize the cord and vascular structures and to measure hemoglobin oxygen saturation through the complete spinal cord, respectively. The model was also used for intravital imaging of spinal micrometastases resulting from primary brain tumor using fluorescence and bioluminescence imaging. Our SCWC model overcomes previous in vivo imaging challenges, and our data provide evidence of the broader utility of hybridized optical-acoustic imaging methods for obtaining

In vivo degradation of a new concept of magnesium-based rivet-screws in the minipig mandibular bone

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Schaller, Benoit [Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern (Switzerland); National Dental Centre Singapore, 168938 (Singapore); Saulacic, Nikola [Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern (Switzerland); Beck, Stefan, E-mail: SBECK2@its.jnj.com [Synthes Biomaterials, Eimattstr. 3, CH-4436 Oberdorf (Switzerland); Imwinkelried, Thomas [RMS Foundation, Bischmattstr. 12, CH-2544 Bettlach (Switzerland); Goh, Bee Tin [National Dental Centre Singapore, 168938 (Singapore); Nakahara, Ken [Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern (Switzerland); Hofstetter, Willy [Department of Clinical Research, University of Bern, CH-3010 Bern (Switzerland); Iizuka, Tateyuki [Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital and University of Bern, CH-3010 Bern (Switzerland)

2016-12-01

Self-tapping of magnesium screws in hard bone may be a challenge due to the limited torsional strength of magnesium alloys in comparison with titanium. To avoid screw failure upon implantation, the new concept of a rivet-screw was applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside were expanded inside drill holes of minipig mandibles. During the expansion with a hexagonal mandrel, the threads engaged the surrounding bone and the inside of the screw transformed into a hexagonal screw drive to allow further screwing in or out of the implant. The in vivo degradation of the magnesium implants and the performance of the used coating were studied in a human standard-sized animal model. Four magnesium alloy rivet-screws were implanted in each mandible of 12 minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy implants; another six received the uncoated magnesium alloy rivet-screws. Two further animals received one titanium rivet-screw each as control. In vivo radiologic examination was performed at one, four, and eight weeks. Euthanasia was performed for one group of seven animals (three animals with coated, three with uncoated magnesium alloy implants and one with titanium implant) at 12 weeks and for the remaining seven animals at 24 weeks. After euthanasia, micro-computed tomography and histological examination with histomorphometry were performed. Significantly less void formation as well as higher bone volume density (BV/TV) and bone-implant contact area (BIC) were measured around the coated implants compared to the uncoated ones. The surface coating was effective in delaying degradation despite plastic deformation. The results showed potential for further development of magnesium hollow coated screws for bone fixation. - Highlights: • A new concept of rivet screws as an alternative to classical screws is presented • The rivet screw concept was tested in vivo in a mini-pig pilot study • Un-coated and

In vivo degradation of a new concept of magnesium-based rivet-screws in the minipig mandibular bone

International Nuclear Information System (INIS)

Schaller, Benoit; Saulacic, Nikola; Beck, Stefan; Imwinkelried, Thomas; Goh, Bee Tin; Nakahara, Ken; Hofstetter, Willy; Iizuka, Tateyuki

2016-01-01

Self-tapping of magnesium screws in hard bone may be a challenge due to the limited torsional strength of magnesium alloys in comparison with titanium. To avoid screw failure upon implantation, the new concept of a rivet-screw was applied to a WE43 magnesium alloy. Hollow cylinders with threads on the outside were expanded inside drill holes of minipig mandibles. During the expansion with a hexagonal mandrel, the threads engaged the surrounding bone and the inside of the screw transformed into a hexagonal screw drive to allow further screwing in or out of the implant. The in vivo degradation of the magnesium implants and the performance of the used coating were studied in a human standard-sized animal model. Four magnesium alloy rivet-screws were implanted in each mandible of 12 minipigs. Six animals received the plasmaelectrolytically coated magnesium alloy implants; another six received the uncoated magnesium alloy rivet-screws. Two further animals received one titanium rivet-screw each as control. In vivo radiologic examination was performed at one, four, and eight weeks. Euthanasia was performed for one group of seven animals (three animals with coated, three with uncoated magnesium alloy implants and one with titanium implant) at 12 weeks and for the remaining seven animals at 24 weeks. After euthanasia, micro-computed tomography and histological examination with histomorphometry were performed. Significantly less void formation as well as higher bone volume density (BV/TV) and bone-implant contact area (BIC) were measured around the coated implants compared to the uncoated ones. The surface coating was effective in delaying degradation despite plastic deformation. The results showed potential for further development of magnesium hollow coated screws for bone fixation. - Highlights: • A new concept of rivet screws as an alternative to classical screws is presented • The rivet screw concept was tested in vivo in a mini-pig pilot study • Un-coated and

A novel orbital tissue expander (OTE): design, in vitro, and in vivo studies

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Lee, Elizabete; Tse, David; Pinchuk, Leonard; Acosta, Ana C.; Martin, John B.; Davis, Stewart B.; Hernandez, Eleut; Yamamoto, Hideo; Denham, David B.; Dubovy, Sander; Parel, Jean-Marie

2006-02-01

Purpose: To assess the efficacy of a novel orbital tissue expander (OTE) in treating congenital anophthalmic and microphthalmic infants. Methods: The OTE implant is an inflatable (0.5 to >6cc) silicone rubber globe sliding on a titanium T-shaped bone plate secured to the temporal bone with 1mm titanium screws. In vitro testing was performed to assess injection volume versus diameter measurements to determine consistency between devices, flex fatigue for durability of the implants when compressed, weight change in isotonic saline at 37°C to mimic human body temperature, seal durability by puncturing the globe numerous times while inflating, capacity before rupture to determine the maximum amount of saline it is able to contain, and effective sterilization. Ex-vivo testing was performed for adjustments prior to in vivo study. An OTE was then implanted in five 2-week old kittens (OS only) and inflated in 0.5cc increments. Three control animals received enucleation alone. All 8 animals were followed for 18 weeks and underwent euthanasia for morphological and histopathological analysis. Results: In vitro testing confirmed a effects in the normal maturation, weight gain, and food intake of the cats. Light microscopy showed no signs of foreign body reaction. Pictures of the implants were obtained by using a shadow-photogrammetry system to compare the explanted OTE with the OD control eye. Conclusion: In vitro and in vivo studies show the implant's potential to safely treat anophthalmic and microphthalmic infants.

Animal models of cardiac cachexia.

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Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

2016-09-15

Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiovascular Imaging: What Have We Learned From Animal Models?

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Arnoldo eSantos

2015-10-01

Full Text Available Cardiovascular imaging has become an indispensable tool for patient diagnosis and follow up. Probably the wide clinical applications of imaging are due to the possibility of a detailed and high quality description and quantification of cardiovascular system structure and function. Also phenomena that involve complex physiological mechanisms and biochemical pathways, such as inflammation and ischemia, can be visualized in a nondestructive way. The widespread use and evolution of imaging would not have been possible without animal studies. Animal models have allowed for instance, i the technical development of different imaging tools, ii to test hypothesis generated from human studies and finally, iii to evaluate the translational relevance assessment of in vitro and ex-vivo results. In this review, we will critically describe the contribution of animal models to the use of biomedical imaging in cardiovascular medicine. We will discuss the characteristics of the most frequent models used in/for imaging studies. We will cover the major findings of animal studies focused in the cardiovascular use of the repeatedly used imaging techniques in clinical practice and experimental studies. We will also describe the physiological findings and/or learning processes for imaging applications coming from models of the most common cardiovascular diseases. In these diseases, imaging research using animals has allowed the study of aspects such as: ventricular size, shape, global function and wall thickening, local myocardial function, myocardial perfusion, metabolism and energetic assessment, infarct quantification, vascular lesion characterization, myocardial fiber structure, and myocardial calcium uptake. Finally we will discuss the limitations and future of imaging research with animal models.

Real-time in vivo detection of biomaterial-induced reactive oxygen species.

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Liu, Wendy F; Ma, Minglin; Bratlie, Kaitlin M; Dang, Tram T; Langer, Robert; Anderson, Daniel G

2011-03-01

The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to subcutaneously-implanted materials in live animals. We compared the real-time generation of ROS in response to two representative materials, polystyrene and alginate, over the course of 28 days. High levels of ROS were observed near polystyrene, but not alginate implants, and persisted throughout the course of 28 days. Histological analysis revealed that high levels of ROS correlated not only with the presence of phagocytic cells at early timepoints, but also fibrosis at later timepoints, suggesting that ROS may be involved in both the acute and chronic phase of the foreign body response. These data are the first in vivo demonstration of ROS generation in response to implanted materials, and describe a novel technique to evaluate the host response. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Versatile Vector for In Vivo Monitoring of Type I Interferon Induction and Signaling.

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Estanislao Nistal-Villan

Full Text Available Development of reporter systems for in vivo examination of IFN-β induction or signaling of type I interferon (IFN-I pathways is of great interest in order to characterize biological responses to different inducers such as viral infections. Several reporter mice have been developed to monitor the induction of both pathways in response to different agonists. However, alternative strategies that do not require transgenic mice breeding have to date not been reported. In addition, detection of these pathways in vivo in animal species other than mice has not yet been addressed. Herein we describe a simple method based on the use of an adeno-associated viral vector (AAV8-3xIRF-ISRE-Luc containing an IFN-β induction and signaling-sensitive promoter sequence controlling the expression of the reporter gene luciferase. This vector is valid for monitoring IFN-I responses in vivo elicited by diverse stimuli in different organs. Intravenous administration of the vector in C57BL/6 mice and Syrian hamsters was able to detect activation of the IFN pathway in the liver upon systemic treatment with different pro-inflammatory agents and infection with Newcastle disease virus (NDV. In addition, intranasal instillation of AAV8-3xIRF-ISRE-Luc showed a rapid and transient IFN-I response in the respiratory tract of mice infected with the influenza A/PR8/34 virus lacking the NS1 protein. In comparison, this response was delayed and exacerbated in mice infected with influenza A/PR/8 wild type virus. In conclusion, the AAV8-3xIRF-ISRE-Luc vector offers the possibility of detecting IFN-I activation in response to different stimuli and in different animal models with no need for reporter transgenic animals.

Bioethical Problems: Animal Welfare, Animal Rights.

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March, B. E.

1984-01-01

Discusses various bioethical issues and problems related to animal welfare and animal rights. Areas examined include: Aristotelian views; animal welfare legislation; Darwin and evolutionary theory; animal and human behavior; and vegetarianism. A 14-point universal declaration of the rights of animals is included. (JN)

In vivo assessment of 111In-labeled hematoporphyrin derivative in breast tumor-bearing animals

International Nuclear Information System (INIS)

Wong, D.W.; Mandal, Ashis; Brown, Jerry; Reese, I.C.; Siegler, Richard; Hyman, Shigeyo

1989-01-01

The biological behavior of 111 In-labeled HPD has been investigated in tumor-bearing animals. Mice mammary adenocarcinomas and 7,12-dimethylbenz(a)anthracine induced breast tumors in Sprague-Dawley female rats were clearly visualized by 111 In-HPD nuclear scintigraphy. Optimal scans were obtained after a 48 h delay. In normal and tumor-bearing animals, the highest uptake of 111 In-HPD 72 h post-injection was found in the liver, the spleen and the kidneys. Depending on the size and the extent of necrosis, the uptake of 111 In-HPD by malignant breast tumors varied from 2.5% injected dose (ID) in mice to 1% ID in rats. Benign breast tumor uptake of 111 In-HPD was less than 1% ID. No significant amount of the radiopharmaceutical was found in pulmonary abscesses and abdominal cysts. Scintigrams of these infectious or inflammatory lesions were normal. Malignant tumor to blood, heart and lung ratios averaged 50:1, 10:1 and 3:1 respectively. Tumor to brain ratio ranged from 72 to 444:1. (author)

MicroRNA-based Therapy in Animal Models of Selected Gastrointestinal Cancers

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Jana Merhautova

2016-09-01

Full Text Available Gastrointestinal cancer accounts for the 20 most frequent cancer diseases worldwide and there is a constant urge to bring new therapeutics with new mechanism of action into the clinical practice. Quantity of in vitro and in vivo evidences indicate, that exogenous change in pathologically imbalanced microRNAs (miRNAs is capable of transforming the cancer cell phenotype. This review analyzed preclinical miRNA-based therapy attempts in animal models of gastric, pancreatic, gallbladder, and colorectal cancer. From more than 400 original articles, 26 was found to assess the effect of miRNA mimics, precursors, expression vectors, or inhibitors administered locally or systemically being an approach with relatively high translational potential. We have focused on mapping available information on animal model used (animal strain, cell line, xenograft method, pharmacological aspects (oligonucleotide chemistry, delivery system, posology, route of administration and toxicology assessments. We also summarize findings in the field pharmacokinetics and toxicity of miRNA-based therapy.□

Scalable electrophysiology in intact small animals with nanoscale suspended electrode arrays

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Gonzales, Daniel L.; Badhiwala, Krishna N.; Vercosa, Daniel G.; Avants, Benjamin W.; Liu, Zheng; Zhong, Weiwei; Robinson, Jacob T.

2017-07-01

Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires invasive dissections and is low-throughput. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans. We can also use nano-SPEARs to record from multiple animals in parallel and even from other species, such as Hydra littoralis. Furthermore, we use nano-SPEARs to establish the first electrophysiological phenotypes for C. elegans models for amyotrophic lateral sclerosis and Parkinson's disease, and show a partial rescue of the Parkinson's phenotype through drug treatment. These results demonstrate that nano-SPEARs provide the core technology for microchips that enable scalable, in vivo studies of neurobiology and neurological diseases.

Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

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Veidal Sanne Skovgård

2012-12-01

Full Text Available Abstract Background Accumulation of extracellular matrix (ECM and increased matrix metalloproteinase (MMP activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M, known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model. Findings In vivo: Rats were treated for 8 weeks with CCl4/Intralipid. Liver slices were cultured for 48 hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control or treated with IBMX (phosphodiesterase inhibitor. Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p 4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals. Conclusions We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

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Andrejka, Laura; Wen, Hong; Ashton, Jonathan; Grant, Megan; Iori, Kevin; Wang, Amy; Manak, J. Robert; Lipsick, Joseph S.

2011-01-01

Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within the same highly conserved multiprotein transcriptional repressor complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as Drosophila Rb E2F and Myb-interacting proteins (dREAM). We now report that the animal-specific C terminus of Drosophila Myb but not the more highly conserved N-terminal DNA-binding domain is necessary and sufficient for (i) adult viability, (ii) proper localization to chromosomes in vivo, (iii) regulation of gene expression in vivo, and (iv) interaction with the highly conserved core of the MuvB/dREAM transcriptional repressor complex. In addition, we have identified a conserved peptide motif that is required for this interaction. Our results imply that an ancient function of Myb in regulating G2/M genes in both plants and animals appears to have been transferred from the DNA-binding domain to the animal-specific C-terminal domain. Increased expression of B-MYB/MYBL2, the human ortholog of Drosophila Myb, correlates with poor prognosis in human patients with breast cancer. Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics. PMID:21969598

In vivo quantitative assessment of myocardial structure, function, perfusion and viability using cardiac micro-computed tomography

NARCIS (Netherlands)

E.D. van Deel (Elza); Y. Ridwan (Yanto); van Vliet, J.N. (J. Nicole); Belenkov, S. (Sasha); J. Essers (Jeroen)

2016-01-01

textabstractThe use of Micro-Computed Tomography (MicroCT) for in vivo studies of small animals as models of human disease has risen tremendously due to the fact that MicroCT provides quantitative high-resolution three-dimensional (3D) anatomical data non-destructively and longitudinally. Most

Real-time in-vivo μ-imaging with Medipix2

International Nuclear Information System (INIS)

Dammer, J.; Frallicciardi, P.M.; Jakubek, J.; Jakubek, M.; Pospisil, S.; Prenerova, E.; Vavrik, D.; Volter, L.; Weyda, F.; Zemek, R.

2009-01-01

An X-ray micro-radiographic system based on the Medipix2 semiconductor pixel detector for dynamic high spatial resolution and for high contrast imaging has been developed. Our system is based on a micro-focus and nano-focus X-ray tube and the hybrid single-photon counting silicon pixel detector Medipix2 (matrix 256x256 sq. pixels of 55 μm pitch). This compact table-top system stands promising as a new tool in the field of small animal imaging as well as in the in-vivo observation of dynamic processes inside living organisms. The main advantages of these Medipix2 pixel detectors include: high sensitivity to low-energy X-ray photons; position sensitive and noiseless single-photon detection with preselected photon energies; single-quantum counting in each pixel performed by digital counter (therefore there is no dark current); digital integration (providing unlimited dynamic range and absolute linearity in device response to number of photons, high sensitivity and high contrast); real-time digital information, high-speed digital communication and data transfer. We improve the picture quality with the help of statistical data analysis and extended the calibration of individual pixels response. 2D and 3D radiographic images of samples demonstrate the potential and applicability of our system for precise in-vivo X-ray high-resolution dynamic diagnostic and biological studies. Obtained results are shown on small animal and organic samples.

Real-time in vivo detection of biomaterial-induced reactive oxygen species

OpenAIRE

Liu, Wendy F.; Ma, Minglin; Bratlie, Kaitlin M.; Dang, Tram T.; Langer, Robert; Anderson, Daniel G.

2010-01-01

The non-specific host response to implanted biomaterials is often a key challenge of medical device design. To evaluate biocompatibility, measuring the release of reactive oxygen species (ROS) produced by inflammatory cells in response to biomaterial surfaces is a well-established method. However, the detection of ROS in response to materials implanted in vivo has not yet been demonstrated. Here, we develop a bioluminescence whole animal imaging approach to observe ROS released in response to...

Performance of the first Japanese large-scale facility for radon inhalation experiments with small animals

International Nuclear Information System (INIS)

Ishimori, Y.; Mitsunobu, F.; Yamaoka, K.; Tanaka, H.; Kataoka, T.; Sakoda, A.

2011-01-01

A radon test facility for small animals was developed in order to increase the statistical validity of differences of the biological response in various radon environments. This paper illustrates the performances of that facility, the first large-scale facility of its kind in Japan. The facility has a capability to conduct approximately 150 mouse-scale tests at the same time. The apparatus for exposing small animals to radon has six animal chamber groups with five independent cages each. Different radon concentrations in each animal chamber group are available. Because the first target of this study is to examine the in vivo behaviour of radon and its effects, the major functions to control radon and to eliminate thoron were examined experimentally. Additionally, radon progeny concentrations and their particle size distributions in the cages were also examined experimentally to be considered in future projects. (authors)

New quantitative and multi-modal approach for in-vivo studies of small animals: coupling of the β-microprobe with magnetic techniques and development of voxelized rat and mouse phantoms

International Nuclear Information System (INIS)

Desbree, A.

2005-09-01

For the last 15 years, animal models that mimic human disorders have become ubiquitous participants to understand biological mechanisms and human disorders and to evaluate new therapeutic approaches. The necessity to study these models in the course of time has stimulated the development of instruments dedicated to in vivo small animal studies. To further understand physiopathological processes, the current challenge is to couple simultaneously several of these methods. Given this context, the combination of the magnetic and radioactive techniques remains an exciting challenge since it is still limited by strict technical constraints. Therefore we propose to couple the magnetic techniques with the radiosensitive Beta-Microprobe, developed in the IPB group and which shown to be an elegant alternative to PET measurements. In this context, the thesis was dedicated to the study of the coupling feasibility from a physical point of view, by simulation and experimental characterizations. Then, the determination of a biological protocol was carried out on the basis of pharmacokinetic studies. The experiments have shown the possibility to use the probe for radioactive measurements under intense magnetic field simultaneously to anatomical images acquisitions. Simultaneously, we have sought to improve the quantification of the radioactive signal using a voxelized phantom of a rat brain. Finally, the emergence of transgenic models led us to reproduce pharmacokinetic studies for the mouse and to develop voxelized mouse phantoms. (author)

Cell-specific monitoring of protein synthesis in vivo.

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Nikos Kourtis

Full Text Available Analysis of general and specific protein synthesis provides important information, relevant to cellular physiology and function. However, existing methodologies, involving metabolic labelling by incorporation of radioactive amino acids into nascent polypeptides, cannot be applied to monitor protein synthesis in specific cells or tissues, in live specimens. We have developed a novel approach for monitoring protein synthesis in specific cells or tissues, in vivo. Fluorescent reporter proteins such as GFP are expressed in specific cells and tissues of interest or throughout animals using appropriate promoters. Protein synthesis rates are assessed by following fluorescence recovery after partial photobleaching of the fluorophore at targeted sites. We evaluate the method by examining protein synthesis rates in diverse cell types of live, wild type or mRNA translation-defective Caenorhabditis elegans animals. Because it is non-invasive, our approach allows monitoring of protein synthesis in single cells or tissues with intrinsically different protein synthesis rates. Furthermore, it can be readily implemented in other organisms or cell culture systems.

Behavior of cardiac variables in animals exposed to cigarette smoke

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Sergio Alberto Rupp de Paiva

2003-09-01

Full Text Available OBJECTIVE: To assess the behavior of cardiac variables in animals exposed to cigarette smoke. METHODS: Two groups of Wistar rats were studied as follows: control group (C, comprising 28 animals; and smoking group (S, comprising 23 animals exposed to cigarette smoke for 30 days. Left ventricular cardiac function was assessed in vivo with transthoracic echocardiography, and myocardial performance was analyzed in vitro in preparations of isolated left ventricular papillary muscle. The cardiac muscle was assessed in isometric contractions with an extracellular calcium concentration of 2.5 mmol/L. RESULTS: No statistical difference was observed in the values of the body variables of the rats and in the mechanical data obtained from the papillary muscle between the control and smoking groups. The values of left ventricular systolic diameter were significantly greater in the smoking animals than in the control animals (C= 3.39 ± 0.4 mm and S= 3.71 ± 0.51 mm, P=0.02. A significant reduction was observed in systolic shortening fraction (C= 56.7 ± 4.2% and S= 53.5 ± 5.3%, P=0.02 and in ejection fraction (C= 0.92 ± 0.02 and S= 0.89 ± 0.04, P=0.01. CONCLUSION: The rats exposed to cigarette smoke had a reduction in left ventricular systolic function, although their myocardial function was preserved.

Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

Science.gov (United States)

Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

2014-01-01

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

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Meixensberger Jürgen

2010-01-01

Full Text Available Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu, were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p Conclusion As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Waning of "conditioned pain modulation": a novel expression of subtle pronociception in migraine.

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Nahman-Averbuch, Hadas; Granovsky, Yelena; Coghill, Robert C; Yarnitsky, David; Sprecher, Elliot; Weissman-Fogel, Irit

2013-01-01

To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. One of the most explored mechanisms underlying the pain modulation system is "diffuse noxious inhibitory controls," which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) "test-stimulus" (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition "0" consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028). Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine. © 2013 American Headache Society.

A rapid method for selecting suitable animal species for studying pathogen interactions with plasma protein ligands in vivo.

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Naudin, Clément; Schumski, Ariane; Salo-Ahen, Outi M H; Herwald, Heiko; Smeds, Emanuel

2017-05-01

Species tropism constitutes a serious problem for developing relevant animal models of infection. Human pathogens can express virulence factors that show specific selectivity to human proteins, while their affinity for orthologs from other species can vary significantly. Suitable animal species must be used to analyse whether virulence factors are potential targets for drug development. We developed an assay that rapidly predicts applicable animal species for studying virulence factors binding plasma proteins. We used two well-characterized Staphylococcus aureus proteins, SSL7 and Efb, to develop an ELISA-based inhibition assay using plasma from different animal species. The interaction between SSL7 and human C5 and the binding of Efb to human fibrinogen and human C3 was studied. Affinity experiments and Western blot analyses were used to validate the assay. Human, monkey and cat plasma interfered with binding of SSL7 to human C5. Binding of Efb to human fibrinogen was blocked in human, monkey, gerbil and pig plasma, while human, monkey, gerbil, rabbit, cat and guinea pig plasma inhibited the binding of Efb to human C3. These results emphasize the importance of choosing correct animal models, and thus, our approach is a rapid and cost-effective method that can be used to prevent unnecessary animal experiments. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Infection routes of Aeromonas salmonicida in rainbow trout monitored in vivo by real-time bioluminescence imaging

DEFF Research Database (Denmark)

Bartkova, Simona; Kokotovic, Branko; Dalsgaard, Inger

2017-01-01

Recent development of imaging tools has facilitated studies of pathogen infections in vivo in real time. This trend can be exemplified by advances in bioluminescence imaging (BLI), an approach that helps to visualize dissemination of pathogens within the same animal over several time points. Here...

Contralateral prophylactic mastectomy: current perspectives

Science.gov (United States)

Yao, Katharine; Sisco, Mark; Bedrosian, Isabelle

2016-01-01

There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) in the United States among women diagnosed with unilateral breast cancer, particularly young women. Approximately one-third of women CPM in the US. Most studies have shown that the CPM trend is mainly patient-driven, which reflects a changing environment for newly diagnosed breast cancer patients. The most common reason that women choose CPM is based on misperceptions about CPM’s effect on survival and overestimation of their contralateral breast cancer (CBC) risk. No prospective studies have shown survival benefit to CPM, and the CBC rate for most women is low at 10 years. Fear of recurrence is also a big driver of CPM decisions. Nonetheless, studies have shown that women are mostly satisfied with undergoing CPM, but complications and subsequent surgeries with reconstruction have been associated with dissatisfaction with CPM. Studies on surgeon’s perspectives on CPM are sparse but show that the most common reasons surgeons discuss CPM with patients is because of a suspicious family history or for a patient who is a confirmed BRCA mutation carrier. Studies on the cost–effectiveness of CPM have been conflicting and are highly dependent on patient’s quality of life after CPM. Most recent guidelines for CPM are contradictory. Future areas of research include the development of interventions to better inform patients about CPM, modification of the guidelines to form a more consistent statement, longer term studies on CBC risk and CPM’s effect on survival, and prospective studies that track the psychosocial effects of CPM on body image and sexuality. PMID:27382334

A clinically relevant in vivo model for the assessment of scaffold efficacy in abdominal wall reconstruction

Directory of Open Access Journals (Sweden)

Jeffrey CY Chan

2016-12-01

Full Text Available An animal model that allows for assessment of the degree of stretching or contraction of the implant area and the in vivo degradation properties of biological meshes is required to evaluate their performance in vivo. Adult New Zealand rabbits underwent full thickness subtotal unilateral rectus abdominis muscle excision and were reconstructed with the non-biodegradable Peri-Guard®, Prolene® or biodegradable Surgisis® meshes. Following 8 weeks of recovery, the anterior abdominal wall tissue samples were collected for measurement of the implant dimensions. The Peri-Guard and Prolene meshes showed a slight and obvious shrinkage, respectively, whereas the Surgisis mesh showed stretching, resulting in hernia formation. Surgisis meshes showed in vivo biodegradation and increased collagen formation. This surgical rabbit model for abdominal wall defects is advantageous for evaluating the in vivo behaviour of surgical meshes. Implant area stretching and shrinkage were detected corresponding to mesh properties, and histological analysis and stereological methods supported these findings.

Comparison of the in vitro and in vivo dissolution rates of two diuranates and research on an early urinary indicator of renal failure in humans and animals poisoned with uranium

International Nuclear Information System (INIS)

Henge-Napoli, M.H.; Rongier, E.; Ansoborlo, E.; Chalabreysse, J.

1989-01-01

The objective of this study was to investigate the solubility of industrial calcined diuranate in various in vitro systems and to test the sensitivity of biological parameters in detecting renal alterations after intoxication in animals and in human subjects. The dissolution rates in in vitro static and dynamic tests are consistent for each solution for both types of test. The in vivo results are comparable to the in vitro results obtained with Gamble solution for both compounds. The excretion kinetics observed are compared with the values calculated from ICRP standards. Urinary GGT excretion measurements are found to be a satisfactory indicator of uranium-induced kidney alterations. GGT excretion increases for injected doses exceeding 50 μg.kg -1 . Initial results in human subjects suggest that following accidental exposure to uranium, GGT is a more sensitive indicator of kidney damage than glycosuria. (author)

Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing.

Science.gov (United States)

Aida, Tomomi; Imahashi, Risa; Tanaka, Kohichi

2014-01-01

Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically improved our understanding of the functions of genes in vivo and the genetic diversity that characterizes health and disease. However, the generation of targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a time-consuming, laborious, and expensive process. The recent groundbreaking development of several genome editing technologies has enabled the targeted alteration of almost any sequence in any cell or organism. These technologies have now been applied to mouse zygotes (in vivo genome editing), thereby providing new avenues for simple, convenient, and ultra-rapid production of knockout or knockin mice without the need for ES cells. Here, we review recent achievements in the production of gene-targeted mice by in vivo genome editing. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

New 'ex vivo' radioisotopic method of quantitation of platelet deposition

International Nuclear Information System (INIS)

Badimon, L.; Mayo Clinic, Rochester, MN; Thrombosis and Atherosclerosis Unit, Barcelona; Mayo Clinic, Rochester, MN; Fuster, V.; Chesebro, J.H.; Dewanjee, M.K.

1983-01-01

We have developed a sensitive and quantitative method of 'ex vivo' evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion. (orig.)

In Vitro and In Vivo Leishmanicidal Activity of Astronium fraxinifolium (Schott and Plectranthus amboinicus (Lour. Spreng against Leishmania (Viannia braziliensis

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Silvio César Gomes de Lima

2014-01-01

Full Text Available The aim of the present work was to evaluate antileishmanial activity of Astronium fraxinifolium and Plectranthus amboinicus. For the in vitro tests, essential oil of P. amboinicus (OEPA and ethanolic extracts from A. fraxinifolium (EEAF were incubated with 106  promastigotes of L. (Viannia braziliensis. The OEPA was able to reduce the parasite growth after 48 h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c mice were infected subcutaneously (s.c. with 107  L. braziliensis promastigotes. Treatment was done by administering OEPA intralesionally (i.l. for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 106  L. braziliensis promastigotes. The first protocol of treatment consisted of ethanolic leaf extract from A. fraxinifolium (ELEAF administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract from A. fraxinifolium.

Oxide nano crystals for in vivo imaging

International Nuclear Information System (INIS)

Heinrich, E.

2005-01-01

For small animal, fluorescence imaging is complementary with other techniques such as nuclear imaging (PET, SPECT). In vivo imaging studies imply the development of new luminescent probes, with a better sensitivity and a better biological targeting. These markers must filled biological and optical conditions. Our goal is to study new doped lanthanides oxide nano-crystals, their properties, their functionalization and their ability to target biological molecules. Characterizations of Y 2 O 3 :Eu and Y 2 SiO 5 :Eu nano-crystals (light diffusion, spectrometry, microscopy) allowed the determination of their size, their fluorescence properties but also their photo-bleaching. Means of stabilization of the nanoparticles were also studied in order to decrease their aggregation. Gd 2 O 3 :Eu nano-crystals were as well excited by X rays. Nano-crystals of Y 2 SiO 5 :Eu were functionalized, and organic ligands grafting evidenced by fluorescence and NMR. The functionalized nano-crystals could then recognized biological targets (streptavidin-biotin) and be incubated in the presence of HeLa cells. This report deals with the properties of these nano-crystals and their ability to meet the optical and biological conditions required for the application of in vivo imaging. (author)

The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo.

Science.gov (United States)

Chowdhury, Golam M I; Jiang, Lihong; Rothman, Douglas L; Behar, Kevin L

2014-07-01

The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4-(13)C₂]-D-β-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies (V(acCoA-kbN)) and pyruvate (V(pdhN)), and the glutamate-glutamine cycle (V(cyc)) were determined by metabolic modeling of (13)C label trapped in major brain amino acid pools. V(acCoA-kbN) increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate (V(tcaN)), supporting a decreasing percentage of neuronal ketone oxidation: ∼100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels >17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38%) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half of the activity-dependent oxidative needs of neurons.

Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

Directory of Open Access Journals (Sweden)

Al Asmari AK

2016-10-01

Full Text Available Abdulrahman K Al Asmari, Abdul Quaiyoom Khan Research Centre, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Abstract: Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo antitumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone. Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 µg, 35 µg, and 52.5 µg per animal were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. Keywords: Leiurus quinquestriatus, skin cancer, apoptosis, immunosuppression

Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.